Springer Science and Business Media LLCActa Medica Okayama2168-818418112026Palbociclib (CDK4/6 Inhibitor)-Related Uveitis With Cystoid Macular Edema in Metastatic Breast Cancer: A Case Report and Review of Small-Molecule Targeted Drug-Related Uveitise119100ENToshihikoMatsuoDepartment of Ophthalmology, Ochiai HospitalYukoTakahashiDepartment of Breast and Endocrine Surgery, Okayama University HospitalTadahikoShienDepartment of Breast and Endocrine Surgery, Okayama University HospitalTakehiroTanakaDepartment of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityNaoyukiIdaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityShojiNagaoDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKasumiTakahashiDepartment of Obstetrics and Gynecology, Ochiai HospitalTsunemasaKondoDepartment of Obstetrics and Gynecology, Ochiai HospitalPalbociclib is one of the cyclin-dependent kinase 4/6 (CDK4/6) inhibitors that are used together with hormone therapy for relapsed and metastatic breast cancer as standard therapy. In this report, we describe the case of a patient who presented with bilateral anterior uveitis with cystoid macular edema in the right eye while on palbociclib with fulvestrant. The patient underwent partial breast resection for estrogen receptor-positive, progesterone receptor-positive, and human epidermal growth factor receptor 2 (HER2)-negative breast cancer with no involvement of sentinel lymph nodes at the age of 44 years. She had undergone right breast radiation at a total dose of 50 Gy and hormone therapy for five years with no relapse or metastasis. At the age of 59 years, she was found to have uterine endometrial cancer, and systemic evaluation disclosed metastatic lesions in lymph nodes, lungs, and bones. Biopsy of the iliac bone proved breast cancer metastasis. She began to take anastrozole initially and, one month later, underwent total hysterectomy and bilateral salpingo-oophorectomy. She was then started on abemaciclib with denosumab for four months but developed a marked elevation of serum liver enzymes. Abemaciclib was then switched to palbociclib with anastrozole in the following nine months. After a change to capecitabine, in one year, the patient was started on another course of palbociclib, this time with fulvestrant, at the age of 62 years, when she developed bilateral uveitis with cystoid macular edema in the right eye. The uveitis and macular edema showed a good response to topical 0.1% betamethasone alone, and she continued palbociclib with fulvestrant. We also reviewed the literature on uveitis in association with small-molecule targeted drugs to inhibit specific intracellular signaling in the treatment of malignancies.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0012-369217042026Impact of Preexisting Schizophrenia Spectrum Disorders on the Receipt of Surgery and Other Treatments for Non-Small Cell Lung Cancer: A Multicenter Nationwide Cohort Study in JapanENYutoYamadaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasakiFujiwaraDepartment of Neuropsychiatry, Medical Development Field, Okayama UniversityTaisukeIshiiDivision of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer CenterTomoneWatanabeDivision of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer CenterMaikoFujimoriDivision of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer CenterNaokiNakayaTohoku Medical Megabank Organization, Tohoku UniversityToshihikoKawamuraDepartment of Medical Informatics, Shimane University HospitalKojiOtsukiDepartment of Psychiatry, Faculty of Medicine, Shimane UniversityEikiIchiharaCenter for Clinical Oncology, Okayama University HospitalTaichiShimazuDivision of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer CenterShiroHinotsuDepartment of Biostatistics and Data Management, Sapporo Medical UniversityYosukeUchitomiDepartment of Cancer Survivorship and Digital Medicine, The Jikei University School of MedicineMasatoshiInagakiDepartment of Psychiatry, Faculty of Medicine, Shimane UniversityBackground: Patients with schizophrenia spectrum disorders (SSDs) experience higher cancer mortality than the general population. Disparities in treatments for non-small cell lung cancer (NSCLC) among this population remain underexamined.<br>
Research Question: Are patients with SSDs less likely to receive surgery, adjuvant chemotherapy for stage II/IIIA, concurrent chemoradiotherapy for stage III, and systemic therapy for stage IV NSCLC compared with those without psychiatric disorders?<br>
Study Design and Methods: This retrospective cohort study used national Hospital-Based Cancer Registry data linked to hospital-based administrative data in Japan. It included patients who received initial treatment for NSCLC between 2018 and 2021. Presence of SSDs was defined as a diagnosis using F20 to F29 codes from International Classification of Diseases, 10th Revision. The primary outcome was receipt of surgery for NSCLC. Secondary outcomes were receipt of the following: (1) adjuvant chemotherapy within 180 days in patients with pathologic stage II/IIIA NSCLC; (2) concurrent chemoradiotherapy in clinical stage III NSCLC; and (3) systemic therapy in stage IV NSCLC. Multivariable logistic regression adjusted for age, sex, clinical stage, comorbidities, and functional status was performed.<br>
Results: The final cohort comprised 166,663 patients, 1,346 of whom had SSDs. Patients with SSDs were more likely to be diagnosed at stage IV NSCLC (45.0% vs 31.4%) and less likely to undergo surgery (31.5% vs 49.9%; adjusted OR [aOR], 0.70; 95% CI, 0.57-0.85), receive adjuvant chemotherapy (aOR, 0.31; 95% CI, 0.17-0.57), or receive systemic therapy (aOR, 0.54; 95% CI, 0.45-0.65). No significant difference was observed in concurrent chemoradiotherapy for stage III NSCLC (aOR, 0.99; 95% CI, 0.73-1.34).<br>
Interpretation: Patients with SSDs were less likely to receive surgery and other stage-appropriate treatments for NSCLC, highlighting the need for targeted interventions to promote equitable cancer care for these individuals.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2075-441816202026Association Between Urine pH and Kidney Outcomes in Patients with Biopsy-Proven Kidney Disease3418ENKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaruhikoUchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroyukiNakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshitakaInoueDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground/Objectives: Lower urine pH has been associated with reduced kidney function and increased risk of kidney disease, but its prognostic and pathological significance in biopsy-proven kidney disease remains unclear. Medullary cast formation has been shown to predict adverse renal outcomes beyond cortical interstitial fibrosis and tubular atrophy (IFTA), although its clinical determinants are not fully understood. We examined the associations of urine pH with kidney outcomes and medullary cast formation in patients undergoing native kidney biopsy. Methods: Among 1167 adults who underwent native kidney biopsy between 2011 and 2024, 503 patients with evaluable medullary tissue were included. Urine pH was analyzed in relation to clinical and histological variables and kidney outcomes. The primary outcome was a ≥40% decline in estimated glomerular filtration rate (eGFR) or initiation of renal replacement therapy. Results: Mean baseline eGFR was 60.7 ± 26.2 mL/min/1.73 m2 and urine pH was 6.15 ± 0.84. During a median follow-up of 2.11 years, 113 patients (22.5%) reached the outcome. Lower urine pH was associated with higher risk of kidney outcomes. In multivariable Cox models, urine pH remained independently associated with outcomes (hazard ratio per 1-unit increase, 0.69; 95% CI, 0.52–0.92). Addition of urine pH modestly improved discrimination (C-index 0.642 to 0.654; likelihood ratio test, p = 0.009). Lower urine pH was associated with greater medullary cast formation in unadjusted analysis. Conclusions: Lower urine pH was independently associated with adverse kidney outcomes and with greater medullary cast formation, suggesting that urine pH may reflect intratubular pathological changes associated with CKD progression.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8052026Ruptured Intrahepatic Arterial Aneurysm due to Segmental Arterial Mediolysis Treated with Coil Embolization327332ENYurikaHataDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterMotoyasuTabuchiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterShinyaSakamotoDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterShutaTamuraDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterSunaoUemuraDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterTeppeiTokumaruDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterRikaYoshimatuDepartment of Radiology, Kochi Health Sciences CenterTakehiroOkabayashiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterCase Report/10.18926/AMO/71342A 67-year-old man presented with sudden-onset abdominal pain and hemorrhagic shock. Contrast-enhanced CT revealed a large hematoma in hepatic segments VI-VII with capsular rupture and hemoperitoneum. CT angiography demonstrated a saccular pseudoaneurysm in a posterior segmental branch of the right hepatic artery and a beaded appearance with irregular dilatation and segmental narrowing of the right hepatic artery branches, without inflammatory or atherosclerotic findings, supporting a diagnosis of segmental arterial mediolysis (SAM). Emergency angiography followed by coil embolization achieved hemostasis. Follow-up CT at 5 months showed complete exclusion of the aneurysmal lesions, with no evidence of recurrence or new vascular lesions. Coil embolization may be an effective, minimally invasive option for ruptured intrahepatic SAM lesions.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8052026Dynamics of Serum Amyloid A Levels in the Blood, Brain and Liver in a Mouse Model of Focal Cerebral Ischemia309316ENSakiEgashiraDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversityTakafumiNakanoDepartment of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka UniversityKeiichiIrieDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversitySoichiroUshioDepartment of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka UniversityAkikoManabeDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversityAyukoMasakiDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversityRieMukaiDepartment of Microbiology Laboratory, Faculty of Pharmaceutical Sciences, Fukuoka UniversityYoshihikoNakamuraDepartment of Emergency and Critical Care Medicine, Fukuoka University HospitalMasatoHosokawaDepartment of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversityTomomitsuSathoDepartment of Microbiology Laboratory, Faculty of Pharmaceutical Sciences, Fukuoka UniversityKazunoriSanoDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversityKenichiMishimaDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversityOriginal Article10.18926/AMO/71340This study examined the dynamics of serum amyloid A (SAA) levels in the blood, brain, and liver over time using a mouse model of focal cerebral ischemia induced by occlusion of the middle cerebral artery (MCA) for 4 h followed by reperfusion. Blood SAA concentrations increased transiently after cerebral infarction, coinciding with changes in brain and liver SAA gene expression and protein levels. SAA concentrations in the brain, liver, and blood increased at similar time points after cerebral infarction, suggesting that SAA may serve as an important indicator of the associated pathological condition.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8052026Prognostic Value of Combined Preoperative CALLY and SII Assessment in Patients Undergoing Resection for Esophageal Squamous Cell Carcinoma299308ENTaoXuDepartment of Oncology, The General Hospital of Western Theater CommandYingZhengDepartment of Oncology, The General Hospital of Western Theater CommandXuemeiHuangDepartment of Oncology, The General Hospital of Western Theater CommandHongLuoDepartment of Oncology, The General Hospital of Western Theater CommandOriginal Article/10.18926/AMO/71339This study evaluated the prognostic significance of the C-reactive protein–albumin–lymphocyte (CALLY) index and systemic immune-inflammation (SII) index in predicting postoperative outcomes in patients with esophageal squamous cell carcinoma (ESCC). A retrospective analysis was performed on clinical data from 102 patients with ESCC who underwent surgical resection at Western Theater General Hospital of China between January 2020 and July 2023. The associations between preoperative CALLY and SII indices and relapse-free survival (RFS) and overall survival (OS) were examined. Survival curves were generated using the Kaplan–Meier method, and prognostic factors were identified using Cox proportional hazards regression analysis. Patients with a high CALLY index had significantly longer RFS (HR=0.30, 95% CI: 0.13-0.71), and those with a low SII index also had significantly longer RFS (HR=2.23, 95% CI: 1.12-4.41). Similarly, patients with a high CALLY index had significantly longer OS (HR=0.27, 95% CI: 0.13-0.55), and those with a low SII index had significantly longer OS (HR=2.27, 95% CI: 1.09-4.71). When patients were stratified into four groups, the low-CALLY–high-SII group showed significantly shorter RFS than the high-CALLY–low-SII group (HR=0.26, 95% CI: 0.11-0.61; p=0.013), and OS was also significantly worse in the low-CALLY–high-SII group (HR=0.22, 95% CI: 0.09-0.54; p=0.016). Univariate Cox regression analysis identified both CALLY and SII as significant prognostic factors. In multivariate analysis, the CALLY index and N stage were independently associated with RFS, whereas only tumor size remained independently associated with OS. The combined assessment of preoperative CALLY and SII indices may be useful for prognostic stratification in patients with ESCC undergoing upfront surgical resection. It may help identify high-risk patient subgroups with distinct survival outcomes, thereby providing a potential rationale for stratifying postoperative surveillance and tailoring individualized adjuvant strategies, although validation in larger prospective cohorts is warranted.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0047-63742342026The eukaryotic host–microbe–phage–nutrition interplay determines the bacterial effectors of supplemental lysine’s health benefits: An experimental cellular senescence model of digestive conditions in older adults112260ENDarabGhadimiDepartment of Microbiology and Biotechnology, Max Rubner-InstitutSophiaBlömerFaculty of Medicine, Christian-Albrechts-University of KielAysel ŞAHİNKAYADepartment of Nutrition and Dietetics, Faculty of Health Sciences, Antalya Bilim UniversitySandraKrügerInstitute of Pathology, Kiel University, University Hospital, Schleswig-HolsteinChristophRöckenInstitute of Pathology, Kiel University, University Hospital, Schleswig-HolsteinHeinerSchäferLaboratory of Molecular Gastroenterology & Hepatology, Christian-Albrechts-University & UKSH Campus KielGeraldinede HeerUniversity Center for Nutritional Medicine, University Medical Centre Hamburg-EppendorfDominikJarczakUniversity Center for Nutritional Medicine, University Medical Centre Hamburg-EppendorfJumpeiUchiyamaDepartment of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityShigenobuMatsuzakiDepartment of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen UniversityWilhelmBockelmannDepartment of Microbiology and Biotechnology, Max Rubner-InstitutRecently, the consumption of various forms of the nutritive amino acid lysine (e.g., nutraceuticals and dietary supplements) has increased, particularly among the elderly, as it cannot be synthesized by the human body and plays a crucial role in several cellular physiological processes, including intestinal calcium and iron absorption, proteinogenesis, and fatty acid metabolism. However, the biochemical and immunological events that occur within the eukaryotic host-microbe-phage-nutrition interaction, especially when high amounts of lysine are consumed in nutraceutical or dietary supplement form by the elderly due to age-related requirements, as well as the impact on gut bacteria-derived metabolites, have not yet been fully studied. We hypothesized that (1) within an infectious-inflamed digestive milieu, the metabolism of excess extracellular lysine differs between young and senescent digestive cells, and (2) phages within the milieu exhibit alterations in host-microbe cometabolite signal profiles. To address this, we examined how gut microbes and phages, key regulators of eukaryotic host physiology, influence the immunometabolism of excess lysine. By combining two models of young and senescent digestive cells, the pathogenic P. aeruginosa PAO1, the Pseudomonas phage KPP22, and the anti-inflammatory bacterium Intestinimonas butyriciproducens, and simulating the pathogenesis of the interactive process of excessive lysine ingestion, we developed a five-way screening approach to explore key cell readouts, including viability, integrity, and function of the epithelial barrier, as well as cellular immunometabolic responses to exogenous lysine supplementation in cultures under infectious inflammation. Our findings are consistent with the possibility that host–microbe–microbe interactions involving lysine utilization and cross-feeding may influence the effects of lysine supplementation. These effects, whether beneficial or detrimental, can depend on the bacterial community, including the presence of pathogenic or potentially beneficial bacteria, interactions with intestinal phages, and the physiological conditions and metabolic requirements of the host and individual microbial taxa.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2198-38442026SPRED2 Negatively Regulates CD8+ T Cell-Mediated Antitumor Immunity in Breast Cancere77909ENMiaoTianDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTeizoYoshimuraDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKunZhaoDepartment of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChunningLiDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTongGaoDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityZiyiWangDepartment of Advanced International and Information Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasayoshiFujisawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiakiOharaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAkihiroMatsukawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityActivation of the RAS/RAF/ERK pathway is crucial for adaptive immunity. Here, we provide evidence that Sprouty-related EVH1 domain containing 2 (SPRED2), an endogenous inhibitor of this pathway, negatively regulates CD8+ T cell-mediated antitumor immunity in breast cancer. In EO771 and 4T1 mouse models, Spred2−/− mice exhibit reduced tumor growth, with lower endpoint lung metastatic burden in the 4T1 model, accompanied by increased T-cell infiltration and activation. Spred2−/− T cells show enhanced cytokine expression, proliferation,survival, in vitro cytotoxicity, and memory-like phenotypes, particularly among CD8+ T cells. Adoptive transfer of Spred2−/− CD8+ T cells into tumor-bearing wild-type hosts similarly reduces endpoint lung metastatic burden. MEK inhibition with U0126 attenuates increased interferon-gamma and granzyme B expression in Spred2−/− CD8+ T cells. Transcriptomic analyses reveal an inverse correlation between SPRED2 expression and antitumor CD8+ T cell states in both humans and mice. In tumor-infiltrating T cells from patients with breast cancer, SPRED2low T cells show enriched effector and cytotoxicity programs and are associated with “immune-hot” tumors, whereas survival associations vary with CD8+ T cell context. Collectively, these findings suggest that SPRED2 functions as a cell-intrinsic negative regulator of CD8+ T-cell activation and highlight its potential as a therapeutic target to enhance T cell–based cancer immunotherapy.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0361-860910042025Exploring the Clinical Diversity of Castleman Disease and TAFRO Syndrome: A Japanese Multicenter Study on Lymph Node Distribution Patterns592605ENMizunaOtsukaDepartment of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical SciencesTomohiroKogaDepartment of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical SciencesRemiSumiyoshiDepartment of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical SciencesShoichiFukuiDepartment of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical SciencesYukoKanekoDivision of Rheumatology, Department of Internal Medicine Keio University School of Medicine Tokyo JapanTakayukiShimizuDivision of Hematology, Department of Medicine, Keio University School of MedicineAtsushiKatsubeDivision of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of MedicineShingoYanoDivision of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of MedicineYasufumiMasakiDepartment of Hematology and Immunology, Kanazawa Medical UniversityMakotoIdeDepartment of Hematology, Takamatsu Red Cross HospitalHajimeYoshifujiDDepartment of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto UniversityMasayasuKitanoDepartment of Collagen Disease and Rheumatology, Sumitomo HospitalYasuharuSatoDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesNaokiSawaNephrology Center and Department of Rheumatology, Toranomon Hospital KajigayaHiroakiNiiroDepartment of Clinical Immunology and Rheumatology/Infectious Disease, Kyushu University HospitalNaoyaNakamuraDepartment of Pathology, Tokai University School of MedicineDavid C.FajgenbaumCenter for Cytokine Storm Treatment & Laboratory, University of PennsylvaniaFritsvan RheeMyeloma Center, University of Arkansas for Medical SciencesAtsushiKawakamiDepartment of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical SciencesIndividuals diagnosed with Castleman disease (CD) and TAFRO syndrome (characterized by thrombocytopenia, anasarca, fever, bone marrow fibrosis, and organomegaly) displays a wide range of clinical symptoms, including varying patterns of lymph node enlargement, systemic inflammation, and impaired organ function. Some patients may present with both CD and TAFRO syndrome concurrently. A retrospective study conducted across multiple centers in Japan examined 321 cases to determine if the quantity and position of swollen lymph nodes could forecast the clinical progression and intensity of these conditions. Interestingly, the study revealed that patients with TAFRO syndrome exhibited lymphadenopathy across all ranges of lymph node region counts. Moreover, no specific clinical patterns were associated with the number of affected lymph node regions in CD patients, regardless of whether they also had TAFRO syndrome. These results enhance our understanding of the clinical variability in CD and TAFRO syndrome, suggesting that a comprehensive clinical evaluation, rather than relying solely on lymph node count, is crucial for effectively managing these conditions. Additional studies are required to establish reliable diagnostic markers and to predict disease severity at the time of diagnosis, ultimately improving patient outcomes.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1328-80676712025A case of fetal myocardial calcification with hyperechoic area in fetal echocardiographye15868ENTakeshiSatoDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYosukeWashioDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHotakaKawaiDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiBabaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesErikoEtoDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHisashiMasuyamaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHirokazuTsukaharaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.BMJActa Medica Okayama2044-60551682026Study protocol for a phase II clinical trial evaluating the safety and efficacy of favipiravir injection combined with oseltamivir in influenza treatmente106715ENSayakaHikidaDisease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health SecurityHidetoshiNomotoDisease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health SecurityYukariUemuraLaboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health SecurityTadakiSuzukiDepartment of Infectious Disease Pathology, National Institute of Infectious Diseases, Japan Institute for Health SecurityKoichiIzumikawaDepartment of Infectious Diseases, Nagasaki University Graduate School of Biomedical SciencesHirokiOhgeProject Research Center for Nosocomial Infectious Diseases, Hiroshima UniversityMasayaYamatoInfectious Diseases Center, Rinku General Medical CenterYasuyukiKatoDepartment of Infectious Diseases, International University of Health and Welfare Narita HospitalRyotaHaseDepartment of Infectious Diseases, Japanese Red Cross Narita HospitalTetsujiAoyagiDepartment of Clinical Microbiology and Infection, Tohoku University Graduate School of MedicineHideharuHagiyaDepartment of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYokoNukuiDepartment of Infection Control & Laboratory Medicine, Kyoto Prefectural University of MedicineKazukoYamamotoFirst Department of Internal Medicine, Division of Infectious, Respiratory, and Digestive Medicine, University of the Ryukyus Graduate School of MedicineYoshioTakesueChita Peninsula General Medical Organization, Rinku HospitalKotaSawadaLaboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health SecurityYosukeShimizuLaboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health SecurityShoMiyamotoDepartment of Infectious Disease Pathology, National Institute of Infectious Diseases, Japan Institute for Health SecurityNamikoTamuraDisease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health SecurityKozueTakahashiDisease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health SecurityShoSaitoDisease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health SecurityKazukiMiyazakiCenter for Clinical Sciences, Japan Institute for Health SecurityErikoMorinoCenter for Clinical Sciences, Japan Institute for Health SecurityDaisukeTokitaCenter for Clinical Sciences, Japan Institute for Health SecurityNorioOhmagariDisease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health SecurityIntroduction Older adults are at an increased risk of influenza-related hospitalisation and mortality due to a combination of risk factors. Severe influenza and excess mortality in this population remain major public health concerns, underscoring the need for novel treatment strategies.<br>
Methods and analysis This multicentre, investigator-initiated, randomised, double-blind clinical trial evaluated the efficacy and safety of the investigational drug favipiravir injection (T-705IV) in combination with oseltamivir phosphate, compared with oseltamivir monotherapy in hospitalised patients with influenza aged ≥65 years. Both T-705IV and oseltamivir phosphate will be administered for 5 days. The primary endpoint is time from randomisation to recovery within 15 days. Recovery is defined as either actual hospital discharge or sustained clinical status permitting discharge for 3 consecutive days. Clinical status will be assessed using a 7-point ordinal scale based on hospitalisation status and oxygen requirement. The primary analysis employs a Bayesian Cox proportional hazards model with a non-informative prior to estimate the posterior probability that the HR exceeds 1.0. The secondary endpoints include the distribution of 7-point scale scores over a 29-day period; rates of clinical worsening at days 15 and 29; duration of fever; all-cause mortality; intensive care unit admission within 29 days; pneumonia complication rate at 15 days; and changes in viral titre and viral RNA load on days 1, 2, 3 and 7. Safety will be assessed through the collection of adverse events (AEs) up to day 29. Pharmacokinetic evaluation will include measurement of plasma favipiravir concentrations on day 3. The planned sample size is 80 patients (40 per group).<br>
Ethics and dissemination Written informed consent will be obtained from all participants. This study was approved by the Center Hospital of the National Center for Global Health and Medicine Institutional Review Board (approval number: NCGM-I-022-24a) and registered in the Japan Registry of Clinical Trials. Study findings will be disseminated through peer-reviewed publications and/or presentations at academic conferences.<br>
Trial registration number jRCT2031240586,No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1345-26302026Macroscopic and microscopic visualization of Pseudomonas syringae pv. tabaci infection using complementary bioluminescent and fluorescent reporter systemsENKanaKuroeGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNanamiSakataGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYasuhiroIshigaFaculty of Life and Environmental Sciences, University of TsukubaYoshiteruNoutoshiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKazuhiroToyodaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYukiIchinoseGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHidenoriMatsuiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThe development of bioluminescent and fluorescent reporter systems has enabled visualization of plant-pathogenic bacterial infection dynamics, providing insights into detailed mechanisms of infection and potential applications for disease control. Pseudomonas syringae pv. tabaci 6605 (Pta) possesses quorum sensing systems and produces fluorescent pigments, which make it difficult to directly apply commonly used reporter systems. In this study, we first constructed a homologous recombination-based genomic insertion system for stable chromosomal integration of reporter genes in Pta. Using this system, we established a LuxCDABE bioluminescent system driven by the nptII promoter, which successfully enabled macroscale tracking of bacterial populations during infection. We then attempted to construct an sGFP fluorescent reporter using the same nptII promoter. However, the endogenous autofluorescence of Pta masked the sGFP signal, making quantitative detection difficult. To overcome this autofluorescence problem, we screened constitutively highly expression promoters based on transcriptome data and identified two effective promoters suitable for fluorescent monitoring of Pta infection. Together with the LuxCDABE system, this integrated platform provides comprehensive spatiotemporal analysis of virulence mechanisms and plant defense responses in the Pta pathosystem, with potential applicability to other plant-pathogenic bacteria.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1758-59021912026Transcystostomal Bladder Tumor Resection in a Transgender Man After Phalloplastye70330ENTakatoshiMoriwakeDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYusukeTominagaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNariakiOzakiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukoMatsumotoDepartment of Urology, Miyakekai Good Life HospitalTomokoKobayashiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIchiroTsuboiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKasumiYoshinagaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoakiYamanoiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTatsushiKawadaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuyaSadahiraDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiKatayamaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShingoNishimuraDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKensukeBekkuDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuzaburoNambaGender Center, Okayama University HospitalMotooArakiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIntroduction<br>
Phalloplasty in transgender men is frequently complicated by a neourethral stricture, precluding standard transurethral access for bladder tumor resection. We describe the first reported case of a transcystostomal bladder tumor resection in a transgender man after a radial forearm free flap (RFFF) phalloplasty.<br>
Materials and Surgical Technique<br>
A 65-year-old transgender man, 23 years after an RFFF phalloplasty, presented with gross hematuria and a 15-mm posterior bladder tumor. A 7.95 Fr flexible ureteroscope reached the bladder but with markedly limited maneuverability. A two-stage transcystostomal approach was used: a 14 Fr suprapubic cystostomy (SPC) was placed 1 month before resection for tract maturation, followed by balloon dilation and insertion of a 24 Fr resectoscope. The modified Valdivia position enabled simultaneous transcystostomal and transurethral access with gravity-assisted irrigation drainage. Complete tumor resection was achieved without complications, and pathology confirmed noninvasive papillary urothelial carcinoma (pTa, low-grade) with negative margins. A single immediate intravesical instillation of pirarubicin was administered. Surveillance cystoscopy via the cystostomy tract at 3 and 6 months revealed no recurrence; the patient continues to void while standing with the cystostomy catheter capped.<br>
Discussion<br>
The two-stage transcystostomal approach, combining prior SPC placement, balloon tract dilation, and the modified Valdivia position, enabled safe oncological control while preserving phallic anatomy and standing voiding function. This technique offers a reproducible option for bladder tumor resection in patients with functionally inadequate transurethral access after phalloplasty.No potential conflict of interest relevant to this article was reported.XMLinkActa Medica Okayama2005-0380372026Nationwide survey of hereditary breast and ovarian cancer–related clinical practice in gynecologic oncology in Japan: a joint study by the Japan Society of Gynecologic Oncology (JSGO) and the Japan Society of Obstetrics and Gynecology (JSOG)e122ENKentaMasudaDepartment of Obstetrics and Gynecology, Keio University School of MedicineKatsutoshiOdaDivision of Integrative Genomics, Graduate School of Medicine, The University of TokyoHidemichiWatariDepartment of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine and Faculty of MedicineAkiraHirasawaDepartment of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShinyaSatoDepartment of Obstetrics and Gynecology, Tottori University School of MedicineKenichiHaranoDepartment of Medical Oncology, National Cancer Center Hospital EastSatoruNagaseDepartment of Obstetrics and Gynecology, Faculty of Medicine, Yamagata UniversityKazuhiroTakeharaDepartment of Gynecologic Oncology, NHO Shikoku Cancer CenterMasakiMandaiDepartment of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto UniversityYukoSasajimaDepartment of Pathology, Teikyo University HospitalTamotsuSudoDepartment of Cancer Genetics & Genomics, Fujita Health University, School of MedicineHiroyukiYanaiDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHitoshiTsudaDepartment of Basic Pathology, National Defense Medical CollegeYusukeKobayashiDepartment of Obstetrics and Gynecology, Institute of Medicine, University of TsukubaKeiKawanaDepartment of Obstetrics and Gynecology, Nihon University School of MedicineMikioMikamiDepartment of Medical Science, Shonan University of Medical ScienceKiyokoKatoDepartment of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu UniversityDaisukeAokiInternational University of Health and Welfare Graduate SchoolAikouOkamotoDepartment of Obstetrics and Gynecology, The Jikei University School of MedicineObjective: To evaluate the current status of hereditary breast and ovarian cancer (HBOC)–related clinical practice in Japan, including genetic testing, risk-reducing surgery, and surveillance systems, and to identify institutional gaps and unmet needs.<br>
Methods: A nationwide questionnaire survey was conducted between February and April 2024 targeting 647 Japan Society of Obstetrics and Gynecology–affiliated training facilities and gynecologic oncology centers. Institutional-level data on genetic testing, homologous recombination deficiency (HRD) testing, risk-reducing salpingo-oophorectomy (RRSO), postoperative management, surveillance practices, and healthcare infrastructure were collected. Responses from 248 institutions (response rate, 38.3%) were analyzed descriptively.<br>
Results: BRCA1/2 genetic testing was performed in 83% of institutions, and HRD testing using the myChoice® CDx system in 87%. However, only 30% offered universal BRCA1/2 testing for ovarian, fallopian tube, or peritoneal cancer, and testing indications varied widely. Genetic counseling resources were uneven, with 29% lacking on-site genetic specialists, driven mainly by institutional characteristics rather than geographic location. RRSO was performed in 50% of institutions, predominantly laparoscopically. While management of occult carcinoma after RRSO was largely consistent, postoperative management of serous tubal intraepithelial carcinoma (STIC) and positive peritoneal cytology varied substantially. Over 70% of institutions reported a need for expanded insurance coverage for genetic services and preventive care.<br>
Conclusion: Although HBOC-related genetic testing and preventive strategies are widely implemented in Japan, this nationwide survey revealed critical structural and evidence gaps, particularly in institutional capacity and the management of evidence-limited scenarios such as STIC, underscoring the need for system-level improvement.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0941-43553482026Machine learning approaches to predict early cardiac immune-related adverse events in patients receiving immune checkpoint inhibitors809ENMichaelSayerSchool of Pharmacy & Pharmaceutical Sciences, University of CaliforniaPeter D.ChangSchool of Medicine, Pathology & Laboratory Medicine, University of CaliforniaHirofumiHamanoDepartment of Pharmacy, Medical Development Field, Okayama UniversityReinaYamamotoDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMisakoNagasakaDivision of Hematology and Oncology, University of CaliforniaAli A.NaqviMary & Steve Wen Cardiovascular Division, Department of Medicine, University of CaliforniaPranav M.PatelMary & Steve Wen Cardiovascular Division, Department of Medicine, University of CaliforniaYoshitoZamamiDepartment of Pharmacy, Medical Development Field, Okayama UniversityAya F.OzakiSchool of Pharmacy & Pharmaceutical Sciences, University of CaliforniaPurpose Immune checkpoint inhibitor (ICI)–induced cardiac immune-related adverse events (cardiac irAEs) are rare yet serious complications. Clinical assessment tools to identify at-risk patients would allow for more effective prevention strategies, thus improving clinical outcomes. We constructed various machine learning (ML) models to predict these events among patients receiving ICI therapy.<br>
Methods A cohort of patients receiving ICI therapy from 2010 to 2023 was identified from the TriNetX database. Cardiac irAEs were defined as the occurrence of relevant diagnosis codes within 90 days of ICI initiation, with corresponding hospital visits. We created ML models to predict these events, including elastic net logistic regression and multiple tree-based approaches (gradient boosted trees and random forest). We evaluated model performance with different performance measures and utilized assigned risk scores to stratify risk of cardiac irAEs into low, medium, and high-risk tiers.<br>
Results We identified 61,117 patients receiving ICI therapy, with nearly 2% of patients experiencing cardiac irAEs. Model performance on testing data was comparable with all approaches (AUC = 0.71–0.72, balanced accuracy = 65–66%). Each model emphasized distinct features to make classifications, as observed with feature importance and SHAP values. Comparing cardiac irAE rates among assigned risk strata, patients identified as high risk were significantly more likely to experience cardiac irAEs compared to lower tiers.<br>
Conclusion Our preliminary exploration of ML methods demonstrated the potential for risk assessment tools to predict rare cardiac irAEs in patients receiving ICI therapy. Follow-up studies can implement time series approaches to harness longitudinal data that incorporates real-time labs, new diagnoses, and new therapy, to refine predictions further.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2075-441816172026Granular Swollen Epithelial Cells in Native Kidney Biopsies: Prevalence, Clinicopathological Associations and Kidney Outcomes2822ENNaruhikoUchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiNakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground/Objectives: Granular swollen epithelial cells (GSECs) have been described primarily in mitochondrial cytopathies, in which they are regarded as a characteristic pathological finding that may aid in the diagnosis of mitochondrial dysfunction; however, their prevalence and clinical significance in native kidney disease remain unclear. We aimed to evaluate the prevalence, clinicopathological associations, and prognostic significance of GSECs in native kidney biopsy specimens. Methods: Among 1165 adults who underwent native kidney biopsy between 2011 and 2024, 501 patients with evaluable medullary tissue were included in this retrospective cohort study. GSECs were defined as enlarged tubular epithelial cells with conspicuous granular cytoplasm in medullary tubules, and cases were classified as GSEC-positive when at least one unequivocal GSEC was identified. Clinical and histopathological characteristics were compared between groups, and kidney outcomes were evaluated using Cox proportional hazards models. Results: The mean baseline eGFR was 60.8 ± 26.3 mL/min/1.73 m2, and the median urinary protein excretion was 1.1 g/gCr. During a median follow-up of 2.3 years, 112 patients (22.3%) reached the composite kidney outcome. GSECs were identified in 18% of native kidney biopsy specimens containing evaluable medullary tissue, and were observed across a broad spectrum of kidney diseases. GSEC positivity was associated with older age and underlying pathological diagnoses but was not associated with baseline kidney function or proteinuria. Kaplan–Meier and multivariable Cox analyses revealed no significant association between GSECs and kidney prognosis. Conclusions: GSECs are not specific to kidney allografts and are observed in a subset of diverse native kidney diseases. Although associated with certain clinical characteristics, no independent association between GSECs and kidney outcomes was observed in this cohort. These findings suggest that GSECs may reflect disease-dependent biological responses to tubular epithelial stress, potentially related to metabolic or mitochondrial alterations, rather than a marker of progressive kidney injury.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1873-96012022026Species‐specific roles of cellular communication network proteins in cartilage development: A comparative study using in vitro chondrogenic modelse70089ENZhangzhengWangDepartment of Anatomy, Histology and Embryology Faculty of Medicine, University of DebrecenJuditVágóDepartment of Anatomy, Histology and Embryology Faculty of Medicine, University of DebrecenRolandTakácsDepartment of Anatomy, Histology and Embryology Faculty of Medicine, University of DebrecenSzilárdPóliskaGenomic Medicine and Bioinformatics Core Facility Department of Biochemistry and Molecular Biology Faculty of Medicine, University of DebrecenEe HyunKimDepartment of Biomedical Materials Science Graduate School of JABA, Wonkwang UniversityEun‐JungJinDepartment of Biomedical Materials Science Graduate School of JABA, Wonkwang UniversitySatoshiKubotaDepartment of Biochemistry and Molecular Dentistry, Okayama University, Faculty of Medicine, Dentistry and Pharmaceutical ScienceCelina GKleerDepartment of Pathology, University of Michigan Medical SchoolBernardPerbalInternational CCN SocietyCsabaMattaDepartment of Anatomy, Histology and Embryology Faculty of Medicine, University of DebrecenCellular communication network (CCN) proteins are key matricellular regulators of cartilage development, yet their species-specific roles and network-level context remain unclear. This study integrated bulk RNA sequencing from chicken and mouse embryonic limb bud micromass cultures and human mesenchymal stem cell chondrogenesis with co-expression, protein–protein interaction, and ortholog analyses to construct CCN-centered regulatory networks across models. CCN1 and CCN2 emerged as dominant, conserved hubs enriched in collagen-containing extracellular matrix, cartilage development, and growth factor signaling modules, whereas CCN3–CCN6 showed lower context-dependent expression and connectivity. Functional and ortholog analyses revealed moderate pathway conservation, with high conservation of IGF, EGFR, and HIF-1 signaling, but reduced overlap in hypoxia and mechanosensing/Hippo categories, indicating species-specific tuning of environmental sensing. A focused ortholog screen identified multifunctional conserved hubs, including COL2A1, TGFBR1, SMAD3, RUNX2, HIF1A, IGF1, SPP1, and CD44. Single-cell RNA-seq meta-analysis of human iPSC-derived chondrogenesis and embryonic limb datasets showed CCN1/2 expression and homologous network activity peaking in mesenchymal and early chondrocyte populations, consistent with model-dependent persistence into hypertrophic and ossification stages in vivo. Overall, this work defines a conserved CCN1/2-centered axis integrating extracellular matrix formation with growth factor and mechanical cues, providing a framework for model selection and CCN-targeted cartilage regeneration strategies.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0300-81265442026Rectal syphilis: a great imitator of rectal malignancy21552156ENHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalTakehiroTanakaDepartment of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityA 48-year-old transgender woman presented with a sudden onset of bloody stool. Colonoscopy revealed an ulcerated, circumscribed mass in the lower rectum, closely resembling a Borrmann type 2 malignancy. The patient lacked classic signs of syphilis, such as anal pain, primary genital chancres, or localized lymphadenopathy. However, serological assays were highly reactive, and immunohistochemical analysis of the biopsy specimen confirmed the presence of Treponema pallidum, establishing the diagnosis of syphilitic proctitis. A four-week oral amoxicillin regimen (1,500 mg/day) led to complete clinical and serological resolution. This elusive condition must be considered when evaluating anorectal mucosal abnormalities.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1422-006727172026Assessment of the Association of Periodontitis and Diabetes Mellitus with Alzheimer’s Disease in a Mouse Model7542ENMomokoNakaharaDepartment of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKotaKataokaDepartment of Preventive Dentistry, Division of Dentistry, Medical Development Field, Okayama UniversityTakayukiMaruyamaDepartment of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMohammadNurhamimDepartment of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityYixuanZhangDepartment of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityDaikiFukuharaDepartment of Preventive Dentistry, Dental School, Okayama UniversityYokoUchida-FukuharaLaboratory of Biological Anthropology, Research Center for Integrative Evolutionary Science, The Graduate University for Advanced Studies, SOKENDAIMd MonirulIslamCentre for Policy Studies, University College CorkManabuMoritaDepartment of Oral Health Sciences, Faculty of Health Care Sciences, Takarazuka University of Medical and Health CareTakashiSaitoDepartment of Neuropathology, Graduate School of Medicine, The University of TokyoDaisukeEkuniDepartment of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThe purpose of the present study was to investigate how periodontitis and diabetes mellitus (DM) are associated with Alzheimer’s disease (AD) through microRNA (miRNA) using AD model mice. The experimental period was 8 weeks. Twenty-four male knock-in mice (B6-AppNL-G-F/NL-G-F/J) were divided into four groups: control group fed a normal diet (C), DM group fed a high-fat/sucrose diet (DM), periodontitis (P) group, and DM + periodontitis (DM+P) group. Memory performance was compared using the Y-maze test. Next-generation sequencing was performed on brain samples, and fold changes in miRNA expression were calculated by comparing the DM+P and C groups. Integrated miRNA–mRNA analysis identified putative miRNA-targeted mRNAs, and protein expression of the top candidate gene was assessed. Memory function in the DM+P group was significantly lower than in the C group. Among the seven mRNAs identified by the integrated analysis, Neurod1 showed the greatest decrease in expression, and it was predicted to be regulated by miR-693-3p. Neurod1 protein expression in the hippocampus was significantly lower in the DM+P group than the C group. Our results suggest that the combined exposure to periodontitis and DM was associated with AD-like pathological changes and identified the miR-693-3p/Neurod1 pair as a candidate regulatory axis.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155813822026病理診断の国際的標準化7173ENHidetakaYamamotoDepartment of Pathology and Oncology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155813822026自然脱落した子宮原発 DLBCL に対して Pola-R-CHP 療法と CNS 再発予防を行った１例5861ENHikaruOsadaDepartment of Hematology, Japanese Red Cross Okayama HospitalMaikoKimuraDepartment of Hematology, Japanese Red Cross Okayama HospitalManakaMuneishiDepartment of Hematology, Japanese Red Cross Okayama HospitalKozoMurayamaDepartment of Hematology, Japanese Red Cross Okayama HospitalDaigoNiiyaDepartment of Hematology, Japanese Red Cross Okayama HospitalMakotoTakeuchiDepartment of Hematology, Japanese Red Cross Okayama HospitalSoichiroFujiiDepartment of Hematology, Japanese Red Cross Okayama Hospital A 55-year-old woman presented to her local physician with the chief complaint of genital bleeding. A 22×19-mm mass was noted on the patient's cervix, and during the internal examination the mass auto-amputated. The pathological examination of the auto-amputated mass revealed diffuse large B-cell lymphoma (DLBCL). An examination by F-fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) showed FDG uptake at physiological levels in the cervix, with no abnormal uptake in other organs. Cervical tissue was sampled after the spontaneous detachment of the cervical mass, and the biopsy of the cervical mass did not reveal findings suggestive of lymphoma. Six courses of chemotherapy with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisolone (Pola-R-CHP) plus an intramedually injection of methotrexate, cytarabine, and predonisolone (IT-triple), followed by two courses of high-dose intrathecal methotrexate (HD-MTX) were adiministered, and the patient has remained recurrence-free for the more than 8 months since the completion of this treatment. Primary uterine DLBCL is an extremely rare disease with a high rate of recurrence in the central nervous system and a poor prognosis. Our search of the relevant literature identified very few reports describing the prognoses of cases with spontaneous tumor detachment.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2452-302X10102025Inhibition of Scarb1 on Endothelial Cells Attenuates Pressure Overload-Induced Heart Failure Progression101308ENToshiomiKatsukiDepartment of Cardiology, Keio University School of MedicineDaiKusumotoDepartment of Cardiology, Keio University School of MedicineYoheiAkibaDepartment of Cardiology, Keio University School of MedicineMaiKimuraDepartment of Cardiology, Keio University School of MedicineJinKomuroDepartment of Cardiology, Keio University School of MedicineTakahiroNakamuraDepartment of Cardiology, Keio University School of MedicineHisayukiHashimotoDepartment of Cardiology, Keio University School of MedicineThukaaKoukaDepartment of Cardiology, Keio University School of MedicineKazuhisaSugaiInstitute for Integrated Sports Medicine, School of Medicine, Keio UniversityYoshinoriKatsumataDepartment of Cardiology, Keio University School of MedicineMasakiMiyasakaDepartment of Computational Biology and Medical Sciences, the University of TokyoYutakaSuzukiDepartment of Computational Biology and Medical Sciences, the University of TokyoJunkoKuramotoDepartment of Pathology, Keio University School of MedicineYoshiakiKubotaDepartment of Anatomy, Keio University School of MedicineKeiichiFukudaDepartment of Cardiology, Keio University School of MedicineShinsukeYuasaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasakiIedaDepartment of Cardiology, Keio University School of MedicineInappropriate endothelial cell (EC) interactions contribute to heart failure; however, their precise mechanisms remain poorly understood. This study investigated EC-fibroblast interactions mediated by Scarb1 using single-cell RNA-sequencing analysis in a mouse heart failure model. ECs exhibited inflammatory and fibrotic gene expression, with Scarb1-mediated fibroblast-EC interactions driving disease progression. EC-specific Scarb1 knockout and systemic SCARB1 inhibition attenuated heart failure progression. In vitro and spatial omics analyses confirmed the role of SCARB1 in ECs and cell-cell interaction during heart failure progression. These findings highlight SCARB1 as a promising therapeutic target for EC-focused interventions.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8042026Spinous Process Plate Fixation Alone for an AO Spine Osteoporotic Fracture (OF) 5 Diffuse Idiopathic Skeletal Hyperostosis (DISH)-Associated Thoracolumbar Fracture in a Nonagenarian259264ENSatoruYabunoDepartment of Neurosurgery, Kagawa Rosai HospitalMasatoshiYunokiDepartment of Neurosurgery, Kagawa Rosai HospitalSaoriTakeuchiDepartment of Neurosurgery, Kagawa Rosai HospitalKojiHirashitaDepartment of Neurosurgery, Kagawa Rosai HospitalCase Report10.18926/AMO/71070Diffuse idiopathic skeletal hyperostosis (DISH) predisposes the spine to highly unstable fractures because of long lever-arm biomechanics. Unstable injuries, including AO Spine Osteoporotic Fracture (OF) type 5, are typically treated with long-segment posterior instrumentation; however, pedicle-screw fixation may be infeasible in very elderly patients with severe osteoporosis, critically narrow pedicles, and/or significant comorbidities. A 93-year-old Japanese woman presented with severe back pain without apparent trauma. Computed tomography (CT) revealed a T12 fracture with DISH, classified as OF5. The pedicles were critically narrow (3.7-4.1 mm), and dual-energy X-ray absorptiometry confirmed severe osteoporosis. Because conventional pedicle-screw fixation was considered technically unsafe and excessively invasive, limited posterior stabilization was performed using a single spinous process plate spanning T10-L1. The operative time was 48 min and the estimated blood loss was 10 ml. Immediate postoperative CT confirmed appropriate implant positioning and maintained alignment. At the 1-year follow-up, CT demonstrated solid bony union with preserved alignment and no implant failure; the patient had remained pain-free and ambulatory. This case demonstrates that spinous process-plate fixation can be a minimally invasive salvage option for carefully selected very-elderly patients with DISH when pedicle-screw instrumentation is not feasible.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8042026Hemorrhage from a Jejunal Lymphangioma253257ENSachikoIshikamiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterShutaTamuraDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterMotoyasuTabuchiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterNaoYamamotoDepartment of General Medicine, Kochi Health Sciences CenterYukiOkamotoDepartment of Gastroenterology and Hepatology, Kochi Health Sciences CenterRikaYoshimatsuDepartment of Radiology, Kochi Health Sciences CenterManabuMatsumotoDepartment of Diagnostic Pathology, Kochi Health Sciences CenterJunIwataDepartment of Diagnostic Pathology, Kochi Health Sciences CenterTakehiroOkabayashiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterCase Report/10.18926/AMO/71069Lymphangioma is a benign tumor arising from lymphatic vessel proliferation and most commonly occurs in the head, neck, or axilla. Involvement of the small intestine is rare and is often overlooked as a source of obscure gastrointestinal bleeding. Because jejunal lymphangiomas frequently present with nonspecific symptoms and may escape detection by conventional upper and lower gastrointestinal endoscopy or cross-sectional imaging, diagnosis is often delayed. Advances in balloon-assisted enteroscopy have enabled direct visualization of small intestinal lesions, facilitating accurate diagnosis and appropriate therapeutic decision-making. Here, we report a case of jejunal lymphangioma presenting with severe anemia due to active bleeding, which was detected by double-balloon endoscopy and successfully managed by laparoscopic-assisted resection. This case highlights the importance of considering small intestinal lymphangioma in the differential diagnosis of unexplained gastrointestinal bleeding and underscores the clinical utility of deep enteroscopy in identifying rare but clinically significant small bowel tumors.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8042026Video-Assisted Thoracoscopic Resection of an Upper Mediastinal Ectopic Parathyroid Adenoma241246ENYutaHasegawaDepartment of Surgery, National Defense Medical College HospitalHironoriTsujimotoDepartment of Surgery, National Defense Medical College HospitalNaoyukiUehataDepartment of Surgery, National Defense Medical College HospitalRisaKariyaDepartment of Surgery, National Defense Medical College HospitalAsumaIdeDepartment of Surgery, National Defense Medical College HospitalTakafumiSuzukiDepartment of Surgery, National Defense Medical College HospitalSeiichiroFujishimaDepartment of Surgery, National Defense Medical College HospitalKeitaKouzuDepartment of Surgery, National Defense Medical College HospitalYoshihisaYaguchiDepartment of Surgery, National Defense Medical College HospitalKosukeMiyaiDepartment of Laboratory Medicine, National Defense Medical College HospitalAyumuKuriharaDepartment of Laboratory Medicine, National Defense Medical College HospitalShoOgataDepartment of Laboratory Medicine, National Defense Medical College HospitalSusumuMatsukumaDepartment of Laboratory Medicine, National Defense Medical College HospitalHidekiUenoDepartment of Surgery, National Defense Medical College HospitalCase Report/10.18926/AMO/71067Primary hyperparathyroidism (pHPT) is typically caused by a parathyroid adenoma, although some cases arise from ectopic glands. Accurate preoperative localization is essential for guiding surgical strategy, particularly for mediastinal lesions. We report successful video-assisted thoracoscopic surgery (VATS) for an upper mediastinal parathyroid adenoma. A 68-year-old woman was referred for hypercalcemia during evaluation for recurrent ureteral stones. Laboratory tests revealed elevated serum calcium (13.2 mg/dl) and intact parathyroid hormone (iPTH) levels (266 pg/ml). Contrast-enhanced computed tomography, magnetic resonance imaging, and 99mTc-methoxyisobutylisonitrile scintigraphy identified a 20-mm mass adjacent to the right esophageal wall. VATS was performed due to the tumor’s mediastinal location. The lesion was resected with intraoperative nerve monitoring (IONM) to avoid recurrent laryngeal nerve damage. Postoperatively, iPTH and calcium levels rapidly normalized. Transient hypocalcemia and mild hoarseness occurred but resolved with calcium supplementation and conservative management. Pathological examination confirmed a parathyroid adenoma without malignancy. VATS offers a safe and minimally invasive approach for upper mediastinal parathyroid adenomas. IONM and vigilant calcium management are crucial for minimizing these complications. This case highlights the importance of comprehensive imaging, surgical planning, and postoperative care in managing upper mediastinal pHPT.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1341-96252026Workforce and institutional factors associated with comprehensive genomic profiling utilization in gynecologic oncology: a nationwide questionnaire survey in JapanENTamotsuSudoDepartment of Cancer Genetics and Genomics, School of Medicine, Fujita Health UniversityKentaMasudaDepartment of Obstetrics and Gynecology, Keio University School of MedicineKatsutoshiOdaDivision of Integrative Genomics, Graduate School of Medicine, The University of TokyoHidemichiWatariDepartment of Obstetrics and Gynecology, Graduate School of Medicine and Faculty of Medicine, Hokkaido UniversityAkiraHirasawaDepartment of Clinical Genomic Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShinyaSatoDepartment of Obstetrics and Gynecology, Tottori University School of MedicineKenichiHaranoDepartment of Medical Oncology, National Cancer Center Hospital EastSatoruNagaseDepartment of Obstetrics and Gynecology, Faculty of Medicine, Yamagata UniversityKazuhiroTakeharaDepartment of Gynecologic Oncology, NHO Shikoku Cancer CenterMasakiMandaiDepartment of Gynecology and Obstetrics, Kyoto University Graduate School of MedicineYukoSasajimaDepartment of Pathology, Teikyo University HospitalHiroukiYanaiDepartment of Pathology, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHitoshiTsudaDepartment of Basic Pathology, National Defense Medical CollegeYusukeKobayashiDepartment of Obstetrics and Gynecology, Institute of Medicine, University of TsukubaKeiKawanaDepartment of Obstetrics and Gynecology, Nihon University School of MedicineMikioMikamiDepartment of Medical Science, Shonan University of Medical ScienceKiyokoKatoDepartment of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu UniversityDaisukeAokiInternational University of Health and Welfare Graduate SchoolAikouOkamotoDepartment of Obstetrics and Gynecology, The Jikei University School of MedicineBackground Comprehensive genomic profiling (CGP) has been widely introduced into precision oncology; however, its real-world implementation in gynecologic oncology remains unclear. This study evaluated nationwide CGP utilization, treatment translation, and management of secondary germline findings in Japanese gynecologic oncology.<br>
Methods A nationwide survey was conducted across 98 institutions participating in gynecologic oncology training and/or Japan’s cancer genomic medicine network. Institutional characteristics, workforce composition, treatment translation, and management of germline findings were assessed. Associations between institutional factors and CGP utilization or trial-related treatment translation were analyzed using incidence rate ratios (IRRs) with 95% confidence intervals.<br>
Results Among 68 institutions with complete CGP volume data, 6,964 CGP tests were performed, including 922 for gynecologic malignancies. The median number of gynecologic CGP tests per institution was 10. In multivariate analysis, the number of board-certified obstetrician–gynecologists was associated with CGP utilization (IRR, 1.05; 95% CI 1.01–1.08). CGP-guided therapy was delivered to 80 patients (8.7%). Trial-related treatment translation was associated with the number of board-certified obstetrician–gynecologists (IRR, 1.09; 95% CI 1.02–1.16) and the presence of a medical oncology department (IRR, 7.93; 95% CI 1.41–44.72). Presumed germline pathogenic variants were identified in 100 cases (10.8%); however, confirmatory germline testing was performed in only 38 cases.<br>
Conclusion CGP utilization in Japanese gynecologic oncology was associated with gynecologic workforce capacity and multidisciplinary genomic infrastructure. Collaboration between gynecologic oncology and medical oncology may facilitate treatment translation. CGP may also serve as an entry point for hereditary cancer evaluation despite incomplete downstream germline evaluation.No potential conflict of interest relevant to this article was reported.BMJActa Medica Okayama0022-25932026Updated ENIGMA recommendations for reporting germline variants in cancer susceptibility genes and their translation into twenty languagesENArcangelaDe NicoloDepartment of Experimental Oncology, Unit of Predictive Medicine: Molecular Bases of Genetic Risk, Fondazione IRCCS Istituto Nazionale dei TumoriDiana MEcclesFaculty of Medicine, University of SouthamptonKirsimariAaltonenDuodecim Medical Publications LtdPiaAlhopuroHUS Diagnostic Center, Laboratory of Genetics, Helsinki University Hospital and University of HelsinkiSarah LouiseAriansenDepartment of Medical Genetics, Oslo University HospitalMichelaBiancolellaDepartment of Biology, University of Rome Tor VergataSandrine MCaputoDepartment of Genetics, Institut CurieOlivierCaronDépartement de Médecine Oncologique, Gustave RoussyPietroCavalliMedical Genetics, IRCCS Humanitas Research HospitalJianbangChiangDivision of Medical Oncology, Cancer Genetics Service, National Cancer Centre SingaporeKathleen B MClaesCenter for Medical Genetics, Ghent University HospitalEdgar Christian SCuaresmaSt. Luke’s Medical CenterMiguelde la HoyaHospital Clínico San Carlos, Molecular Oncology Laboratory, Instituto de Investigación Sanitaria del Hospital Clínico San CarlosAntoineDe PauwDepartment of Genetics, Institut CurieOrlandDíezVall d’Hebron Hospital Universitari, Area of Clinical and Molecular Genetics, Vall d’Hebron Barcelona Hospital CampusMevDomínguez-ValentinInstitute of Cancer Research, Department of Tumor Biology, The Norwegian Radium HospitalHansEhrencronaDepartment of Clinical Genetics, Pathology and Molecular Diagnostics, Skåne University HospitalMagnhild KFjeldværDepartment of Medical Genetics, Oslo University HospitalFlorentiaFostiraINRASTES, Human Molecular Genetics Laboratory, National Centre for Scientific Research-DemokritosMarie Belle DFranciaSt. Luke’s Medical CenterJavierGalego-CarroFundación Pública Galega de Medicina Xenómica and Instituto de Investigación Sanitaria de Santiago de CompostelaEncarna BGómez GarcíaDepartment of Clinical Genetics, Maastricht University Medical CentreNur TiaraHassanCancer Research MalaysiaJanHaukeFaculty of Medicine and Center for Familial Breast and Ovarian Cancer, University of Cologne, University Hospital CologneAkiraHirasawaGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Department of Clinical Genomic Medicine, Okayama UniversityXinHuangDepartment of Breast Surgery, Peking Union Medical College HospitalElaine Marisse HIlagan-CargulloSt. Luke’s Medical CenterIsseiImotoAichi Cancer Center Research InstituteSowmyaJonnagadlaDivision of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore, SiManasadeviKarthikeyanDivision of Medical Oncology, Cancer Genetics Service, National Cancer Centre SingaporePetraKleiblovaInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in PragueIreneKonstantopoulouINRASTES, Human Molecular Genetics Laboratory, National Centre for Scientific Research-DemokritosArturKowalikDepartment of Molecular Diagnostics, Holy Cross Cancer CentreAndersKvistDepartment of Clinical Sciences Lund, Division of Oncology, Lund UniversityFabienneLesueurPSL Research UniversityShao-TzuLiDivision of Medical Oncology, Cancer Genetics Service, National Cancer Centre SingaporeAdriàLópez-FernándezHereditary Cancer Genetics Group, Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebron Institute of Oncology (VHIO)EvaMachackovaCenter for Medical Genetics, Masaryk Memorial Cancer InstituteAlexandraMartinsUniv Rouen Normandie, Inserm U1245Arjen RMensenkampDepartment of Human Genetics, Radboud University Medical CenterYukihideMomozawaLaboratory for Genotyping Development, RIKEN Center for Integrative Medical SciencesGemmaMontalbanDepartment of Oncogenetics, MRC HollandAlvaro N AMonteiroDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research InstituteHeliNevanlinnaHUS Diagnostic Center, Laboratory of Genetics, Helsinki University Hospital and University of HelsinkiJoanneNgeowDivision of Medical Oncology, Cancer Genetics Service, National Cancer Centre SingaporeEdenir InezPalmeroMolecular Oncology Research Center, Barretos Cancer HospitalInge SokildePedersenMolecular Diagnostics and Clinical Cancer Research Centre, Aalborg University HospitalFrances Victoria FQueSt. Luke’s Medical CenterMartaSantamariñaFundación Pública Galega de Medicina Xenómica and Instituto de Investigación Sanitaria de Santiago de CompostelaElizabethSantana dos SantosDepartment of Medical Oncology, A.C. Camargo Cancer CenterChristian FSingerComprehensive Cancer Center, Department of Obstetrics and Gynecology, Medical University of ViennaMonikaSiołekGenetic Clinic, Holy Cross Cancer CentreAngela RSolanoDepartmento de Analisis Clinicos, Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno" (CEMIC)JanaSoukupovaInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in PraguePriyadharshini d/oSureshDivision of Medical Oncology, Cancer Genetics Service, National Cancer Centre SingaporeMagdalenaSzczepaniakDepartment of Molecular Diagnostics, Holy Cross Cancer CentreYen YTanComprehensive Cancer Center, Department of Obstetrics and Gynecology, Medical University of ViennaSoo HwangTeoCancer Research MalaysiaEmmaThamDepartment of Clinical Genetics and Genomics, Karolinska University HospitalMadsThomassenDepartment of Clinical Genetics, Odense University HospitalGeorgiosTsaousisGenekor Medical S.AThomas van OvereemHansenDepartment of Clinical Genetics, Copenhagen University Hospital RigshospitaletAnaVegaFundación Pública Galega de Medicina Xenómica and Instituto de Investigación Sanitaria de Santiago de CompostelaEladio AVelasco-SampedroInstituto de Biología y Genética Molecular, Splicing and Genetic Susceptibility to Cancer, Consejo Superior de Investigaciones Científicas - Universidad de Valladolid (CSIC-UVa)TeresiaWangensteenDepartment of Medical Genetics, Oslo University HospitalBarbaraWappenschmidtFaculty of Medicine and Center for Familial Breast and Ovarian Cancer, University of Cologne, University Hospital CologneDrakoulisYannoukakosINRASTES, Human Molecular Genetics Laboratory, National Centre for Scientific Research-DemokritosSook-YeeYoonCancer Research MalaysiaAmanda BSpurdlePopulation Health Program, QIMR Berghofer Medical Research InstitutePaoloRadiceDepartment of Experimental Oncology, Unit of Predictive Medicine: Molecular Bases of Genetic Risk, Fondazione IRCCS Istituto Nazionale dei TumoriGenetic testing for cancer susceptibility underpins precision cancer prevention and care. Gaps in the healthcare providers’ genetic literacy and an ambiguous lexicon for variant description may hinder proper delivery and clinical application of consistently trustworthy test results. The Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) international consortium supports controlled terminology and recommends a framework for reporting germline variants in cancer susceptibility genes, using breast cancer as an exemplar. Moving forward towards terminological coherence across disciplines and borders, the ENIGMA Clinical Working Group launched a multinational effort to release consortium-approved translations of the published recommendations. The herein reported Vocabulary Translation Project offered an opportunity to reappraise and align the reference text to the recent BRCA1 and BRCA2 specifications to the American College of Medical Genetics and Genomics/Association for Molecular Pathology rules by the ENIGMA Variant Curation Expert Panel and to highlight country-specific differences in breast cancer risk assessment and management. The updated recommendations and their 20 translations are now provided as easy to handle documents, covering 11 of the most widely spoken languages in the world. They will contribute to minimised erroneous inferences, more informed decision-making, improved health outcomes and equity in the use of genetic testing for cancer predisposition and in translational oncology.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2050-09041472026A Biologically Dominant Trophoblastic Component Guiding Neoadjuvant EMA/CO in Endometrial Carcinoma: A Clinical Case Reporte72982ENShinsukeShirakawaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShojiNagaoDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYuiTanakaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAtsushiFujikawaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyokoImataniDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMomokoTaniokaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshinoriTaniDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHanakoSugiharaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroOkamotoDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaoyukiIdaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirofumiMatsuokaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunkoHaragaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChikakoOgawaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeiichiroNakamuraDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroyukiYanaiDepartment of Diagnostic Pathology, Okayama UniversityHisashiMasuyamaDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityEndometrial carcinoma with choriocarcinomatous components (ECCC) is a rare and aggressive malignancy for which optimal management remains undefined. We report a case illustrating how preoperative identification of a biologically dominant trophoblastic component can guide treatment sequencing and achieve durable remission. A 61-year-old postmenopausal woman presented with abnormal uterine bleeding. Endometrial biopsy revealed a mixed tumor composed predominantly of choriocarcinomatous elements with a minor grade 1 endometrioid carcinoma component. Despite only superficial myometrial invasion, imaging demonstrated multiple pulmonary nodules, and serum human chorionic gonadotropin (hCG) was markedly elevated (46,538 mIU/mL). This clinicopathological incongruity suggested that the trophoblastic component, rather than the low-grade endometrioid carcinoma, was driving disease progression. Neoadjuvant EMA/CO chemotherapy was therefore prioritized to achieve rapid systemic control. After six cycles, serum hCG normalized and pulmonary lesions completely resolved. The patient subsequently underwent total hysterectomy and bilateral salpingo-oophorectomy, which revealed no residual choriocarcinoma. She remains disease-free more than two years after completion of treatment. This case highlights the importance of recognizing clinicopathological incongruity and identifying the biologically dominant tumor component when determining treatment sequencing in rare mixed malignancies.No potential conflict of interest relevant to this article was reported.Japanese Society for Lymphoreticular Tissue ResearchActa Medica Okayama1346-42806622026RHOA G17V mutation analysis redirecting diagnosis: nodal T-follicular helper cell lymphoma with classic Hodgkin lymphoma feature122129ENRioYamadaDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesMidori FilizNishimuraDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesAsamiNishikoriDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesTakuyaFukumiDepartment of Hematology, Okayama City HospitalKumikoOhsawaDepartment of Pathology, Saitama Medical Center, Saitama Medical UniversityShujiMomoseDepartment of Pathology, Saitama Medical Center, Saitama Medical UniversityYasuharuSatoDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesNodal T-follicular helper cell lymphoma (nTFHL) may present with Hodgkin/Reed–Sternberg (HRS)-like cells and can morphologically mimic classic Hodgkin lymphoma (CHL), although these entities are usually distinguishable. We report an unusual case showing marked morphologic and molecular overlap with CHL, creating a diagnostic challenge but ultimately considered biologically consistent with nTFHL.<br>
An 81-year-old woman presented with stage IV disease involving the bone marrow and markedly elevated serum soluble interleukin-2 receptor levels. Excisional lymph node biopsy revealed scattered HRS cells in a T-cell–rich background, with strong CD30 and PD-L1 expression and weak PAX5 positivity, findings consistent with CHL. Fluorescence in situ hybridization demonstrated copy-number alterations at the 9p24.1 locus in HRS cells, further supporting molecular features characteristic of CHL.<br>
However, the presence of two T-follicular helper markers, detection of the RHOA p.Gly17Val (G17V) mutation, and oligoclonal T-cell receptor rearrangements with shared peaks in lymph node and bone marrow indicated an underlying nTFHL. The differential therapeutic response also supported a diagnosis of nTFHL, which could not have been established on morphology alone.<br>
In this case, although the HRS cells displayed morphological, immunophenotypic, and molecular features highly suggestive of CHL, the biological nature of the lesion was consistent with nTFHL. Compared with previously reported cases of nTFHL with HRS-like cells, this case more closely resembled CHL and may represent a distinct subset best described as “nTFHL with CHL features,” a concept warranting greater recognition among pathologists and clinicians.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818416102024Vonoprazan-Associated Mucosal Redness: A Report of Two Casese71325ENMasayaIwamuroGastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshiyasuKonoGastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaPathology, Okayama University HospitalSeijiKawanoGastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNobumasaIkedaInternal Medicine, Clinic IkedaVonoprazan, a potassium-competitive acid blocker, is effective at treating acid-related gastrointestinal disorders but has been linked to gastric mucosal redness, a novel condition. This report describes two cases of vonoprazan-associated mucosal redness. Case 1 involved a 73-year-old woman who developed longitudinal erythema and mild mucosal changes after starting vonoprazan seven years ago. Case 2 involved a 70-year-old man who exhibited significant erythema and atrophic gastritis after seven months of treatment. In both cases, the pathological findings included hemorrhage in the superficial mucosa, highlighting that microhemorrhage may be the corresponding pathological finding for vonoprazan-associated mucosal redness.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841692024Decreased CD3+CD56+ Natural Killer T Lymphocytes and Increased Human Leukocyte Antigen-DR+ Cells in the Inflamed Area of Pouchitis in Ulcerative Colitis Patientse70066ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University HospitalMasahiroTakaharaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshihiroInokuchiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSakikoHiraokaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground: Pouchitis is an inflammatory condition that affects the ileal pouch during ileal pouch-anal anastomosis surgery. Despite its clinical significance, precise immunological mechanisms underlying pouchitis remain unclear. This study aimed to investigate the lymphocyte profile in the ileal pouch of patients with pouchitis compared to those with familial adenomatous polyposis (FAP) and ulcerative colitis without pouchitis using flow cytometry and immunohistochemical techniques.<br>
Methods: We prospectively analyzed endoscopic biopsy specimens from the ileal pouches of 15 patients and categorized them into three groups: FAP, ulcerative colitis with an inflammation-free pouch (UC-I), and ulcerative colitis with ulcers and/or erosions in the pouch (UC-UE). Flow cytometry was used to assess various T-lymphocyte markers, including cluster of differentiation (CD) 4, CD8, CD56, and human leukocyte antigen (HLA)-DR. Immunohistochemistry was performed to visualize the spatial distribution of CD3+, CD56+, and HLA-DR+ cells in the pouch mucosa.<br>
Results: We observed significantly reduced CD56+/CD3+ and CD8+/CD3+ ratios in the UC-UE group compared to those in the FAP group, indicating a disruption in natural killer T-cell populations. Immunohistochemical analysis revealed that the spatial distribution of lymphocytes differed among the non-inflamed mucosa, dense lymphocyte infiltration, and lymphoid follicles, with these components frequently intermingling. CD56 + cells were less abundant in areas with dense lymphocyte infiltration, whereas HLA-DR+ cells were more abundant.<br>
Conclusion: Our study revealed a decrease in CD56+ natural killer T cells and an increase in HLA-DR+-activated T cells in areas with dense lymphocyte infiltration, suggesting an association between these cells and pouchitis in ulcerative colitis. The distinct patterns observed in non-inflamed mucosa, areas with dense lymphocyte infiltration, and lymphoid follicles underscore the need for further analyses of these three segments to elucidate the immunological mechanisms underlying pouchitis.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1936-05682012026Early-Stage Oral Squamous Cell Carcinoma in Adolescents and Young Adults Compared with Older Patients Exhibits Distinct Clinicopathological Features88ENSawakoOnoDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsutoshiHiroseDepartment of Oral and Maxillofacial Pathology, Osaka University Graduate School of DentistryHotakaKawaiDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTatsuyaAbeDivision of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityShintaroSukegawaDepartment of Oral and Maxillofacial Surgery, Kagawa University Faculty of MedicineMasanoriMasuiDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChihokoIkedaDepartment of Oral Pathology, Osaka Dental UniversityMadokaIsomuraDepartment of Diagnostic Pathology, School of Medicine, Fujita Health UniversityYuriTachibanaDepartment of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Faculty of MedicineJunyaOnoDepartment of Pathology, The Nippon Dental University School of Life Dentistry at NiigataKatsumitsuShimadaDepartment of Clinical Pathophysiology, School of Dentistry, Matsumoto Dental UniversityHitoshiNagatsukaDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHidetakaYamamotoDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPurpose This study aimed to compare the clinicopathological features of stage I–II oral squamous cell carcinoma (OSCC) between adolescents and young adults (AYAs) and older patients, and to identify prognostic factors in AYA OSCC.<br>
Methods Forty-eight AYA patients aged 15–39 years and 69 older patients aged ≥ 65 years with surgically treated stage I–II OSCC were retrospectively analyzed. Histological evaluation, survival analysis, immunohistochemistry for p53, p16, and MTAP, high-risk HPV RNA in situ hybridization, and fluorescence in situ hybridization for CDKN2A and MTAP were performed.<br>
Results Compared with older patients, OSCCs in AYAs were more frequently located on the tongue (93.7% vs. 47.8%) and more often exhibited a superficial spreading growth pattern (60.4% vs. 31.8%). AYA tumors more frequently showed modified WPOI-1, high tumor budding, and abnormal p53 immunophenotypes (85.4% vs. 68.1%). AYA patients showed significantly better overall and disease-free survival than older patients. Within the AYA group, depth of invasion (DOI) > 5 mm was associated with distant metastasis and poorer overall and disease-free survival. Postoperative lymph node metastasis occurred in 31.2% of AYAs. Univariable analysis suggested that clinical stage II, tumor thickness > 5 mm, DOI > 5 mm, and tumor budding scores 1–2 were associated with postoperative lymph node metastasis. Molecular status, including p53, p16/CDKN2A, and MTAP, did not provide robust prognostic stratification.<br>
Conclusion Early-stage AYA OSCC exhibits distinct clinicopathological features. DOI was the strongest prognostic indicator, whereas clinical stage, tumor thickness, and tumor budding may provide additional prognostic information regarding the risk of late nodal metastasis.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818416112024Assessment of All-Inside Sutures to the Posteromedial Capsule in Medial Meniscus Posterior Root Repair: Findings From a Retrospective Three-Dimensional Magnetic Resonance Imaging Studye73778ENYukiOkazakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakayukiFurumatsuDepartment of Orthopaedic Surgery, Japanese Red Cross Okayama HospitalKeisukeKintakaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYusukeYokoyamaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasanoriTamuraDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKokiKawadaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTsubasaHasegawaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPurpose: Medial meniscus (MM) posterior root tears (PRT) cause pathological medial extrusion (MMME) and posterior extrusion (MMPE), particularly during knee flexion, leading to rapidly progressive knee osteoarthritis. We investigated pre- and postoperative MM extrusion using three-dimensional open magnetic resonance imaging (MRI) following two pullout repair techniques: two simple stitches (TSS) and TSS with an additional all-inside suture to the posteromedial capsule (TSS-PM). We hypothesized that TSS-PM would decrease MM extrusion more effectively than TSS.<br>
Methods: Thirty patients who underwent MM posterior root repair were retrospectively evaluated. TSS and TSS-PM techniques were used for pullout repair. Open MRI was performed at 10/90° of knee flexion preoperatively and three months postoperatively. MMME, MMPE, and MM extrusion volume (MMEV) were measured and compared between groups.<br>
Results: At 90° of knee flexion, postoperative MMPE and MMEV were significantly decreased compared to preoperative values in both the TSS and TSS-PM groups. Furthermore, a significantly decreased ΔMMPE was observed in the TSS group compared to the TSS-PM group, whereas no significant difference was observed in ΔMMEV.<br>
Conclusion: TSS and TSS-PM repair techniques helped decrease MMEV at 90° of knee flexion, whereas a significantly decreased ΔMMPE was observed in the TSS group at 90° of knee flexion. An additional all-inside suture at the posteromedial capsule may be insufficient to decrease MMEV and may negatively affect the decrease in ΔMMPE at 90° of knee flexion.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2090-6447202612026Carcinoma ex Pleomorphic Adenoma With an Epithelial‐Myoepithelial Carcinoma Component in the Submandibular Gland: A Case ReportENTomohiroYasuharaDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasanoriMasuiDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiKunisadaDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroakiTakakuraDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityEijiIwataDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKoichiKadoyaDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKokiUmemoriDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNorieYoshiokaDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeisukeNakanoDepartment of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySoichiroIbaragiDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground: Carcinoma ex pleomorphic adenoma (CXPA) is an uncommon malignant salivary gland tumor arising from pleomorphic adenoma, whereas epithelial-myoepithelial carcinoma (EMC) is a rare low-grade salivary gland malignancy. CXPA with an EMC component in the submandibular gland is uncommon.<br>
Case Report: A 65-year-old man presented with a painless, firm mass in the left submandibular region and weakness of the left lower lip. Computed tomography and magnetic resonance imaging demonstrated an irregular submandibular mass, and FDG-PET/CT showed increased uptake (maximum standardized uptake value, 9.2). Core biopsy suggested pleomorphic adenoma; however, the clinical and radiological findings strongly indicated malignancy. Incisional biopsy was therefore performed under general anesthesia, with a plan to proceed to definitive treatment if malignancy was confirmed. Intraoperative histopathological examination revealed a malignant salivary gland tumor, and tumor resection with neck dissection was completed during the same procedure. Histopathological examination showed invasive CXPA with an EMC component, accompanied by extracapsular invasion exceeding 6 mm, perineural invasion, and extension into adjacent muscle (pT3N0). Although surgical margins were negative, pulmonary metastases developed 12 months after surgery, followed by suspected pleural dissemination and spinal canal extension. The patient declined further aggressive treatment and died of the disease 48 months after surgery.<br>
Conclusion: This case highlights the importance of integrating clinical, radiological, and pathological findings for accurate diagnosis of salivary gland tumors, particularly when biopsy results are inconsistent with clinical suspicion.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2045-89401622026Recurrence of Pulmonary Hypertension After Unilateral Lung Transplantation: Histological Evidence of Vasoconstrictive Mechanisme70289ENSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMegumiKondoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoichiIchimuraDepartment of Pathology, Hiroshima City Hiroshima Citizens HospitalTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Organ Transplant Center, Okayama University HospitalKentaroEjiriDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazufumiNakamuraCenter for Advanced Heart Failure, Okayama University HospitalShinsukeYuasaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPulmonary hypertension (PH) is widely recognized as a disease driven by both vasoconstriction and vascular remodeling. Vasoconstriction is thought to play a predominant role in the early stages of PH, whereas the contribution of vascular remodeling increases as the disease progresses. However, clinical or histological evidence of this pathological progression has not been reported. We describe a case of recurrent PH after unilateral right lung transplantation, ultimately requiring bilateral transplantation 9 years later, and discuss the pathogenesis of PH based on histological findings in the transplanted normal lungs and changes in pulmonary blood flow observed by lung perfusion scintigraphy. Serial lung perfusion scintigraphy revealed a dynamic shift in pulmonary blood flow, initially favoring the transplanted lung, followed by a gradual decline. Histological examination demonstrated that the right lung of the second transplantation showed minimal vascular remodeling. These findings provide compelling evidence that vasoconstriction was the predominant contributor to PH after the first transplantation, offering unique insight into early PH pathobiology.No potential conflict of interest relevant to this article was reported.Japan Atherosclerosis SocietyActa Medica Okayama1340-34783322026A Case of Acquired LCAT Deficiency with the Discrepancy between Spontaneous Resolution of Proteinuria and Continually Low HDL Cholesterol Levels228236ENMikiMatsuoDepartment of Nephrology and Hypertension, National Cerebral and Cardiovascular CenterMasatsuneOguraDepartment of Clinical Laboratory Technology, Faculty of Medical Science, Juntendo UniversityMasayukiKurodaCenter for Advanced Medicine, Chiba University Hospital, Chiba UniversityTetsuyaArisatoDepartment of Nephrology and Hypertension, National Cerebral and Cardiovascular CenterMasatsuguKishidaDepartment of Nephrology and Hypertension, National Cerebral and Cardiovascular CenterMarikoHarada-ShibaCardiovascular Center, Osaka Medical and Pharmaceutical UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoutaroYokoteDepartment of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of MedicineFumikiYoshiharaDepartment of Nephrology and Hypertension, National Cerebral and Cardiovascular CenterA 79-year-old Chinese man was referred for nephrotic syndrome (proteinuria 4.4 g/day). In blood tests, serum high-density lipoprotein (HDL) cholesterol was undetectable, and the esterified cholesterol to total cholesterol ratio was very low. Lecithin: cholesterol acyltransferase (LCAT) activity was also undetectable. Since he had neither corneal opacity nor pathological mutations in the LCAT gene and anti-LCAT antibodies were detected in serum, a diagnosis of acquired LCAT deficiency was made. Renal biopsy revealed glomerulopathy associated with LCAT deficiency and membranous nephropathy (MN). Since the patient’s proteinuria did not improve despite prescribing an angiotensin II receptor blocker (ARB), we suggested the prescription of prednisolone, but he returned to China due to the expiration of his residence visa for Japan. One year after the initial visit, his proteinuria had improved to 0.9 g/day without immunosuppressive therapy. However, his HDL cholesterol level was still low at around 3 mg/dL, indicating a discrepancy between remission of nephrotic syndrome and lack of improvement in lipid levels.<br>
Of the 11 patients with acquired LCAT deficiency reported to date, 4 with undetectable LCAT activity and MN on renal biopsy required immunosuppressive therapy to alleviate proteinuria. The present patient was prescribed only an ARB according to his preference, which happened to be consistent with the MN treatment guideline that states, “Wait 6 months for spontaneous remission while using maximal antiproteinuric therapy.” The clinical course of acquired LCAT deficiency varies, and further case reports are needed to determine the necessity of immunosuppressive therapy.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1745-62152712025Oral health care during pregnancy to prevent preterm birth and low birth weight: study protocol for a randomized controlled trial35ENJunkoYasuokaDivision of Global Health Sciences, Graduate School of Public Health, St. Luke’s International UniversityYoheiTakeshitaDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShunsukeOkadaDepartment of Oral and Maxillofacial Radiology, Medical Development Field, Okayama UniversityProdhan MD RubayetAlamDepartment of Orthodontics, Dental Unit, TMSS Medical College & Rafatullah Community HospitalAkiraShibanumaDepartment of Community and Global Health, Graduate School of Medicine, The University of TokyoKeikoNanishiOffice of International Academic Affairs, Graduate School of Medicine, The University of TokyoYokoSatoDepartment of Health Sciences, Graduate School of Medical Sciences, Kyushu UniversityMd. ZahidHossainDepartment of Periodontology and Oral Pathology, Holy Family Red Crescent Medical College HospitalMusfiqaAmanDepartment of Periodontology, Dental Unit, TMSS Medical College & Rafatullah Community HospitalFahmidaKarimDepartment of Obstetrics & Gynecology, Holy Family Red Crescent Medical College HospitalSultanaRaziaDepartment of Obstetrics & Gynecology, TMSS Medical College & Rafatullah Community HospitalRifatRezwanaDepartment of Molecular and Cellular Biochemistry, Division of Oral Health, Brain Health and Total Health, Faculty of Dental Science, Kyushu UniversityMd MahmudurRahmanGlobal Communication Center, Grameen CommunicationsNusratJahan KhanGlobal Communication Center, Grameen CommunicationsNaokiNakashimaDepartment of Medical Informatics, Graduate School of Medical Sciences, Kyushu UniversityRafiqulIslamDivision of Healthcare Digital Transformation, Kyushu UniversityKimiyoKikuchiDepartment of Research Promotion, Institute for Asian and Oceanian Studies, Kyushu UniversityBackground Periodontal disease during pregnancy has been associated with an increased risk of preterm birth (PTB) and low birth weight (LBW). However, most previous interventional studies have reported that scaling and root planing (SRP), a form of basic periodontal treatment, is insufficient to effectively prevent PTB and LBW. Recent systematic reviews and meta-analyses suggest that combining SRP with routine use of chlorhexidine gluconate (CHG) mouthwash may reduce the risk of these adverse birth outcomes by approximately half. This study will be among the first randomized controlled trials (RCTs) to evaluate the potential synergistic effects of this combined approach on improving birth outcomes.<br>
Methods This multi-center, three-arm RCT will be conducted at two hospitals in Dhaka and Bogura, Bangladesh, between April 2025 and September 2026. A total of 480 pregnant women less than 20 weeks’ gestation attending antenatal checkups will be recruited. Participants diagnosed with periodontal disease will be randomly assigned to either an intervention group or a positive control group. Participants without periodontal disease will be assigned to a negative control group. The intervention consists of SRP combined with continued use of CHG mouthwash throughout pregnancy. The primary outcome will be the rate of PTB. Secondary outcomes include the birth weight of the newborn baby, maternal periodontal status, and oral health-related quality of life (OHRQoL). Effectiveness will be assessed by comparing outcomes across the study groups.<br>
Discussion The oral health intervention is expected to improve both birth outcomes and maternal oral health. Demonstrating its effectiveness in a real-world setting may support the integration of oral health care into broader maternal, neonatal, and child health strategies, particularly in resource-limited settings.<br>
Trial registration UMIN Clinical Trials Registry. UMIN000057519. Registered on April 4, 2025. https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000065719.No potential conflict of interest relevant to this article was reported.Japanese Society of Internal MedicineActa Medica Okayama0918-29186582026Autopsy Case of a Disseminated Cytomegalovirus Infection with a Cutaneous Ulcer Mimicking Rheumatoid Vasculitis11721177ENKoheiOguniDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalYukichikaYamamotoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoharuIshidaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokaOhkiDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesA 60-year-old woman with rheumatoid arthritis and an impaired consciousness was referred to our hospital. Prior to transfer, the patient underwent intensified immunosuppressive therapy under a diagnosis of rheumatoid vasculitis that had developed in her buttocks. Upon hospitalization, she developed severe multiorgan failure and hemophagocytic syndrome. Four days after admission, both blood cytomegalovirus (CMV) antigenemia and the DNA load were markedly elevated. Despite intensive care, the patient died. Later, a histopathological examination revealed that the cutaneous manifestation represented CMV disease, not rheumatoid vasculitis, as was initially suspected. Failure to identify CMV as the underlying cause may result in the inappropriate administration of immunosuppressive therapy, potentially worsening the patient's condition.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1572-1000582026Pathological features of residual head and neck cancer after near-infrared photoimmunotherapy: implications of an unfavorable tumor immune microenvironment105422ENTakumaMakinoDepartment of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuharuSatoDepartment of Hematopathology, Okayama University Graduate School of Health SciencesAsamiNishikoriDepartment of Hematopathology, Okayama University Graduate School of Health SciencesYutoNaoiDepartment of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMizuoAndoDepartment of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPurpose: Near-infrared photoimmunotherapy has been approved in Japan for unresectable locally advanced or recurrent head and neck cancer. While this therapy theoretically induces selective necrosis of epidermal growth factor receptor-expressing tumor cells following administration of cetuximab sarotalocan sodium and irradiation with 690-nm light, residual disease is not uncommon in clinical practice. The mechanisms underlying such persistence remain poorly understood.<br>
Methods: We examined two patients with head and neck squamous cell carcinoma who underwent salvage resection due to residual disease after four cycles of near-infrared photoimmunotherapy. Resected specimens were subjected to histopathological evaluation, including immunohistochemistry for epidermal growth factor receptor, cluster of differentiation 8, programmed cell death protein 1, and forkhead box P3 proteins.<br>
Results: In both cases, residual tumor cells were predominantly localized in the superficial mucosal layers, while deeper layers were replaced by fibrosis. All residual tumors retained expression of epidermal growth factor receptor. Lymphocytic infiltration was sparse, with scattered cluster of differentiation 8-positive cells but few programmed cell death protein 1-positive or forkhead box P3-positive lymphocytes. These findings suggest that the tumor microenvironment surrounding residual tumors may have been unfavorable for the induction of robust antitumor immune responses.<br>
Conclusion: Residual tumors after near-infrared photoimmunotherapy can occur despite adequate laser irradiation and epidermal growth factor receptor expression. Our observations imply that insufficient immune activation within the tumor microenvironment may contribute to treatment resistance. Further characterization of the post-photoimmunotherapy tumor microenvironment will be essential to better understand treatment mechanisms and to optimize therapeutic efficacy.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2090-6447202612026A Rare Case of Hyperplastic Dental Follicle Presenting With an Unusually Large Radiolucent Area2879891ENSatoshiOtsukiDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiKunisadaDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKoichiKadoyaDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChizuruKobayashiDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeisukeNakanoDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiyukiKawazuDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySoichiroIbaragiDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHyperplastic dental follicle (HDF) is a rare odontogenic hamartomatous lesion typically associated with unerupted teeth in children and adolescents and is often found incidentally on radiographic imaging. HDF usually presents as a pericoronal radiolucency of 2–3 mm in diameter and is commonly difficult to distinguish from dentigerous cysts on radiographs. We report an unusual case of HDF in an 11-year-old male who was referred for evaluation of delayed eruption of the left maxillary canine. Panoramic radiography and cone-beam computed tomography (CBCT) revealed a remarkably large radiolucent area, with a maximum dimension of 25.3 mm. The initial clinical diagnosis was a dentigerous cyst; however, incisional biopsy revealed solid tissue characteristics, and histopathological examination confirmed HDF, with no evidence of cystic lining, neoplastic transformation, or inflammation. Following the patient′s and parents′ preference for complete removal, resection of the lesion together with extraction of the impacted canine was performed under general anesthesia. At the 6-month follow-up, no recurrence was observed and bone regeneration was confirmed on radiographic examination. This case underscores the diagnostic challenge posed by atypical radiographic findings and highlights the necessity of histopathological confirmation. Given the exceptional size and potential for recurrence, long-term follow-up is warranted.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2041-17231712026The role of Pth1r in posterior cranium cartilage regulation and craniosynostosis5862ENKatsuhikoAmanoDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeOkuzakiLaboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, University of OsakaYujiFujimotoLaboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, University of OsakaYu-ChenLiuLaboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, University of OsakaMikihikoKogoThe First Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of DentistrySeijiIidaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCraniosynostosis is a major craniofacial congenital disorder that causes developmental complications. During normal cranial development, intramembranous ossification forms the flat bones and sutures, while cartilage appears transiently in the posterior calvarial region. However, in craniosynostosis, premature suture fusion disturbs normal calvarial morphogenesis. To clarify the role of transient cartilage in this morphogenetic disruption, we investigated its molecular regulation and pathology in mice, focusing on parathyroid hormone 1 receptor (Pth1r) signaling. Conditional deletion of Pth1r in the cranial mesenchyme unexpectedly caused acrocephalic dysmorphology and craniosynostosis, with altered cartilage differentiation. Occipito–interparietal synostosis consistently occurred in Pth1r-ablated Gli1+ and Acan+ lineages, but not after adult Gli1-CreERT2 deletion, indicating a developmental role. Bulk and single-cell RNA-seq analysis revealed nine mesenchymal subsets, with mutant cells showing abnormal chondrocyte differentiation and upregulated Indian hedgehog (Ihh) signaling. These findings indicate that Pth1r maintains proper chondrogenic regulation during calvarial development, and its loss induces craniosynostosis through Ihh overactivation.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama1465-36212026Impact of pre-existing schizophrenia spectrum disorder on the receipt of invasive and systemic therapy for gastric cancer: a multicenter nationwide cohort study in Japanhyag102ENMyo MinKhantDepartment of Psychiatry, Faculty of Medicine, Shimane UniversityMasakiFujiwaraDepartment of Neuropsychiatry, Medical Development Field, Okayama UniversityYutoYamadaDivision of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer CenterTaisukeIshiiDivision of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer CenterTomoneWatanabeDivision of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer CenterTakashiFukaoDepartment of Neuropsychiatry, Medical Development Field, Okayama UniversityMaikoFujimoriDivision of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer CenterNaokiNakayaTohoku Medical Megabank Organization, Tohoku UniversityToshihikoKawamuraDepartment of Medical Informatics, Shimane University HospitalKojiOtsukiDepartment of Psychiatry, Faculty of Medicine, Shimane UniversityYoshihikoKakiuchiDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTaichiShimazuDivision of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer CenterShiroHinotsuDepartment of Biostatistics and Data Management, Sapporo Medical UniversityYosukeUchitomiDepartment of Cancer Survivorship and Digital Medicine, The Jikei University School of MedicineMasatoshiInagakiDepartment of Psychiatry, Faculty of Medicine, Shimane UniversityBackground: Patients with schizophrenia spectrum disorders (SSD) experience higher cancer mortality, partly because of later-stage diagnosis and lower rates of recommended treatments. While treatment disparities have been reported across several cancer types, no study has specifically examined stage-appropriate treatment for gastric cancer among patients with SSD.<br>
Methods: We conducted a retrospective cohort study using a nationwide Hospital-Based Cancer Registry linked to administrative data in Japan. Patients who received initial treatment for gastric cancer between 2018 and 2021 were included. Multivariable logistic regression models examined the association between SSD and the receipt of stage-appropriate cancer treatments, adjusting for age, sex, clinical stage, Charlson Comorbidity Index, and Barthel Index.<br>
Results: Among 189 447 patients from 709 hospitals, 1312 had SSD. Patients with SSD were more likely to be diagnosed at advanced stages. In crude analysis, SSD was associated with lower rates of surgical or endoscopic treatment; however, this association was not statistically significant after adjustment (adjusted odds ratio [aOR], 0.90; 95% confidence interval [CI], 0.75–1.08). In contrast, SSD was independently associated with lower rates of postoperative adjuvant chemotherapy for pathological stage II/III disease (aOR, 0.64; 95% CI, 0.45–0.91) and systemic therapy for stage IV disease (aOR, 0.36; 95% CI, 0.28–0.47).<br>
Conclusions: Among patients with gastric cancer, SSD was associated with reduced receipt of systemic therapy but not surgical or endoscopic treatment. Efforts to improve early detection among patients with SSD may be important for reducing treatment disparities, alongside strengthened support for systemic therapy to ensure equitable access to guideline-recommended gastric cancer care.No potential conflict of interest relevant to this article was reported.American Society for Clinical InvestigationActa Medica Okayama1558-8238136102026Spatial single-cell proteotyping reveals immunotherapy-resistant features within the complex tumor microenvironment of metastatic NSCLCe195021ENKohsukeIsomotoDepartment of Medical Oncology, Kindai University Faculty of MedicineKojiHarataniDepartment of Medical Oncology, Kindai University Faculty of MedicineTakahiroTsujikawaDepartment of Otolaryngology–Head and Neck Surgery, Kyoto Prefectural University of MedicineShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalYusukeMakutaniDepartment of Surgery, Kindai University Faculty of MedicineMasayukiTakedaDepartment of Medical Oncology, Kindai University Faculty of MedicineKimioYonesakaDepartment of Medical Oncology, Kindai University Faculty of MedicineKaoruTanakaDepartment of Medical Oncology, Kindai University Faculty of MedicineTsutomuIwasaDepartment of Medical Oncology, Kindai University Faculty of MedicineKazukoSakaiDepartment of Genome Biology, Kindai University Faculty of MedicineKazutoNishioDepartment of Genome Biology, Kindai University Faculty of MedicineAkihikoItoDepartment of Pathology, Kindai University Faculty of MedicineKazuhikoNakagawaDepartment of Medical Oncology, Kindai University Faculty of MedicineHidetoshiHayashiDepartment of Medical Oncology, Kindai University Faculty of MedicineBACKGROUND. Immune checkpoint inhibitors (ICIs) targeting the programmed cell death 1 axis have revolutionized metastatic non–small cell lung cancer (mNSCLC) treatment. However, disease progression remains a concern, and the role of the complex tumor microenvironment (TME) in treatment failure is not fully understood.<br>
METHODS. In this biomarker study involving 103 patients with mNSCLC, including 81 patients who received ICI treatment, we evaluated the association between heterogeneous immune cell subsets and ICI efficacy through single-cell spatial profiling of pretreatment tumor tissue, using a 29-marker multiplex IHC platform built for in-depth dissection of the TME.<br>
RESULTS. Among various types of intratumoral lymphocytes, including Th1, Treg, and NK cells, only CD8+ T cells (tumor-infiltrating lymphocytes [TILs]) were associated with ICI efficacy. Computational tissue segmentation underscored the importance of direct physical interactions between CD8+ TILs and cancer cells for ICI efficacy. TIL phenotyping identified CD39/CD103/Ki-67 positivity as a hallmark of exhausted yet functional tumor-reactive CD8+ TILs. Immunosuppressive tumor-associated macrophages (TAMs) and cancer-associated fibroblasts were independent unfavorable adversaries. High CD73 expression on cancer cells was suggested to confer tolerance to ICI in EGFR/ALK-oncogene+ NSCLC, potentially through M2-TAM accumulation and aberrant angiogenesis.<br>
CONCLUSION. Our study delineates the clinical relevance of heterogeneous immune cell subsets in ICI-treated mNSCLC, aiding the development of targeted therapeutic strategies.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Metastatic promoting role of mesenchymal stem cells in oral squamous cell carcinoma revealed by an improved bone marrow chimeric model20445ENHtoo ShweEainDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityHotakaKawaiDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityShoSanouDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityYaminSoeDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityMay WathoneOoDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityTianyanPiaoDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityZin ZinMinDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityKiyofumiTakabatakeDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityKeisukeNakanoDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversitySoichiroIbaragiDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityHitoshiNagatsukaDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityMesenchymal stem cells (MSCs) are essential stromal regulators that coordinate tissue repair, angiogenesis, and immune balance. Within tumours, MSCs remodel the microenvironment and influence disease progression, yet their systemic contribution remains unclear due to the limited recovery of functional MSCs in conventional bone marrow transplantation models. Here, we developed an improved bone marrow collection (iBMC) method using enzymatic digestion, which markedly increases MSC yield while preserving their native phenotype. GFP bone marrow chimeric mice generated by iBMC and conventional transplantation displayed comparable hematopoietic reconstitution but differed in MSC abundance, enabling direct analysis of MSC-specific effects under physiological conditions. In mouse models of oral squamous cell carcinoma (OSCC), MSCs profoundly affected tumour development. MSC-deficient tumours exhibited necrosis and infiltration of immature myeloid-derived suppressor cells (MDSCs), whereas MSC-rich tumours showed enhanced vascularisation, adaptive immune infiltration, and stromal remodelling. Notably, lung metastasis occurred only in MSC-rich mice, accompanied by bone marrow–derived endothelial activation and TNF-α–driven inflammation. Pharmacological inhibition of LepR signalling using SHU9119 unexpectedly increased metastasis, underscoring the dual, context-dependent functions of MSCs. These findings establish iBMC as a reproducible and physiologically relevant model to study MSC-mediated regulation of tumour immunity, angiogenesis, and metastasis.No potential conflict of interest relevant to this article was reported.Pharmaceutical Society of JapanActa Medica Okayama0918-615847122024Staphylococcus aureus δ-Toxin Induces Ca2+ Influx-Independent Degranulation of Murine Cultured Mast Cells20582064ENKangLiuLaboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical UniversityTomoakiKatayamaDivision of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHitomiSatoDivision of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYuhoHamaoka-TamuraLaboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical UniversityMichikoSaitoBioscience Research Center, Kyoto Pharmaceutical UniversityKazuyukiFurutaDivision of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSatoshiTanakaLaboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical UniversityCutaneous colonization with Staphylococcus aureus (SA) is frequently observed in patients with atopic dermatitis. SA produces a wide variety of bacterial toxins, among which δ-toxin was found to induce degranulation of mast cells. Degranulation of mast cells could enhance bacterial clearance and protection from future SA infection but lead to exacerbation of atopic dermatitis. Because it remains to be determined how δ-toxin triggers degranulation, we investigated δ-toxin-induced changes in murine bone marrow-derived cultured mast cells in this study. We found that δ-toxin-induced degranulation could be classified into two phases, an early Ca2+-independent and a late Ca2+-dependent phase. Recent studies suggest that NOD-like receptor family, pyrin domain containing 3 is involved in the degranulation of mast cells, raising a possibility that leakage of K+ induced by δ-toxin is involved in the Ca2+-independent phase. However, Ca2+-independent degranulation remains unchanged although Ca2+-influx and degranulation induced by δ-toxin were significantly suppressed in the presence of high concentrations of K+. Because actin depolymerization was reported to induce degranulation in the absence of Ca2+ in the permeabilized rat peritoneal mast cells, a slow but steady decrease in the amount of filamentous actin observed here may be involved in Ca2+-independent degranulation induced by δ-toxin. Although Mas-related G protein-coupled receptor (MRGPR) X2 in humans and Mrgprb2 in mice are regarded as the receptors responsible for immunoglobulin E-independent degranulation, δ-toxin-induced degranulation remained unchanged in Mrgprb2−/− mast cells. Our findings pave the way for identification of the target receptors of δ-toxin.No potential conflict of interest relevant to this article was reported.Georg Thieme Verlag KGActa Medica Okayama0013-726X57042024Efficacy and safety of endoscopic ultrasonography-guided ethanol injections of small pancreatic neuroendocrine neoplasms: a prospective multicenter study321329ENKazuyukiMatsumotoGastroenterology and Hepatology, Okayama University HospitalHironariKatoGastroenterology and Hepatology, Okayama University HospitalTakaoItoiGastroenterology and Hepatology, Tokyo Medical UniversityMasayukiKitanoSecond Department of Internal Medicine, Wakayama Medical UniversityKazuoHaraGastroenterology, Aichi Cancer Center HospitalMasakiKuwataniGastroenterology and Hepatology, Hokkaido University HospitalMamoruTakenakaGastroenterology and Hepatology, Kindai University Faculty of Medicine Graduate School of Medical SciencesReikoAshidaSecond Department of Internal Medicine, Wakayama Medical UniversityShuntaroMukaiGastroenterology and Hepatology, Tokyo Medical UniversityNozomiOkunoGastroenterology, Aichi Cancer Center HospitalKazumichiKawakuboGastroenterology and Hepatology, Hokkaido University HospitalTatsuhiroYamazakiGastroenterology and Hepatology, Okayama University HospitalJunSakuraiCenter for Innovative Clinical Medicine, Okayama University HospitalYukiNakatsukaCenter for Innovative Clinical Medicine, Okayama University HospitalMichihiroYoshidaCenter for Innovative Clinical Medicine, Okayama University HospitalMotoyukiOtsukaGastroenterology and Hepatology, Okayama University HospitalBackground Endoscopic ultrasonography (EUS)-guided ethanol injection (EI) has recently been introduced as one of the management strategies for pancreatic neuroendocrine neoplasms (PNENs); however, its role as a surgical alternative is unclear. We evaluated the efficacy and safety of EUS-EI in treating small PNENs through a prospective multicenter study.<bR>
Methods Patients with grade 1 tumors of ≤15 mm confirmed by pathology were included. The primary end point assessed efficacy and safety, measuring complete ablation using computed tomography at 1 and 6 months, prevention of adverse events (AEs) within 1 month, severe pancreatic fistula at 1 month, and incidence/worsening of diabetes mellitus (DM) at 6 months. The composite end point of EUS-EI was compared with that of historical results of a study based on surgical treatment.<br>
Results 25 patients with PNENs, with a median tumor size of 10.1 mm, were treated using EUS-EI. The composite primary end point was achieved by 76.0% of patients (19/25; 95%CI 54.9%–90.6%), a proportion significantly higher than that of surgical treatment (P = 0.008). Regarding efficacy, 88.0% (22/25) of patients achieved complete ablation at 1 and 6 months (95%CI 68.8%–97.5%). Regarding safety, 96.0% (24/25) of patients had no severe AEs within 1 month (95%CI 79.7%–99.9%). No patients had severe pancreatic fistulas at 1 month, and 84.0% (21/25) had no incidence or exacerbation, or both, of DM at 6 months (95%CI 63.9%–95.5%).<br>
Conclusion EUS-EI is safe and could be a potent treatment option for patients with small PNENs.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0911-60284042024Central dentinogenic ghost cell tumor of the maxilla: a case report with new imaging findings and review of the literature561568ENSuzukaYoshidaDepartment of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoheiTakeshitaDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiyukiKawazuDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMikiHisatomiDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShunsukeOkadaDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMamikoFujikuraDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKyoichiObataDepartment of Oral and Maxillofacial Surgery, Okayama University HospitalKiyofumiTakabatakeDepartment of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySaoriYoshidaPreliminary Examination Room, Okayama University HospitalJunichiAsaumiDepartment of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesA dentinogenic ghost cell tumor (DGCT) is a rare benign odontogenic tumor that commonly shows characteristics of solid proliferation and has a relatively high risk of recurrence after surgical treatment. We herein report a case of a central DGCT that occurred in the maxilla and resulted in bone expansion. This study highlights new imaging findings (particularly magnetic resonance imaging) along with histopathological observations. In addition, we conducted a review of the existing literature on this rare tumor. A 37-year-old man developed swelling around the right cheek. A benign odontogenic tumor such as ameloblastoma was suspected based on the imaging examination findings (including bone expansion and the internal characteristics of the tumor) on panoramic imaging, computed tomography, and magnetic resonance imaging. The lesion was surgically excised from the right maxilla. Postoperative histopathological examination led to a definitive diagnosis of central DGCT. The tumor comprised epithelial neoplastic islands, resembling ameloblastoma, inside tight fibroconnective tissue; masses of ghost cells and formation of dentin were also observed. We had suspected that the minute high-density region around the molars on the imaging examinations represented alveolar bone change; however, it represented dentin formation. This led to difficulty diagnosing the lesion. Although DGCT may present characteristic findings on imaging examinations, its occurrence is infrequent, and in some cases, the findings may include the presence or absence of an impacted tooth without obvious calcification. The present case suggests that we should consider the possibility of an odontogenic tumor with calcification when high-density structures are observed inside the lesion.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2673-8937512025The Early Response After Radiation Therapy on Three-Dimensional Oral Cancer Model Using Patient-Derived Cancer-Associated Fibroblasts12ENIzumiYamamotoNeutron Therapy Research Center, Okayama UniversityKazuyoIgawaNeutron Therapy Research Center, Okayama UniversityNatsukoKondoParticle Radiation Oncology Center, Institute for Integrated Radiation and Nuclear Science, Kyoto UniversityYoshinoriSakuraiParticle Radiation Oncology Center, Institute for Integrated Radiation and Nuclear Science, Kyoto UniversityAtsushiFujimuraDepartment of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKiyofumiTakabatakeDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPengHuangNeutron Therapy Research Center, Okayama UniversityHiroyukiMichiueNeutron Therapy Research Center, Okayama UniversitySoichiroIbaragiDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenjiIzumiDivision of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityBackground/Objectives: Cancer-associated fibroblasts (CAFs), which are an important component of the tumor microenvironment, have been reported to have an adverse effect on conventional radiotherapy. This study aims to elucidate the effects of CAFs in boron neutron capture therapy (BNCT) using a three-dimensional (3D) oral cancer model. Methods: Three-dimensional cancer models were fabricated using patient-derived CAFs or patient-derived normal oral fibroblasts (NOFs) and a human oral squamous cell carcinoma cell line. Each 3D cancer model was performed with either a conventional X-ray treatment or BNCT and additionally analyzed histomorphologically. Results: The 3D oral cancer-CAFs model demonstrated a greater depth of cancer cell invasion than the 3D oral cancer-NOFs model. Radiation therapy for the 3D oral cancer models indicated a trend for decreasing cancer cell invasion and cell number with dose dependence in both X-ray and BNCT. In comparison with X-rays, BNCT showed a consistent increase in the number of NOFs and a significant reduction in the number of CAFs. Conclusions: BNCT for the 3D oral cancer model was shown to be effective against cancer cells and CAFs but not against NOFs, indicating its usefulness as a minimally invasive treatment for advanced cancer. Furthermore, it is indicated that the 3D oral cancer-CAFs model is a valuable tool to evaluate cancer treatment and research, particularly in high-grade malignant tumors with invasion.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1471-24072512025Long-term outcomes of salvage high-dose-rate brachytherapy for localized recurrence of prostate cancer following definitive radiation therapy: a retrospective analysis524ENKentaWatanabeDepartment of Radiology, Okayama University HospitalNobuhikoKamitaniDepartment of Radiology, Kawasaki Medical SchoolNaokiIkedaDepartment of Radiology, Kawasaki Medical SchoolYujiroKawataDepartment of Radiology, Kawasaki Medical SchoolRyojiTokiyaDepartment of Radiology, Kawasaki Medical SchoolTakafumiHayashiDepartment of Radiology, Kawasaki Medical SchoolYoshiyukiMiyajiDepartment of Urology, Kawasaki Medical SchoolTsutomuTamadaDepartment of Radiology, Kawasaki Medical SchoolKuniakiKatsuiDepartment of Radiology, Kawasaki Medical SchoolBackground Salvage high-dose-rate brachytherapy (HDR-BT) is a potential treatment for localized recurrence of prostate cancer following definitive radiation therapy. This study aimed to evaluate the long-term safety and efficacy of HDR-BT alone, without androgen deprivation therapy (ADT), in this patient population.<br>
Methods We conducted a retrospective analysis of patients with prostate cancer who developed pathologically confirmed local recurrence after definitive radiation therapy and were treated with salvage HDR-BT alone at Kawasaki Medical School Hospital between 2007 and 2021. The prescribed HDR-BT dose was 22 Gy in 2 fractions. Biochemical relapse-free survival (bRFS), cause-specific survival (CSS), and overall survival (OS) were assessed using the Kaplan–Meier method. Adverse events were evaluated based on the Common Terminology Criteria for Adverse Events.<br>
Results Thirty-five patients were included, with a median follow-up of 66.0 months (range, 8.1–169.1). The 5-year bRFS, CSS, and OS rates were 29.7%, 100%, and 89.3%, respectively. Biochemical recurrence occurred in 21 patients (60.0%). Grade 2 adverse events were reported in eight patients (22.9%), while two (5.7%) experienced grade 3 adverse events. All grade 3 adverse events occurred in patients who had HDR-BT as their initial definitive radiation therapy.<br>
Conclusions Salvage HDR-BT without ADT is a safe and effective treatment option for localized prostate cancer recurrence after definitive radiation therapy. It provides excellent CSS rates with acceptable toxicity while potentially reducing the need for ADT. Further prospective studies are warranted to confirm these findings.No potential conflict of interest relevant to this article was reported.Ferrata Storti Foundation (Haematologica)Acta Medica Okayama1592-872111152025Distinct interleukin-6 production in IPL and TAFRO subtypes of idiopathic multicentric Castleman disease17051715ENAsamiNishikoriDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesMidori FilizNishimuraDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesYoshitoNishimuraDivision of Hematology/Oncology, Mayo ClinicRioYamadaDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesTomokaHaratakeDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesDaisukeEnnishiCenter for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama, Japan; Department of Hematology and Oncology, Okayama University HospitalRyotaChijimatsuCenter for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama, Japan; Department of Hematology and Oncology, Okayama University HospitalToshihiroItoDepartment of Immunology, Nara Medical UniversityTomohiroKogaDepartment of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical SciencesSayakaOchiDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesYuriKawaharaDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesHimawariUetaDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesYudaiTakedaDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesMichael V.GonzalezCenter for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of PennsylvaniaDavid C.FajgenbaumCenter for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of PennsylvaniaFritsVan RheeUniversity of Arkansas for Medical SciencesShujiMomoseDepartment of Pathology, Saitama Medical Center, Saitama Medical UniversityYasuharuSatoDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesIdiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder characterized by systemic inflammation and lymphadenopathy. Two major clinical subtypes, idiopathic plasmacytic lymphadenopathy (iMCD-IPL) and iMCD with thrombocytopenia, anasarca, fever, renal dysfunction/reticulin fibrosis, and organomegaly (iMCD-TAFRO), have distinct pathophysiological mechanisms. While interleukin-6 (IL-6) is known to be elevated in iMCD, differences in the sources of IL-6 production between subtypes remain unclear. We examined the source of IL-6 production and its transcriptional regulation across iMCD subtypes using immunohistochemistry, in situ hybridization, and gene expression profiling. Immunohistochemistry and in situ hybridization revealed that plasma cells were the predominant IL-6-expressing cells in iMCD-IPL, whereas vascular endothelial cells expressed IL-6 in iMCD-TAFRO. Plasma cells exhibited stronger IL-6 protein expression in iMCD-IPL than in iMCD-TAFRO. Gene expression analysis revealed upregulation of XBP1, MZB1, DERL3, SSR4, FKBP11, FKBP2, PIM2, RABAC1, and SDF2L1 in iMCD-IPL, implicating endoplasmic reticulum stress and plasma cell differentiation in IL-6 dysregulation. Our findings suggest that XBP1-mediated IL-6 production may contribute to the pathogenesis of iMCD-IPL, potentially explaining its favorable responses to IL-6 blockade therapy. In contrast, IL-6 production in iMCD-TAFRO may be predominantly from vascular endothelial cells, suggesting that elevated serum IL-6 is a secondary phenomenon of the cytokine storm in this subtype. Future studies should clarify how proteomics and gene expression profiling could inform subtype-specific therapeutic strategies in iMCD.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1931-52442952026A novel spontaneous rat model of chronic kidney disease with mitochondrial dysfunction driven by thioredoxin insufficiency5164ENIori K.OhmoriSection of Developmental Physiology and Pathology, Faculty of Education, Okayama UniversityMamoruOuchidaDepartment of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshikoHadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShinyaToyokuniDepartment of Pathology and Biological Responses, Nagoya University Graduate School of MedicineTomojiMashimoDivision of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, The University of TokyoBackground: Chronic kidney disease (CKD) is a global health burden with high prevalence and poor prognosis. Although oxidative stress and mitochondrial dysfunction have been implicated in its pathogenesis, in vivo causal evidence remains limited. Thioredoxin (Trx), encoded by Txn1, is a redox-active protein that plays a central role in controlling oxidative stress and maintaining intracellular redox homeostasis.<br>
Methods: To address this gap, we investigated the lifelong phenotypes of Txn1-F54L mutant rats harboring approximately one-third of the normal Trx activity. These rats were generated via N-ethyl-N-nitrosourea mutagenesis and validated by clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 genome editing. Comprehensive analyses included biochemical testing, histopathology, immunohistochemistry, transmission electron microscopy, RNA-sequencing, western blotting, and cytokine profiling.<br>
Results: Txn1-F54L mutant rats spontaneously developed progressive CKD, with median survival times of 110–119 days for homozygotes and 303–346 days for heterozygotes. Their clinical features—elevated blood urea nitrogen, hypoalbuminemia, hypercholesterolemia, hypertension, and arterial medial sclerosis—closely resembled those of human CKD. Histopathological evaluation revealed extensive tubular injury, interstitial fibrosis, and glomerulosclerosis. Transcriptomic profiling identified 3,418 differentially expressed genes significantly enriched in immune activation and fibrosis pathways. Mitochondrial dysfunction was prominent in proximal tubules, accompanied by oxidative stress accumulation and concurrent activation of regulated cell death pathways (apoptosis, necroptosis, and pyroptosis). Elevated serum levels of interleukin-1β, interleukin-6, and interferon-γ indicated systemic inflammation.<br>
Conclusions: Our findings demonstrate that lifelong Trx deficiency induces oxidative stress–mediated mitochondrial dysfunction and regulated cell death, leading to inflammation and progressive CKD. This study establishes the Txn1 mutant rat as a valuable spontaneous CKD model, providing translational insights and a platform for developing therapeutic strategies targeting oxidative stress–induced pathways.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8032026Common Bile Duct Stone Formed Around an Ingested Fish Bone219223ENKaitaroHigashiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterMotoyasuTabuchiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterShinyaSakamotoDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterShutaTamuraDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterSunaoUemuraDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterTeppeiTokumaruDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterTakehiroOkabayashiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterCase Report/10.18926/AMO/70858An 86-year-old man presented with epigastric pain. He had previously undergone distal gastrectomy with Roux-en-Y reconstruction. Computed tomography (CT) revealed a 32×17 mm common bile duct (CBD) stone with an internal 20 mm linear hyperdense component. Endoscopic removal was unsuccessful due to the size and impaction of the stone. Open choledochotomy retrieved multiple stones and a calcified fish bone, which was confirmed by infrared spectroscopy using the potassium bromide (KBr) wafer method. Although fish bone ingestion is relatively common, this case highlights that such foreign bodies can occasionally serve as a nidus for CBD stone formation, leading to unexpected and clinically significant pathologies. When CT demonstrates a linear high-attenuation intraductal structure, clinicians should suspect a bone fragment and follow a stepwise approach, considering early surgical intervention when endoscopic extraction is unsuccessful or likely to be challenging.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8032026Peripheral Blood T-Cell Receptor Repertoire and Host Immune Background in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy169178ENYukiNakamuraDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalTakayukiIwamotoDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalYukikoKajiwaraDepartment of Breast Surgery, Hiroshima City Hiroshima Citizens HospitalAkiraHidaDepartment of Pathology, Matsuyama Shimin HospitalShogoNakamotoDepartment of Breast and Endocrine Surgery, Okayama University HospitalYuichiroMiyoshiDepartment of Breast Endocrine Surgery, Kagawa Prefectural Center HospitalTadahikoShienDepartment of Breast and Endocrine Surgery, Okayama University HospitalMasahikoIkedaDepartment of Breast and Thyroid Surgery, Fukuyama City HospitalHiroyoshiDoiharaDepartment of General Surgery, Kawasaki Medical School General Medical CenterRyoheiOgataDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalYoshikazuKoikeDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalTsunehisaNomuraDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalKatsuhiroTanakaDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalKazutakaNakashimaDepartment of General Surgery, Kawasaki Medical School General Medical CenterTomokiYamatsujiDepartment of General Surgery, Kawasaki Medical School General Medical CenterNarutoTairaDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalOriginal Article10.18926/AMO/70852The association between peripheral blood T-cell receptor (TCR) repertoire and chemotherapy response remains unclear. We evaluated peripheral blood TCR repertoire and gut microbiota in 21 breast cancer patients receiving neoadjuvant chemotherapy (NAC) who were enrolled in the SBP-14 prospective cohort study between October 2019 and March 2022. We analyzed stool samples obtained pre-NAC and peripheral blood samples obtained pre- and post-NAC. The primary endpoint was the association between baseline peripheral blood TCR repertoire and treatment response. Eleven patients (52%) had hormone receptor-positive breast cancer. All patients received anthracyclines and taxanes, with anti-HER2 therapy for HER2-positive disease. TCR diversity (TCR alpha chain [TRA], p=0.095; TCR beta chain [TRB], p=0.051) and clonality (TRA, p=0.271; TRB, p=0.500) were not significantly associated with treatment response. Gut microbiota diversity was not correlated with TCR diversity (TRA: ρ=0.046, p=0.845; TRB: ρ=0.021, p=0.929); however, three bacterial orders (Erysipelotrichales, Bacillales, and Pasteurellales) were significantly associated with TCR repertoire. Baseline TCR repertoire was not associated with treatment response in this cohort of breast cancer patients.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0950-923245182026Trisomy 8 alters chromatin conformations and activates Y chromosome genes in stem cells to drive a pre-leukemic state16751687ENJieBaiLaboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto UniversityKimiArakiInstitute of Resource Development and Analysis, Kumamoto UniversityDaisukeKurotakiLaboratory of Chromatin Organization in Immune Cell Development, International Research Center for Medical Sciences, Kumamoto UniversityEerdundulengLaboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto UniversitySupannikaSorinLaboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto UniversityKeiHiramatsuDepartment of Chromosome Biomedical Engineering, Integrated Medical Sciences, Graduate School of Medical Sciences, Tottori UniversityNarumiUnoLaboratory of Bioengineering, School of Life Sciences, Tokyo University of Pharmacy and Life SciencesAiHamashimaLaboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto UniversityMihokoIimoriLaboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto UniversityKentaKikuchiLaboratory of Chromatin Organization in Immune Cell Development, International Research Center for Medical Sciences, Kumamoto UniversityMinoruTerashimaLaboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto UniversityShoKubotaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKensakuKohrogiDepartment of Pediatrics, Graduate School of Medical Sciences, Kumamoto UniversityGangHuangDepartment of Cell Systems & Anatomy, Department of Pathology & Laboratory Medicine, UT Health San Antonio, Joe R. and Teresa Lozano Long School of Medicine, Mays Cancer Center at UT Health San AntonioMinetaroOgawaDepartment of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto UniversityMitsuoOshimuraChromosome Engineering Research Center, Tottori UniversityYasuhiroKazukiDepartment of Chromosome Biomedical Engineering, Integrated Medical Sciences, Graduate School of Medical Sciences, Tottori UniversityGoroSashidaLaboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto UniversityThe mechanistic role of trisomy 8 in the development of myelodysplastic syndrome (MDS) remains poorly defined. Here, we generated a trisomy 8 mouse model by transferring a human chromosome 8 into murine embryonic stem cells and prospectively examined the effects on hematopoietic stem cells (HSC) by trisomy 8. The expression of inflammatory genes was enhanced, and hematopoietic programs mediated by transcription factors and polycomb repressive complex 2 (PRC2) were dysregulated in trisomy 8 HSC, which impaired their self-renewal and balanced differentiation. Trisomy 8 HSC altered the chromatin accessibility and conformations and activated Y chromosome genes, such as Uty/Kdm6c epigenetic modifier, which is known to demethylate histone H3K27me3 modification. The Uty gene facilitated the activation of PRC2-target and Runx1-target genes in leukemogenesis and drove the proliferation of human trisomy 8 leukemic cells. Since the RUNX1 gene is frequently mutated in patients with trisomy 8 MDS, its deletion attenuated the enhanced expression of inflammatory genes and mitigated the impaired self-renewal of trisomy 8 HSC in mice. Our findings reveal that trisomy 8 altered the transcriptional programs and chromatin conformations in HSC and drove a pre-malignant state through activating the expression of Uty, suggesting a route for the development of trisomy 8 MDS.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0039-60601952026Biliverdin supplementation in perfusate and preservation solution attenuates ischemia-reperfusion injury in a rat donation-after-circulatory-death heart transplantation model110231ENKoheiTokiokaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTsuyoshiNojimaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahiroHirayamaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiHongoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakafumiObaraDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoheiAgetaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuroIgawaDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyukiAokageBiological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and GerontologyKoheiTsukaharaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTetsuyaYumotoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Heart transplantation faces a persistent donor shortage; therefore, hearts from donation after circulatory death have become a feasible option despite unavoidable warm ischemia and subsequent ischemia-reperfusion injury. Biliverdin, an endogenous bile pigment with strong antioxidant and anti-inflammatory properties, has shown protective effects against ischemia-reperfusion injury in several organ transplantation models. Whether biliverdin attenuates warm ischemic injury in donation after circulatory death heart transplantation remains unclear. This study evaluated biliverdin supplementation in the perfusate and preservation solution in a rat donation after circulatory death model.<br>
Methods: Circulatory death was induced under deep anesthesia, and warm ischemia was maintained for 18 minutes, including the mandatory 5-minute stand-off period. Donor hearts were then flushed and subsequently cold-stored in the same biliverdin-supplemented extracellular-type trehalose–containing Kyoto solution, whereas control grafts received extracellular-type trehalose–containing Kyoto without biliverdin at both stages before heterotopic transplantation. Grafts were assessed at 3 and 24 hours after reperfusion (n = 6 per group). Evaluations included early graft recovery, myocardial injury markers, histological and ultrastructural changes, and inflammatory and stress-response gene expression.<br>
Results: Biliverdin significantly improved early graft recovery, shortening reanimation time and increasing left ventricular fractional shortening at 24 hours. Serum troponin I levels were lower in biliverdin-treated grafts. Biliverdin also reduced histological injury and inflammatory cell infiltration. Ultrastructural analysis showed preserved mitochondrial architecture and ultrastructural integrity. Early proinflammatory gene expression was suppressed.<br>
Conclusion: Biliverdin supplementation in the perfusate and preservation solution attenuates ischemia-reperfusion injury in the experimental rat donation after circulatory death heart transplantation model. These findings provide proof of concept for further mechanistic and translational evaluation of biliverdin for myocardial protection in donation after circulatory death.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0897-38062026What Is the Pterygomandibular Raphe? A Confluence of Fasciae Rather Than a Discrete Structure19ENJoeIwanagaDepartment of Neurosurgery, Tulane Center for Clinical Neurosciences, Tulane University School of MedicineShionHamaSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu UniversityKeikoFukinoDepartment of Oral and Maxillofacial Anatomy, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental UniversityShogoKikutaDental and Oral Medical Center, Kurume University School of MedicineMi‐SunHurDepartment of Anatomy, Daegu Catholic University School of MedicineMaria Cristina ManzanaresCespedesHuman Anatomy and Embryology Unit. Experimental Pathology and Therapeutics Department, Faculty of Medicine and Health Sciences, University of BarcelonaYoshioOhyamaOral and Maxillofacial Surgery, Shizuoka City Shizuoka HospitalMasayaAkashiDepartment of Oral and Maxillofacial Surgery, Kobe University Graduate School of MedicineNoritakaKomuneDepartment of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu UniversityHideakiKamochiDepartment of Maxillofacial Surgery, Institute of Science TokyoSoichiroIbaragiDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThe pterygomandibular raphe (PMR) has traditionally been described as a fibrous or tendinous band connecting the bucinator (BM) and superior pharyngeal constrictor (SPCM) muscles. However, recent evidence has questioned its existence. This study aimed to reevaluate the anatomy of the pterygomandibular region by preserving fascial continuity and examining the relationships among adjacent muscles and connective tissues. Twenty-five sides from formalin-fixed cadaveric heads were examined. Twenty sides underwent macroscopic dissection under a surgical microscope, and five sides were sectioned axially and analyzed histologically using Masson's trichrome staining to assess muscle–fascia continuity. The buccopharyngeal fascia (BpF) adhered tightly to the posterolateral surface of the BM. A ligament-like bundle observed between the BM and medial pterygoid muscle corresponded to an artificial continuation of the BpF created by dissection. Axial sections revealed that the BpF, masseteric, and temporalis fasciae converged anteriorly on the lateral surface of the BM, while posteriorly, the BpF and temporalis fascia also merged, forming a confluence of fasciae. No discrete tendinous or ligamentous PMR was identified. The so-called PMR represents a dissection artifact rather than a true anatomical structure. These findings emphasize the importance of preserving fascial relationships and using precise terminology in anatomical and clinical contexts.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0753-33221942026Elucidation of mechanisms underlying the therapeutic effects of cordycepin on pulmonary hypertension, with a focus on cell senescence and gut microbiota118923ENGaopengLiDepartment of Cardiovascular Physiology, Faculty of Medicine, Kagawa UniversityZhixinZhaoInner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural UniversityMitsuhiroMachitaniDivision of Cancer Stem Cell, National Cancer Center Research InstituteRyouIshikawaDepartment of Diagnostic Pathology, Kagawa University HospitalKaoriIshikawaDepartment of General Medicine, Kagawa University HospitalNaoyaYokotaDepartment of General Thoracic Surgery, Faculty of Medicine, Kagawa UniversityReijiHabaDepartment of Diagnostic Pathology, Kagawa University HospitalKazufumiNakamuraCenter for Advanced Heart Failure, Okayama University HospitalZhihongSunInner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural UniversityLin-HaiKuraharaDepartment of Cardiovascular Physiology, Faculty of Medicine, Kagawa UniversityKatsuyaHiranoDepartment of Cardiovascular Physiology, Faculty of Medicine, Kagawa UniversityIntroduction: Pulmonary hypertension (PH) is a progressive cardiopulmonary disorder characterized by excessive pulmonary vascular remodeling and aberrant proliferation of pulmonary artery smooth muscle cells (PASMCs). Emerging evidence suggests that gut microbiota dysbiosis contributes to PH development. Cordycepin, a natural adenosine analogue derived from Cordyceps militaris, has demonstrated antiproliferative and microbiota-modulating properties; however, its mechanism of action in PH remains unclear.<br>
Objective: Elucidate the mechanisms underlying the therapeutic effects of cordycepin on PH, focusing on cellular senescence and gut microbiota.<br>
Methods: The effects of cordycepin on PH pathology were investigated by transcriptome analysis of PASMCs from patients, and metagenomic analysis of rodent PH models. Cellular senescence was analyzed in lung tissue from p16Ink4a-CreERT2 reporter mice and in rat bone marrow-derived macrophages (BMDMs).<br>
Results: RNA sequencing analysis revealed activation of p53 signaling by cordycepin in PASMCs. Cordycepin suppressed CDK1 expression and TERT phosphorylation at threonine 249. It ameliorated vascular and cardiac remodeling in PH rat and mouse models. Cordycepin induced M1-like macrophage senescence in p16 Ink4a reporter mice lungs and rat BMDMs. Cordycepin significantly reshaped the gut microbiota, increasing beneficial genera (e.g. Alistipes and Acetatifactor) and reducing proinflammatory taxa (e.g., Ruminococcus), with modulating key metabolic pathways, including short-chain fatty acid, tryptophan, and vitamin K2 metabolism.<br>
Conclusion: Cordycepin exerts multi-target therapeutic effects in PH by inhibiting PASMC proliferation via the p53–CDK1/pTERT axis, modulating gut microbiota-linked immunometabolism and induces proinflammatory macrophage senescence. These findings support cordycepin as a promising candidate for PH therapies targeting the vascular, immune, and gut–lung axes.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1349-00796812026Roles of the aryl hydrocarbon receptor and its ligands in osteoclast differentiation and temporomandibular joint osteoarthritis100726ENTakashiIzawaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIslamy RahmaHutamiDepartment of Orthodontics, Universitas Islam Sultan AgungYuriYoshikawaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityGohjiKozakiDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYusakuHamadaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiNambaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMisaTaguchiDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJiaminChenDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJanvierHabumugishaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiKamiokaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays an essential role in skeletal homeostasis. Increasing evidence indicates that AhR critically regulates osteoclast differentiation and activity, thereby influencing bone mass, bone resorption, and susceptibility to skeletal diseases. Although AhR has also been implicated in osteoblast-lineage cells, its regulatory roles in osteoclasts and immune cells are less well understood but are increasingly recognized as central to bone remodeling. In particular, AhR signaling modulates immune cell subsets relevant to bone metabolism and governs the differentiation of bone marrow-derived macrophages into osteoclasts.<br>
Highlight: This review summarizes the recent findings regarding the regulation of osteoclast differentiation by AhR and its ligands under both physiological and pathological conditions. Special emphasis is placed on the interaction between AhR and the RANKL signaling axis in osteoclasts, as well as on how exogenous and endogenous ligands, including benzo[a]pyrene (B[a]P) and 6-formylindolo[3,2-b]carbazole (FICZ), modulate bone resorption and subchondral bone remodeling in temporomandibular joint osteoarthritis. Furthermore, the role of macrophages as osteoclast progenitors and immunomodulators has been highlighted, positioning AhR as a critical intermediary that links environmental exposure, inflammation, and skeletal metabolism.<br>
Conclusion: In this review, we outlined the diverse functions of AhR signaling and its ligands in oral and temporomandibular joint osteoarthritis. AhR plays a central role in bone remodeling. The harmful exogenous ligand B[a]P generally promotes bone loss, whereas the endogenous ligand FICZ exerts protective actions. These insights highlight AhR as a key regulatory switch linking the skeletal and immune systems and as a promising therapeutic target for bone-destructive disorders.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1865-72571932026Successful management and 10-year survival of a rectal neuroendocrine tumor with rare systemic metastases via a non-portal venous pathway491498ENShigeruHoriguchiDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyaMiyamotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalAkihiroMatsumiDepartment of Gastroenterology and Hepatology, Okayama University HospitalHiroyukiTerasawaDepartment of Gastroenterology and Hepatology, Okayama University HospitalYukiFujiiDepartment of Gastroenterology and Hepatology, Okayama University HospitalKoseiTakagiDepartment of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTakashiKuiseDepartment of Gastroenterological Surgery, Okayama Red Cross HospitalTakehiroTanakaDepartment of Pathology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University HospitalMetastatic neuroendocrine tumors (NETs) typically involve the liver and lymph nodes. Metastases in the orbit, heart, and ovary are rare and present unique clinical challenges. We report a woman who was 70 years old at the time of initial presentation with liver metastases from a rectal neuroendocrine tumor. Following a right hepatectomy for liver metastases, she remained free of hepatic recurrence for 10 years. Notably, four years after the right hepatectomy, she developed new metastases in the left orbit, right ventricle, and left ovary, with diplopia as the sole clinical symptom. This clinical course suggests a distinct metastatic pathway associated with the lower rectum that bypasses the portal circulation, consistent with the dual drainage system of the rectal region. Management involved a strategic multimodal approach that includes systemic therapy with everolimus and lanreotide as well as targeted surgical resectioning of the cardiac and ovarian lesions. The orbital lesion achieved a complete response through systemic therapy alone, preserving visual function. Currently, 10 years after the initial treatment, the patient maintains an excellent performance status (ECOG PS 0) while receiving peptide receptor radionuclide therapy (PRRT). This case demonstrates that recognizing atypical metastatic pathways and employing strategic multimodal therapies can achieve long-term survival and functional preservation in rectal NETs.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2090-6528202612026Selective ARID1A Loss Restricted to the Undifferentiated Component of a Mismatch Repair‐Deficient Gastric Carcinoma: A Case Report8863202ENRikaOmoteDepartment of Diagnostic Pathology, NHO Fukuyama Medical CenterRyosukeHamanoDepartment of Surgery, NHO Fukuyama Medical CenterShinyaOtsukaDepartment of Surgery, NHO Fukuyama Medical CenterTakehiroTanakaDepartment of Pathology, Okayama University HospitalHiroyukiYanaiDepartment of Pathology, Okayama University HospitalMismatch repair-deficient (dMMR) gastric carcinomas often harbor ARID1A alteration, but a sharply demarcated undifferentiated/rhabdoid component with selective ARID1A loss is uncommon and may create a diagnostic dilemma. An 80-year-old man underwent esophagogastroduodenoscopy for anemia, which revealed a circumferential Borrmann Type 3 lesion in the gastric body, and distal gastrectomy was performed. Histologically, the tumor was composed predominantly of undifferentiated carcinoma with focal rhabdoid features and a minute well-differentiated adenocarcinoma component, with an abrupt transition between the two. Immunohistochemistry showed loss of nuclear MLH1 and PMS2 in both components, whereas loss of ARID1A expression was confined to the undifferentiated component; SMARCB1 (INI1), SMARCA2 (BRM), and SMARCA4 (BRG1) were retained. EBER in situ hybridization was negative. Because gene-level testing, MSI testing, and MLH1 promoter methylation analysis were not performed, the molecular basis of the dMMR phenotype and ARID1A loss could not be determined. The restricted scope of molecular testing limits the ability to draw broad or generalizable conclusions and to fully establish clinicopathological correlations. The value of this report is, therefore, not mechanistic proof but recognition of a practical morphologic-immunophenotypic observation: When a gastric carcinoma shows a sharply demarcated shift from differentiated to undifferentiated/rhabdoid morphology, dMMR should be considered, and selective ARID1A loss in the undifferentiated component may be associated with dedifferentiation. These findings should be interpreted with caution as preliminary, hypothesis-generating observations that require validation in larger studies with more extensive molecular profiling.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2072-669418102026Activation of TAS2R Signaling by Diphenidol Suppresses Tumor Growth and Remodels the Tumor Immune Microenvironment in Oral Squamous Cell Carcinoma1527ENNisrina EkayaniNasrunDivision of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of HokkaidoAkihikoTanimuraDivision of Pharmacology, Department of Oral Biology, School of Dentistry, Health Sciences University of HokkaidoKokiYoshidaDivision of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of HokkaidoOsamuUeharaDivision of Disease Control and Molecular Epidemiology, Department of Oral Growth and Development, School of Dentistry, Health Sciences University of HokkaidoYukiKunisadaDepartment of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKiyofumiTakabatakeDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkihiroHosoyaDivision of Craniofacial Development and Tissue Biology, Tohoku University Graduate School of DentistryHiroakiTakebeDivision of Histology, Department of Oral Biology, School of Dentistry, Health Sciences University of HokkaidoHitoshiNagatsukaDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihiroAbikoDivision of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of HokkaidoMuhammadRuslinDepartment of Oral and Maxillofacial Surgery, Faculty of Dentistry, Hasanuddin UniversityTsuyoshiShimoDivision of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of HokkaidoBackground: Oral squamous cell carcinoma (OSCC) remains a clinically challenging malignancy characterized by aggressive behavior and limited therapeutic options. Bitter taste receptors (TAS2Rs), expressed across multiple tissues and cancer types, have recently emerged as regulators of tumor biology and immune responses; however, their functional significance in OSCC remains poorly understood. Methods: Immunohistochemical analysis was performed using surgically resected human tongue OSCC specimens and a tissue microarray (TMA) cohort. In parallel, four TAS2R agonists were evaluated in SCC7 cells to assess intracellular calcium responses. RNA sequencing was conducted to analyze transcriptional changes following diphenidol treatment, and functional assays, including proliferation, migration, and apoptosis analyses, were performed in vitro. Antitumor effects were further evaluated in a syngeneic SCC7 mouse model, followed by TUNEL staining and flow cytometry to assess apoptosis and immune cell infiltration. Results: TAS2R38 expression was markedly upregulated in dysplastic and invasive OSCC lesions with predominant nuclear localization and was associated with histological grade and clinical stage, indicating an early and sustained alteration during tumor progression. Among the agonists tested, diphenidol most strongly induced IP3-dependent intracellular Ca2+ elevation. RNA sequencing revealed upregulation of Il1rl1 and Lzts2. Functionally, diphenidol significantly suppressed SCC7 cell proliferation and migration and induced apoptosis in vitro. In vivo, diphenidol reduced tumor volume and weight and increased apoptotic activity. Flow cytometry demonstrated a marked reduction in tumor-infiltrating CD4+CD25+Foxp3+ regulatory T cells, indicating modulation of the tumor immune microenvironment. Conclusions: TAS2R activation by diphenidol suppresses tumor growth through both tumor-intrinsic mechanisms and modulation of the tumor immune microenvironment in OSCC. These findings define TAS2R-mediated calcium signaling as a novel axis linking tumor progression and immunoregulation. Given that diphenidol is a clinically approved drug with an established safety profile, our results provide a strong rationale for TAS2R-targeted drug repurposing strategies in cancer therapy.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2666-3643732026Potential Immune Microenvironment Biomarkers in SCLC: J-TAIL-2 Observational Study100926ENMasayukiShirasawaDepartment of Thoracic Oncology, National Cancer Center HospitalMakotoNishioDepartment of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer ResearchKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalAtsushiOsoegawaDepartment of Thoracic and Breast Surgery, Oita University Faculty of MedicineEikiKikuchiDepartment of Respiratory Medicine, Faculty of Medicine, Hokkaido UniversityHideharuKimuraDepartment of Respiratory Medicine, Kanazawa University HospitalYasushiGotoDepartment of Thoracic Oncology, National Cancer Center HospitalJunichiShimizuDepartment of Thoracic Oncology, Aichi Cancer Center HospitalEisakuMiyauchiDepartment of Respiratory Medicine, Tohoku University HospitalHiroshigeYoshiokaDepartment of Thoracic Oncology, Kansai Medical UniversityIchiroYoshinoInternational University of Health and Welfare Narita HospitalToshihiroMisumiDepartment of Data Science, National Cancer Center Hospital EastYasushiYatabeDepartment of Diagnostic Pathology, National Cancer Center HospitalTatsuyaYoshidaDepartment of Thoracic Oncology, National Cancer Center HospitalJumpeiKashimaDepartment of Diagnostic Pathology, National Cancer Center HospitalMasahideOkiDepartment of Respiratory Medicine, NHO Nagoya Medical CenterHisaoAshimuraChugai Pharmaceutical Co., Ltd.YukiKobayashiChugai Pharmaceutical Co., Ltd.MisaTanakaChugai Pharmaceutical Co., Ltd.AkihikoGemmaNippon Medical SchoolIntroduction: Effective predictors of response to atezolizumab plus carboplatin/etoposide (CE) therapy in extensive-stage SCLC (ES-SCLC) remain limited. This exploratory analysis from J-TAIL-2 aimed to identify markers of survival benefit with atezolizumab plus CE therapy in ES-SCLC.<br>
Methods: J-TAIL-2 (ClinicalTrials.gov ID, NCT04501497) was a multicenter observational study that enrolled patients receiving atezolizumab plus CE (ES-SCLC cohort) in clinical practice in Japan per local label and treatment guidelines. In this exploratory analysis, the association of CD8+ tumor-infiltrating lymphocyte (TIL) density and SCLC subtypes (SCLC-A [ASCL1 dominant], SCLC-N [NEUROD1 dominant], SCLC-P [ASCL1/NEUROD1 double-negative with POU2F3 expression], and SCLC-O [ASCL1/NEUROD1 double-negative not otherwise specified]) with overall survival (OS) and progression-free survival (PFS) was evaluated. SCLC subtyping was performed by immunohistochemistry.<br>
Results: SCLC samples (n = 100; data cutoff, February 3, 2023) were categorized as SCLC-A (73%), SCLC-N (16%), SCLC-P (8%), and SCLC-O (3%). Among 96 patients who received first-line atezolizumab plus CE, median age was 72 (range, 39–87) years and 81% were male. Furthermore, 56 patients were classified into the CD8+ TIL-high subgroup and 40 into the TIL-low subgroup. Median (m)PFS with atezolizumab plus CE was 6.1 months (95% confidence interval [CI]: 4.5–7.5) in the TIL-high versus 4.4 months (95% CI: 4.0–5.1) in the TIL-low subgroup (p = 0.01); mOS was 18.4 (95% CI: 11.8–not estimable) versus 10.8 months (95% CI: 7.7–16.2; p = 0.04). mOS and mPFS were not significantly different between SCLC subtypes but were numerically shorter in the SCLC-N group.<br>
Conclusions: CD8+ TIL density is a potential biomarker of clinical benefit in ES-SCLC and may facilitate patient selection for atezolizumab combination therapy.No potential conflict of interest relevant to this article was reported.American Association for Cancer Research (AACR)Acta Medica Okayama2767-9764642026Constitutive EGFR Activation Induced by PTPRR Downregulation Confers Resistance to KRAS Inhibitors728 741ENHiroakiKanemuraDepartment of Medical Oncology, Kindai University Faculty of MedicineToshiyukiTakeharaDivision of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of MedicineOsamuMaenishiDepartment of Pathology, Kindai University Faculty of MedicineShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalNatsumiIwawakiDivision of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of MedicineKeiKunimasaDepartment of Thoracic Oncology, Osaka International Cancer InstituteTomohiroNakayamaDepartment of Medical Oncology, Kishiwada City HospitalSatomiWatanabeDepartment of Medical Oncology, Kishiwada City HospitalShinichiroSuzukiDepartment of Medical Oncology, Kindai University Faculty of MedicineKazukoSakaiDepartment of Genome Biology, Kindai University Faculty of MedicineKoichiAzumaDivision of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of MedicineKeitaKudoDepartment of Medical Oncology, National Hospital Organization Osaka Minami Medical CenterKazutoNishioDepartment of Genome Biology, Kindai University Faculty of MedicineKazuhikoNakagawaDepartment of Medical Oncology, Kindai University Faculty of MedicineHidetoshiHayashiDepartment of Medical Oncology, Kindai University Faculty of MedicineTakeshiTeramuraDivision of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of MedicineKimioYonesakaDepartment of Medical Oncology, Kindai University Faculty of MedicineKRASG12C inhibitors, such as sotorasib, show clinical efficacy for non–small cell lung cancer (NSCLC) positive for the G12C mutations of KRAS, but primary and acquired resistance to these drugs remains a clinical problem. In this study, we show that the development of resistance to sotorasib in KRASG12C-positive NSCLC cells was mediated by constitutive activation of EGFR resulting from downregulation of the protein tyrosine phosphatase receptor type R (PTPRR). PTPRR has been identified as a physiologic regulator of ERK signaling in several cancer types. In our study, PTPRR was demonstrated to bind directly to EGFR, facilitating its dephosphorylation on tyrosine residues. Resumption of PTPRR expression in the resistant cells attenuated EGFR phosphorylation and restored sotorasib sensitivity. PTPRR downregulation was associated with gene promoter hypermethylation in the sotorasib-resistant cells and NSCLC tissue samples. Furthermore, low PTPRR expression in tumor specimens was associated with shorter progression-free and overall survival for patients with NSCLC treated with sotorasib. In contrast to sotorasib, high PTPRR expression was associated with a poor response to EGFR tyrosine kinase inhibitors in EGFR-mutated NSCLC, suggesting that PTPRR may broadly regulate EGFR dependence in NSCLC. Finally, dual blockade of KRASG12C and EGFR showed a substantial antitumor effect in a xenograft model of sotorasib-resistant NSCLC. This approach is therefore a rational therapeutic strategy for KRASG12C-positive NSCLC, especially for tumors showing PTPRR downregulation.<br>
Significance: The current study shows that downregulation of PTPRR induces EGFR activation and resistance to KRASG12C inhibitors in NSCLC, suggesting dual KRAS-EGFR blockade as a rational therapy. PTPRR may help identify patient subgroups that would benefit from the addition of EGFR inhibitors to KRASG12C-targeted therapies.No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama2673-253X82026Development of a generative AI agent for family support in implementing family-based treatment for children and adolescents with anorexia nervosa1759690ENManaHanzawaDepartment of Pediatrics, Okayama University Hospital Medical Center for ChildrenJoeHaseiDepartment of Medical Informatics and Clinical Support Technology Development, Faculty of Medicine, Dentistry and Pharmaceutical SciencesAyumiOkadaDepartment of Pediatrics, Okayama University Hospital Medical Center for ChildrenChieTanakaDepartment of Pediatrics, Okayama University Hospital Medical Center for ChildrenYoshieShigeyasuDepartment of Pediatrics, Okayama University Hospital Medical Center for ChildrenChikakoFujiiDepartment of Pediatrics, Okayama University Hospital Medical Center for ChildrenMakikoHoriuchiClinical Psychology Section, Department of Medical Support, Okayama University HospitalAkikoSugiharaDepartment of Pediatrics, Okayama University Hospital Medical Center for ChildrenKoichiTakeuchiLife Natural Science and Technology, Graduate School of Environmental, Okayama UniversityRyuichiNakaharaDepartment of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical SciencesHidekiKatayamaDepartment of Palliative and Supportive Care, Okayama University HospitalYasushiTakahashiNEC CorporationToshifumiOzakiDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirokazuTsukaharaDepartment of Pediatrics, Okayama University Hospital Medical Center for ChildrenIntroduction: Family-based treatment (FBT) is a first-line psychotherapy for children and adolescents with anorexia nervosa (AN). However, families must understand the principles of FBT, provide meal support, and manage their children's pathological behaviors. Difficulties occur outside clinic hours when it is impossible to consult professionals. This “support gap” increases caregivers’ psychological distress and threatens their treatment continuity. To the best of our knowledge, this is the first domain-specific generative artificial intelligence (AI) agent designed to provide situation-specific, FBT-concordant advice and psychological support.<br>
Methods: The system integrates three components: (1) an FBT-specific knowledge base constructed from treatment manuals, family guides, guideline-compliant resources, and a clinical Q&A corpus; (2) a multistage natural language processing pipeline using Retrieval-Augmented Generation (RAG), with intent and sentiment analyses; and (3) safety guardrails that prohibit unsolicited numerical goals or direct hospitalization recommendations and standardized escalation to clinicians. When strong negative emotions are detected, empowerment messages are dynamically incorporated to maintain caregivers’ confidence. Six clinicians with expertise with pediatric mental health authored queries that simulated common FBT-related concerns and evaluated each response for clinical appropriateness and safety, and classified problems as information insufficiency, not FBT concordant, or escalation insufficiency.<br>
Results: Of the 477 queries, 57.0% were FBT-related, 24.5% were general AN, 16.5% were parental psychological distress, and 1.8% were related to other topics. The clinically appropriate response rate was 91.6% (437/477), including 92.3% for FBT-related questions, 88.0% for general knowledge, 93.7% for psychological distress, and 100.0% for other questions. Clinically inappropriate responses (8.4%) were mainly attributable to information insufficiency; not FBT concordant (1.8% of FBT-related responses) and escalation insufficiency (0.6% of all dialogs) rarely occurred.<br>
Discussion: In this expert review, the safety-gated RAG system predominantly generated FBT-concordant responses that provided meal-level guidance and empathic empowerment-oriented support to families. By proceduralizing complex FBT concepts and presenting multiple response options for pathological behaviors, the system translates FBT principles into practical guidance supporting refeeding adherence, preserving family self-efficacy, and suggesting that domain-specific AI may help bridge structural limitations in FBT. Usability studies and randomized controlled trials are warranted to determine their impact on caregiver burden, self-efficacy, treatment adherence, and clinical outcomes.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841862026Pathway Enrichment Analysis of Whole-Exome Sequencing Data from Formalin-Fixed, Paraffin-Embedded Enucleated Eyes with Retinoblastoma and Choroidal Malignant Melanomae110548ENToshihikoMatsuoOphthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakehiroTanakaPathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityDaisukeEnnishiMedical Oncology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityAkiraSaitoGenomic Statistics, Stagen Co. Ltd.MitsuhiroAmemiyaGenomic Statistics, Stagen Co. Ltd.ShigeoKamitsujiGenomic Statistics, Stagen Co. Ltd.Objectives: Intraocular tumors are extremely rare, small in size, and difficult to approach by biopsy. In the era of cancer genome analysis, we designed a pilot study to perform whole-exome sequencing of formalin-fixed paraffin-embedded enucleated eyes of retinoblastoma and choroidal malignant melanoma as two major intraocular malignancies.<br>
Methodology: Genomic DNA was isolated from intraocular tumor areas of 105 paraffin sections with a 5 μm thickness of seven enucleated eyes with retinoblastoma and seven eyes with choroidal malignant melanoma. One of 7 samples of retinoblastoma and another of seven samples of choroidal malignant melanoma were excluded from the study since the sequencing output and depth of reads were lower compared with the other samples. The sequencing data after quality control were aligned to the reference genome sequence (hg38, GRCh38 Assembly, Genome Reference Consortium Human Build 38), and the mapped reads were processed to improve data quality. Somatic mutations (single nucleotide variants, insertions and deletions, and multiple nucleotide variants) in each sample were extracted after excluding variants reported in a Panel of Normals (PON) from the 1000 Genomes Project. Additional selection criteria included a mutation depth of ≥5 reads and either no registration in or an allele frequency of less than 5% in the Tohoku Medical Megabank of Japan (ToMMo 60KJPN-SNV/INDEL Allele Frequency Panel).<br>
Results: Candidate genes with somatic mutations were selected by three criteria: genes with the same mutation shared by two samples or more, recurrently mutated genes three times or over, and genes of driver candidates identified in combining several different driver mutation-detecting programs by Integrative OncoGenomics (IntOGen). Using candidate genes detected by any of the three criteria as input, enrichment analyses identified 28 pathways in Gene Ontology (GO) and 2 pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) for retinoblastoma, while 385 pathways in GO, 12 in KEGG, 2 in the Hallmark gene set of the Molecular Signatures Database (MSigDB), and 47 in Reactome were identified for choroidal malignant melanoma. The enrichment maps showed three major pathways differently in retinoblastoma and choroidal malignant melanoma: one with dynein in retinoblastoma and another with MET in choroidal malignant melanoma.<br>
Conclusions: Although there were limitations related to the small amounts of DNA available from formalin-fixed, paraffin-embedded small-sized tissues and the absence of matched normal control tissue, whole-exome sequencing provided clues to somatic mutations that were enriched in specific pathways and differed between retinoblastoma and choroidal malignant melanoma.No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama1664-042X172026Bee larvae ameliorate andropause-like symptoms via a hormone-independent, antioxidant mechanism1850114ENTakashiItoDepartment of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama UniversityNobuakiOkumuraInstitute for Bee Products & Health Science, Yamada Bee Company, Inc.TakumiOtiDepartment of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama UniversityHirotakaSakamotoDepartment of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama UniversityLate-onset hypogonadism (LOH), also known as the male menopause, is characterized by a decline in sexual function as well as various physical and psychological symptoms, including anxiety. Although bee larvae have historically been utilized as a traditional food and medicine, their efficacy and physiological mechanisms of action against male menopausal symptoms remain unclear. In this study, we investigated the effects of bee larvae (BL) on sexual and anxiety-like behaviors using two rodent models of the male menopause: aged rats and castrated mice. In the aged rat model (64 weeks old), dietary BL supplementation for 4 weeks significantly attenuated the age-associated decline in ejaculation frequency compared to controls, while no significant effects were observed on mount or intromission frequencies. Notably, plasma analysis revealed no significant differences in testosterone or dihydrotestosterone levels between the BL and control groups. To elucidate the underlying mechanism, we evaluated sexual function using a castrated mouse model. While BL supplementation did not affect sexual behavior in intact mice, post-castration BL treatment significantly shortened intromission latency without altering mount frequency. In the elevated plus maze test, BL significantly alleviated castration-induced anxiety-like behaviors and improved exploratory activity. Furthermore, in vitro assays demonstrated that the BL extract exerts potent protective effects against oxidative stress, a pathological factor contributing to both erectile dysfunction and anxiety. These results suggest that BL improves erectile function and anxiety via hormone-independent mechanisms, potentially by mitigating oxidative stress in vascular and neural tissues. Thus, bee larvae represent a promising functional food for ameliorating the multi-faceted physical and psychological symptoms associated with male menopause.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0021-925830262026A photoactivatable Cre-loxP system for spatiotemporal genetic manipulation in mouse taste buds113085ENYuZuoDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKengoHorieDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshihiroMitohDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYasuhiroYamadaDepartment of Molecular Pathology, Graduate School of Medicine and Faculty of Medicine, The University of TokyoTomokaTakaoFaculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakeshiTakaradaFaculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShoichiroKokabuDivision of Biochemistry, Kyushu Dental UniversityRyusukeYoshidaDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityConventional genetic approaches, including global gene KO and conditional KO strategies such as the Cre-loxP system, have some limitations arising from systemic effects or insufficient temporal resolution. The recently developed photoactivatable Cre (PA-Cre) system may have a potential to improve spatiotemporal control of gene manipulation. In this study, we established and validated the feasibility of the PA-Cre system using taste buds as a model. We generated TRE-PA-Cre:R26-rtTA/tdTomato mice to evaluate blue-light-induced Cre recombinase activity. Through systematic optimization of illumination parameters, we found that a single session of blue-light-illumination resulted in limited recombination efficiency, whereas a multisession illumination strategy markedly increased recombination efficiency. To further assess the utility of the PA-Cre system for gene KO, we generated TRE-PA-Cre:R26-rtTA:Tas1r3-flox mice and targeted a taste-related gene Tas1r3. Genomic DNA quantitative PCR and reverse transcription-quantitative PCR both showed partial reductions in Tas1r3 at the DNA and mRNA levels, respectively. Behavioral assays further revealed a selective decrease in sensitivity to sweet and umami stimuli. Together, these findings demonstrate PA-Cre-mediated gene manipulation in taste buds and establish a practical optical activation paradigm, providing a high-spatiotemporal-resolution tool for investigating gene function in optically targeted regions.No potential conflict of interest relevant to this article was reported.American Association for Cancer Research (AACR)Acta Medica Okayama1078-04322026Incidence of B-cell Malignancies in Patients with Lung Cancer Receiving PD-1 Blockade TherapyENToshifumiNinomiyaDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityCaiyangFangDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirofumiHamanoDepartment of Pharmacy, Okayama University Hospital, Okayama UniversityTeruyaMorinagaDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityWenhaoZhouDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshihiroKoyamaDepartment of Pharmaceutical Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversitySakuraMikiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityLiZhuDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYusukeNaoiDepartment of Hematology, Oncology and Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDaisukeEnnishiDepartment of Hematology, Oncology and Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomoyaKatsutaDepartment of Respiratory Medicine, Ehime Prefectural Central HospitalKadoakiOhashiDepartment of Respiratory Medicine, Okayama University Hospital, Okayama UniversityShinMorizaneDepartment of Dermatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomokaOhki-IkedaDepartment of Pathology, Okayama University Hospital, Okayama UniversityTatsuyaNishiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoukiUedaDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakamasaIshinoDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIsamuOkamotoDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityYoshitoZamamiDepartment of Pharmacy, Okayama University Hospital, Okayama UniversityJojiNagasakiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYosukeTogashiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPurpose: Many patients with various cancer types have received immune checkpoint inhibitors (ICI) worldwide since their approval, and novel unexpected complications from their long-term use are apparent. We identified some cases of B-cell lymphoma occurring during PD-1 blockade therapy as such unexpected complications. In this study, we aimed to evaluate the incidence of hematologic malignancies in patients with lung cancer receiving PD-1 blockade therapy and to elucidate the mechanisms underlying the progression of these malignancies.<br>
Experimental Design: We performed IHC staining on the clinical samples from patients with B-cell lymphoma that developed during PD-1 blockade therapy and analyzed large-scale real-world datasets. We further investigated the underlying mechanisms through in vitro and in vivo experiments.<br>
Results: A higher incidence of B-cell malignancies has been observed in patients with lung cancer treated with PD-1 blockade therapies based on large-scale real-world data analyses (n = 15,670). The identified lymphomas had a large amount of CD4+ T follicular helper (TFH) cell infiltration. In addition, PD-1 blockade activated PD-1+ TFH cells, which promoted lymphoma proliferation via the IL4/IL4R, IL21/IL21R, and CD40L/CD40 axes. Notably, the lymphomas exhibited high expression of IL4R, IL21R, and CD40.<br>
Conclusions: Our findings highlight the need for careful monitoring and consideration of the potential B-cell malignancy complications in clinical settings in which ICIs are used.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1868-69742026Feasibility of Comprehensive Genomic Profiling for Biliary Tract Cancer Using Transpapillary Biopsy Samples: A Prospective StudyENKazuyaMiyamotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyukiMatsumotoDepartment of Endoscopy, Okayama University HospitalToshiakiOharaDepartment of Pathology and Experimental Medicine, Okayama University HospitalMasayoshiFujisawaDepartment of Pathology and Experimental Medicine, Okayama University HospitalHirohumiInoueDepartment of Medical Support, Okayama University HospitalRyosukeSatoDepartment of Gastroenterology and Hepatology, Okayama University HospitalAkihiroMatsumiDepartment of Endoscopy, Okayama University HospitalYukiFujiiDepartment of Endoscopy, Okayama University HospitalDaisukeUchidaDepartment of Gastroenterology and Hepatology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University HospitalBackground: Patients with biliary tract cancer (BTC) often have actionable mutations, and comprehensive genomic profiling (CGP) plays an important role. However, the feasibility of CGP using transpapillary biopsy (TPB) samples remains unclear.<br>
Methods: Thirty patients with suspected BTC based on radiographic imaging were enrolled. Pre-analytical criteria for CGP suitability were based on the OncoGuide NCC Oncopanel System (NCCOP) and FoundationOne CDx (F1CDx). Each patient underwent six biopsies using an endoscopic introducer: five biopsy samples were preserved as formalin-fixed paraffin-embedded (FFPE) samples and one as a fresh frozen (FF) sample. DNA quality indicators were compared between the two groups.<br>
Results: Malignancy was confirmed in 29 patients, and one had a benign biliary stricture. Suitability rate was 31% (9/29) for NCCOP and 3.4% (1/29) for F1CDx. Compared to FFPE samples, FF samples demonstrated significantly higher DNA concentration [ng/μL, interquartile range (IQR)], [0.34 (0.16–0.95) vs. 37.8 (11.6–67.6), p < 0.001] and DNA integrity number (IQR) [7.1 (6.8–7.3) vs. 8.9 (8.3–9), p = 0.021].<br>
Conclusions: Introducer-assisted multipass TPB may increase the rate of obtaining adequate CGP specimens, but its suitability remains limited and strongly panel dependent. Since FF samples have better DNA quality, establishing a system detailing their use is desirable.<br>
Trial Registration: ClinicalTrials.gov identifier: UMIN 000049826No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2589-00422952026Wnt3-mediated fibrosis and carcinogenesis of lung squamous cell carcinoma in idiopathic pulmonary fibrosis115667ENAtsushiMatsuokaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalMasayoshiOhkiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHidejiroTorigoeDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyaHisamatsuDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyotaFujiwaraDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoseiIshimuraDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeMoriDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyunosukeFujiiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAsukaMimataDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroOkadaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoYoshichikaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMaoYoshikawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYumaFukumotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruchikaYamamotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKumiNakajimaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinTanakaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentarohMiyoshiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikioOkazakiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHirofumiInoueCenter for Comprehensive Genomic Medicine, Okayama University HospitalDaisukeEnnishiCenter for Comprehensive Genomic Medicine, Okayama University HospitalShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIdiopathic pulmonary fibrosis (IPF) increases the risk of lung squamous cell carcinoma (LUSC), yet its molecular pathogenesis remains unclear. We conducted multi-omics analysis, including single-cell RNA sequencing and digital spatial profiling, on LUSC specimens from seven patients with usual interstitial pneumonia (UIP). In UIP lung tissue, metaplastic basal cells arising from the transdifferentiation of alveolar type 2 (AT2) cells were increased. LUSC tumors arising within UIP exhibited molecular profiles and trajectory dynamics suggesting derivation from these metaplastic basal cells. Both UIP-affected tissue and associated tumors showed activation of Wnt signaling, particularly WNT3 expression. Additionally, enrichment of the nuclear factor erythroid 2-related factor 2 (NRF2)-linked antioxidant response was observed in LUSC within UIP. Targeting Wnt/β-catenin signaling restored the sensitivity of these stress-adapted cancer cell lines to oxidative damage. These findings suggest that LUSC within UIP originates from AT2-derived metaplastic basal cells and involves aberrant Wnt3 activation, linking fibrosis to carcinogenesis and highlighting a potential therapeutic strategy.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1353-80201452026Real-world evaluation of Armstrong's criteria in corticobasal degeneration: Phenotypic overlap and diagnostic challenges108229ENRyutaMoriharaDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEmiNomuraDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYosukeOsakadaDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTaijunYunokiDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMamiTakemotoDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruYamashitaDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiIshiuraDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Corticobasal degeneration (CBD) is a four-repeat tauopathy with heterogeneous clinical manifestations. Armstrong's criteria involve a two-step diagnostic approach: first, classifying patients into five clinical phenotypes—probable/possible corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), non-fluent/agrammatic variant primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS); second, determining whether they meet the clinical research criteria for probable CBD (cr-CBD) or the clinical criteria for possible CBD (p-CBD), which are distinct from the initial CBS classifications.<br>
Objective: To investigate how real-world patients with suspected CBD fulfill Armstrong's clinical phenotypes and diagnostic criteria, and to compare clinical and imaging features between the Alzheimer's disease (AD) group and the non-AD group defined by CSF amyloid biomarkers.<br>
Methods: We retrospectively reviewed 137 patients undergoing differential diagnosis for CBS, frontotemporal dementia, primary progressive aphasia, or PSPS. Of these, 78 met the criteria for cr-CBD (n = 36) or p-CBD (n = 42). CSF was examined in 32 patients, and based on the CSF Aβ42/40 ratio, patients were classified into an AD-group (AD-CBS; n = 6) and a non-AD group (n = 26).<br>
Results: Among patients classified as cr-CBD or p-CBD, 79% fulfilled two or more clinical phenotypes, with FBS and PSPS most commonly. Compared with the AD group, the non-AD group showed more parkinsonian features and frontal hypoperfusion on [123I]-IMP SPECT.<br>
Conclusion: Armstrong's criteria captured a spectrum of overlapping clinical features. While helpful in clinical phenotyping, further validation with biomarkers is essential to distinguish CBD from AD and related disorders. Prospective studies with pathological confirmation are warranted.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8022026Complete Transection of the Common Bile Duct Caused by Blunt Abdominal Trauma: A Rare Case Report147152ENShinyaSakamotoDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterMotoyasuTabuchiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterAkiraHamadaDepartment of Intensive Care Medicine, Kochi Health Sciences CenterRikaYoshimatsuDepartment of Radiology, Kochi Health Sciences CenterYuichiSaisakaDepartment of Emergency and Critical Care Medicine, Kochi Health Sciences CenterManabuMatsumotoDepartment of Diagnostic Pathology, Kochi Health Sciences CenterJunIwataDepartment of Diagnostic Pathology, Kochi Health Sciences CenterTakehiroOkabayashiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterCase Report/10.18926/AMO/70457Common bile duct (CBD) injury after blunt abdominal trauma is rare and difficult to diagnose. Delayed recognition leads to severe morbidity. A 70-year-old Japanese man was admitted after sustaining blunt abdominal trauma. Ultrasonography revealed intra-abdominal fluid, suggesting bleeding. Contrast-enhanced computed tomography revealed pancreatic head injury, intra-abdominal bleeding, and pseudoaneurysm of the anterior superior pancreatoduodenal artery (ASPDA). Bile duct injury was not evident. The application of transarterial embolization (TAE) controlled the bleeding. Canulation into the pancreatic or biliary duct was not possible during endoscopic retrograde cholangiopancreatography. An emergency laparotomy revealed severe pancreatic head and extrahepatic bile duct injuries. Pancreaticoduodenectomy/Child reconstruction was performed. Complete CBD transection was confirmed. The patient was ultimately discharged without complications. Early recognition, timely surgical management, and intensive care are essential for favorable outcomes in patients who have sustained abdominal trauma.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Pseudohypoxia induced by iron chelators preserves working memory performance in aged mice11550ENToshiakiOharaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshiakiIwasakiHealth Service Section, Environment Health & Safety Intelligence Department, Okayama UniversityTomonariKasaiDepartment of Applied Energy, Graduate School of Engineering, Nagoya UniversityToruYamashitaDepartment of Neurology, Graduate School of Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShihoKomakiDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYusukeHamadaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasayoshiFujisawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAkihiroMatsukawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPseudohypoxia refers to a physiological condition wherein hypoxia-inducible factor (HIF) is pharmacologically upregulated under normoxia, thereby modulating immune responses. We hypothesized that pseudohypoxia, induced by iron chelators, may similarly potentiate systemic immune responses in aged mice, concurrently triggering neuro-regenerative signaling pathways and enhancing cognitive performance. In this study, aged mice (43–48 weeks old) were orally administered two iron chelators, Super Polyphenol 10 (SP10) or Roxadustat, to induce a pseudohypoxia. An 8-week oral regimen of SP10 and Roxadustat significantly preserved working memory, as assessed by the Y-maze test (YMT). White blood cell counts and hippocampal volume, as assessed by magnetic resonance imaging (MRI), were elevated in the treatment groups relative to controls. Pseudohypoxia induced by SP10 tended to enhance neuro-regenerative signaling, specifically involving the Tau and JNK pathways, and potentially modulated Doublecortin (DCX) expression, although statistical significance was limited by sample size. Importantly, inflammatory markers, such as ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP), were not elevated by treatment. Collectively, these findings suggest that pseudohypoxia induced by iron chelators preserves working memory performance accompanied by leukocytosis, without concomitant neuroinflammation.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1422-00672752026Aerobic Exercise Attenuates Epidermal Hyperplasia in an Obesity-Associated Psoriasiform Dermatitis Model2308ENYoshihiroMatsudaDepartment of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShinMorizaneDepartment of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDaikiTakezakiDepartment of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYumaSakamotoDepartment of Immunology and Molecular Genetics, Kawasaki Medical SchoolNobuyasuBabaDepartment of Immunology and Molecular Genetics, Kawasaki Medical SchoolMasanoriIsekiDepartment of Immunology and Molecular Genetics, Kawasaki Medical SchoolYoshioKawakamiDepartment of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTatsushiShiomiDepartment of Pathology, Kawasaki Medical SchoolTomoyukiMukaiDepartment of Immunology and Molecular Genetics, Kawasaki Medical SchoolObesity is an important risk factor for psoriasis, and clinical studies indicate that exercise interventions can improve disease severity. However, the mechanisms by which exercise influences psoriatic pathogenesis remain insufficiently understood. To investigate the effects of aerobic exercise on obesity-associated psoriasis, wild-type mice were fed a high-fat diet (HFD) for 7 weeks to induce obesity and subsequently underwent moderate-intensity treadmill running for 3 weeks. Psoriasiform dermatitis was induced by daily topical application of imiquimod (IMQ) to the skin for five consecutive days. HFD increased body weight, epididymal fat mass, and serum cholesterol. HFD-fed mice developed more severe IMQ-induced psoriatic skin changes compared with normal diet-fed mice. Treadmill exercise modestly reduced body weight gain and attenuated epidermal hyperplasia in HFD-fed mice. In contrast, inflammatory cytokine expression, including Tnfa, Il17a, and Il23a, showed modest increases in the skin of HFD-fed exercised mice, which did not parallel the improvement in epidermal hyperplasia. Overall, these findings indicate that while obesity exacerbates psoriasiform dermatitis, aerobic exercise ameliorates epidermal hyperplasia in obese mice without corresponding changes in inflammatory cytokine expression in the skin, suggesting that exercise may influence psoriatic skin changes through multiple metabolic and immunological pathways.No potential conflict of interest relevant to this article was reported.Pharmaceutical Society of JapanActa Medica Okayama0918-61584922026Functional Transport Properties of Human Zinc Transporter 1: Kinetics and pH-Dependency364370ENYumaYoshiokaDepartment of Molecular Membrane Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakaakiMiyajiDepartment of Molecular Membrane Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIntracellular zinc (Zn2+) homeostasis is essential for physiological and pathological processes and is strictly regulated by Zn2+ transporters. Zinc transporter 1 (ZnT1) is a ubiquitously expressed plasma membrane-localized Zn transporter that exports Zn2+ from the cytoplasm to the extracellular space. However, the functional transport properties regarding kinetics and driving forces of ZnT1 remain debatable. In this study, we established a cell-free proteoliposome assay system and demonstrated that ZnT1 transports Zn2+ with high affinity in pH-dependent and pH-independent manners. The Km and Vmax of pH-dependent Zn2+ transport were 0.40 μM and 15.13 nmol/min/mg protein, and those of pH-independent Zn2+ transport were 0.52 μM and 8.88 nmol/min/mg protein (low concentrations of Zn2+), 3.02 μM and 17.59 nmol/min/mg protein (high concentrations of Zn2+), respectively, suggesting biphasic kinetic components of Zn2+ transport. Even without pH gradient formation, ZnT1 exhibits potent Zn2+ transport activity. In pH dependency, Zn2+ transport activity was higher at an inside pH of 6.0 than at 6.5–7.5 for proteoliposomes, despite the same ΔpH of 0.5–1.5. The Zn2+ transport activity decreased at an outside pH of 8.0, despite an increase in ΔpH. Although previous studies have proposed that ZnT1-mediated Zn2+ transport activity is driven by a calcium (Ca2+) gradient and not by a pH gradient, Ca2+ does not enhance Zn2+ transport activity in the presence or absence of a pH gradient. These results strongly suggest that ZnT1 protein transports Zn2+ optimally at a specific pH and exports excess intracellular Zn2+ even without ΔpH.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1422-00672772026CXCR2-Dependent Infiltration of Tumor-Associated Neutrophils Is Linked to Enhanced CD8+ T Cell Effector Function and Reduced Lung Metastasis in 4T1 Breast Cancer3143ENTiantianLiDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTeizoYoshimuraDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMiaoTianDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityGakushiNishidaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChunningLiDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasayoshiFujisawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiakiOharaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAkihiroMatsukawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTriple-negative breast cancer (TNBC) is characterized by prominent neutrophil infiltration; however, its significance remains controversial. Here, we investigated the role of neutrophil chemoattractant receptors in TNBC progression and metastasis. In contrast to wild-type (WT), Fpr1−/−, and Fpr2−/− mice, neutrophils were almost completely absent in 4T1 tumors from Cxcr2−/− mice, indicating a dominant role for CXCR2 in the recruitment of tumor-associated neutrophils, leading us to use Cxcr2−/− mice for further studies. Primary tumor growth was comparable between WT and Cxcr2−/− mice, whereas lung metastasis was significantly increased in Cxcr2−/− mice, with reduced expression of inflammatory cytokines, chemokines and cytotoxic molecules, including granzyme B and perforin, in primary tumors and metastatic lungs of Cxcr2−/− mice. In vitro, WT, but not Cxcr2−/−, neutrophils enhanced CD8+ T cell activation, partly via ICAM-1, and directly induced tumor cell death, supporting their anti-tumor function. To assess clinical relevance, transcriptomic data were analyzed. High neutrophil infiltration combined with elevated CXCR2 expression, and to a lesser extent CXCR1 expression, was associated with improved prognosis in patients with basal-like BC that largely overlaps with TNBC. Collectively, these findings suggest that CXCR2-mediated neutrophil recruitment exerts protective, anti-tumor effects and may represent a new prognostic marker for TNBC patients.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0309-01672026Clinicopathological and transcriptomic profiles of 101 patients with diffuse large B-cell lymphoma/high-grade B-cell lymphoma with double-hit MYC and BCL2 or BCL6 and triple hitENMasashiMiyaokaDepartment of Pathology, School of Medicine, Tokai UniversityJoaquimCarrerasDepartment of Pathology, School of Medicine, Tokai UniversityYara YukieKikutiDepartment of Pathology, School of Medicine, Tokai UniversityHarukaIkomaDepartment of Pathology, School of Medicine, Tokai UniversityShunsukeNagaseDepartment of Pathology, School of Medicine, Tokai UniversityAtsushiItoDepartment of Pathology, School of Medicine Tokai University Isehara JapanMakotoOritaDepartment of Pathology, School of Medicine, Tokai UniversityHiroshiKawadaDepartment of Hematology, School of Medicine, Tokai UniversityRikaSakaiDepartment of Medical Oncology, Kanagawa Cancer CenterYasuharuSatoDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesMidori FilizNishimuraDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesKunihiroTsukasakiDepartment of Hematology, International Medical Center, Saitama Medical UniversityShujiMomoseDepartment of Pathology, Saitama Medical Center, Saitama Medical UniversityYoshihiroKameokaDepartment of Hematology, Nephrology and Rheumatology, Akita University Graduate School of MedicineMasahiroYoshidaDepartment of Hematology, Osaka City General HospitalAkiraSatouDepartment of Surgical Pathology, Aichi Medical University HospitalSeiichiKatoCenter for Clinical Pathology, Fujita Health University HospitalNaokiOishiDepartment of Pathology, University of YamanashiAkioSaitoDepartment of Hematology, NHO Shibukawa Medical CenterKenSadahiraDivision of Hematology, Kawasaki Municipal Kawasaki HospitalYoheiMasugiDepartment of Pathology, School of Medicine, Tokai UniversityNaoyaNakamuraDepartment of Pathology, School of Medicine, Tokai UniversityAims: Diffuse large B-cell lymphoma/high-grade B-cell lymphoma (DLBCL/HGBCL) with MYC and BCL2 rearrangements (double-hit lymphoma with BCL2, DHL-BCL2) is a mature aggressive B-cell lymphoma that also includes concurrent triple hit with BCL6 translocation (TH). DHL with MYC and BCL6 (DH-BCL6) can also occur. The differences among these three DLBCL/HGBCL subtypes have not yet been definitively determined.<br>
Methods and Results: This study characterized the clinicopathological features and transcriptomic profiles of a series of 101 cases of DLBCL/HGBCL that were subclassified according to MYC, BCL2 and BCL6 FISH data, including cell-of-origin (COO)-like, molecular high-grade (MHG)-like and double-hit/dark-zone (DHIT/DZsig)-like signatures. DLBCL/HGBCL-DH-BCL2 was characterized by higher HGBCL morphology, CD10 positivity, GCB Hans's, GCB COO and MHG molecular subtype. DLBCL/HGBCL-TH had higher LDH levels and worse overall survival. DLBCL/HGBCL-DH-BCL6 had higher MUM1 expression, non-GCB Hans', ABC/Unclassified COO, non-MHG and low DHIT/DZ signatures. Transcriptomic analysis showed that DLBCL/HGBCL-DH-BCL2 and DLBCL/HGBCL-TH were close but separated from DLBCL/HGBCL-DH-BCL6. Gene set enrichment analysis (GSEA) revealed different levels of enrichment between the subtypes.<br>
Conclusions: DLBCL/HGBCL-DH-BCL6 differs from the DLBCL/HGBCL-DH-BCL2, and the DLBCL/HGBCL-TH is associated with the worst survival. Analysis of all three genes of MYC, BCL2 and BCL6 is recommended in the context of DLBCL/HGBCL diagnosis.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2688-4046632026PPy‐Coated Wire Actuators for the Micromechanostimulation of Cells: Fabrication and Characterizatione202500639ENAmaia B.Ortega‐SantosSensor and Actuator Systems, Department of Physics Chemistry and Biology (IFM), Linköping UniversitySatoruHayanoDepartment of Orthodontics, Okayama University HospitalEmilio SatoshiHaraAdvanced Research Center for Oral and Craniofacial Sciences Dental School, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJose G.MartínezSensor and Actuator Systems, Department of Physics Chemistry and Biology (IFM), Linköping UniversityHiroshiKamiokaDepartment of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEdwin W. H.JagerSensor and Actuator Systems, Department of Physics Chemistry and Biology (IFM), Linköping UniversityCellular mechanotransduction signals play a crucial role in physiological and pathological conditions, including skeletal disorders. Although various systems exist to mechanically stimulate cultured cells, most are constrained by incubator incompatibility, limited physiological relevance, nonuniform stimulation, or complexity. The objective of this article is to develop and validate a compact, incubator-compatible tool capable of delivering localized and physiologically relevant mechanical stimulation to small cell populations. Here, we introduce a polypyrrole-based wire-shaped microactuator designed to induce localized mechanical stress to adjacent cells. These wire-shaped microactuators are biocompatible, easy-to-use, and compact for use within standard in vitro cell culture systems. Using a noncontact optical method, we characterize the actuation of polypyrrole-coated wires in an aqueous NaDBS electrolyte, showing radial expansion of 1.5–8 µm depending on the deposited polypyrrole film thickness, comparable to cellular dimensions. Next, the actuation is confirmed to be robust and stable to use in cell culture media at physiological temperature. To evaluate biological relevance, osteoblastic KUSA-A1 cells are mechanically stimulated inside the incubator and transcriptomic changes are assessed. Mechanical stimulation resulted in upregulation of genes previously associated with mechanotransduction, including Fos and Fosb. Additionally, several uncharacterized long noncoding RNAs are differentially expressed, suggesting potential novel players in the mechanotransduction pathway.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0923-181111912025Big data-driven target identification by machine learning: DRD2 as a therapeutic target for psoriasis917ENTakashiSakaiDepartment of Dermatology, Faculty of Medicine, Oita UniversityRyusukeSawadaDepartment of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOtohaIchinoseDepartment of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of TechnologyTakeshiTerabayashiDepartment of Pharmacology, Faculty of Medicine, Oita UniversityYutakaHatanoDepartment of Dermatology, Faculty of Medicine, Oita UniversityYoshihiroYamanishiDepartment of Complex Systems Science, Graduate School of Informatics, Nagoya UniversityToshimasaIshizakiDepartment of Pharmacology, Faculty of Medicine, Oita UniversityBackground: The development of medical treatments has traditionally relied on researchers leveraging scientific knowledge to hypothesize disease mechanisms and identify therapeutic agents. However, the depletion of novel therapeutic targets has become a significant challenge, resulting in stagnation within pharmaceutical research.<br>
Objective: To address the scarcity of therapeutic targets, we developed a machine learning (ML)-based system capable of predicting therapeutic target molecules for diseases. To validate its utility, we applied this system to psoriasis, aiming to identify novel treatment strategies.<br>
Methods: Our approach utilized a large clinical database to calculate reporting odds ratios for all drugs associated with the prevention of diseases of interest. We identified target proteins by analyzing large chemical structure databases to discover proteins commonly associated with preventive drug candidates. Experimental validation was conducted by administering a predicted therapeutic candidate in an imiquimod-induced psoriasis mouse model.<br>
Results: The ML-based predictions identified drugs for Parkinson’s disease as potential preventive candidates for psoriasis. Further analysis highlighted dopamine receptor D2 (DRD2) as a therapeutic target. Administration of a DRD2 agonist alleviated psoriasis symptoms in mice, evidenced by the downregulation of mRNA expression in the IL-17 pathway and reduced serum tumor necrosis factor-α levels.<br>
Conclusion: This study demonstrates the utility of a novel ML-based system for identifying therapeutic targets, as shown by its successful application in uncovering the role of DRD2 in psoriasis. Beyond psoriasis, this system offers significant potential for exploring pathological mechanisms and discovering therapeutic targets across various diseases.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2398-8835932026Effects of Overload on Imiquimod‐Induced Psoriasis Model Mice: A Basic Experimental Studye72040ENTomokiFurutaniDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTaichiSaitoDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAsahiIkedaOkayama University Medical School Faculty of MedicineKentaMashimaOkayama University Medical School Faculty of MedicineNatsumiYukihiroOkayama University Medical School Faculty of MedicineSatokiKusakabeOkayama University Medical School Faculty of Medicine Okayama JapanRyoNakamichiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAkiYoshidaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKeiichiroNishidaLocomotive Pain Center, Okayama University HospitalToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground and Aim: Psoriasis is a skin disorder complicated by arthritis and enthesitis. The cytokines interleukin (IL)-17, IL-23, and tumor necrosis factor (TNF)-α are reportedly key effectors of psoriasis. Additionally, gamma delta (γδ) T cells exacerbate inflammation by producing inflammatory cytokines such as IL-17 and TNF-α. However, details regarding the mechanisms linking pathogenesis and mechanical stress remain unclear. This study aimed to investigate the effect of strenuous exercise on the pathology of psoriasis using mouse models of imiquimod (IMQ)-induced psoriasis.<br>
Methods: Twenty mice were randomly assigned to four groups: IMQ − TRED− (control), IMQ − TRED+ (treadmill running mice), IMQ + TRED− group (IMQ treated mice), and IMQ + TRED+ group (IMQ treated and treadmill running mice). The tissue sections from back skin and thymus were immunostained with antibodies against IL-17, IL-23, and γδ T cells. Shoulder sections were stained using hematoxylin and eosin, and Toluidine Blue and Picrosirius Red. Additionally, the shoulder tissue sections were immunostained with antibodies against TNF-α and matrix metalloproteinase (MMP)-13. Serum cytokine level was measured to evaluate systemic inflammation.<br>
Results: Strenuous exercise exacerbated pathological changes associated with psoriasis, including increased γδ T cell infiltration and upregulated IL-17 and IL-23 expression in the skin, as well as enhanced γδ T cell development and IL-17 expression in the thymus. Although strenuous exercise did not further worsen the modified PASI scores, histological and immunological markers of inflammation were significantly enhanced. Serum levels of TNF-α and IL-17 were significantly elevated in IMQ-induced psoriasis model mice. Moreover, pathological changes induced by strenuous exercise were observed in the enthesis, including angiogenesis and upregulated expression of TNF-α and MMP-13.<br>
Conclusion: This study revealed that strenuous exercise exacerbates pathological changes in IMQ-induced psoriasis model mice.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2666-6065672026Alcohol consumption, smoking, and the implications of their cessations for field carcinogenesis in the esophagus: a 10-year prospective cohort study101798ENChikatoshiKatadaDepartment of Medical Oncology, Kyoto University Graduate School of MedicineTetsujiYokoyamaDepartment of Health Promotion, National Institute of Public HealthTomonoriYanoDepartment of Gastroenterology and Endoscopy, National Cancer Center Hospital EastYasuakiFurueDepartment of Endoscopy, Saitama Cancer CenterHaruhisaSuzukiDivision of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of MedicineKenjiIshidoDepartment of Gastroenterology, Kitasato University School of MedicineKeikoYamamotoDivision of Endoscopy, Hokkaido University HospitalHiroyoshiNakanishiDepartment of Gastroenterology, Ishikawa Prefectural Central HospitalTomoyukiKoikeDivision of Gastroenterology, Tohoku University Graduate School of MedicineMasashiTamaokiDepartment of Medical Oncology, Kyoto University Graduate School of MedicineNoboruKawataDivision of Endoscopy, Shizuoka Cancer CenterMotohiroHiraoDepartment of Surgery, NHO Osaka National HospitalYoshiroKawaharaDepartment of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakashiOgataDepartment of Gastrointestinal Surgery, Kanagawa Cancer CenterAtsushiKatagiriDivision of Gastroenterology, Department of Medicine, Showa Medical University HospitalTakenoriYamanouchiDepartment of Gastroenterology, Kumamoto Regional Medical CenterHirofumiKiyokawaDepartment of Gastroenterology, St. Marianna University School of MedicineHirofumiKawakuboMakiKonnoDepartment of Gastroenterology, Tochigi Cancer CenterAkiraYokoyamaDepartment of Medical Oncology, Kyoto University Graduate School of MedicineShinyaOhashiDepartment of Medical Oncology, Kyoto University Graduate School of MedicineTaiOmoriDepartment of Surgery, Kawasaki Municipal Kawasaki HospitalTadakazuShimodaDepartment of Diagnostic Pathology, Shizuoka Cancer CenterAtsushiOchiaiExploratory Oncology Research and Clinicai Trial Center, National Cancer CenterHidekiIshikawaDepartment of Molecular-Targeting Prevention, Kyoto Prefectural University of MedicineAkiraYokoyamaClinical Research Unit, National Hospital Organization Kurihama Medical and Addiction CenterManabuMutoDepartment of Medical Oncology, Kyoto University Graduate School of MedicineBackground Alcohol and tobacco are established carcinogens, which promote field carcinogenesis for esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the long-term effects of alcohol and tobacco cessations, and background mucosal status, on risk for metachronous ESCC (mESCC) after endoscopic resection (ER).<br>
Methods This was a multicentre prospective cohort study of patients with intramucosal ESCC treated by ER. All participants received structured education on cessation, and underwent regular endoscopic surveillance. Patients were stratified by Lugol-voiding lesion (LVL) grade (A: none, B: 1–9, C: ≥10). The impacts of alcohol and smoking cessation on field carcinogenesis were assessed.<br>
Findings Among 331 enrolled patients, the median follow-up was 120 months (range: 1.3–176.9). The cumulative incidences of mESCC were 10.4%, 27.2%, and 61.8% in grades A, B, and C, respectively. An increment of 1 unit (22 g ethanol) of alcohol consumption and higher LVL grade independently increased the risk for mESCC. Alcohol or smoking cessation reduced this risk (hazard ratio [HR] 0.52, 95% confidence interval [CI]: 0.31–0.88; HR 0.44, 95% CI: 0.25–0.78, respectively), and combined cessation had the greatest impact (HR 0.21, 95% CI: 0.07–0.65). Complete cessation, rather than partial reduction, was necessary to achieve meaningful risk reduction.<br>
Interpretation Alcohol and tobacco exposure, and a large number of LVL, are major determinants of mESCC. Complete cessation markedly reduces risk, underscoring the importance of behavioural interventions for secondary prevention of field carcinogenesis after ER.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1478-811X2412026MMP-3 cleavage of Lamin A induces pro-migratory nuclear deformity, nucleophagy, and their autophagic secretion with extracellular vesicles in metastatic cancer146ENTakanoriEguchiDepartment of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityEman A.TahaDepartment of Biochemistry, Faculty of Science, Ain Shams UniversityKeisukeNakanoDepartment of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityVikasTiwariCouncil of Scientific & Industrial Research-Indian Institute of Toxicological ResearchKatsukiTakebeDepartment of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomohiroInoueDepartment of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityLiziXingDepartment of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChiharuSogawaDepartment of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of TechnologyKuniakiOkamotoDepartment of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityStuart K.CalderwoodDivision of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolMatrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that cleave a plethora of substrates, including components of the extracellular matrix and cell-surface-associated proteins, as well as intracellular targets. MMPs have also been found in extracellular vesicles (EVs), such as exosomes. MMP-3 promotes tumor growth, epithelial-to-mesenchymal transition, genome instability, migration, invasion, and metastasis of cancer cells, and nuclear MMP-3 controls gene transcription. Intranuclear proteolysis by MMPs may significantly alter cancer progression. However, the nuclear substrates of MMP-3 have not been well investigated. In this study, we performed proteomic analyses to identify the nuclear substrates and EV proteins regulated by MMP-3. While rabidly metastatic colon cancer (LuM1) three-dimensionally cultured tumoroids secreted EVs containing 30 protein types, including Lamin A (LMNA), MMP-3, fibronectin (FN1), HSPA8 (Hsc70), β-actin (ACTB), and vimentin (VIM), CRISPR/Cas9-based knockout of MMP-3 reduced the secretion of these proteins in EVs. Notably, EV-bound cleaved Lamin secretion was confirmed by immunoelectron microscopy. Also, MMP-3 formed proteolytic dimers via its hemopexin-like repeat domains in nuclei. Many nuclear MMP-3-binding proteins, including Lamin A/C, histones, topoisomerases, and hnRNPs, were screened by co-immunoprecipitation followed by proteomics. Proteolytic MMP-3 overexpression generated a C-terminal 30-kDa fragment of Lamin A, whose cleavage site was defined via structural analysis. MMP-3 digestion of Lamin A induced nuclear deformity (atypia) required for cell migration in confined space. The cleaved Lamin A and MMP-3 were transported with autophagosomes (LC3B+), nucleophagosomes, and amphisomes (CD63 + LC3B+) and co-secreted with EVs. Proteolytic MMP-3 also induced nuclear speckles of Lamin A, suggesting their roles in transcription and splicing. Clinical analysis revealed that high expressions of MMP3 and LMNA were significantly seen in head and neck squamous cell carcinoma (HNSC) than in the other 16 cancer types, and predicted poor prognosis of patients suffering from HNSC, pancreatic, rectum and lung adenocarcinomas at specific stages. Immunohistochemistry revealed that nuclear MMP-3 and cleaved Lamin were significantly higher expressed in stage IV metastatic HNSC cases than in stage I non-metastatic cases. Taken together, MMP3-cleavage of Lamin A induces nuclear deformity, nucleophagy, and their autophagic co-secretion with EVs in metastatic cancer. Also, high expression of MMP-3 and secretion of Lamin A can predict poor prognosis in multiple cancer types at specific stages.No potential conflict of interest relevant to this article was reported.JMIR Publications Inc.Acta Medica Okayama2369-3762122026Prescription Support Practice for Pharmacy Students: Pre-Post Educational Intervention Studye79545ENFukaAizawaClinical Research Center for Developmental Therapeutics, Tokushima University HospitalKentaYagiDepartment of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima UniversityTsukasaHigashionnaDepartment of Pharmacy, Okayama University HospitalHirofumiHamanoDepartment of Pharmacy, Okayama University HospitalShimonTakahashiDepartment of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima UniversityYoshitoZamamiDepartment of Pharmacy, Okayama University HospitalKazuakiShinomiyaDepartment of Pharmaceutical Care and Clinical Pharmacy, Tokushima Bunri UniversityTakahiroNiimuraClinical Research Center for Developmental Therapeutics, Tokushima University HospitalMitsuhiroGodaDepartment of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima UniversityKeiKawadaDepartment of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima UniversityKeisukeIshizawaClinical Research Center for Developmental Therapeutics, Tokushima University HospitalBackground: In the field of team-based care, pharmacists are vital for optimizing medication therapy. However, many medical professionals lack the opportunity to learn how to propose prescription changes with precision.<br>
Objective: This study aimed to address this knowledge gap by developing and assessing a new educational program for pharmacy students focused on prescription support and interprofessional collaboration.<br>
Methods: We recruited 191 fifth-year pharmaceutical students during the 2022‐2024 academic years. The program featured a 7-day intensive curriculum that included learning how to assist with prescriptions, analyzing clinical data, and engaging in role-playing exercises. A web-based questionnaire and a paper test were used to evaluate students’ awareness and knowledge both before and after the program. Statistical analyses were performed to verify the significance of changes; we utilized the Wilcoxon signed-rank test for the ordinal data derived from the specific behavioral objectives and 2-tailed paired t tests for the interval data from the knowledge tests. The magnitude of change was quantified using r for Wilcoxon tests and Cohen dz for 2-tailed t tests, with 95% CI calculated to ensure the stability and reliability of the observed results.<br>
Results: Analysis of the primary outcome specific behavioral objectives revealed statistically significant effects across all items (Wilcoxon signed-rank test; P<.001). Effect sizes (r=0.505‐0.835) ranged from moderate to large, with particularly large effects observed in identifying contents issue (r=0.835, 95% CI 0.126-0.330; P<.001). Knowledge test scores showed significant improvement in the following 3 subjects: pharmacology (r=−0.504, 95% CI –0.215 to 0.127; P<.001), organic chemistry (r=0.254, 95% CI –0.148 to –0.193; P=.004), and communication (r=0.221, 95% CI –0.151 to –0.190; P=.01). No significant changes were observed in pathology or pharmacokinetics.<br>
Conclusions: This program provides strong evidence that practical, hands-on learning with hospital pharmacists helps improve pharmacy students’ professional skills and optimize pharmaceutical therapies in interprofessional care. By teaching pharmacists to effectively propose prescription changes, the program equips them to become integral members of interprofessional care, ultimately leading to optimized pharmaceutical care for patients.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1462-891027102025D3 lymph node dissection in colon cancer patients aged 90 years and over: Is it justified? A multi‐institutional retrospective studye70269ENFuminoriTeraishiDepartment of Gastroenterological Surgery, Okayama University HospitalSatoeTakanagaDepartment of Gastroenterological Surgery, Okayama University HospitalRyoInadaDepartment of Surgery, Kochi Health Sciences CenterToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Medical Development Field, Okayama UniversityToshiakiToshimaDepartment of Surgery, Kagawa Rosai HospitalTsuyoshiOhtaniDepartment of Surgery, Saiseikai Okayama HospitalRyosukeYoshidaDepartment of Surgery, Okayama Rosai HospitalRyoheiShojiDepartment of Gastroenterological Surgery, Okayama University HospitalToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University HospitalSetouchi Colorectal Neoplasm Registration study group collaboratorsAim: The oncological benefit of D3 lymph node dissection (D3 LND) for colon cancer in patients aged ≥90 years remains unclear. This study aimed to evaluate the impact of D3 LND on outcomes in this specific, vulnerable population.<br>
Method: This retrospective cohort study evaluated 166 patients aged ≥90 years with pathological Stages II–III colon cancer undergoing non-D3 or D3 LND from a multicentre database (2011–2022). Postoperative complications, overall survival and cancer-specific survival were compared between LND groups using propensity score-weighted analyses.<br>
Results: D3 LND group had significantly more females and laparoscopic procedures. Operation time was longer, and blood loss was lower in the D3 LND group. Postoperative complications and severe complications were significantly fewer, and postoperative hospital stay was shorter in the D3 LND group. The number of harvested lymph nodes and distal margin was significantly higher in the D3 group. While unadjusted analysis showed better overall survival with D3 LND (p < 0.001), adjusted cancer-specific survival showed no significant difference (p = 0.10). Adjusted mortality risk was significantly higher in the non-D3 group (p = 0.001).<br>
Conclusion: In nonagenarian colon cancer patients, D3 LND is safe and feasible without increasing complications, but lacks survival benefit. Careful consideration is warranted, and high-quality D2 LND must be consistently ensured when limited surgery is chosen.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841762025Severe Anemia Caused by a Colorectal Lipoma With Central Erosions: A Case Reporte85768ENYusukeYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRyoheiShojiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYukiMatsumiDepartment of Gastroenterological Surgery, Okayama University HospitalKoWatanabeDepartment of Pathology, Okayama University HospitalToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesColorectal lipomas are benign tumors that are often asymptomatic and discovered incidentally. In most cases, they can be managed conservatively with observation. We report the case of a man in his 70s with a colorectal lipoma located in the cecum. An investigation into his severe anemia led to the suspicion that the cecal lipoma was the underlying cause. An ileocecal resection was performed. Erosions were observed at the center of the lipoma. Although small colorectal lipomas are generally asymptomatic and rarely cause anemia, periodic endoscopic examinations are recommended. These lesions should be considered in the differential diagnosis of lower gastrointestinal bleeding.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1435-245141112025Surgical outcomes and patient selection in nonagenarians with colon cancer: a comparative multi-institutional study of laparoscopic and open approaches21ENRyoheiShojiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFuminoriTeraishiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoeTakanagaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Okayama University HospitalRyoInadaDepartment of Surgery, Kochi Health Sciences CenterToshiakiToshimaDepartment of Surgery, Kagawa Rosai HospitalTsuyoshiOhtaniDepartment of Surgery, Saiseikai Okayama HospitalRyosukeYoshidaDepartment of Surgery, Okayama Rosai HospitalNaotoHoriDepartment of Surgery, Tottori Municipal HospitalKaoruShigemitsuDepartment of Surgery, Tsuyama Chuo HospitalSumiharuYamamotoDepartment of Surgery, Okayama City HospitalTetsushiKubotaDepartment of Surgery, Kobe Red Cross HospitalYukaOkanoDepartment of Surgery, Onomichi City HospitalTetsujiNobuhisaDepartment of Surgery, Himeji Red Cross HospitalFumitakaTaniguchiDepartment of Surgery, National Hospital Organization Iwakuni Clinical CenterWataruIshikawaDepartment of Surgery, Fukuyama City HospitalTatsuoMatsudaDepartment of Surgery, Matsuda HospitalTatsuoUmeokaDepartment of Surgery, Matsuyama City HospitalToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSetouchi Colorectal Neoplasm Registration study group collaboratorsPurpose The appropriate surgical approach for colon cancer (CC) in nonagenarian patients remains a subject of clinical debate. This study aimed to compare the short-term outcomes of laparoscopic (Lap) versus open (Open) surgery in patients aged ≥ 90 years with resectable colon cancer.<br>
Methods This multi-institutional retrospective cohort study included oldest-old patientswith pathological Stage II/III CC who underwent elective surgery at 15 hospitals between 2011 and 2022. Patients with rectal cancer, Stage 0/I/IV disease, or emergency surgery were excluded. To address selection bias, inverse-probability-weighted regression adjustment and stabilized inverse probability of treatment weighting (sIPTW) were applied. The primary outcome was postoperative complications; secondary outcomes included overall survival (OS).<br>
Results Median age was 92 years in both groups. Before adjustment, the Lap group had a higher proportion of female patients (p = 0.038) and lower ASA scores (p = 0.01). Laparoscopic surgery was associated with a significantly longer operative time (220 vs. 171 min, p = 0.046) but less intraoperative blood loss (10 vs. 78 mL, p < 0.01). Postoperative complication rates were comparable (Lap: 31.8%, Open: 33.8%), while the Lap group had a significantly shorter hospital stay (13 vs. 17 days, p < 0.01). D3 lymph node dissection was more frequently performed in the Lap group (p < 0.01). After sIPTW, overall survival did not differ significantly between groups (p = 0.61).<br>
Conclusion Both laparoscopic and open surgery are feasible options for selected nonagenarians with colon cancer. Laparoscopic surgery may offer benefits in terms of reduced blood loss and shorter hospitalization, despite longer operative times. Careful patient selection considering frailty and comorbidities is essential in determining the most appropriate surgical approach.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0309-01678852025Claudin-18 expression in gastric type adenocarcinoma and HPV-associated adenocarcinoma of the uterine cervix10031015ENNobukoYasutakeDepartment of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu UniversityYukiYokawaDepartment of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama UniversityTakehiroTanakaDepartment of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama UniversityRiriMishimaDepartment of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama UniversityMisatoKomamizuDepartment of Gynecology and Obstetrics, Graduate School of Medical Sciences Kyushu University Fukuoka JapanRyosukeKugaDepartment of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu UniversityRinaJiromaruDepartment of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu UniversityShinichiroKawatokoDepartment of Medicine and Clinical Science, Kyushu University Beppu HospitalKenzoSonodaDepartment of Gynecology, Kyushu University Beppu HospitalHideakiYahataDepartment of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu UniversityKiyokoKatoDepartment of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu UniversityYoshinaoOdaDepartment of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu UniversityHidetakaYamamotoDepartment of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama UniversityAims: Claudin-18 (CLDN18) is both a marker for the gastric phenotype and a therapeutic target. However, little is known about its immunoexpression in endocervical adenocarcinomas (ECAs), particularly as detected using the clone 43-14A antibody, or about the gene expression of its isoforms in ECAs.<br>
Methods and results: We examined CLDN18, HIK1083, p16 and Rb expression by immunohistochemistry and high-risk human papillomavirus (HR-HPV) mRNA by in situ hybridization (ISH) in 121 ECAs, including 35 HPV-independent adenocarcinomas (gastric type [GAS], n = 24; non-GAS, n = 11) and 86 HPV-associated ECAs. We also analysed mRNA expression of the CLDN18.1 (lung type) and CLDN18.2 (gastric type) isoforms by quantitative polymerase chain reaction (qPCR) in selected cases. CLDN18 positivity was detected in 8/24 (33%) GASs, 0/11 (0%) non-GASs and 2/86 (2%) HPV-associated ECAs, with positivity defined as staining in ≥75% of tumour cells, as in gastric cancer. When a 5% cut-off was used, CLDN18 positivity was detected in 22/24 (92%) GASs, 0/11 (0%) non-GASs and 6/86 (7%) HPV-associated ECAs; CLDN18 expression was thus significantly associated with GAS histology (P < 0.0001). Among the 6 cases of HPV-associated ECAs with CLDN18 expression (ranging from 5% to 80%), the histological patterns included a mix of usual and mucinous features in 4 cases, pure usual type in 1 and villoglandular variant in 1. Otherwise features such as p16 overexpression and the Rb partial loss pattern were consistent with those of HPV-associated ECAs. Six of 22 (27%) CLDN18-positive GASs were also positive for p16, but their other features—such as CLDN18 expression and the Rb preserved pattern—were the same as in p16 negative GASs. Expression of CLDN18.2 mRNA but not CLDN18.1 mRNA was confirmed in both GASs and HPV-associated ECAs.<br>
Conclusions: CLDN18 (43-14A) emerged as a potential diagnostic and therapeutic marker for GAS. A minor subset of HPV-associated ECAs also can be immunoreactive for CLDN18 and express CLDN18.2 mRNA, suggesting divergent gastric phenotypic differentiation. The caution is that GAS and HPV-associated ECAs can share overlapping histological features and similar expression of CLDN18 and p16.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841772025The Challenge of Diagnosing Scirrhous Gastric Cancer by Endoscopic Biopsy: A Case Reporte87334ENYukaIkedaDepartment of Internal Medicine, Clinic IkedaDepartment of Internal Medicine, Clinic IkedaMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTadashiYoshinoDepartment of Pathology, Okayama UniversityTakehiroTanakaDepartment of Pathology, Okayama University HospitalNobumasaIkedaDepartment of Internal Medicine, Clinic IkedaMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesScirrhous gastric cancer, also known as linitis plastica, is a rare and aggressive subtype of gastric carcinoma that poses significant diagnostic challenges due to its submucosal infiltration and often normal-appearing mucosa. We report a case involving a 30-year-old Japanese woman who presented with a six-month history of epigastric pain and postprandial vomiting. Initial endoscopic examination revealed erythema and mucosal swelling, with limited antral distensibility and resistance during duodenal intubation. Despite 12 mucosal biopsies, histopathological examination revealed no evidence of malignancy. Given the strong clinical and endoscopic suspicion of scirrhous gastric cancer, additional deep sections and immunohistochemical staining were performed. These revealed scattered signet-ring cell carcinoma and poorly differentiated adenocarcinoma, with positive immunostaining for p53 and Ki67. The patient underwent total gastrectomy, and the diagnosis of scirrhous gastric cancer was confirmed on the resected specimen. This case highlights the importance of a high index of clinical suspicion, close collaboration between endoscopists and pathologists, and the utility of ancillary diagnostic tools, such as immunohistochemistry, in identifying subepithelial gastric malignancies that may be missed on conventional biopsy.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1345-26302026Tabtoxin biosynthetic gene cluster in Pseudomonas syringae pv. tabaci 6605 genomic island 1 (GI-1Pta6605) is required for severe disease symptomsENKotomiKunishiThe Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNorikaFujisawaThe Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHidenoriMatsuiThe Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNanamiSakataThe Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYoshiteruNoutoshiThe Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKazuhiroToyodaThe Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYukiIchinoseThe Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityOne of the genomic islands in Pseudomonas syringae pv. tabaci 6605 (GI-1Pta6605) has been identified as a pathogenicity island required for virulence because the deletion almost completely eliminated disease symptoms in inoculation tests at 4 × 105 CFU/ml. GI-1Pta6605 contains four cargo regions (CRs) named CR-1 to CR-4. The ∆CR-4 mutant did not produce tabtoxin like ∆GI-1 and disease symptoms did not develop in tobacco. However, it grew, although to a lesser extent than the wild-type strain. These results indicate that the tabtoxin biosynthetic gene cluster in GI-1 is required for virulence but not for establishment of compatibility.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1757-22151912025Pan-cancer profiling links C1orf50 to DNA repair and immune modulation in ovarian cancer13ENAnnaRogachevskayaDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolYusukeOtaniDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineAkiraOhtsuHarvard Medical SchoolVanessa D.ChinUMass Chan Medical School, UMass Memorial Medical CenterTirsoPeñaDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolSeijiAraiDepartment of Urology, Gunma University Graduate School of MedicineShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineAtsushiFujimuraDepartment of Molecular Physiology, Faculty of Medicine, Graduate School of Medicine, Kagawa UniversityAtsushiTanakaDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolBackground C1orf50 encodes a small, evolutionarily conserved protein, the function of which remains unclear. Its significance across various human cancers, particularly its specific role in ovarian cancer within an immunogenomic context, is not yet fully understood. Utilizing The Cancer Genome Atlas and single-cell RNA sequencing (scRNA-seq) public datasets, we conducted a comprehensive profiling of C1orf50 across multiple cancer types, with a particular focus on ovarian cancer, to investigate its associations with copy-number status, genomic instability, tumor programs, and the immune microenvironment.<br>
Results Across cancer types, copy-number gain or amplification of C1orf50 was most frequent in ovarian cancer and closely tracked with higher messenger RNA levels. Higher C1orf50 expression was associated with a greater tumor mutational burden and homologous recombination deficiency, as indicated by gene-set patterns that suggested heightened cell-cycle and cellular stress responses accompanied by reduced oxidative phosphorylation, enrichment of regulatory T cells, and depletion of resting memory CD4 T cells. In ovarian cancer, focal events at chromosome 1p34.2 were accompanied by stepwise increases in C1orf50 expression by clinical stage and were linked to higher tumor mutational burden, homologous recombination deficiency, and greater loss of heterozygosity, together with more frequent gene alterations in BRCA1 or BRCA2. Immune composition clustered into profiles consistent with an immunosuppressive context in tumors with higher C1orf50 expression. The scRNA-seq data further revealed that cancer cells enhanced immune-suppressive interactions with various immune cell populations and diminished antigen-presentation signals. Analyses of genomic instability in ovarian cancer suggested mutational processes compatible with base-substitution patterns associated with cytidine deaminase activity and with insertion-deletion patterns characteristic of homologous recombination failure, while transcript-level patterns pointed to a broad downshift of canonical DNA repair activity with apparent compensatory adjustments in related pathways rather than a uniform change in any single pathway.<br>
Conclusions The overexpression of C1orf50 characterizes an aggressive immunogenomic phenotype in ovarian cancer, distinguished by genomic instability, impaired DNA repair mechanisms, and extensive immunosuppression. These findings indicate that C1orf50 warrants consideration as a potential biomarker and a prospective target for therapeutic investigation. Furthermore, they advocate for the progression to prospective validation and functional studies to ascertain its clinical significance.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2589-5370802025Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone combined with high-dose methotrexate plus intrathecal chemotherapy for newly diagnosed intravascular large B-cell lymphoma (PRIMEUR-IVL): long-term results of a multicentre, single-arm, phase 2 trial103078ENKazuyukiShimadaDepartment of Hematology and Oncology, Nagoya University Graduate School of MedicineMotokoYamaguchiDepartment of Hematological Malignancies, Mie University Graduate School of MedicineYachiyoKuwatsukaDepartment of Advanced Medicine, Nagoya University HospitalKoseiMatsueDivision of Hematology/Oncology, Internal Medicine, Kameda Medical CenterKeijiroSatoDepartment of Hematology, Nagano Red Cross HospitalShigeruKusumotoDepartment of Hematology and Oncology, Nagoya City University Graduate School of Medical SciencesHirokazuNagaiDepartment of Hematology, National Hospital Organization Nagoya Medical CenterJunTakizawaDepartment of Hematology, Endocrinology and Metabolism, Niigata University Faculty of MedicineNorikoFukuharaDepartment of Hematology and Rheumatology, Tohoku University HospitalKojiNagafujiDivision of Hematology and Oncology, Department of Medicine, Kurume University School of MedicineKanaMiyazakiDepartment of Hematology and Oncology, Mie University Graduate School of MedicineEiichiOhtsukaDepartment of Hematology, Oita Prefectural HospitalAkinaoOkamotoDepartment of Hematology, Fujita Health University School of MedicineYasumasaSugitaDepartment of Hematology, Oami Municipal HospitalToshikiUchidaDepartment of Hematology and Oncology, Japanese Red Cross Aichi Medical Center Nagoya Daini HospitalSatoshiKayukawaDepartment of Clinical Oncology, Nagoya Memorial HospitalAtsushiWakeDepartment of Hematology, Toranomon Hospital KajigayaDaisukeEnnishiDepartment of Hematology and Oncology, Okayama University HospitalYukioKondoDepartment of Internal Medicine, Toyama Prefectural Central HospitalAkikoMeguroDivision of Hematology, Tochigi Cancer CenterYoshihiroKinDepartment of Hematology, Daini Osaka Police HospitalYosukeMinamiDepartment of Hematology, National Cancer Center Hospital EastDaigoHashimotoDepartment of Hematology, Hokkaido University Faculty of Medicine, Graduate School of MedicineTakahiroNishiyamaDivision of Hematology, Ichinomiya Municipal HospitalSatokoShimadaDepartment of Pathology and Clinical Laboratories, Nagoya University HospitalYasufumiMasakiDepartment of Hematology and Immunology, Kanazawa Medical UniversityMasatakaOkamotoDepartment of Hematology, Fujita Health University School of MedicineYoshikoAtsutaJapanese Data Center for Hematopoietic Cell TransplantationHitoshiKiyoiDepartment of Hematology and Oncology, Nagoya University Graduate School of MedicineRitsuroSuzukiDepartment of HSCT Data Management and Biostatistics, Nagoya University School of MedicineShigeoNakamuraDepartment of Pathology and Clinical Laboratories, Nagoya University HospitalTomohiroKinoshitaDepartment of Hematology and Cell Therapy, Aichi Cancer CenterBackground Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma for which prognosis is typically poor without a timely diagnosis. To explore the safety and efficacy of standard chemotherapy combined with central nervous system (CNS)-directed therapy, we conducted a multicentre, single-arm, phase 2 trial in untreated IVLBCL patients without CNS involvement at diagnosis (PRIMEUR-IVL). In the primary analysis, the PRIMEUR-IVL study demonstrated 2-year progression-free survival (PFS) of 76% and 2-year overall survival (OS) of 92% with a low incidence (3%) of secondary CNS involvement (sCNSi).<br>
Methods We present a prespecified final analysis of the PRIMEUR-IVL study including 5-year PFS, OS and cumulative incidence of sCNSi. Participants were enrolled between June 2011 and July 2016, and the data cutoff date for the final analysis was 16 November 2021. The trial was registered in the UMIN Clinical Trial Registry (UMIN000005707) and the Japan Registry of Clinical Trials (jRCTs041180165).<br>
Findings With a median follow-up of 7.1 years (interquartile range 5.6–8.7), 5-year PFS in all 37 eligible patients was 68% (95% confidence interval [CI] 50%–80%) and OS was 78% (95% CI 61%–89%). No additional sCNSi was observed after the primary analysis. Severe adverse events after the primary analysis were grade 4 neutropenia (n = 1) and grade 4 myelodysplastic syndrome that did not require specific treatment (n = 1). Eight deaths occurred during the observation period after enrolment, due to primary disease (n = 6), sepsis (n = 1) and unknown sudden death (n = 1).<br>
Interpretation Long-term follow-up data demonstrated durable response for PFS and OS, and low cumulative incidence of sCNSi, indicating the efficacy of standard chemotherapy combined with CNS-directed therapy for untreated IVLBCL patients.<br>
Funding This study received financial support from the Japan Agency for Medical Research and Development, Center for Supporting Hematology-Oncology Studies, and National Cancer Center.No potential conflict of interest relevant to this article was reported.Japanese Society of Internal MedicineActa Medica Okayama0918-291864142025Myeloid Sarcoma in the Small Intestine21552159ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomohiroKamioDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShoichiroHirataDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKatsunoriMatsuedaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDaisukeKametakaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSeijiKawanoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMyeloid sarcoma is a rare extramedullary tumor of immature myeloid cells that is often associated with acute myeloid leukemia (AML). We herein report an 81-year-old man who presented with intestinal obstruction due to myeloid sarcoma of the small intestine. Diagnostic challenges were overcome using double-balloon enteroscopy and a biopsy, which confirmed the diagnosis of myeloid sarcoma. The patient subsequently developed AML but responded well to chemotherapy. This case underscores the importance of considering myeloid sarcoma in the differential diagnosis of small-bowel tumors. Highlighting the significance of a histological analysis, even in patients presenting with small bowel obstruction, the early diagnosis and treatment are crucial for improving outcomes, particularly in patients without a history of hematologic malignancies.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841752025Pseudoachalasia Due to Malignant Pleural Mesothelioma Involving the Esophaguse84161ENManamiHondaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuyaMiyamotoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesWe report a rare case of pseudoachalasia secondary to malignant pleural mesothelioma involving the esophagus. A 66-year-old man presented with progressive dysphagia, weight loss, and postprandial hiccups. Endoscopic examination showed esophageal dilation with luminal narrowing at the esophagogastric junction, but no mucosal abnormalities. Computed tomography revealed an irregular-shaped mass extending from the peri-esophagogastric junction to the retroperitoneum, accompanied by pleural effusion, right-sided hydronephrosis, and multiple hepatic lesions. Endoscopic ultrasound-guided fine-needle aspiration from the mass lesion through the esophageal lumen revealed epithelioid malignant mesothelioma. This case highlights the importance of considering malignant mesothelioma in the differential diagnosis of pseudoachalasia, particularly when imaging reveals extrinsic esophageal compression without mucosal lesions.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841742025Gastrointestinal Stromal Tumors in the Stomach With Tumor Growth and Hemorrhage During Conservative Management: A Report of Two Casese82046ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShinjiKurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesGastrointestinal stromal tumors (GISTs) are often detected incidentally during esophagogastroduodenoscopy. Although surgical resection is the standard treatment for GISTs, patients with significant comorbidities may not be eligible for surgery and are managed conservatively. Herein, we report two cases of gastric GISTs that were initially observed during the management of other comorbidities but subsequently became enlarged, resulting in gastrointestinal bleeding. These cases highlight the potential risks of tumor progression and bleeding in patients undergoing conservative management.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1865-72571822025Microsatellite-high intrahepatic cholangiocarcinoma with favorable treatment outcome using pembrolizumab363368ENShigeruHoriguchiDepartment of Gastroenterology and Hepatology, Okayama University HospitalHironariKatoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyaMiyamotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKosakuMorimotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalAkihiroMatsumiDepartment of Gastroenterology and Hepatology, Okayama University HospitalHiroyukiTerasawaDepartment of Gastroenterology and Hepatology, Okayama University HospitalYukiFujiiDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalTakehiroTanakaDepartment of Pathology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University HospitalIntrahepatic cholangiocarcinoma has a poor prognosis. In unresectable cases, the survival period is short despite combination therapy with cytotoxic anticancer agents and immune checkpoint inhibitors. The usefulness of immune checkpoint inhibitors against malignant tumors with microsatellite instability-high (MSI-H) mutations was shown in the KEYNOTE158 study; however, data for intrahepatic cholangiocarcinoma are insufficient. In the present case, a 65-year-old man with intrahepatic cholangiocarcinoma and lymph node metastasis could not be treated with a combination of gemcitabine, CDDP, and S-1. A comprehensive cancer genomic profiling (CGP) test showed MLH1 pathogenic mutation and MSI-H. When pembrolizumab was administered, the tumor shrinkage effect was rapidly observed, which was sustained even after 30 months. No pathogenic mutations were observed in the germline test, and MSI-high was considered to be due to the MLH1 pathogenic mutation occurring sporadically in somatic cells. MSI-H intrahepatic cholangiocarcinoma is extremely rare. However, because pembrolizumab is expected to be effective, CGP testing should be actively performed.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841722025Gastric Metastasis of Renal Cell Carcinoma Initially Diagnosed by Esophagogastroduodenoscopye79651ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomohiroKamioDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShoichiroHirataDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHere, we report a rare case of renal cell carcinoma (RCC) initially detected as a gastric metastasis. A 58-year-old man with epigastric discomfort underwent esophagogastroduodenoscopy, which revealed a reddish semi-pedunculated lesion with a whitish coating. Biopsy and imaging confirmed clear cell RCC metastasis. Contrast-enhanced computed tomography (CT) revealed a primary renal tumor with pancreatic and lymph node metastases. Despite chemotherapy treatment, the patient died after 10 months. Gastric metastases from RCC, although rare, should be considered in highly vascular gastric lesions with white coatings. Clinicians must be vigilant for metastatic diseases with atypical gastric findings.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2072-66941842026Antigen Remodeling in Colorectal Cancer: How Radiotherapy and Chemotherapy Enhance Immunotherapy Responsiveness715ENYukiMatsumiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKunitoshiShigeyasuDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshiakiTakahashiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuyaMoriwakeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasashiKayanoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesColorectal cancer (CRC) is traditionally considered a “cold tumor” characterized by low immunogenicity and limited responsiveness to immune checkpoint inhibitors (ICIs). However, recent findings reveal that cytotoxic modalities can reprogram this immunologically inert landscape. This review integrates these evolving concepts to guide the optimization of future treatments. Radiotherapy induces extensive DNA double-strand breaks, which may generate de novo mutations through error-prone repair while simultaneously exposing cryptic antigens via increased transcriptional instability, alternative splicing, and enhanced proteasomal processing. Chemoradiation also amplifies epigenetic and epitranscriptomic sources of neoepitope diversity, including RNA editing and stress-induced splicing alterations, expanding the immunopeptidome beyond canonical mutation-driven neoantigens. These changes collectively enhance antigen presentation and facilitate T-cell priming. Chemotherapy further reduces immunosuppressive cell populations and promotes dendritic cell activation, creating a permissive milieu for subsequent immune engagement. Clinically, the VOLTAGE studies demonstrated that long-course chemoradiotherapy can sensitize even mismatch repair–proficient rectal cancers to PD-1 blockade, yielding clinically meaningful pathological responses. In contrast, mismatch repair–deficient rectal tumors may respond completely to ICIs alone. Short-course radiotherapy combined with chemotherapy and ICIs has also shown encouraging activity in the setting of total neoadjuvant therapy. Collectively, these findings support a paradigm in which radiotherapy, chemotherapy, and epigenetic/epitranscriptomic alterations—including RNA editing—act as potent modulators of tumor antigenicity. By expanding the neoantigen repertoire and reshaping the tumor microenvironment, these strategies can transform CRC from a cold tumor into one that is increasingly responsive to immunotherapy.No potential conflict of interest relevant to this article was reported.Ovid Technologies (Wolters Kluwer Health)Acta Medica Okayama1743-915911222025Total thymectomy is oncologically superior to partial thymectomy in patients with thymic carcinoma: insights from a multicenter real-world data analysis23012310ENTatsuyaHayashiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikioOkazakiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiharuMitsuhashiCenter of Innovative Clinical Medicine, Okayama University HospitalHidetakaYamamotoDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomohiroHabuOkayama University Thoracic Surgery Study Group (OUTSSG)KazuhikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiromasaYamamotoOkayama University Thoracic Surgery Study Group (OUTSSG)TomoakiOtsukaOkayama University Thoracic Surgery Study Group (OUTSSG)MototsuguWatanabeOkayama University Thoracic Surgery Study Group (OUTSSG)TakeshiKurosakiOkayama University Thoracic Surgery Study Group (OUTSSG)EijiYamadaOkayama University Thoracic Surgery Study Group (OUTSSG)EisukeMatsudaOkayama University Thoracic Surgery Study Group (OUTSSG)TatsurouHayashiOkayama University Thoracic Surgery Study Group (OUTSSG)ToshiyaFujiwaraOkayama University Thoracic Surgery Study Group (OUTSSG)MakioHayamaOkayama University Thoracic Surgery Study Group (OUTSSG)HiroyukiTaoOkayama University Thoracic Surgery Study Group (OUTSSG)MasaomiYamaneOkayama University Thoracic Surgery Study Group (OUTSSG)HidetoshiInokawaOkayama University Thoracic Surgery Study Group (OUTSSG)YujiHiramiOkayama University Thoracic Surgery Study Group (OUTSSG)KazuhiroWashioOkayama University Thoracic Surgery Study Group (OUTSSG)TakahikoMisaoOkayama University Thoracic Surgery Study Group (OUTSSG)MotohiroYamashitaOkayama University Thoracic Surgery Study Group (OUTSSG)YoshifumiSanoOkayama University Thoracic Surgery Study Group (OUTSSG)MasaoNakataOkayama University Thoracic Surgery Study Group (OUTSSG)OsamuKawamataOkayama University Thoracic Surgery Study Group (OUTSSG)ShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Although total thymectomy has been the standard surgical approach for thymic epithelial tumors, an increasing number of recent reports suggest that partial thymectomy for early-stage thymomas may yield outcomes comparable to those of total thymectomy. However, whether partial thymectomy is a viable alternative for thymic carcinoma remains unclear.<br>
Materials and methods: A total of 106 patients with thymic carcinoma underwent curative intended resection at 19 institutions between January 2010 and December 2021. Excluding 14 patients with incomplete resection, 92 patients with thymic carcinoma who underwent total (n = 73) or partial thymectomy (n = 19) were compared. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan–Meier curves and Cox proportional hazard models. Overlap weighting was applied to adjust for potential confounding factors.<br>
Results: Among patients with clinical stage I disease, 79.3% were upstaged to stage II or higher postoperatively. Unadjusted analyses revealed no statistically significant differences in OS and RFS between the total and partial thymectomy groups, although a trend toward poorer outcomes in the partial thymectomy group was observed. After overlap weighting, partial thymectomy was associated with significantly poorer OS (P = 0.0027) and higher recurrence risk (P < 0.0001). Early postoperative recurrence occurred more frequently in the partial thymectomy group.<br>
Conclusion: Partial thymectomy was associated with significantly worse survival and recurrence outcomes in thymic carcinoma. Given the limitations of preoperative diagnosis, total thymectomy should remain the preferred surgical approach for undiagnosed thymic epithelial tumors to achieve optimal oncologic control and minimize the risk of recurrence.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8012026Effective Treatment of Advanced Hepatocellular Carcinoma with Extensive Peritoneal Dissemination Using Lenvatinib6974ENShinyaWakatsukiDepartment of Obstetrics and Gynecology, Kochi Health Sciences CenterShinyaSakamotoDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterAkikoUenoDepartment of Obstetrics and Gynecology, Kochi Health Sciences CenterTakaomiNambaDepartment of Obstetrics and Gynecology, Kochi Health Sciences CenterYoritoYamamotoDepartment of Obstetrics and Gynecology, Kochi Health Sciences CenterManabuMatsumotoDepartment of Diagnostic Pathology, Kochi Health Sciences CenterJunIwataDepartment of Diagnostic Pathology, Kochi Health Sciences CenterTakehiroOkabayashiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterCase Report/10.18926/AMO/70075Patients with hepatocellular carcinoma (HCC) and extensive peritoneal dissemination generally have a poor prognosis and are often resistant to systemic therapy. We report the case of a 47-year-old woman with HCC and massive peritoneal dissemination who presented with malignant ascites requiring repeated cell-free and concentrated ascites reinfusion therapy and peritoneovenous shunt placement, as well as malignant pleural effusion requiring pleurodesis. Combined immunotherapy with durvalumab/tremelimumab was initiated;however, disease progression was observed after three treatment courses, prompting a switch to lenvatinib therapy. Two months after initiation of lenvatinib, CT imaging demonstrated complete disappearance of arterial enhancement in the primary hepatic lesion, along with reduction in the size of peritoneal dissemination nodules. Thirteen months after switching to lenvatinib (16 months after the initial diagnosis), the alpha-fetoprotein level continued to decrease, and the disease remained stable under treatment. Despite the extremely high tumor burden, lenvatinib achieved disease stabilization and symptomatic improvement.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2950-32993342025Collagen depletion by pirfenidone enhances antitumor effect of oncolytic adenovirus against peritoneal metastases of gastric cancer201045ENTomohiroOkuraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiTazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuMikaneDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuhikoKanayaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEmaMitsuiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYutaUneDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKunitoshiShigeyasuDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiakiOharaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunkoOhtsukaLaboratory of Fundamental Oncology, National Cancer Center Research InstituteRiekoOhkiLaboratory of Fundamental Oncology, National Cancer Center Research InstituteShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuoUrata Oncolys BioPharma, Inc.ToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCancer-associated fibroblasts (CAFs) play a crucial role in collagen accumulation, which develops and promotes peritoneal metastasis (PM) in gastric cancer (GC). In addition, the abundant stromal collagens in the tumor microenvironment function as a physical barrier against penetration of antitumor drugs and oncolytic viruses. This study investigated whether collagen depletion by pirfenidone (PFD), an antifibrotic drug, enhances the antitumor effects of oncolytic adenoviruses. Analysis of the clinical samples revealed a significant association of high expression of collagen 1 and α-smooth muscle actin (α-SMA) with PM development and poor prognosis of advanced GC. Human and murine GC cells enhanced collagen production by fibroblasts, which was suppressed by PFD. Abundant fibroblasts and collagen inhibited the penetration of OBP-702, which reduced the antitumor effects of OBP-702 in the spheroid model. Intraperitoneal co-injection of GC cells and fibroblasts promoted the development of collagen-rich PM and reduced the antitumor effects of OBP-702 in vivo model. PFD suppressed collagen production in PM and improved viral penetration into the tumors, which enhanced the antitumor effects of OBP-702 against PM of GC. Collagen depletion by PFD enhances the penetration of OBP-702 into PM of GC, in turn enhancing the antitumor effects of OBP-702 against PM of GC.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841812026Central Serous Chorioretinopathy in Parallel With Onset and Relapses of Minimal Change Nephrotic Syndrome: A 28-Year Case Follow-Upe102426ENToshihikoMatsuoDepartment of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakehiroTanakaDepartment of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology, and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityCentral serous chorioretinopathy is an idiopathic disease that manifests as one or several localized, small, dome-shaped serous retinal detachments on fundus examination. The pathophysiology involves fluid leakage from the choroidal capillaries, known as the choriocapillaris, into the subretinal space through sites of damage in the retinal pigment epithelium. This case report discusses the underlying causes of central serous chorioretinopathy-like findings in minimal change nephrotic syndrome.<br>
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The patient was a 33-year-old woman who developed nephrotic syndrome that was confirmed to be minimal change disease by renal biopsy. She experienced two major relapses of nephrotic syndrome at the ages of 36 and 41 years. She also had a minor relapse at the age of 37 years, five months after the first major relapse at the age of 36 years, as well as four additional minor relapses at the ages of 44, 46, 50, and 51 years. The onset of central serous chorioretinopathy-like manifestations, which were localized to the left eye, occurred three months after the initial onset of nephrotic syndrome at the age of 33 years. Two subsequent episodes of relapse of central serous chorioretinopathy-like manifestations were observed in both eyes at intervals of five months and one month, respectively, after major relapses of nephrotic syndrome at the ages of 36 and 41 years. Thereafter, she did not develop further central serous chorioretinopathy-like manifestations.<br>
<br>
She discontinued oral prednisolone at the age of 54 years and experienced no further relapses of nephrotic syndrome through her latest visit at the age of 61 years. She maintained normal renal function and good visual acuity in both eyes. The long-term, consistent temporal association between episodes of central serous chorioretinopathy and the onset and relapses of minimal change nephrotic syndrome is strongly supported by longitudinal clinical observations spanning 28 years. This parallel course suggests a possible shared pathophysiological mechanism or common triggering factors underlying both diseases.No potential conflict of interest relevant to this article was reported.China Anti-cancer AssociationActa Medica Okayama2095-39412026SPRED2 suppresses the stemness of hepatocellular carcinoma through the p53/miR-506-3p/KLF4 pathwayENTongGaoDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySachioItoDepartment of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAyeMoh-Moh-AungDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTianyiWangDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasayoshiFujisawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiakiOharaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTeizoYoshimuraDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAkihiroMatsukawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityObjective: We previously reported that endogenous Sprouty-related, EVH1 domain-containing protein 2 (SPRED2), an inhibitor of the Ras/Raf/ERK-MAPK pathway, controls hepatocellular carcinoma (HCC) cell stemness by downregulating the expression of pluripotency factors, such as Nanog, c-Myc, and KLF4, in an ERK-dependent fashion. However, the exact mechanisms by which SPRED2 regulates HCC cell stemness have not been established.<br>
Methods: Three human HCC cell lines [HepG2 (parental and SPRED2-deficient), HLE, and Hep3B] were used. Cells were transfected to downregulate or overexpress proteins. Western blot and RT-qPCR were used to evaluate the level of protein and mRNA expression. Co-immunoprecipitation and ChIP-qPCR were used to examine protein-protein interactions and the activation of gene transcription. Clinical HCC tissues were also used to validate in vitro data.<br>
Results: KLF4 was identified as the major pluripotency factor responsible for SPRED2-mediated downregulation of HCC cell stemness and KLF4 expression was regulated by miR-506-3p. SPRED2 formed a protein complex with the tumor suppressor (p53) and upregulated miR-506 gene transcription by binding to the promoter region, resulting in subsequent downregulation of KLF4 mRNA expression. There was a negative correlation between KLF4 expression and miR-506-3p and a positive correlation between miR-506-3p expression and SPRED2 in human HCC samples, highlighting the relevance of the study findings.<br>
Conclusions: The current study revealed a novel SPRED2/p53/miR-506-3p/KLF4 axis through which SPRED2 contributes to the suppression of HCC cell stemness and provides a potential new target to prevent HCC progression.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1873-149X3312026Bridging the Gap Between Static Histology and Dynamic Organ-on-a-Chip Models10ENZheyiWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeijiNaruseDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityFor more than a century, pathology has served as a cornerstone of modern medicine, relying primarily on static microscopic assessment of tissue morphology—such as H&E staining—which remains the “gold standard” for disease diagnosis. However, this conventional paradigm provides only a snapshot of disease states and often fails to capture their dynamic evolution and complex functional mechanisms. Moreover, animal models are constrained by marked interspecies differences, creating a persistent gap in translational research. To overcome these limitations, we propose the concept of New Pathophysiology, a research framework that transcends purely morphological descriptions and aims to resolve functional dynamics in real time. This approach integrates Organ-on-a-Chip (OOC) technology, multi-omics analyses, and artificial intelligence to reconstruct the entire course of disease initiation and to enable personalized medicine. In this review, we first outline the foundations and limitations of traditional pathology and animal models. We then systematically summarize more than one hundred existing OOC disease models across multiple organs—including the kidney, liver, and brain. Finally, we elaborate on how OOC technologies are reshaping the study of key pathological processes such as inflammation, metabolic dysregulation, and fibrosis by converting them into dynamic, mechanistic disease models, and we propose future perspectives in the field. This review adopts a relatively uncommon classification strategy based on pathological mechanisms (mechanism-based), rather than organ-based categorization, allowing readers to recognize shared principles underlying different diseases. Moreover, the focus of this work is not on emphasizing iteration or replacement of existing approaches, but on preserving past achievements from a historical perspective, with an emphasis on overcoming current limitations and enabling new advances.No potential conflict of interest relevant to this article was reported.Baishideng Publishing Group Inc.Acta Medica Okayama1948-519017122025Endoscopic features of oral and pharyngolaryngeal papillomas and their role in distinguishing squamous cell carcinoma110594ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University HospitalKentaHamadaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshiyasuKonoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSeijiKawanoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshiroKawaharaDepartment of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBACKGROUND<br>
Oral and pharyngolaryngeal papillomas are occasionally detected during esophagogastroduodenoscopy. However, their endoscopic features have not been sufficiently investigated.<br>
AIM<br>
To distinguish oral and pharyngolaryngeal papillomas from elevated squamous carcinomas, this study examined their endoscopic features.<br>
METHODS<br>
Forty-seven patients with oral or pharyngeal papilloma participated in this study. The endoscopic characteristics of papillomas were identified by focusing on narrowband and blue laser imaging representations.<br>
RESULTS<br>
Papillomas were classified into three patterns based on their endoscopic features: Salmon roe-like polyps, polyps without capillary transparency, and pinecone-like polyps, with salmon roe-like polyps most prevalent (48.9%). We subsequently analyzed features differentiating papillomas and squamous cell carcinomas in the same region and found that squamous cell carcinomas exhibited at least one of the following three features: Uneven or absent lobulated structure, irregular morphology of capillaries, and coexistence of flat lesions. In contrast, papillomas displayed a uniform lobulated structure, homogeneous or non-visible capillaries, and an absence of flat components. When any of these characteristics were present, two endoscopic specialists evaluated the lesions for the diagnosis of squamous cell carcinoma, with sensitivities of 100% and 97.6% and specificities of 68.9% and 93.3%.<br>
CONCLUSION<br>
Understanding distinct endoscopic patterns of oropharyngeal papillomas and squamous cell carcinomas provides valuable guidance to endoscopists performing esophagogastroduodenoscopy.No potential conflict of interest relevant to this article was reported.American Society of Clinical Oncology (ASCO)Acta Medica Okayama2473-427692025Development and Validation of an Ipsilateral Breast Tumor Recurrence Risk Estimation Tool Incorporating Real-World Data and Evidence From Meta-Analyses: A Retrospective Multicenter Cohort Studye2500182ENYasuakiSagaraDepartment of Breast and Thyroid Surgical Oncology, Hakuaikai Sagara HospitalAtsushiYoshidaDepartment of Breast Surgical Oncology, St Luke's International HospitalYuriKimuraDepartment of Breast Surgical Oncology, The Cancer Institute Hospital of JFCRMakotoIshitobiDepartment of Breast Surgery, Osaka Habikino Medical CenterYukaOnoDepartment of Radiation Oncology and Image-Applied Therapy, Kyoto UniversityYukoTakahashiDepartment of Breast and Endocrine Surgery, Okayama University HospitalTakahiroTsukiokiDepartment of Breast and Endocrine Surgery, Okayama University HospitalKojiTakadaDepartment of Breast Surgical Oncology, Osaka Metropolitan University Graduate School of MedicineYuriItoDepartment of Medical Statistics, Osaka Medical and Pharmaceutical UniversityTomoOsakoDivision of Pathology, The Cancer Institute of Japanese Foundation for Cancer ResearchTakehikoSakaiDepartment of Breast Surgical Oncology, The Cancer Institute Hospital of JFCRPurpose Ipsilateral breast tumor recurrence (IBTR) remains a critical concern for patients undergoing breast-conserving surgery (BCS). Reliable risk estimation tools for IBTR risk can support personalized surgical and adjuvant treatment decisions, especially in the era of evolving systemic therapies. We aimed to develop and validate models to estimate IBTR risk.<br>
Patients and Methods This multicenter retrospective cohort study included 8,938 women who underwent partial mastectomy for invasive breast cancer between 2008 and 2017. Prediction models were developed using Cox proportional hazards regression and validated via bootstrap resampling. Model performance was assessed using Harrell's C-index, Brier scores, calibration plots, and goodness-of-fit tests.<br>
Results During a median follow-up of 9.0 years (IQR, 6.6-10.9), IBTR occurred in 320 patients (3.6%). The initial model, based on variables from Sanghani et al, achieved a Harrell's C-index of 0.74. Incorporating hormonal receptor status, human epidermal growth factor receptor 2 status, radiotherapy, and targeted therapy as predictors reduced the C-index to 0.65, despite their clinical relevance. Importantly, the inclusion of these factors improved calibration, demonstrating better alignment between predicted and observed IBTR probabilities. Although the hazard ratios (HRs) for radiotherapy aligned with the Early Breast Cancer Trialists’ Collaborative Group meta-analyses (MA), those for chemotherapy and endocrine therapy showed slight differences. Therefore, HRs from the MA were used to represent treatment effects in our model.<br>
Conclusion We have developed and internally validated a new risk estimation model for IBTR using Cox regression and bootstrap methods. A Web-based risk estimation tool is now available to facilitate individualized risk assessment and treatment planning.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0014-48001452026Assessing the role of folate syntrophy and folate cross-feeding in the pathobiology of infectious-inflamed milieu caused by Fusobacterium nucleatum105021ENDarabGhadimiDepartment of Microbiology and Biotechnology, Max Rubner-InstitutSophiaBlömerFaculty of Medicine, Christian-Albrechts-University of KielAyselŞahin KayaDepartment of Nutrition and Dietetics, Faculty of Health Sciences, Antalya Bilim UniversitySandraKrügerInstitute of Pathology, Kiel University, University Hospital, Schleswig-HolsteinChristophRöckenInstitute of Pathology, Kiel University, University Hospital, Schleswig-HolsteinHeinerSchäferLaboratory of Molecular Gastroenterology & Hepatology, Christian-Albrechts-University & UKSH Campus KielJumpeiUchiyamaDepartment of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityShigenobuMatsuzakiDepartment of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen UniversityWilhelmBockelmannDepartment of Microbiology and Biotechnology, Max Rubner-InstitutDiet and nutrition affect almost every biological process, including multiple chronic diseases, diabetes, and some cancers. However, there are still significant gaps in our understanding of the importance of nutrition and healthy diets in syntrophy with respect to cross-feeding of the microbe-microbe and the microbe-host in the pathobiology of the infectious-inflamed intestinal milieu caused by anaerobic opportunistic bacteria such as Fusobacterium nucleatum (F. nucleatum). We examined the immune outcomes of three-member folate syntrophy and cross-feeding between F. nucleatum bacteria, endogenous folate-producing gut bacteria, and host cells at the host-pathogen interface using a triple co-culture model. T84, THP-1, and Huh7 cells were inoculated with F. nucleatum for 6 h in regular DMEM, DMEM with 9.5 μM folic acid, or with/without a mixture of Bifidobacterium longum subsp. infantis (B. infantis) and Escherichia coli Nissle 1917 (EcN). Cytokine secretion, cometabolite levels (ammonia, indoles), cell viability, and barrier integrity were assessed. F. nucleatum-induced folate depletion was associated with increased IL-1β and IL-6 and decreased IL-22, along with reduced transepithelial electrical resistance (TEER) and cell viability in T84 cells. Folate supplementation mitigated these effects. The mixture of B. infantis and EcN reduced F. nucleatum-induced pro-inflammatory cytokines, increased IL-22, and improved TEER and cell viability. These protective effects were enhanced by the addition of folate. F. nucleatum also elevated ammonia and reduced indoles, effects reversed by B. infantis and EcN. In addition to the intrinsic pathogenicity of harmful bacteria, folate deprivation, microbe–microbe folate syntrophy, and microbe–host folate cross-feeding contribute to the pathobiology of anaerobic opportunistic bacteria and influence the physiological fate of host cells. A combination of B. infantis and EcN modulates the infectious-inflamed interface through a cytoprotective effect and mechanical competitive extrusion of pathogenic F. nucleatum. These results provide potential insights into the mechanisms of early-onset colorectal cancer, and evidently, require future studies using patient-derived organoids and in vivo systems to improve clinical relevance.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1341-321X31122025Clinical and molecular characteristics of urinary catheter-associated Pseudomonas aeruginosa prostatic infection: A case series of four postoperative nosocomial infections102853ENShinnosukeFukushimaDepartment of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakayukiSanoLaboratory of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato UniversityTakashigeKashimotoLaboratory of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato UniversityHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalPseudomonas aeruginosa is a causative pathogen of nosocomial catheter-associated urinary tract infections (CAUTI), but prostate involvement, including prostatitis and prostatic abscess, is rare. The clinical characteristics of P. aeruginosa-associated CAUTI with prostatic lesions, as well as the contribution of genetic backgrounds remain unclear. We describe four cases of urinary catheter-associated prostatic infection caused by P. aeruginosa following postoperative catheterization. All patients developed fever within 10 days after surgery, and three of the four patients developed bacteremia. Three patients were diagnosed with prostatic abscess by contrast-enhanced computed tomography or magnetic resonance imaging, while one case presented with prostatitis without abscess formation. Prostate-specific antigen levels were elevated over 20 ng/mL in all three measured cases. All patients were treated successfully with prolonged antibiotic therapy (28–39 days) without surgical drainage. Notably, all three abscess cases were successfully managed with fluoroquinolone-based combination therapy, highlighting its potential role in the management of prostatic abscesses. Three of four isolates were submitted for molecular investigations. All isolates harbored exoT and exoY, whereas exoU was absent. Biofilm-associated genes were detected in two cases, but not in the remaining case. Our findings suggested that P. aeruginosa strains carrying T3SS genes (exoT and exoY) potentially develop prostatic infections, independent of biofilm-associated genes. Host and iatrogenic factors, such as catheter manipulation, may play more critical roles in the development of prostatic pathology than strain-specific determinants. Assessment of prostate-specific antigen levels and early imaging may facilitate appropriate diagnosis and effective management when P. aeruginosa is detected as a cause of CAUTI.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1758-59021812025A Procedural Transhiatal Approach for the Thoracic Para‐Aortic Lymph Node: A Case Reporte70066ENMasashiHashimotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasushigeTakedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHijiriMatsumotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentoKawasakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoyoshiKunitomoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaoakiMaedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeTanabeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe thoracic posterior para-aortic lymph node (TPAN) is classified as an extra-regional lymph node in esophageal cancer, with metastasis indicating poor prognosis. However, some cases with suspected TPAN metastasis may benefit from esophagectomy with lymph node dissection, including TPAN. This report presents the case of a 58-year-old man with upper thoracic esophageal squamous cell carcinoma and suspected simultaneous TPAN metastasis who underwent neoadjuvant chemotherapy followed by thoracoscopic subtotal esophagectomy and procedural transhiatal TPAN dissection. This transhiatal approach provided direct access to the lymph node without additional thoracic incisions, ensuring safe resection in coordination with the assistant and following anatomical landmarks systematically. Pathological examination showed a false-positive TPAN finding, though the patient later developed distant recurrence. Compared with conventional approaches, this transhiatal technique allows for procedural and reproducible lymphadenectomy while minimizing respiratory burden. This case highlights the feasibility of a transhiatal approach for TPAN dissection.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2772-5723522026Feasibility and Diagnostic Utility of Mucosal T-Cell Flow Cytometry for Intestinal Graft-Versus-Host Disease100820ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakumiKondoDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDaisukeEnnishiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNobuharuFujiiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMaiHiramatsuDivision of Medical Support, Okayama University HospitalArakiHirabataDivision of Medical Support, Okayama University HospitalTakahideTakahashiDivision of Medical Support, Okayama University HospitalTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground and Aims: Timely diagnosis of intestinal complications after hematopoietic stem cell transplantation (HSCT), including graft-versus-host disease (GVHD), transplant-associated thrombotic microangiopathy, and cytomegalovirus infection, is essential for appropriate management. This study evaluated whether mucosal T-cell profiling from endoscopic biopsies could support the diagnosis of these post-transplant conditions.<br>
Methods: We prospectively analyzed 58 intestinal biopsy specimens from 21 post-HSCT patients. Paired samples were obtained from the stomach and duodenum during upper endoscopy and from the ileum and large intestine during colonoscopy. Lymphocytes were isolated from each specimen and analyzed using flow cytometry. These data were integrated with those of a previously collected cohort (35 patients, 51 samples) for comparative immunophenotypic analysis across histologically defined groups.<br>
Results: Duodenal biopsies yielded more lymphocytes than did gastric biopsies (mean ± standard deviation: 532 ± 823 vs 233 ± 392 cells; P = .070), with comparable yields between the ileum and colon. Among 41 evaluable cases, the CD56+:CD3+ ratio was significantly lower in patients with GVHD (5.5 ± 2.2%) than in those with nonspecific or no inflammation (28.4 ± 16.3%; P = .006). A cutoff value of <11% provided 85.7% sensitivity and 83.3% specificity for diagnosing GVHD (area under the curve = 0.91).<br>
Conclusion: Mucosal T-cell profiling using endoscopic biopsies is feasible and may aid in the diagnosis of GVHD after HSCT. A decreased CD56+:CD3+ ratio is a promising marker for distinguishing GVHD from other post-transplant intestinal conditions.No potential conflict of interest relevant to this article was reported.American Society for Clinical InvestigationActa Medica Okayama2379-370810242025Enhancement of drug delivery through fibroblast activation protein–targeted near-infrared photoimmunotherapye195776ENSeitaroNishimuraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceTasukuMatsumotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceYasushigeTakedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceTatsuyaTakahashiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceHijiriMatsumotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceKentoKawasakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceHotakaKawaiDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceTomoyoshiKunitomoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceMasaakiAkaiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceTerukiKobayashiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceNoriyukiNishiwakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceHajimeKashimaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceTakuyaKatoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceSatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceShunsukeTanabeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceToshiakiOharaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceHiroshiTazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceYasuhiroShirakawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencePeter L.ChoykeMolecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIHHisatakaKobayashiMolecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIHToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceThe tumor microenvironment plays a key role in cancer progression and therapy resistance, with cancer-associated fibroblasts (CAFs) contributing to desmoplasia, extracellular matrix (ECM) remodeling, and elevated interstitial fluid pressure, all of which hinder drug delivery. We investigated fibroblast activation protein–targeted (FAP-targeted) near-infrared photoimmunotherapy (NIR-PIT) as a strategy to improve drug penetration in CAF-rich tumors. In clinical esophageal cancer samples, FAP expression strongly correlated with increased collagen I, hyaluronic acid, and microvascular collapse. CAF-rich 3D spheroids demonstrated elevated ECM deposition and significantly impaired drug uptake compared with CAF-poor models. FAP-targeted NIR-PIT selectively reduced CAFs, reduced ECM components, and restored drug permeability. In vivo, FAP-targeted NIR-PIT enhanced the accumulation of panitumumab and Abraxane in CAF-rich tumors and improved antitumor efficacy when combined with chemotherapy. These findings highlight FAP-targeted NIR-PIT as a promising therapeutic approach to remodel the tumor stroma and overcome drug resistance in desmoplastic solid tumors.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1347-90322025Genomic Profiling of Pediatric Solid Tumors With a Dual DNA/RNA Panel: JCCG-TOP2 StudyENKayokoTaoDepartment of Pediatrics, National Cancer Center HospitalTakakoYoshiokaDepartment of Pathology, National Center for Child Health and DevelopmentMihoKatoDepartment of Childhood Cancer Data Management, National Center for Child Health and DevelopmentKazuyukiKomatsuDepartment of Pediatrics, Hamamatsu University School of MedicineShinichiTsujimotoDepartment of Pediatrics, Yokohama City UniversityKenichiSakamotoDepartment of Pediatrics, Shinshu University School of MedicineKazukiTanimuraDepartment of Pediatrics, National Cancer Center HospitalMinakoSugiyamaDepartment of Pediatrics, National Cancer Center HospitalMasahiroSekiguchiDepartment of Pediatrics, The University of TokyoYoshikoNakanoDepartment of Pediatrics, The University of TokyoYoshihiroOtaniDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasushiYatabeDepartment of Diagnostic Pathology, National Cancer Center HospitalAkihikoYoshidaDepartment of Diagnostic Pathology, National Cancer Center HospitalHajimeOkitaDepartment of Pathology, Keio University School of MedicineJunkoHiratoDepartment of Pathology, Public Tomioka General HospitalKenichiKohashiDepartment of Pathology, Graduate School of Medicine, Osaka Metropolitan UniversityYukichiTanakaDepartment of Pathology, Kanagawa Children's Medical CenterShinjiKohsakaDivision of Cellular Signaling, National Cancer Center Research InstituteTakashiKuboDepartment of Clinical Genomics, National Cancer Center Research InstituteKunikoSunamiDepartment of Laboratory Medicine, National Cancer Center HospitalMakotoHirataDepartment of Genetic Medicine and Services, National Cancer Center HospitalShuichiTsutsumiGenome Science & Medicine Division, Research Center of Advanced Science and Technology, The University of TokyoHiroyukiAburataniGenome Science & Medicine Division, Research Center of Advanced Science and Technology, The University of TokyoKatsuyoshiKohDepartment of Hematology and Oncology, Saitama Children's Medical CenterMasahiroHirayamaDepartment of Pediatrics, Mie University Graduate School of MedicineShuheiKarakawaDepartment of Pediatrics, Hiroshima University HospitalYukayoTerashitaDepartment of Pediatrics, Hokkaido University HospitalHiroyukiFujisakiDepartment of Pediatric Hematology and Oncology, Osaka City General HospitalTakeshiYagiOkinawa Prefectural Nanbu Medical Center & Children's Medical CenterAkihiroYonedaDepartment of Pediatric Surgery, National Center for Child Health and DevelopmentShinjiMochizukiDepartment of Pediatrics, National Center for Global Health and Medicine, Japan Institute for Health SecurityHiroyukiShichinoDepartment of Pediatrics, National Center for Global Health and Medicine, Japan Institute for Health SecurityTatsuyaSuzukiDepartment of Hematology, National Cancer Center HospitalTetsuyaTakimotoDepartment of Childhood Cancer Data Management, National Center for Child Health and DevelopmentKoichiIchimuraDepartment of Pathology, Kyorin University Faculty of MedicineChitoseOgawaDepartment of Pediatrics, National Cancer Center HospitalKimikazuMatsumotoChildren's Cancer Center National Center for Child Health and DevelopmentHitoshiIchikawaDepartment of Clinical Genomics, National Cancer Center Research InstituteMotohiroKatoDepartment of Pediatrics, The University of TokyoTo develop an optimized genomic medicine platform for pediatric cancers, a nationwide cancer genome profiling project was conducted from January 2022 to February 2023 in collaboration with the Japan Children's Cancer Group. This prospective observational study analyzed matched blood and FFPE tumor samples from patients aged 0–29 years with solid tumors. Genomic analysis used the TOP2 hybrid capture–enrichment system, targeting 737 and 455 genes in the DNA and RNA panels, along with allele-specific genome copy number alterations. A total of 210 patients from 50 institutions were enrolled across Japan (median age, 8 years; range, 0–25). Of these, 154 (77%) were enrolled at diagnosis or during/after initial treatment and 56 (27%) at disease progression or relapse. The TOP2 findings had great benefits in clarifying the diagnosis of pediatric solid tumors. Among the 204 patients with genomic results, 147 (72%) had potentially actionable findings, including diagnostic, prognostic, and therapeutic findings in 111 (54%), 61 (30%), and 64 (31%), respectively. Oncogenic fusions were noted in 45 (23%) patients. A copy number alteration was identified in at least one genomic region in 170 (83%) patients. Two patients exhibited a high tumor mutation burden. Seventeen (8%) patients harbored a germline pathogenic/likely pathogenic variant in cancer-predisposing genes. This study highlighted the feasibility of implementing a nationwide precision medicine platform and the clinical utility of the TOP2 system for pediatric cancers. The results support the integration of genomic data into the standard clinical care of pediatric patients with cancer, both at diagnosis and at relapse.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2467-981X102025Favorable outcomes of epilepsy with gait-induced seizures after resection of the unilateral supplementary motor area489492ENSatoshiKodamaDepartment of Neurology, Graduate School of Medicine, The University of TokyoNaotoKuniiDepartment of Neurosurgery, Jichi Medical UniversityYuichiroShirotaDepartment of Neurology, Graduate School of Medicine, The University of TokyoTakuseiChouDepartment of Neurology, Graduate School of Medicine, The University of TokyoMizuhoKawaiDepartment of Neurology, Graduate School of Medicine, The University of TokyoSeijiroShimadaDepartment of Neurosurgery, Graduate School of Medicine, The University of TokyoMeikoMaedaDepartment of Neurology, Graduate School of Medicine, The University of TokyoHiroyukiIshiuraDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiHamadaDepartment of Neurology, Graduate School of Medicine, The University of TokyoMasakoIkemuraDepartment of Pathology, Graduate School of Medicine, The University of TokyoYukoSaitoDepartment of Neuropahtology (Brain Bank for Aging Research), Tokyo Metropoliran Institute for Geriatrics and GerontologyNaokiAkamatsuDepartment of Neurology, International University of Health and Walfare Narita HospitalTairaUeharaDepartment of Neurology, International University of Health and Walfare Narita HospitalNobuhitoSaitoDepartment of Neurosurgery, Graduate School of Medicine, The University of TokyoTatsushiTodaDepartment of Neurology, Graduate School of Medicine, The University of TokyoBackground: Gait-induced seizures are a rare manifestation of reflex epilepsy. Pathophysiology of this phenomenon has not been fully understood.<br>
Case presentation: A 28-year-old woman presented with a long history of “falls” following paroxysmal bilateral leg stiffness triggered by walking. Scalp electroencephalogram (EEG) revealed low-amplitude rhythmic beta activity, maximal at the Cz electrode, during these events. Magnetoencephalography demonstrated repetitive sharp waves source-localized to the right primary motor cortex. Multiple anti-seizure medications failed to improve her symptoms; however, the clinical manifestation was consistent with epilepsy with gait-induced seizures. Intracranial subdural EEG recording was performed and confirmed ictal activity originating from the right supplementary motor area. Resection of this area resulted in complete resolution of her symptoms.<br>
Discussion: This is the first reported case of successful resective surgery for epilepsy with gait-induced seizure. Brain networks involving cortical regions responsible for the initiation or execution of walking presumably played a key role in the generation of gait-induced seizures. Careful assessment using non-invasive neurophysiological studies facilitated accurate diagnosis, successful intracranial recordings, and effective resective surgery.No potential conflict of interest relevant to this article was reported.Informa UK LimitedActa Medica Okayama2167-84212025Novel in-frame duplication variant of SOD1 in a Japanese family with familial amyotrophic lateral sclerosisENMasanoriNakajimaDepartment of Neurology, Kyorin University School of MedicineHiroyaNaruseDepartment of Neurology, Graduate School of Medicine, The University of TokyoYuichiRikuDepartment of Neuropathology, Institute for Medical Science of Aging, Aichi Medical UniversityKunihiroUedaDepartment of Neurology, Graduate School of Medicine, The University of TokyoTakashiMatsukawaDepartment of Neurology, Graduate School of Medicine, The University of TokyoJunMitsuiDepartment of Neurology, Graduate School of Medicine, The University of TokyoYoshitsuguNakamuraDivision of Neurology, Department of Internal Medicine IV, Osaka Medical and Pharmaceutical UniversityShimonIshidaDivision of Neurology, Department of Internal Medicine IV, Osaka Medical and Pharmaceutical UniversityTakashiYamadaDepartment of Pathology, Osaka Medical and Pharmaceutical UniversityNaokiMoroDepartment of Neurology, Kyorin University School of MedicineNaokiKotsukiDepartment of Neurology, Kyorin University School of MedicineKentaroNagaiDepartment of Neurology, Kyorin University School of MedicineShin-ichiTokushigeDepartment of Neurology, Kyorin University School of MedicineAyumiUchiboriDepartment of Neurology, Kyorin University School of MedicineChizukoOishiDepartment of Neurology, Kyorin University School of MedicineHiroyukiYabataDepartment of Neurology, Shiga University of Medical ScienceMakotoUrushitaniDepartment of Neurology, Shiga University of Medical ScienceYasushiIwasakiDepartment of Neuropathology, Institute for Medical Science of Aging, Aichi Medical UniversityHiroyukiIshiuraDepartment of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTatsushiTodaDepartment of Neurology, Graduate School of Medicine, The University of TokyoShojiTsujiDepartment of Neurology, Graduate School of Medicine, The University of TokyoYaekoIchikawaDepartment of Neurology, Kyorin University School of MedicineObjectives: To analyze the cases of a family with a novel in-frame duplication variant (NM_000454.5:c.357_357 + 2dup, p.Val120dup) of SOD1 and a structural model of the mutated SOD1 protein. Methods: The clinical profiles of three patients in the family were analyzed, including the neuropathological findings of the proband’s mother. Genetic analyses were conducted for three patients. cDNA and in silico structural analyses were performed to evaluate the effects of duplication variants on the structure of SOD1. Results: The clinical features of the patients included predominant involvement of the lower motor neurons, asymmetric onset of motor symptoms in the lower limbs, and a relatively rapid progression of muscular weakness and respiratory insufficiency. Neuropathological findings revealed severe loss of spinal cord motor neurons, and immunohistochemistry using an anti-misfolded SOD1 antibody revealed aggregates in the spinal cord. Genetic analyses revealed a c.357_357 + 2dup at the exon 4–intron 4 boundary of SOD1 in three patients. cDNA analysis of the proband suggested the presence of a valine (p.Val120dup) duplication in the heterozygous state, and the SOD1 transcript level showed no significant differences from those of healthy controls. In silico structural analyses predicted that p.Val120dup could affect the structure of the β-barrels and copper ion binding site of SOD1, suggesting an abnormal conformation of SOD1 that is predicted to interfere with the binding of copper ions. Conclusion: We identified a novel in-frame duplication variant in the C-terminus of β7 of SOD1. This genotype–structure–phenotype study of SOD1 provides valuable insights into disease-causing mechanisms.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7962025MRI Images of a Case of Adenocarcinoma, Human Papillomavirus-Independent, Mesonephric Type, of the Uterine Cervix463468ENYudaiAsanoDepartment of Radiology, Okayama University HospitalChikaNishiharaDepartment of Radiology, Okayama University HospitalTakahiroKitayamaDepartment of Radiology, Okayama University HospitalNanakoOkawaDepartment of Radiology, Okayama University HospitalSatokoMakimotoDepartment of Radiology, Okayama University HospitalFumiyoHigakiDepartment of Radiology, Okayama University HospitalKatsuhideKojimaDepartment of Radiology, Okayama University HospitalHanakoSugiharaDepartment of Obstetrics and Gynecology, Okayama University HospitalNaoyukiIdaDepartment of Obstetrics and Gynecology, Okayama University HospitalHiroyukiYanaiDepartment of Pathology, Okayama University HospitalTakaoHirakiDepartment of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityCase Report/10.18926/AMO/69850We present a case of a woman in her 70s who was diagnosed with mesonephric adenocarcinoma of the uterine cervix, following biopsy and surgery. Preoperative MRI revealed a 7-cm, well-defined circumferential cervical mass with left lateral wall predominance, bulging into the uterine cavity and vagina. The lesion showed intermediate signal intensity on T2-weighted images, diffusion restriction, and early contrast enhancement weaker than that of the myometrium, followed by washout on contrast-enhanced imaging. The circumferential growth pattern with the lateral wall predominance and its imaging characteristics may suggest this rare entity be routinely included in the differential diagnosis of cervical cancers.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7962025Exacerbation of Proteinuria in a Patient with Behçet’s Disease and IgA Nephropathy Following Colchicine Discontinuation457461ENTomohikoAsakawaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYuKatayamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYoshimasaSakurabuDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKatsuyoshiKatayamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroOnishiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHidemiTakeuchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKeikoTanakaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesRyokoUmebayashiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesRikaTakemotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesCase Report/10.18926/AMO/69849This case involves a 23-year-old male who was diagnosed with Behçet’s disease 5 years ago and managed with colchicine. Two months ago, he underwent renal biopsy due to abnormal urinalysis and kidney dysfunction, leading to a diagnosis of IgA nephropathy. He subsequently underwent tonsillectomy followed by glucocorticoid pulse therapy. However, after the tonsillectomy, discontinuing colchicine led to increased proteinuria, despite the glucocorticoid pulse therapy. Upon reintroducing colchicine, urinary protein excretion decreased, achieving incomplete remission. These findings suggest that colchicine may be effective in decreasing proteinuria in patients with Behçet’s disease complicated by IgA nephropathy.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2399-3642812025Single-cell and spatial transcriptomic characterization of pulmonary pleomorphic carcinoma1773ENAtsushiMatsuokaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShutaTomidaMasayoshiOhkiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyaHisamatsuDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyotaFujiwaraDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoseiIshimuraDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyunosukeFujiiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoakiHigashiharaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaohiroHayashiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroOkadaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoYoshichikaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumiakiMukoharaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMaoYoshikawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYumaFukumotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuakiTomiokaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinTanakaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentarohMiyoshiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikioOkazakiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYusukeOtaniDepartment of Pathology, Beth Israel Deaconess Medical CenterAtsushiTanakaDepartment of Pathology, Beth Israel Deaconess Medical CenterHirofumiInoueCenter for Comprehensive Genomic Medicine, Okayama University HospitalYosukeTogashiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHidetakaYamamotoDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeEnnishiCenter for Comprehensive Genomic Medicine, Okayama University HospitalShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPulmonary pleomorphic carcinoma (PPC) is a rare subtype of lung cancer that comprises both epithelial and sarcomatoid components. The molecular basis of PPC, including the cellular dynamics of its components, remains largely unknown. To elucidate potential therapeutic targets for PPC, we perform a multi-omics analysis incorporating digital spatial profiling and single-cell RNA sequencing (scRNA-seq). PPC exhibits diverse driver gene alterations, including MET exon 14 skipping mutation (METex14) and ALK fusion. In spatial transcriptomics, MET gene and protein are overexpressed exclusively within the epithelial component and not in the sarcomatoid component, even in patients harboring METex14. Epithelial-mesenchymal transition (EMT)-related transcriptional changes, along with extracellular matrix (ECM) remodeling between the epithelial and sarcomatoid components, are observed. scRNA-seq identifies cell populations within the epithelial component that contribute to the malignant transformation and differentiation of the sarcomatoid component. They are characterized by an intermediate EMT state with ECM remodeling signature, suggesting their potential as novel therapeutic targets for PPC.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2468-2942452025Neoadjuvant FOLFOXIRI for locally advanced rectal cancer: A retrospective analysis focusing on long-term anal preservation101049ENRyoheiShojiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFuminoriTeraishiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiMatsumiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYusukeYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuhikoKanayaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKunitoshiShigeyasuDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshitakaKondoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshikoMoriDepartment of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical UniversityShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTo investigate the safety and efficacy of FOLFOXIRI as neoadjuvant chemotherapy (NAC) for locally advanced rectal cancer (LARC). The outcomes of preoperative and perioperative treatments, as well as long-term outcomes, were retrospectively compared between 26 patients who underwent FOLFOXIRI as NAC for LARC with cT3–4 and/or N+ at our institute between 2015 and 2022, and 31 patients with LARC who underwent neoadjuvant chemoradiotherapy (CAPOX-RT) at our institute between 2011 and 2022. Grade 3 or higher adverse events due to neoadjuvant treatment were significantly more common in the FOLFOXIRI group (11 cases, 42.3 %) than in the CAPOX-RT group (3 cases, 9.7 %), and most of these were neutropenia. Based on the postoperative pathological findings, the complete response rate was significantly lower in the FOLFOXIRI group (1 case, 3.8 %) than in the CAPOX-RT group (7 cases, 22.6 %), but there were no significant differences in the R0 resection rate, survival rate, or relapse-free survival rate. In the CAPOX-RT group, 17 patients (54.8 %) had anal preservation, and during the observation period, 4 patients required stoma construction due to loss of anal function in the late stage. In contrast, in the FOLFOXIRI group, there were no cases of loss of anal function among the 20 patients (76.9 %) who had anal preservation. FOLFOXIRI as NAC requires caution regarding hematological toxicity, but it can be an effective treatment option for patients with LARC who wish to preserve their anus.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1424-39032572025Efficacy of diagnosing intraductal papillary mucinous neoplasm with mural nodules by contrast-enhanced endoscopic ultrasound using time–intensity curve analysis with a new support program: A multicenter retrospective study (with video)11031108ENKazuyaMiyamotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalDaisukeUchidaDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalYosukeSaragaiDepartment of Internal Medicine, Fukuyama City HospitalTsuneyoshiOgawaDepartment of Internal Medicine, Fukuyama City HospitalToruUekiDepartment of Internal Medicine, Fukuyama City HospitalKeiHaradaDepartment of Gastroenterology and Hepatology, Okayama University HospitalNaoHattoriDepartment of Gastroenterology and Hepatology, Okayama University HospitalTaisukeObataDepartment of Gastroenterology and Hepatology, Okayama University HospitalRyosukeSatoDepartment of Gastroenterology and Hepatology, Okayama University HospitalAkihiroMatsumiDepartment of Gastroenterology and Hepatology, Okayama University HospitalHiroyukiTerasawaDepartment of Gastroenterology and Hepatology, Okayama University HospitalYukiFujiiDepartment of Gastroenterology and Hepatology, Okayama University HospitalShigeruHoriguchiDepartment of Gastroenterology and Hepatology, Okayama University HospitalKoichiroTsutsumiDepartment of Gastroenterology and Hepatology, Okayama University HospitalSoichiroUemotoBusiness Strategy Division, Ryobi Systems Co., Ltd.TakayoshiTanimotoBusiness Strategy Division, Ryobi Systems Co., Ltd.AkimitsuOhtoBusiness Strategy Division, Ryobi Systems Co., Ltd.MotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University HospitalBackground/objectives: Preoperative diagnosis of the pathological grade of intraductal papillary mucinous neoplasms (IPMN) is challenging. This study aimed to evaluate the accuracy of contrast-enhanced endoscopic ultrasound (CE-EUS) using time–intensity curve (TIC) analysis with a newly developed support program to differentiate between low-grade dysplasia (LGD) and high-grade dysplasia (HGD)/invasive carcinoma (IC) in IPMN.<br>
Methods: This study retrospectively analyzed 32 patients who underwent CE-EUS using the support program for TIC analysis and IPMN resection (LGD: 17, HGD/IC: 15) at two medical centers. The TIC parameters of mural nodules (MN) were compared between the LGD and HGD/IC groups, and the diagnostic accuracies of the TIC parameters were evaluated.<br>
Results: The MN/pancreatic parenchyma contrast ratio was significantly higher in the HGD/IC group than in the LGD group (1.53 vs. 0.99; P < 0.0001), and the diagnostic abilities of the contrast ratio were as follows: sensitivity, 67 %; specificity, 100 %; and accuracy, 84 %. There were no differences in the echo intensity reduction rate of the MNs between the two groups (HGD/IC, 61.6 vs. 61.2, 0.99; P = 0.421), and the diagnostic abilities of the reduction rate were as follows: sensitivity, 93 %; specificity, 41 %; and accuracy, 66 %.<br>
Conclusions: The contrast ratio calculated using TIC analysis with the support program is potentially useful for differentiating between IPMNs with LGD and those with HGD/IC.No potential conflict of interest relevant to this article was reported.Japanese Society of Internal MedicineActa Medica Okayama0918-291864232025Remarkable Efficacy of Capmatinib in a Patient with Cancer of Unknown Primary with MET Amplification34603464ENTakaakiTanakaDepartment of Respiratory Medicine, Okayama University HospitalGoMakimotoDepartment of Respiratory Medicine, Okayama University HospitalRyoheiSumiiDepartment of General Internal Medicine, NHO Fukuyama Medical CenterRikaOmoteDepartment of Pathology, NHO Fukuyama Medical CenterYayoiAndoClinical Research Support Office, National Cancer Center HospitalKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalEikiIchiharaCenter for Clinical Oncology, Okayama University HospitalKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalYoshinobuMaedaDepartment of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasahiroTabataCenter for Clinical Oncology, Okayama University HospitalThis case report describes a 70-year-old female with cancer of unknown primary origin (CUP) who exhibited multiple distant lymph node metastases. Despite conventional chemotherapy (carboplatin and paclitaxel) and immunotherapy (nivolumab), disease progression was noted. Genomic profiling revealed MET amplification, leading to the administration of capmatinib, a selective MET tyrosine kinase inhibitor. The patient experienced substantial tumor reduction with dose adjustments due to adverse effects, indicating the potential efficacy of capmatinib in treating CUP with MET amplification.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0167-4889187322026SPRED2 controls the severity of cisplatin-induced acute kidney injury by inhibiting ERK activation and TNFα production in mice120091ENXuYangDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJialiHeDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTongGaoDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasayoshiFujisawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiakiOharaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySteven L.KunkelDepartment of Pathology, University of Michigan Medical SchoolTeizoYoshimuraDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAkihiroMatsukawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityCisplatin is an effective chemotherapeutic agent used to treat solid tumors, but its clinical use is limited by acute kidney injury (AKI), in which ERK signaling plays a crucial role. Here, we investigated whether Sprouty-related EVH1 domain-containing protein 2 (SPRED2), an endogenous inhibitor of the Ras/Raf/ERK pathway, protects against cisplatin-induced AKI. Spred2−/− mice showed more severe renal injury and stronger ERK activation than wild-type (WT) mice, whereas pretreatment with the MEK inhibitor U0126 markedly attenuated the injury. In HK-2 cells (proximal tubular cells), SPRED2 knockdown enhanced cisplatin-induced apoptosis and caspase-3 activation, accompanied by decreased Bcl-2 expression. Spred2−/− kidneys displayed increased macrophage infiltration and elevated Tnfα, Il1b, and Ccl2 expression. Neutralization of TNFα with anti-TNFα antibody ameliorated renal injury and reduced the levels of Il1b and Ccl2 mRNA in Spred2−/− mice. In vitro, TNFα slightly decreased the viability of control and SPRED2 knockdown HK-2 cells without cisplatin treatment, but the decreased viability was augmented in SPRED2 knockdown cells by cisplatin. Immunohistochemistry revealed that macrophages were the predominant TNFα-positive cell population. Bone marrow–derived macrophages from Spred2−/− mice produced higher levels of TNFα in response to cisplatin compared with control cells, and this increase was markedly suppressed by U0126.<br>
These findings indicate that endogenous SPRED2 protects kidneys from cisplatin-induced AKI by limiting ERK activation, tubular apoptosis, and TNFα-mediated inflammation.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1865-72572025Avoiding splenectomy in splenic sclerosing angiomatoid nodular transformation through endoscopic ultrasound-guided tissue acquisition: a 36-month follow-up case reportENTakakiOkuyamaDepartment of Internal Medicine, Tsuyama Chuo HospitalKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKosakuMorimotoDepartment of Internal Medicine, Tsuyama Chuo HospitalShogoKimuraDepartment of Internal Medicine, Tsuyama Chuo HospitalTakayoshiMiyakeDepartment of Pathology, Tsuyama Chuo HospitalTakuyaSatomiDepartment of Internal Medicine, Tsuyama Chuo HospitalKensukeTakeiDepartment of Internal Medicine, Tsuyama Chuo HospitalShogoInoueDepartment of Internal Medicine, Tsuyama Chuo HospitalRyutaTakenakaDepartment of Internal Medicine, Tsuyama Chuo HospitalA 48-mm splenic mass was incidentally discovered in a 78-year-old man upon computed tomography. Follow-up imaging at 12 months revealed enlargement to 60 mm, prompting endoscopic ultrasound-guided tissue acquisition with a 22-gauge needle. Histopathological analysis confirmed that it was a sclerosing angiomatoid nodular transformation. The patient was asymptomatic and had no hematologic abnormalities; therefore, splenectomy was not performed. After biopsy, the lesion regressed from 60 mm to 46 mm, possibly owing to hematoma formation or vascular disruption, and remained stable during 36 months of follow-up. Although splenectomy has been performed in most reported cases of sclerosing angiomatoid nodular transformation because of diagnostic uncertainty, a few recent reports have demonstrated that sclerosing angiomatoid nodular transformation can be diagnosed by endoscopic ultrasound-guided tissue acquisition, thereby avoiding splenectomy. This case highlights the diagnostic utility of endoscopic ultrasound-guided tissue acquisition and supports spleen-preserving management for biopsy-proven sclerosing angiomatoid nodular transformation.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1433-73982025A rare case of supratentorial ependymosarcoma harboring ZFTA::RELA fusionENYujiMatsumotoDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYasukiSurugaDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKaishiSatomiDepartment of Pathology, Faculty of Medicine, Kyorin UniversityYoheiInoueDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYasuhikoHattoriDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineJojiIshidaDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKazuhikoKurozumiDepartment of Neurosurgery, Hamamatsu University HospitalSumihitoNobusawaDepartment of Human Pathology, Gunma University School of MedicineJunkoHiratoDepartment of Pathology, Public Tomioka General HospitalTakehiroTanakaDepartment of Pathology, Okayama University HospitalHiroyukiYanaiDepartment of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKanaWashioDepartment of Pediatrics, Okayama University HospitalKoichiIchimuraDepartment of Pathology, Faculty of Medicine, Kyorin UniversityTomotsuguIchikawaDepartment of Neurosurgery, Kagawa Prefectural Central HospitalYoshihiroOtaniDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShotaTanakaDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineEpendymosarcoma is an exceedingly rare variant of ependymoma characterized by a mixture of ependymomatous and sarcomatous components. We report a case of supratentorial ependymosarcoma harboring a ZFTA::RELA fusion in a 10-year-old girl. Histologically, the tumor comprised an ependymomatous component resembling clear cell ependymoma and a sarcomatous component. ZFTA::RELA fusion was confirmed in both components. Genome-wide methylation profiling classified both components as supratentorial ependymoma, ZFTA fusion–positive by the German Cancer Research Center (DKFZ) CNS tumor classifier v12b8. However, their copy number alteration profiles were distinct. The ependymomatous component exhibited a gain of chromosome 1q and a loss of chromosomes 1p, 9, and 19q, while the sarcomatous component showed a loss of chromosome 14. These findings suggest that both components may have differentiated from a common precursor despite their distinct morphologies. The patient underwent gross total resection followed by adjuvant chemoradiotherapy and remains recurrence-free eight years post-treatment. Further investigation of additional cases is warranted to better understand the pathogenesis of this rare tumor.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818417102025Risk Stratification for the Prediction of Skeletal-Related Events in Patients With Bone Metastases From Non-small Cell Lung Cancere95808ENYoshihiroSakamotoDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEijiNakataDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasanoriHamadaDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshimiKatayamaDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinsukeSugiharaDepartment of Orthopedic Surgery, Shikoku Cancer CenterToshifumiOzakiDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSkeletal-related events (SREs) frequently occur in patients with bone metastases from non-small cell lung cancer (NSCLC). This study aimed to identify risk factors for SREs in patients with NSCLC. Based on these factors, we also aimed to stratify patients into subgroups to facilitate the assessment of SRE risk. This retrospective analysis used medical records of 139 patients with NSCLC bone metastases who received treatment at our institution between 2011 and 2014. The incidence of SREs was assessed, and SRE-free survival was analyzed using the Kaplan-Meier method. Clinical information collected at registration was assessed to identify factors associated with the onset of SREs within six months. Univariate analysis was performed using Fisher’s exact test, and multivariate analysis was performed using Cox regression. Of the 139 patients, 36 (26%) developed SREs after registration. The SRE-free survival rates were 80% and 64% at 6 and 12 months, respectively. The univariate and multivariate analyses revealed that the absence of epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangement (hazard ratio (HR): 4.51, 95% confidence interval (CI): 1.32-15.7, p = 0.017) and a lactate dehydrogenase (LDH) level ≥400 U/L (HR: 8.08, 95% CI: 1.78-36.6, p = 0.0067) were risk factors for SRE presentation within six months. Patients were classified into the following three subgroups: with EGFR mutation or ALK rearrangement and LDH level <400 U/L; without EGFR mutation or ALK rearrangement and LDH level <400 U/L; with/without EGFR mutation or ALK rearrangement and LDH level ≥400 U/L. The corresponding six-month SRE-free survival rates were 92%, 69%, and 34%, respectively, showing significant differences (p < 0.001). Close monitoring is recommended for patients with LDH levels ≥400 U/L in daily clinical practice, particularly with the help of the proficiency of orthopedic and radiological experts, to prevent complications such as pathological fractures and paraplegia.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2025High Prevalence of MYD88 and CD79B Mutations in Primary Sinonasal Diffuse Large B-Cell Lymphoma: Identification of an MCD-like SubtypeENFANGLIPENGGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1320-53583052025A Case of IgA Nephropathy With Membranoproliferative Glomerulonephritis-Like Featurese70057ENMiyuKanazawaOkayama University Medical SchoolKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoyaAokiOkayama University Medical SchoolMihiroSueDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiromasaMiyakeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaruhikoUchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiNakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesA 73-year-old man was referred due to the onset of nephrotic-range proteinuria. He had been diagnosed with rheumatoid arthritis 18 years prior and had achieved remission with treatment, including methotrexate and janus kinase (JAK) inhibitor. Although routine follow-ups had not revealed any urinary abnormalities, subsequent tests detected proteinuria and hematuria in the absence of infection or other symptoms. As the urinary abnormalities persisted, with a serum albumin decrease and proteinuria measuring 5.7 g/day, indicating nephrotic syndrome, the patient was referred to our hospital for further evaluation, and a renal biopsy was performed. Light microscopy revealed mesangial cell proliferation, endocapillary proliferation and double-contoured basement membranes. Immunofluorescence microscopy showed IgA-dominant deposits in both mesangial areas and glomerular capillary walls. Transmission electron microscopy demonstrated electron-dense deposits in the mesangium and subendothelial regions, leading to the diagnosis of membranoproliferative glomerulonephritis (MPGN)-type IgA nephropathy. Immunostaining with the Gd-IgA1 (galactose-deficient IgA1)-specific antibody (KM55) was positive, consistent with the diagnosis. Following the initiation of steroid therapy, proteinuria rapidly decreased, achieving complete remission within 5 months. IgA nephropathy with MPGN-like features often presents as nephrotic syndrome, differing from the typical pathological and clinical presentation of IgA nephropathy, making differentiation from secondary MPGN and other diseases sometimes challenging. This case suggests that KM55 staining may offer additional information in differentiating atypical IgA nephropathy with non-classical pathological features.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0929-19032025p53-armed oncolytic adenovirus induces apoptosis in pancreatic cancer-associated stellate cells via macropinocytosisENTakeyoshiNishiyamaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiTazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuoNagaiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoheiShojiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshinoriKajiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaoyukiHashimotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYosukeTakahashiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiakiOharaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyuichiYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuzoUmedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyoshi Y.TanakaDepartment of Pharmaceutical Biomedicine, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health SystemsMitsunobu R.KanoDepartment of Pharmaceutical Biomedicine, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health SystemsAtsushiMasamuneDivision of Gastroenterology, Tohoku University Graduate School of MedicineYasuoUrataOncolys BioPharma, Inc.ShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPancreatic ductal adenocarcinoma (PDAC)-associated pancreatic stellate cells (PSCs) promote PDAC tumor progression. Notably, PDAC tumors display enhanced macropinocytosis, resulting in enhanced uptake of extracellular particles, including nutrients and viruses. We previously demonstrated the therapeutic potential of telomerase-specific oncolytic adenoviruses OBP-301 and p53-armed OBP-702 against human PDAC cells. However, it remains unclear whether macropinocytosis promotes the virus sensitivity of PDAC-associated PSCs. Here, we show that PSCs activated by human PDAC cells (Panc-1 and BxPC-3) exhibit enhanced sensitivity to wild-type and oncolytic adenoviruses via enhanced macropinocytosis. The virus sensitivity of PSCs was analyzed for the infectivity, replication, and cytopathic activity of wild-type and oncolytic adenoviruses. PDAC-associated PSCs were more sensitive to wild-type and oncolytic adenoviruses than were control PSCs; this sensitivity was mediated by activation of macropinocytosis. In three-dimensional (3D) culture models, p53-armed OBP-702 decreased the viability of PDAC-associated PSCs more strongly than did non-armed OBP-301, reflecting induction of p53-mediated apoptosis. Co-inoculation of PSCs enhanced the growth of PDAC tumors, an effect that was attenuated by OBP-702-mediated p53 activation in the tumor stroma. Our results suggest that p53-armed oncolytic adenovirus OBP-702 eliminates PDAC-associated PSCs via enhancement of macropinocytosis-mediated virus entry and induction of p53-mediated apoptosis.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2073-440914182025Effect of Oral Peritumoral Tissue on Infiltration and Differentiation of Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma1481ENTianyanPiaoDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKiyofumiTakabatakeDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakumaArashimaDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYuluZhaoDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHotakaKawaiDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHtoo ShweEainDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYaminSoeDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityZin ZinMinDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeisukeNakanoDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHitoshiNagatsukaDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThe recruitment of tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) of oral squamous carcinoma (OSCC) affects significant cancer invasion; however, in the normal host tissue that is located in the cancer’s surrounding area, this is poorly investigated. In this study, we examined the impact of gingival connective tissue cells (GCTCs) and periodontal ligament cells (PDLCs), which are involved in the invasive pathway of OSCC, on oral cancer invasion via TAMs recruitment. Transwell (migration) assays were used to examine the effects of GCTCs and PDLCs on the migration of macrophages, which indicated that the interaction between GCTCs and HSC-2/HSC-3 (human oral squamous cell carcinoma cell line) promoted the recruitment of macrophages, whereas the interaction between PDLCs was inhibited. An indirect co-culture was then used to examine the effects of GCTCs and PDLCs on the differentiation of macrophages, which indicated that the interaction between GCTCs enhanced their ability to transform into M2-type macrophages. Furthermore, the effects of GCTCs and PDLCs on the recruitment of CD45(+) monocytes, F4/80(+) M0 macrophages, iNOS(+) M1 macrophages, and CD163(+) M2 TAMs were assayed by immunohistochemistry. The results revealed that the interaction between GCTCs and HSC-2/HSC-3 promoted the infiltration of CD45(+) monocytes, F4/80(+) M0 macrophages, and CD163(+) M2 TAMs, whereas the PDLCs inhibited it, while their effect on iNOS(+) M1 macrophages was limited. Collectively, the GCTCs contributed to the infiltration of TAMs into the TME of OSCC cells, whereas the PDLCs exerted an inhibitory effect. These findings suggest a potential regulatory mechanism underlying the progression of OSCC.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2072-669417172025Refining the Role of Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma2770ENKiyofumiTakabatakeDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPiaoTianyanDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakumaArashimaDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAnqiChangDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHotakaKawaiDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHtoo ShweEainDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYaminSoeDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityZin ZinMinDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasaeFujiiDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeisukeNakanoDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHitoshiNagatsukaDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIn the tumor microenvironment, various immune and stromal cells, such as fibroblasts and vascular endothelial cells, contribute to tumor growth and progression by interacting with cancer cells. Tumor-associated macrophages (TAMs) have attracted attention as major players in the tumor microenvironment. The origin of TAMs is believed to be the infiltration of monocytes derived from bone marrow progenitor cells into tumor tissues and their differentiation into macrophages, whereas tissue-resident macrophages derived from yolk sacs have recently been reported. TAMs infiltrating tumor tissues act in a tumor-promoting manner through immunosuppression, angiogenesis, and the promotion of cancer cell invasion. Reflecting the nature of TAMs, increased TAM invasion and TAM-specific gene expression in tumor tissues may be the new biomarkers for cancer. Moreover, new therapeutic strategies targeting TAMs, such as transformation into immunostimulatory macrophages, suppression of TAM infiltration, and promotion of phagocytosis, are being investigated, and many clinical trials are underway. As the origin and function of TAMs are further elucidated, TAM-targeted therapy is expected to become a new option for the immunotherapy of various cancers, including oral cancers.No potential conflict of interest relevant to this article was reported.Ivyspring International PublisherActa Medica Okayama1837-966416142025CXCR4 Inhibition Induces Tumor Necrosis by Selectively Targeting the Proliferating Blood Vessels in Oral Squamous Cell Carcinoma40554070ENYaminSoeDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama UniversityHotakaKawaiDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama UniversityHtoo ShweEainDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama UniversitySaoriYoshidaPreliminary Examination Room, Okayama University HospitalMay WathoneOoDepartment of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama UniversityZin ZinMinDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama UniversityKiyofumiTakabatakeDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama UniversityKeisukeNakanoDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama UniversityHitoshiNagatsukaDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama UniversityThe C-X-C chemokine receptor type 4 (CXCR4) is a G protein-coupled transmembrane receptor that contributes to tumor growth and angiogenesis. While prior studies have primarily focused on CXCR4 expression in cancer cells and its role in metastasis, a few have examined its involvement in tumor-associated vasculature. In this study, we reported for the first time that CXCR4 expression within the tumor vasculature is significantly associated with higher pathological grades of human oral squamous cell carcinoma (OSCC) (p<0.03). A previous study reported that inhibiting CXCR4 with AMD3100 induces tumor cell death and enhances the efficacy of the chemotherapeutic agent cisplatin. These findings suggest that CXCR4 is an important target for cancer treatment. However, the tumor vascular system is known to be heterogeneous within the tumor microenvironment (TME), which may influence the treatment outcomes. Therefore, this study aimed to explore the effect of CXCR4 antagonism on various blood vessels present within the oral squamous cell carcinoma (OSCC) tumor stroma. Although the efficiency of AMD3100 was not significant in MOC cancer cells, necrosis was induced in the TME when applied to a poorly differentiated OSCC model, highlighting the role of the TME. Notably, CXCR4 is found to be highly overlapped with CD105+ angiogenic tumor vessels among various vascular markers. Treatment with AMD3100 leads to a marked reduction in the CD105+ vessels and impairs the maturation of tumor micro-vessels, explaining the cause of observed necrosis. Thus, CXCR4 serves as a promising biomarker in OSCC, and its inhibition with AMD3100 offers the therapeutic potential, particularly in cases with advanced pathological grades.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2470-92391032025Decreased homovanillic acid and 5‐hydroxyindoleacetic acid levels in the cerebrospinal fluid of patients with Dravet syndrome with parkinsonism965970ENRyoSugiyamaDepartment of Child Neurology, National Center Hospital, National Center of Neurology and PsychiatryTakashiSaitoDepartment of Child Neurology, National Center Hospital, National Center of Neurology and PsychiatryAtsukoKatsumotoDepartment of Neurology, National Center Hospital, National Center of Neurology and PsychiatryShotaYonenoDepartment of Child Neurology, National Center Hospital, National Center of Neurology and PsychiatryTomoyukiAkiyamaDepartment of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University HospitalHirofumiKomakiDepartment of Child Neurology, National Center Hospital, National Center of Neurology and PsychiatryDravet syndrome (DS) is an early onset, developmental, and epileptic encephalopathy characterized by drug-resistant seizures and multiple comorbidities. It has been reported that in adulthood, it may be accompanied by parkinsonism, but the pathogenesis of this condition remains unclear. We performed dopamine transporter single-photon emission computed tomography (DAT SPECT) and measured monoamine metabolite levels in the cerebrospinal fluid (CSF) in two adult patients with DS who developed parkinsonism around the age of 30 years. DAT SPECT showed no abnormalities in either patient, whereas CSF tests revealed significant decreases in the levels of homovanillic and 5-hydroxyindoleacetic acids. One patient with severe symptoms was treated with levodopa–carbidopa, which improved parkinsonism manifestations. The other patient initiated treatment with a low dose and has been continuing the treatment without any reported side effects. In conclusion, CSF testing can detect a decrease in dopamine synthesis and may be useful in monitoring the efficacy of levodopa treatment in patients with DS and parkinsonism.<br>
Plain Language Summary: Dravet syndrome (DS) is an early onset, developmental, and epileptic encephalopathy. DS can lead to the development of parkinsonism in adulthood, a clinical syndrome characterized by tremor, slowed movements, and rigidity. Although parkinsonism is a significant issue for patients, its underlying pathology has not yet been elucidated. In this study, we confirmed that the levels of monoamine metabolites in the CSF were low in two patients, potentially shedding light on the pathology involved.No potential conflict of interest relevant to this article was reported.BioscientificaActa Medica Okayama2052-0573202512025Adult hypophosphatasia presenting with recurrent acute joint paine240121ENHayaoYoshidaDepartment of Diabetes and Endocrinology, Shiga General HospitalTakaakiMurakamiDepartment of Diabetes and Endocrinology, Shiga General HospitalAtsubumiOgawaDepartment of Rheumatology and Clinical Immunology, Kyoto University Graduate School of MedicineTakashiSunouchiDivision of Nephrology and Endocrinology, The University of Tokyo HospitalNaokoHidakaDivision of Nephrology and Endocrinology, The University of Tokyo HospitalNobuakiItoOsteoporosis Center, The University of Tokyo HospitalHiromiMurakamiDepartment of Genomic Medicine, Kyoto University Graduate School of MedicineHidenoriKawasakiDepartment of Genomic Medicine, Kyoto University Graduate School of MedicineTomoyukiAkiyamaDepartment of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsumiNakajimaDepartment of Diabetes and Endocrinology, Shiga General HospitalDaisukeYabeDepartment of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of MedicineTaizoYamamotoDepartment of Diabetes and Endocrinology, Shiga General HospitalHypophosphatasia (HPP) is a genetic disorder due to pathological variants in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP is typically associated with bone-related symptoms, such as bone deformity, fractures and bone pain in children, but can appear in adults with symptoms resembling arthritis. A 22-year-old male experienced repeated and severe sudden attacks of joint pain in the elbows and knees. Magnetic resonance imaging and joint ultrasonography showed joint effusions indicating chronic inflammation. Blood biochemical tests revealed a remarkably low serum ALP level, and repeated examination confirmed a sustained low ALP level; urine phosphoethanolamine, plasma inorganic pyrophosphate and plasma pyridoxal-5′-phosphate levels were elevated, raising concern for HPP. While the patient had no history of premature loss of primary teeth, fragility fractures, muscle weakness or abnormalities in growth, genetic testing revealed a likely pathogenic and a pathogenic heterozygous variant in the ALPL gene, i.e., c.979T>C (p.Phe327Leu) and c.1559del (p.Leu520Argfs), confirming HPP. Additional genetic testing of his parents showed a heterozygous c.1559del variant in his father and a heterozygous c.979T>C variant in his mother. A diagnosis of adult HPP due to compound heterozygous mutations was therefore confirmed. Enzyme replacement therapy with asfotase alfa was then introduced; no attacks of arthralgia occurred in the 1-year period since then. This case highlights the possibility of HPP in adults who present clinically with repeated joint symptoms and low serum ALP levels but without bone-related symptoms.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0007-10482025Efficacy of ciclosporin monotherapy in non-severe aplastic anaemia not requiring transfusions: Results from a multicentre phase II studyENKenIshiyamaDepartment of Hematology, Kanazawa University HospitalMasahideYamazakiDepartment of Internal Medicine, Keiju Medical CenterHiroyukiMaruyamaDepartment of Hematology, Kanazawa University HospitalNaokoHosonoDepartment of Hematology and Oncology, University of Fukui HospitalHirokiYamaguchiDepartment of Hematology, Nippon Medical SchoolNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalKazukiTanimotoDepartment of Hematology and Oncology, Japanese Red Cross Fukuoka HospitalHiroyukiSugiuraDepartment of Hematology, Chugoku Central Hospital of Japan Mutual Aid Association of Public School TeachersKensukeUsukiDepartment of Hematology, NTT Medical Center TokyoKenichiYoshimuraDepartment of Biostatistics and Health Data Science, Graduate School of Medical Science, Nagoya City UniversitySeishiOgawaDepartment of Pathology and Tumor Biology, Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto UniversityYuzuruKanakuraSumitomo HospitalItaruMatsumuraDepartment of Hematology and Rheumatology, Kindai University Faculty of MedicineKoichiAkashiDepartment of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical SciencesShinjiNakaoDepartment of Hematology, Kanazawa University HospitalThe efficacy of ciclosporin (CsA) to treat transfusion-independent non-severe aplastic anaemia (TI-NSAA) has not yet been systematically evaluated. We conducted a prospective trial in patients with TI-NSAA treated with CsA monotherapy. CsA (3.5 mg/kg/day) was administered to patients with TI-NSAA aged ≥16. The CsA dose was adjusted to maintain a blood CsA level of ≥600 ng/mL at 2 h post-administration. Blood cell counts were assessed after 8, 16 and 52 weeks of therapy. Thirty-two evaluable patients from 21 institutions were enrolled. The median age was 63.5 (range: 16–83) years. At 8 weeks, haematological improvement, with increases in haemoglobin (Hb) ≥1.5 g/dL (haematological improvement in erythrocytes [HI-E]) and platelet count ≥30 × 109/L (haematological improvement in platelets [HI-P]), was observed in 0/25 (0%) and 6/32 (19%) evaluable cases respectively. HI-E and HI-P occurred in 1/25 (4%) and 10/32 (31%) patients at 16 weeks, respectively, and at 52 weeks in 5/25 (20%) and 16/32 (50%) patients respectively. Nine grade 3 adverse events (AEs) occurred in six patients, but there were no grade ≥4 AEs. Ten of the 32 patients experienced grade 2 renal toxicity. Low-dose CsA is effective in TI-NSAA patients and demonstrates minimal renal toxicity. However, at least 16 weeks are necessary to adequately evaluate its efficacy.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0040-8166982026The vicious cycle between nutrient deficiencies and antibiotic-induced nutrient depletion at the host cell-pathogen interface: Coenzyme Q10 and omega-6 as key molecular players103224ENDarabGhadimiDepartment of Microbiology and Biotechnology, Max Rubner-InstitutSophiaBlömerFaculty of Medicine, Christian-Albrechts-University of KielAyselŞahi̇n KayaDepartment of Nutrition and Dietetics, Faculty of Health Sciences, Antalya Bilim UniversitySandraKrügerInstitute of Pathology, Kiel University, University Hospital, Schleswig-HolsteinChristophRöckenInstitute of Pathology, Kiel University, University Hospital, Schleswig-HolsteinHeinerSchäferLaboratory of Molecular Gastroenterology & Hepatology, Christian-Albrechts-University & UKSH Campus KielJumpeiUchiyamaDepartment of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityShigenobuMatsuzakiDepartment of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen UniversityWilhelmBockelmannDepartment of Microbiology and Biotechnology, Max Rubner-InstitutThe increasing prevalence of antibiotic resistance and pathological inflammation underscores the importance of understanding the underlying biochemical and immune processes that govern the host-pathogen interface. Nutrient deficiency, compounded by antibiotic-induced nutrient depletion, forms a vicious cycle of overt inflammation, contributing to bacterial toxin translocation in human inter-organ and intra-organs milieus. Coenzyme Q10 (CoQ10) and omega-6 linoleic acid (LA 18:2ω6) are integral to cellular membrane integrity and immune defense. However, the complex enzymatic steps at the host cell-pathogen interface remain poorly understood. This study is particularly timely, as it explores these knowledge gaps, which can inform the development of nutritional and therapeutic strategies that modulate or target these mechanisms. Using an infectious-inflamed cell co-culture model of the gut-liver axis, we exposed triple cell co-cultures of human intestinal epithelial cells (T84), macrophage-like THP-1 cells, and hepatic cells (Huh7) to linoleic acid-producing Lactobacillus casei (L. casei) and Pseudomonas aeruginosa strain PAO1 (PAO1). The cultures were incubated for 6 h in medium with or without ceftazidime antibiotic. PAO1 and L. casei exerted opposing effects on the secretion of Th1 cytokines IL-1β, IL-6, and the Th 2-type cytokine IL-10. Inoculation with PAO1 decreased CoQ10 and linoleic acid levels compared to uninfected controls. L. casei restored cellular health and biofunctionality impaired by PAO1, indicating its benefit to the host's well-being. The antibiotic ceftazidime exerted dual effects, alleviating PAO1 toxicity while marginally disrupting the beneficial effects of L. casei. Our results show how the vicious cycle of nutrient deficiency and antibiotic-induced nutrient loss reinforces pathological inflammation at the host cell-pathogen interface and highlights the need for more appropriate targeted antibiotic use that preserves essential nutrients like CoQ10 and omega-6 fatty acids. Inflammatory responses driven by opportunistic pathogens and LA-producing bacteria represent opposing immunometabolic pathways that may provide insights into novel approaches for treating infection and reducing antibiotic resistance.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1341-96252025Japanese society for cancer of the colon and rectum (JSCCR) guidelines 2024 for the clinical practice of hereditary colorectal cancerENKohjiTanakayaDepartment of Surgery, National Hospital Organization Iwakuni Clinical CenterTatsuroYamaguchiDepartment of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalKeijiHirataDepartment of Surgery 1, University of Occupational and Environmental HealthMasayoshiYamadaEndoscopy Division, National Cancer Center HospitalKensukeKumamotoDepartment of Genome Medical Science and Medical Genetics, Faculty of Medicine, Kagawa UniversityYasukiAkiyamaDepartment of Surgery 1, University of Occupational and Environmental HealthKeiIshimaruDivision of Gastrointestinal Surgery and Surgical Oncology, Graduate School of Medicine, Ehime UniversityKoichiOkamotoDepartment of Gastroenterology and Oncology, Tokushima University Graduate School of Medical ScienceYukoKawasakiCollege of Nursing, University of HyogoKeigoKomineDepartment of Medical Oncology, Tohoku University HospitalAkiraSakamotoDepartment of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalKunitoshiShigeyasuDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshikoShibataHimawari-No-Kai (Sunflower Association), a Patient Advocacy Group for Individuals and Families Affected By Lynch SyndromeYusakuShimamotoDivision of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of MedicineHidekiShimodairaDivision of Medical Oncology, Faculty of Medicine, Tohoku Medical and Pharmaceutical UniversityShigekiSekineDepartment of Pathology, Keio University School of MedicineAkinariTakaoDepartment of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalMisatoTakaoDepartment of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalYasuyukiTakamizawaDepartment of Colorectal Surgery, National Cancer Center HospitalYojiTakeuchiDepartment of Gastroenterology and Hepatology, Gunma University Graduate School of MedicineNorikoTanabeDepartment of Clinical Genetics, Saitama Medical Center, Saitama Medical UniversityFumitakaTaniguchiDepartment of Surgery, Hiroshima City Hospital Organization Hiroshima City Hiroshima Citizens HospitalAkikoChinoDepartment of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer ResearchHourinChoEndoscopy Center, Tokyo Medical University HospitalSatoruDoiHarmony Line (Association for Patients and Families With Familial Adenomatous Polyposis)TakeshiNakajimaDivision of Hereditary Tumors, Department of Genetic Oncology, Osaka International Cancer InstituteSakikoNakamoriDepartment of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalYoshikoNakayamaDepartment of Pediatrics, Shinshu University School of MedicineToshiyaNagasakiDepartment of Gastroenterological Surgery, Saitama Cancer CenterHisashiHasumiDepartment of Urology, Yokohama City UniversityKoujiBannoCenter of Maternal -Fetal/Neonatal Medicine, Hiroshima University HospitalTakaoHinoiDepartment of Clinical and Molecular Genetics, Hiroshima University HospitalKenjiFujiyoshiDepartment of Surgery, Kurume University School of MedicineTakahiroHorimatsuInstitute for Advancement of Clinical and Translational Science, Kyoto University HospitalKentaMasudaDepartment of Obstetrics and Gynecology, Keio University School of MedicineMasashiMiguchiDepartment of Gastroenterological Surgery, Hiroshima Prefectural HospitalYusukeMizuuchiDepartment of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu UniversityYasuyukiMiyakuraDepartment of Colon and Pelvic Surgery, Cancer Prevention and Genetic Counseling, Tochigi Cancer CenterMichihiroMutohDepartment of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of MedicineTakahiroYoshiokaDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterShinjiTanakaJA Onomichi General HospitalKazuhiroSakamotoKoshigaya Municipal HospitalKentaroSakamakiFaculty of Health Data Science, Juntendo UniversityMichioItabashiSaiseikai Kazo HospitalHideyukiIshidaDepartment of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical UniversityNaohiroTomitaDivision of Cancer Treatment , Toyonaka Municipal HospitalKenichiSugiharaInstitute of Science TokyoYoichiAjiokaDivision of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata UniversityApproximately 5% of all colorectal cancers have a strong genetic component and are classified as hereditary colorectal cancer (HCRC). Some of the unique features commonly seen in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics require different management approaches, including diagnosis, treatment or surveillance, from those used in the management of sporadic colorectal cancer. Accurate diagnosis of HCRC is essential because it enables targeted surveillance and risk reduction strategies that improve patient outcomes. Recent genetic advances revealed several causative genes for polyposis and non-polyposis syndromes. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) first published guidelines for the management of HCRC in 2012, with subsequent revisions every 4 years. The 2024 update to the JSCCR guidelines for HCRC was developed by meticulously reviewing evidence from systematic reviews and the consensus of the JSCCR HCRC Guidelines Committee, which includes representatives from patient advocacy groups for FAP and Lynch syndrome. These guidelines provide an up-to-date summary of HCRC, along with clinical recommendations for managing FAP and Lynch syndrome.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1092-9134812026The diagnostic utility and frequency of CD56 expression in plasma cell myeloma152587ENMidoriImaiDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesAsamiNishikoriDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesTomokaHaratakeDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesMidori FilizNishimuraDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesRioYamadaDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesSyomaKatoDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesMizuhaTabeDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesHiroyukiYanaiDepartment of Diagnostic Pathology, Okayama University HospitalHidetakaYamamotoDepartment of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYasuharuSatoDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesPlasma cell myeloma (PCM) is a hematological malignancy characterized by systemic proliferation of neoplastic plasma cells within the bone marrow. Diagnosis requires clinical findings and immunohistochemical staining, including CD138, CD79a, cyclin D1, immunoglobulin κ (Igκ), and λ (Igλ). However, CD79a and cyclin D1 have limited sensitivity and specificity, and Igκ/Igλ assessment is often difficult due to overstaining. Therefore, more reliable antibodies are needed to accurately diagnose PCM. In this study, we examined the diagnostic utility of CD56 expression in PCM. We retrospectively performed immunostaining for CD138, CD56, CD79a, cyclin D1, Igκ, and Igλ in bone marrow samples from 116 patients with PCM.<br>
CD56 expression was observed in 85/116 cases (73.3 %), CD79a was downregulated in 46/116 cases (39.7 %), and cyclin D1 expression was observed in 42/116 cases (36.2 %). The expression of CD56 was significantly higher than that of CD79a and cyclin D1 (both p < 0.001). The combination of two antibodies resulted in the highest detection rate when combining CD56 and CD79a (105/116, 90.5 %), which was significantly higher than the detection rates of CD56 and cyclin D1 (93/116, 80.2 %) and CD79a and cyclin D1 (75/116, 64.7 %) (both p < 0.001). In contrast, lymphoplasmacytic lymphoma and marginal zone lymphoma lacked CD56 and cyclin D1 expression. Furthermore, in cases where light chain restriction was undetectable (11/116, 9.5 %), all could be diagnosed as PCM based on CD56, CD79a, and cyclin D1. Among these, CD56 showed the highest detection rate (8/11, 72.7 %).<br>
These findings highlight CD56 as a helpful marker for PCM diagnosis and support further clinical research.<br>No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1464-672226112025Comparative Genomic Analysis Identifies FleQ and GcbB as Virulence-Associated Factors in Pseudomonas syringae pv. tabaci Strainse70168ENMuhammad TaufiqHidayatGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKeiYoshiokaFaculty of Agriculture, Okayama UniversityTakafumiNishimuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityShutaAsaiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversitySachikoMasudaCenter for Sustainable Resource Science, RIKEN-TRIPKenShirasuCenter for Sustainable Resource Science, RIKEN-TRIPNanamiSakataGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMikihiroYamamotoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYoshiteruNoutoshiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKazuhiroToyodaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYukiIchinoseGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHidenoriMatsuiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityPseudomonas syringae pv. tabaci (Pta) is an important plant pathogen, which causes wildfire disease in Nicotiana species. However, the genetic basis underlying strain-level differences in virulence remains largely unresolved. To address this, we performed a comparative genomic analysis between a highly virulent strain Pta6605 and a less virulent strain Pta7375. Despite high overall genome similarity, we identified key single-nucleotide polymorphisms, including premature stop-codon mutations in seven open reading frames in Pta7375. Notably, point mutations in two regulatory genes, such as fleQ, which encodes a transcription factor essential for flagellar biogenesis and biofilm formation, and gcbB, which encodes a GGDEF domain-containing diguanylate cyclase responsible for cyclic dimeric guanosine monophosphate (c-di-GMP) synthesis, were implicated in virulence disparity. Functional analyses using deletion and locus replacement mutants in the Pta6605 background revealed that the disruption of fleQ markedly reduced motility, flagellin production, c-di-GMP accumulation, biofilm formation and virulence level mirroring the Pta7375 phenotype. The gcbB replacement mutant showed reduced disease symptom development, although c-di-GMP levels remained comparable to the Pta6605 wild type. Locus replacement between strains confirmed that a point mutation in fleQ was the primary driver of reduced motility and flagellin expression in Pta7375. These findings indicate that the reduced virulence of Pta7375 is associated with impaired regulation of flagella-related genes and disruption of the FleQ-mediated c-di-GMP signalling, underscoring the value of comparative genomics in disentangling the complex regulatory networks that govern virulence in plant pathogens.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2198-38442025A Viral RNA Silencing Suppressor Modulates Reactive Oxygen Species Levels to Induce the Autophagic Degradation of Dicer‐Like and Argonaute‐Like Proteinse06572ENShiyuZhaiState Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F UniversityTianxingPangState Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F UniversityShiyuPengState Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F UniversityShenshenZouDepartment of Plant Pathology, College of Plant Protection, Shandong Agricultural UniversityZhipingDengInstitute of Virology and Biotechnology, Zhejiang Academy of Agricultural SciencesNobuhiroSuzukiInstitute of Plant Science and Resources (IPSR), Okayama UniversityZhenshengKangState Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F UniversityIda BagusAndikaState Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F UniversityLiyingSunState Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F UniversityMounting evidence indicates that viruses exploit elevated reactive oxygen species (ROS) levels to promote replication and pathogenesis, yet the mechanistic underpinnings of this viral strategy remain elusive for many viral systems. This study uncovers a sophisticated viral counter-defense mechanism in the Cryphonectria hypovirus 1 (CHV1)-Fusarium graminearum system, where the viral p29 protein subverts host redox homeostasis to overcome antiviral responses. That p29 directly interacts with and inhibits the enzymatic activity of fungal NAD(P)H-dependent FMN reductase 1 (FMR1), leading to increased ROS accumulation and subsequent autophagy activation is demonstrated. Strikingly, this ROS-induced autophagy selectively targets for degradation two core antiviral RNA silencing components against CHV1 in F. graminearum, Dicer-like 2 (DCL2) and Argonaute-like 1 (AGL1), thereby compromising the host's primary antiviral defense system. Genetic analysis confirms this coordinated hijacking of host machineries, as CHV1 shows enhanced accumulation in the FMR1 knockout and reduced accumulation in autophagy-deficient fungal strains. This work reveals a tripartite interplay among oxidative stress, autophagy, and RNA silencing that CHV1 manipulates through p29 multifunctional activity. These findings provide a model for how viruses coordinately regulate distinct host defense systems to optimize infection.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2051-59601312025Rotenone targets midbrain astrocytes to produce glial dysfunction-mediated dopaminergic neurodegeneration234ENIkukoMiyazakiDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNamiIsookaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoKikuokaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFuminoriImafukuDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKaoriMasaiDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKanaTomimotoDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChiharuSogawaDepartment of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of TechnologyNorioSogawaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihisaKitamuraDepartment of Pharmacotherapy, School of Pharmacy, Shujitsu UniversityMasatoAsanumaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesExposure to pesticides, such as rotenone or paraquat, is an environmental factor that plays an important role in the pathogenesis of Parkinson's disease (PD). Rotenone induces PD-like pathology and is therefore used to develop parkinsonian animal models. Dopaminergic neurotoxicity caused by rotenone has been attributed to the inhibition of mitochondrial complex I, oxidative stress and neuroinflammation; however, the mechanisms underlying selective dopaminergic neurodegeneration by rotenone remain unclear. To resolve this, we focused on glial diversity and examined whether the brain region-specific glial response to rotenone could determine the vulnerability of dopaminergic neurons using primary cultured neurons, astrocytes and microglia from the midbrain and striatum of rat embryos and rotenone-injected PD model mice. Direct neuronal treatment with low-dose rotenone failed to damage dopaminergic neurons. Conversely, rotenone exposure in the presence of midbrain astrocyte and microglia or conditioned media from rotenone-treated midbrain glial cultures containing astrocytes and microglia produced dopaminergic neurotoxicity, but striatal glia did not. Surprisingly, conditioned media from rotenone-treated midbrain astrocytes or microglia monocultures did not affect neuronal survival. We also demonstrated that rotenone targeted midbrain astrocytes prior to microglia to induce dopaminergic neurotoxicity. Rotenone-treated astrocytes produced secreted protein acidic and rich in cysteine (SPARC) extracellularly, which induced microglial proliferation, increase in IL-1β and TNF-α, and NF-κB (p65) nuclear translocation in microglia, resulting in dopaminergic neurodegeneration. In addition, rotenone exposure caused the secretion of NFAT-related inflammatory cytokines and a reduction in the level of an antioxidant metallothionein (MT)-1 from midbrain glia. Furthermore, we observed microglial proliferation and a decrease in the number of MT-positive astrocytes in the substantia nigra, but not the striatum, of low-dose rotenone-injected PD model mice. Our data highlight that rotenone targets midbrain astrocytes, leading to SPARC secretion, which promotes the neurotoxic conversion of microglia and leads to glial dysfunction-mediated dopaminergic neurodegeneration.No potential conflict of interest relevant to this article was reported.Japan Neurosurgical SocietyActa Medica Okayama2188-4226122025Endovascular Thrombectomy for Large Vessel Occlusion in a Patient on Venoarterial Extracorporeal Membrane Oxygenation: A Case Report445451ENYukiEBISUDANIDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasafumiHIRAMATSUDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeiichiroIWASAKIDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiSUGIUDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunHARUMADepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyuKIMURADepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatoKAWAKAMIDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYutaSOTOMEDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahiroNISHIHARADepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinsukeYUASADepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShotaTANAKADepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesExtracorporeal membrane oxygenation is utilized in the treatment of severe acute cardiac failure and respiratory failure. While it provides the advantage of oxygenating blood through extracorporeal circulation, it also carries risks of intracranial ischemic and hemorrhagic complications due to the continuous presence of artificial materials within the body. We encountered a case in which venoarterial extracorporeal membrane oxygenation was initiated for fulminant myocarditis, and the patient subsequently developed a large vessel occlusion. The diagnosis was confirmed using perfusion computed tomography. A visible thrombus was observed on the arterial cannula of the extracorporeal membrane oxygenation circuit, and the large vessel occlusion was determined to have been caused by thromboembolism. An immediate extracorporeal membrane oxygenation circuit exchange was performed, followed by endovascular thrombectomy. The patient experienced no perioperative complications and achieved a favorable neurological outcome. Endovascular thrombectomy in extracorporeal membrane oxygenation patients requires careful perioperative management and should be promptly performed in eligible cases of thromboembolic events. Furthermore, because patients on extracorporeal membrane oxygenation are often sedated and under intensive systemic management, regular neurological assessments and intracranial monitoring are essential for the early detection of intracranial pathologies.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2072-669417202025Tertiary Lymphoid Structures Are Associated with Favorable Clinical Outcomes and Negatively Correlated with Cancer-Associated Fibroblasts in Esophageal Cancer3351ENTomoyoshiKunitomoDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroNomaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNoriyukiNishiwakiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySeitaroNishimuraDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYasushigeTakedaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHijiriMatsumotoDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTatsuyaTakahashiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKentoKawasakiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasaakiAkaiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaoakiMaedaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySatoruKikuchiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShunsukeTanabeDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiakiOharaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiTazawaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYasuhiroShirakawaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground: Esophageal cancer remains a highly aggressive malignant tumor with poor prognosis, despite advances in combination therapies and novel immunotherapies. Tertiary lymphoid structures (TLSs), characterized by densely packed CD20+ B cells in a germinal-center-like structure, have recently been recognized as immune-stimulating components within the tumor microenvironment. In contrast, cancer-associated fibroblasts (CAFs) are stromal cells expressing fibroblast-activating protein (FAP) involved in immunosuppression. Methods: In this retrospective study, 124 clinical samples from patients who underwent radical surgery for esophageal cancer at our institute were analyzed. We investigated whether TLSs could serve as a prognostic factor and examined their association with tumor microenvironment factors. Results: The presence of TLSs was an independent prognostic factor for overall and progression-free survival in multivariate analyses. A high level of TLS formation correlated with better nutritional status, fewer M2 macrophages, and greater plasma cell infiltration. Additionally, little TLS formation was observed in areas with abundant CAFs, and quantitative analyses revealed a significant negative correlation between TLSs and CAFs. Conclusions: TLSs enhance antitumor immunity via macrophages and plasma cells and can be a valuable prognostic indicator in patients undergoing surgery for esophageal cancer. Targeting CAFs may prove to be a promising therapeutic strategy to enhance tumor-immunity-related TLSs.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818417102025Histopathological Study of Regenerative Endodontic Therapy on an Immature Mandibular Second Premolar With Pulp Necrosis: A Case Reporte95647ENHidefumiSakoDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalKazuhiroOmoriDepartment of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiShinoda-ItoDepartment of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKiyofumiTakabatakeDepartment of Oral Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHitoshiNagatsukaDepartment of Oral Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShogoTakashibaDepartment of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRegenerative endodontic therapy (revascularization) for immature permanent teeth with pulp necrosis and/or apical periodontitis is an effective treatment to promote root maturation. Previous histological studies have reported the formation of cementoid or osteoid tissue and periodontal ligament-like tissue within the root canals. This case report presents the histopathological findings of a human immature permanent tooth with pulp necrosis following revascularization.<br>
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A 11-year-old male patient presented with tenderness on biting and the formation of a sinus tract in the mandibular right second premolar (tooth #29), diagnosed as pulp necrosis with symptomatic apical periodontitis. Revascularization was performed using calcium hydroxide as an intracanal medicament, with reference to the American Association of Endodontists (AAE) 2018 Position Paper on Regenerative Endodontics. At the 12-month follow-up, radiographs showed thickening of the canal walls, apical narrowing, root elongation, and recovery of pulp sensibility. The tooth was later extracted for orthodontic reasons at 42 months and processed for histological examination.<br>
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Histological evaluation revealed cementum-like hard tissue continuous with the existing dentin in the apical region, suggesting apical closure. In contrast, the coronal portion showed less mature cementum-like tissue accompanied by loose connective tissue and neovascularization. These findings indicate that revascularization with calcium hydroxide can induce the formation of cementum-like and dentin-like tissues with vascular regeneration in immature permanent teeth with pulp necrosis.No potential conflict of interest relevant to this article was reported.International Institute of Anticancer ResearchActa Medica Okayama1109-65352262025C1orf50 Accelerates Epithelial-Mesenchymal Transition and the Cell Cycle of Hepatocellular Carcinoma836849ENATSUSHITANAKADepartment of Pathology, Beth Israel Deaconess Medical CenterYUSUKEOTANIDepartment of Pathology, Beth Israel Deaconess Medical CenterMASAKIMAEKAWADepartment of Pathology, Beth Israel Deaconess Medical CenterANNAROGACHEVSKAYADepartment of Pathology, Beth Israel Deaconess Medical CenterTIRSOPEÑADepartment of Pathology, Beth Israel Deaconess Medical CenterVANESSA D.CHINUMass Chan Medical School, UMass Memorial Medical CenterSHINICHITOYOOKADepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMICHAEL H.ROEHRLDepartment of Pathology, Beth Israel Deaconess Medical CenterATSUSHIFUJIMURADepartment of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground/Aim: Hepatocellular carcinoma (HCC) is a heterogeneous liver cancer with limited treatment options and a poor prognosis in advanced stages. To identify novel biomarkers and therapeutic targets, we investigated the role of chromosome 1 open reading frame 50 (C1orf50), a gene with a previously uncharacterized function in HCC.<br>
Materials and Methods: We performed a comprehensive transcriptome data analysis of the human hepatocellular carcinoma project from The Cancer Genome Atlas (TCGA) and subsequently validated the oncogenic roles of C1orf50 using HCC cell lines.<br>
Results: Using transcriptomic and clinical data from TCGA, we stratified 355 primary HCC samples based on C1orf50 expression levels. Patients with high C1orf50 expression exhibited significantly shorter overall survival, suggesting its association with aggressive tumor behavior. Differential expression and enrichment analyses revealed that C1orf50-high tumors were enriched in oncogenic pathways, including epithelial-mesenchymal transition (EMT), cell cycle activation, and stemness-related properties. Transcriptional regulatory network analysis detected 456 significantly dysregulated regulons, including ZEB1/2 and E2F2, key drivers of EMT and cell cycle, in the C1orf50-high group. In addition, we observed increased YAP1/TAZ signaling, further linking C1orf50 to stemness and therapeutic resistance. Functional data from CRISPR-based dependency screening suggested that several transcription factors up-regulated in the C1orf50-high state, such as ZBTB11 and CTCE, are essential for the survival of HCC cells. These findings indicate potential therapeutic vulnerabilities and support the rationale for targeting C1orf50-associated pathways.<br>
Conclusion: C1orf50 is a novel biomarker of poor prognosis in HCC and a key regulator of oncogenic features such as EMT, cell cycle progression, and stemness. This study highlights the therapeutic potential of targeting C1orf50-related networks in aggressive subtypes of liver cancer.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818417102025Primary Lacrimal Sac Diffuse Large B-cell Lymphoma Treated With Local Radiotherapy Alone: A Case With No Relapse After 21 Years of Follow-Upe95411ENToshihikoMatsuoHealthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakehiroTanakaPathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMitsuhiroTakemotoRadiotherapy, Himeji Red Cross HospitalPrimary lacrimal sac lymphoma is rare and diagnosed as diffuse large B-cell lymphoma in a predominant histopathological type. Systemic chemotherapy would be the standard of care, but local radiotherapy may be a treatment option toward a localized lesion. The present patient is a 54-year-old otherwise healthy woman with a right lacrimal sac mass, which was proven by excisional biopsy to be diffuse large B-cell lymphoma. Since she did not have any other systemic lesions on gallium scintigraphy and neck-to-abdominal computed tomography scans, which were the standard procedure at that time, she underwent local radiotherapy at 40 Gy. Two years later, at the age of 56 years, she developed radiation retinopathy with macular edema in the right eye and had spotty laser photocoagulation in the nasal half of the fundus. At the age of 57 years, she developed radiation cataract and underwent cataract surgery with intraocular lens implantation in the right eye. At the age of 58 years, the macular edema in the right eye became worse and remained active, resulting in poor visual acuity of 0.1. She thus underwent 25-gauge vitrectomy in the right eye to peel off the adhering posterior vitreous surface, together with the internal limiting membrane, as the standard procedure at that time. The visual acuity in the right eye was elevated to 0.6. She maintained the visual acuity afterward and had no relapse of lymphoma in 21 years from the diagnosis of primary right lacrimal sac diffuse large B-cell lymphoma. Local radiotherapy would still be a treatment option for localized lymphoma lesions such as primary lacrimal sac lymphoma.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1345-26302025Comparative analysis of interactions between five strains of Pseudomonas syringae pv. tabaci and Nicotiana benthamianaENYunaNakaoGraduate School of Medicine, Science and Technology, Shinshu UniversityShutaAsaiGraduate School of Environmental, Natural Science and Technology, Okayama UniversityHidenoriMatsuiGraduate School of Environmental, Natural Science and Technology, Okayama UniversityYukiIchinoseGraduate School of Environmental, Natural Science and Technology, Okayama UniversityShinpeiKatouGraduate School of Medicine, Science and Technology, Shinshu UniversityPseudomonas syringae pv. tabaci 6605 (Pta 6605), the agent of wildfire disease in tobacco, has been used as a model strain for elucidating the virulence mechanisms of Pta. However, the host genes involved in resistance or susceptibility to Pta remain largely unknown. Nicotiana benthamiana is a model plant species in the Solanaceae family and is useful in functional analyses of genes. We herein compared five Pta strains (6605, 6823, 7372, 7375, and 7380) in terms of their phenotypes on medium and interactions with N. benthamiana. Pta 6605 and Pta 6823 showed more active proliferation than the other strains in a high cell density culture. Moreover, Pta 6605 exhibited markedly higher swarming motility than the other strains. In inoculated leaves of N. benthamiana, Pta 6605 and Pta 6823 caused more severe disease symptoms and proliferated to a higher cell density than the other strains. However, Pta 6823 as well as Pta 7372 and Pta 7380 induced the high accumulation of salicylic acid (SA). Moreover, the inoculations of Pta 6823 and Pta 7372 resulted in the upregulation of ethylene biosynthesis genes. On the other hand, Pta 6605 induced neither SA accumulation nor the expression of ethylene biosynthesis genes, and suppressed the expression of jasmonate biosynthesis genes. Moreover, chlorosis was clearly induced in the upper uninoculated leaves of Pta 6605-infected plants. These results suggest that Pta 6605 escapes from or suppresses plant immune systems and, thus, is the most virulent on N. benthamiana among the five strains tested.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1422-006726202025Neurofibromin Encoded by the Neurofibromatosis Type 1 (NF1) Gene Promotes the Membrane Translocation of SPRED2, Thereby Inhibiting the ERK Pathway in Breast Cancer Cells10072ENNang TheeSu PwintDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChunningLiDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTongGaoDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYuzeWangDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasayoshiFujisawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiakiOharaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasakiyoSakaguchiDepartment of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTeizoYoshimuraDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAkihiroMatsukawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNeurofibromin (NF) inhibits the RAS/RAF/ERK pathway through its interaction with SPRED1 (Sprouty-related EVH1 domain-containing protein 1). Here, we investigated the functional relationship between NF and SPRED2 in breast cancer (BC). Human BC cell lines were transfected to downregulate or overexpress NF and SPRED2 and subsequently subjected to functional assays. Protein and mRNA levels were analyzed by Western blotting and RT-qPCR, respectively. Protein–protein interactions were examined by immunoprecipitation. Database analyses and immunohistochemistry (IHC) of BC tissues were performed to validate the in vitro findings. Downregulating NF or SPRED2 expression in BC cells enhanced cell proliferation, migration and invasion accompanied by RAF/ERK activation, whereas overexpression produced opposite effects. NF formed a protein complex with SPRED2 and facilitated its translocation to the plasma membrane. By IHC, SPRED2 membrane localization was absent in NF-negative luminal A and triple-negative BC (TNBC) but present in a subset of luminal A BC. By database analyses, both NF1 and SPRED2 mRNA levels were reduced in BC tissues, and luminal A BC patients with high expression of both NF1 and SPRED2 mRNA exhibited improved relapse-free survival. These results suggest a critical role for the NF–SPRED2 axis in BC progression and highlight it as a potential therapeutic target.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0929-19032025ATPase copper transporting beta contributes to cisplatin resistance as a regulatory factor of extracellular vesicles in head and neck squamous cell carcinomaENTatsuoOgawaDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKishoOnoDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShojiRyumonDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHotakaKawaiDepartment of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKoheiSatoDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKokiUmemoriDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKunihiroYoshidaDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKyoichiObataDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiKunisadaDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTatsuoOkuiDepartment of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Graduate School of Medical and Dental Sciences, Kagoshima UniversityKuniakiOkamotoDepartment of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHitoshiNagatsukaDepartment of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityFatemehMomen-HeraviDepartment of Orofacial Sciences, School of Dentistry, University of California San FranciscoSoichiroIbaragiDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityCisplatin (CDDP) resistance remains a major clinical challenge in the treatment of head and neck squamous cell carcinoma (HNSC). Our group identified ATPase copper transporting beta (ATP7B) as a mediator of CDDP resistance through its role in drug efflux and small extracellular vesicle (sEV) secretion. Herein, we uncovered a novel mechanism by which ATP7B regulates sEV dynamics and the intercellular transmission of CDDP resistance. Using transcriptomic analyses of HNSC datasets, we demonstrate that ATP7B expression correlates with endocytosis- and epithelial-mesenchymal transition (EMT)-related gene sets and with elevated levels of EV-associated proteins. CDDP-resistant HNSC cells exhibited upregulated ATP7B, Rab5/Rab7, and preferentially secreted HSP90- and EpCAM-rich sEVs. These sEVs were leading to increased ATP7B expression and reduced CDDP sensitivity in recipient cells. A pharmacological inhibition of sEV biogenesis with GW4869 suppressed ATP7B and Atox1 expressions, inhibited late endosome maturation, and significantly enhanced CDDP-induced apoptosis in HNSC cells. In vivo, GW4869 reduced the sEV protein content and ATP7B expression in xenograft tumors. These findings establish that ATP7B is a critical modulator of sEV cargo and resistance propagation. Our results highlight a previously unrecognized ATP7B–sEV axis driving chemoresistance and identify sEV inhibition as a promising strategy to overcome therapeutic failure in HNSC.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7952025Epstein-Barr Virus-Associated Early Gastric Carcinoma with Lymphoid Stroma Mimicking a Submucosal Tumor: A Typical Case Diagnosed by Endoscopic Resection and Treated by Local Resection with Sentinel Node Navigation399404ENHiroshiIsozakiDepartment of Surgery, Oomoto HospitalSasauMatsumotoDepartment of Surgery, Oomoto HospitalTakehiroTakamaDepartment of Surgery, Oomoto HospitalYukaIsozakiDepartment of Surgery, Oomoto HospitalShigekiMurakamiDepartment of Surgery, Oomoto HospitalCase Report/10.18926/AMO/69442Gastric cancer with lymphoid stroma (GCLS) accounts for 1%-7% of gastric cancers; ~80% are Epstein-Barr virus (EBV)-positive. The rate of lymph node metastasis is relatively low, even when an early GCLS has invaded the submucosa. We report an early GCLS with massive submucosal invasion mimicking a submucosal tumor (SMT), diagnosed by endoscopic submucosal resection (ESD) and treated with local resection and sentinel node navigation surgery (SNNS). The patient was a 40-year-old Japanese man. A protruding lesion on the greater curvature of the middle part of his stomach was detected by X-ray, and an endoscopic examination revealed a 2.5-cm protruding tumor covered with a normal mucosa and small ulcers at the apex. ESD was performed for a diagnosis. The pathological diagnosis was lymphoepithelioma-like gastric cancer (GCLS), pT1b(SM2), Ly0, V0, pHM1, pVM1. EBV infection in the cancer cells was confirmed pathologically by EBV-encoded RNA. The local resection was performed using SNNS. The patient has had no recurrence or post-gastrectomy syndrome 4 years postsurgery. EBV-associated early GCLS resembling an SMT is relatively rare, and clinicians need to be aware of this disease. Local resection using SNNS may be a surgical option for GCLS cases with a low rate of lymphatic metastasis.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7952025Immunoglobulin G4-related Disease Mimicking Portal Vein Tumor Thrombus381385ENAtsunobuSakuraiDepartment of Radiology, NHO Iwakuni Clinical CenterTakayukiYabukiDepartment of Radiology, NHO Iwakuni Clinical CenterHidekiAokiDepartment of Gastroenterological Surgery, NHO Iwakuni Clinical CenterAkikoIsekiDepartment of Pathology, NHO Iwakuni Clinical CenterCase Report10.18926/AMO/69439We report the case of a 72-year-old Japanese man with an incidental portal vein mass that was surgically resected and diagnosed as immunoglobulin G4 (IgG4)-related disease. The mass was discovered during an atrial fibrillation examination. The patient had a history of gastric cancer and was also diagnosed with rectal cancer, raising concerns about metastasis. Due to technical challenges, a biopsy was not feasible. Imaging findings suggested portal vein tumor thrombosis, complicating the diagnosis. This case highlights a rare presentation of IgG4-related disease mimicking portal vein tumor thrombus.No potential conflict of interest relevant to this article was reported.SAGE PublicationsActa Medica Okayama2352-37271122025Advancements in systemic therapy for muscle-invasive bladder cancer: A systematic review from the beginning to the latest updates113ENTakafumiYanagisawaDepartment of Urology, The Jikei University School of MedicineAkihiroMatsukawaDepartment of Urology, The Jikei University School of MedicineJeremy Yuen-ChunTeohDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaKeiichiroMoriDepartment of Urology, The Jikei University School of MedicineTatsushiKawadaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiKatayamaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPawełRajwaDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaFahadQuhalDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaBenjaminPradereDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaMarcoMoschiniDepartment of Urology, San Raffaele Hospital and Scientific InstituteShahrokh F.ShariatDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaJunMikiDepartment of Urology, The Jikei University School of MedicineTakahiroKimuraDepartment of Urology, The Jikei University School of MedicineContext: Several phase III randomized controlled trials (RCTs) have shown the importance of perioperative systemic therapy, especially for the efficacy of immune checkpoint inhibitors (ICIs) in both neoadjuvant and adjuvant settings for muscle-invasive bladder cancer (MIBC).<br>
Objective: To synthesize the growing evidence on the efficacy and safety of systemic therapies for MIBC utilizing the data from RCTs.<br>
Evidence acquisition: Three databases and ClinicalTrials.gov were searched in October 2024 for eligible RCTs evaluating oncologic outcomes in MIBC patients treated with systemic therapy. We evaluated pathological complete response (pCR), disease-free survival (DFS), progression-free survival (PFS), event-free survival (EFS), overall survival (OS), and adverse events (AEs).<br>
Evidence synthesis: Thirty-three RCTs (including 14 ongoing trials) were included in this systematic review. Neoadjuvant chemotherapy improved OS compared to radical cystectomy alone. Particularly, the VESPER trial demonstrated that dd-MVAC provided oncological benefits over GC alone in terms of pCR rates, OS (HR: 0.71), and PFS (HR: 0.70). Recently, the NIAGARA trial showed that perioperative durvalumab plus GC outperformed GC alone in terms of pCR rates, OS (HR: 0.75), and EFS (HR: 0.68). Despite the lack of data on overall AE rates in the VESPER trial, differential safety profiles in hematologic toxicity were reported between dd-MVAC and durvalumab plus GC regimens. In the adjuvant setting, no study provided the OS benefit from adjuvant chemotherapy. However, only adjuvant nivolumab had significant DFS and OS benefits compared to placebo.<br>
Conclusions: Neoadjuvant chemotherapy remains the current standard of care for MIBC. Durvalumab shed light on the promising impact of ICIs added to neoadjuvant chemotherapy. Nivolumab is the only ICI recommended as adjuvant therapy in patients who harbored adverse pathologic outcomes. Ongoing trials will provide further information on the impact of combination therapy, including chemotherapy, ICIs, and enfortumab vedotin, in both neoadjuvant and adjuvant settings.No potential conflict of interest relevant to this article was reported.International Institute of Anticancer ResearchActa Medica Okayama0258-851X3952025Accuracy of Contrast-enhanced CT in Diagnosing Small-sized cT3a Renal Cell Carcinoma and Analysis of Factors Predicting Downstaging to pT127872793ENKENSUKEBEKKUDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKASUMIYOSHINAGADepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSHOTAINOUEDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYOSUKEMITSUIDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTOMOAKIYAMANOIDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTATSUSHIKAWADADepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYUSUKETOMINAGADepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTAKUYASADAHIRADepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSATOSHIKATAYAMADepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTAKEHIROIWATADepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSHINGONISHIMURADepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKOHEIEDAMURADepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTOMOKOKOBAYASHIDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMOTOOARAKIDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground/Aim: This study assessed the accuracy of preoperative contrast-enhanced computed tomography (CECT) scans in staging small-sized, locally advanced (cT3a) renal cell carcinoma (RCC) and identified predictors of pathological downstaging following surgery.<br>
Patients and Methods: Seventy-six patients who underwent radical nephrectomy for cT3aN0M0 RCC with tumors ≤7 cm were analyzed. Preoperative CECT evaluated features such as venous, peritumoral, or renal sinus fat, and urinary tract invasion, predictive values, and concordance index between radiological and pathological findings were calculated for these categories. The study also examined the impact of clinicopathologic factors on downstaging.<br>
Results: Of 76 patients with cT3 RCC, 37% were down-staged to pT1. Down-staged cases had a higher proportion of male patients and non-clear cell carcinoma (86% vs. 58%, 32% vs. 6%; p=0.02, p=0.007, respectively). Multiple cT3a factors were less common in down-staged cases (4% vs. 23%, p=0.04). Non-clear cell carcinoma was significantly associated with downstaging compared to clear cell carcinoma (75% vs. 30%, p=0.006). Multivariate analysis confirmed non-clear cell carcinoma as an independent predictor (odds ratio=8.2, p=0.01). For venous invasion, CECT sensitivity and positive predictive value were high (73.5% and 83.3%, respectively) and the degree of agreement was substantial (κ=0.62).<br>
Conclusion: The accuracy of preoperative CECT was acceptable for detecting venous invasion. The downstaging to pT1 occurred in 37% of cT3a RCC cases in the final pathology, with non-clear cell carcinoma being a significant predictor.<br>No potential conflict of interest relevant to this article was reported.Japanese Society of Internal MedicineActa Medica Okayama0918-291864202025Two Cases of Esophageal Mucosal Damage Observed after Peroral Endoscopic Myotomy for Esophageal Motility Disorders29792984ENShoichiroHirataDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomohiroKamioDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakuyaSatomiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKentaHamadaDepartment of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHiroyukiSakaeDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSeijiKawanoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshiroKawaharaDepartment of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNoriakiManabeDivision of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical SchoolMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesThis report presents two cases of esophageal mucosal damage following peroral endoscopic myotomy (POEM) for esophageal motility disorders. In the first case, delayed perforation and mediastinitis occurred on postoperative day 15 and the patient was treated with endoscopic clipping and antibiotics. In the second case, although no perforation was observed, extensive mucosal injury developed the day after POEM which was successfully managed by fasting and antibiotic therapy. These findings highlight the need for careful patient management to minimize the risks associated with POEM, while maximizing its therapeutic benefits.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Periodontitis associated with Porphyromonas gingivalis infection is a risk factor for infertility through uterine hypertrophy34964ENChiakiKamei-NagataDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroOmoriDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHidefumiSakoDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalKyosukeSakaidaDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalMasa-akiNakayamaDepartment of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiakiOharaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirokiMandaiDepartment of Pharmacy, Faculty of Pharmacy, Gifu University of Medical ScienceMoyukaKubota-TakamoriDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityFumikoKiyamaDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakayukiIshiiDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKimitoHiraiDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAtsushiIkedaDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalKazuTakeuchi-HatanakaDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalYukiShinoda-ItoDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasakoTai-TokuzenDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalAiSakamotoCenter for Reproductive Medicine, Miyake ClinicMachikoKiyokawaCenter for Reproductive Medicine, Miyake ClinicTomomiYamanishiCenter for Reproductive Medicine, Miyake ClinicTakashiOdaCenter for Reproductive Medicine, Miyake ClinicMasayukiTakigawaMiyake Hello Dental Clinic, Pediatric Dentistry and OrthodonticsTadashiYamamotoThe Center for Graduate Medical Education (Dental Division), Okayama University HospitalTakahitoMiyakeCenter for Reproductive Medicine, Miyake ClinicShogoTakashibaDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPeriodontitis has recently been recognized as a potential risk factor for infertility due to its adverse effect on conception, although the underlying mechanisms remain unclear. This study investigated serum IgG antibody titers against periodontopathogenic bacteria in women with unexplained infertility and investigated how periodontal inflammation affects pregnancy and uterine function using a ligature-induced periodontitis mouse model infected with Porphyromonas gingivalis (Pg). IgG antibody titers against seven periodontopathogenic bacteria strains were measured by ELISA in 76 spontaneously pregnant women and 70 women undergoing infertility treatment. In the in vivo study, periodontitis mice were bred four weeks after periodontitis induction. Birth numbers, newborn weights, and gestation periods were assessed. To evaluate periodontal inflammation, alveolar bone, serum, and uterus was collected before mating. Uterine tissue was evaluated through histological and immunohistochemical staining. Women receiving infertility treatment were significantly older and had higher IgG titers against three Pg strains. Periodontitis mice had fewer births, lower newborn weights, and increased uterine cross-sectional areas. Additionally, elevated estrogen receptor α and progesterone receptor expression levels were observed in endometrial and stromal tissues. These results suggest that periodontitis may cause uterine hypertrophy and hormone receptor changes, potentially impairing pregnancy.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1573-72092842025Cancer-associated fibroblast-derived SOD3 enhances lymphangiogenesis to drive metastasis in lung adenocarcinoma51ENMay WathoneOoDepartment of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakaoHikitaDepartment of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomohaMashimaDepartment of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKosukeTorigataSchool of Medicine, Kobe UniversityYin MinThuDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomohiroHabuDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHotakaKawaiDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiakiOharaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalSachioItoDepartment of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHitoshiNagatsukaDepartment of Thoracic Surgery, National Hospital Organization, Shikoku Cancer CenterShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasanoriNakayamaDepartment of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDespite advancements in diagnostic and therapeutic strategies, lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality due to its aggressive metastatic potential. Extracellular superoxide dismutase (SOD3) is an antioxidant enzyme that regulates oxidative stress and is regarded as a tumor suppressor. However, studies have demonstrated that SOD3 can either promote or inhibit cell proliferation and survival in various cancers, and its molecular mechanisms within the tumor microenvironment are poorly understood. In this study, we report a breakthrough in uncovering the role of SOD3 derived from cancer-associated fibroblasts (CAFs) in LUAD. Using LUAD xenograft models co-implanted with SOD3-overexpressing CAFs (CAFSOD3), we observe an aggressive tumor phenotype characterized by increased lymphangiogenesis and lymphatic vessel invasion (LVI) of the tumor. Additionally, LUAD patients with elevated SOD3 levels exhibit a higher incidence of LVI and metastasis. Notably, RNA sequencing of CAFSOD3 reveals that SOD3-mediated VEGF-dependent tumor progression and lymphangiogenesis are up-regulated. Furthermore, single-cell transcriptomic analysis of LUAD clinical samples confirms a strong correlation between SOD3 expression in fibroblasts and characteristics of tumor exacerbation, such as lymphangiogenesis and metastasis. These findings underscore new insights into the role of CAF-derived SOD3 in LUAD progression and highlight its potential as a biomarker and therapeutic target.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1422-006726192025Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: From Sarcomere to Clinic9347ENKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahiroOkumuraDepartment of Advanced Cardiovascular Therapeutics, Nagoya University Graduate School of MedicineSeiyaKatoDivision of Pathology, Saiseikai Fukuoka General HospitalKenjiOnoueDepartment of Cardiovascular Medicine, Nara Medical UniversityToruKuboDepartment of Cardiology and Geriatrics, Kochi Medical School, Kochi UniversityHidemichiKouzuDepartment of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of MedicineToshiyukiYanoDepartment of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of MedicineTakayukiInomataDepartment of Cardiovascular Medicine, Niigata University Graduate School of Medical and Dental SciencesHypertrophic cardiomyopathy (HCM) is a primary myocardial disease characterized by unexplained left ventricular hypertrophy, often resulting from pathogenic variants of sarcomeric protein genes. Conventional treatments, such as the use of beta blockers or calcium channel blockers, focus on symptomatic control but do not address the underlying hypercontractility at the sarcomere level. Recent advances in molecular understanding have led to the development of cardiac myosin inhibitors that directly modulate sarcomeric function by reducing myosin–actin cross-bridge formation and adenosine triphosphatase (ATPase) activity. Mavacamten and aficamten have shown promising results in phase 2 and 3 clinical trials, improving symptoms, exercise capacity, and left ventricular outflow tract gradients in patients with obstructive HCM. This review summarizes the current understanding of HCM pathophysiology, diagnostic strategies, and conventional treatments with a focus on the mechanisms of action of myosin inhibitors, clinical evidence supporting their use, and future directions for improvement. We also discuss their potential applications in non-obstructive HCM and the importance of precision medicine guided by genetic profiling.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2072-664317182025Lacticaseibacillus rhamnosus Probio-M9 Alters the Gut Microbiota and Mitigates Pulmonary Hypertension in a Rat Model2927ENZhixinZhaoInner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural UniversityGaopengLiDepartment of Cardiovascular Physiology, Faculty of Medicine, Kagawa UniversityKiyomiOhmichiDepartment of Diagnostic Pathology, Kagawa University HospitalXiaodongLiDepartment of Cardiovascular Physiology, Faculty of Medicine, Kagawa UniversityFeiyanZhaoInner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural UniversityKaoriIshikawaDepartment of General Medicine, Kagawa University HospitalRyouIshikawaDepartment of Diagnostic Pathology, Kagawa University HospitalKazufumiNakamuraCenter for Advanced Heart Failure, Okayama University HospitalNaoyaYokotaDepartment of General Thoracic Surgery, Faculty of Medicine, Kagawa UniversityZhihongSunInner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural UniversityLin HaiKuraharaDepartment of Cardiovascular Physiology, Faculty of Medicine, Kagawa UniversityBackground: Intestinal microbiota plays an important role in the progression of pulmonary hypertension (PH). Colostrum-derived Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9) has shown protective effects against inflammation and remodeling. We investigated whether Probio-M9 supplementation could improve the pathology of PH. Methods: The monocrotaline (MCT)-induced PH model rats are created followed by Probio-M9 treatment. Microbiota and pathological analyses were performed to investigate the therapeutic effects of Probio-M9. Results: Probio-M9 significantly suppressed cardiovascular remodeling and reduced mortality in rats. Analysis of the fecal microbiota revealed that Probio-M9 significantly altered the gut microbiota of MCT model rats. Specifically, Alistipes sp009774895 and Duncaniella muris populations increased, whereas Limosilactobacillus reuteri_D, Ligilactobacillus apodeme and Monoglobus sp900542675 decreased compared to those in the MCT group. Focusing on the expression of GPNMB in macrophages and the localization of CD44, we found that the number of these cells increased in the MCT group but significantly decreased with Probio-M9 treatment. In lung tissue from PH patients, more GPNMB-positive macrophages were found than non-PH lungs, and an increase in CD44-positive cells was confirmed in the vicinity of GPNMB. Conclusions: Probio-M9 had a significant impact on the intestinal microbiota and GPNMB/CD44 positive cells in the lungs of PH rats.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Pharmacokinetics and the effectiveness of pyrogen-free bioabsorbable wet adhesives20056ENRisaOshimaDepartment of Periodontology, Faculty of Dental Medicine, Hokkaido UniversityKumikoYoshiharaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKoNakanishiDepartment of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido UniversityTsukasaAkasakaDepartment of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido UniversityShinjiShimojiDepartment of Periodontology, Faculty of Dental Medicine, Hokkaido UniversityTeppeiNakamuraDepartment of Applied Veterinary Science, Faculty of Veterinary Medicine, Hokkaido UniversityTakumiOkiharaDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityMarikoNakamuraDepartment of Clinical Psychology, School of Clinical Psychology, Kyushu University of Medical and ScienceAkihiroMatsukawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIkkeiTamadaDepartment of Plastic and Reconstructive Surgery, Tokyo Metropolitan Children’s Medical CenterBartVan MeerbeekBIOMAT, Department of Oral Health Sciences, & UZ Leuven, Dentistry, KU LeuvenTsutomuSugayaDepartment of Periodontology, Faculty of Dental Medicine, Hokkaido UniversityYasuhiroYoshidaDepartment of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido UniversityBioabsorbable materials are essential for advanced therapies, including surgical sealing, cell therapy, and drug delivery. Natural bioabsorbable materials, including collagen and hyaluronic acid, have better biocompatibility than synthetic bioabsorbable polymers; however, they are mainly derived from animals, presenting infection risks. Non-animal origin polymers have a lower molecular weight than those of animal origins. Their viscosity increases with increase in molecular weight, making endotoxin removal difficult. Here, using the phosphoryl chloride disposal method, we present a strategy for synthesizing pyrogen-free bioabsorbable adhesives with controlled molecular weight. Phosphopullulan, a polysaccharide derivative, had less than detectable endotoxin levels and controllable average molecular weight of approximately 300,000 to over 1,400,000. Furthermore, it is important to ensure the safety as well as efficacy of bio-implantable materials. We have evaluated the biosafety of polysaccharide derivatives we are developing, and have examined their cell phagocytosis and pharmacokinetics in vitro and in vivo, and have confirmed that they are safe. We have also evaluated their adhesion to wet tissue adhesions and confirmed that they leak less than existing materials.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0014-48001422025Cross-feeding between beneficial and pathogenic bacteria to utilize eukaryotic host cell-derived sialic acids and bacteriophages shape the pathogen-host interface milieu104967ENDarabGhadimiDepartment of Microbiology and Biotechnology, Max Rubner-InstitutReginaFölster-HolstClinic of Dermatology, Venerology und Allergology, University Hospital Schleswig-HolsteinSophiaBlömerClinic of Dermatology, Venerology und Allergology, University Hospital Schleswig-HolsteinMichaelEbsenStädtisches MVZ Kiel GmbH (Kiel City Hospital), Department of PathologyChristophRöckenInstitute of Pathology, Kiel University, University Hospital, Schleswig-HolsteinJumpeiUchiyamaDepartment of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityShigenobuMatsuzakiDepartment of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen UniversityWilhelmBockelmannDepartment of Microbiology and Biotechnology, Max Rubner-InstitutUnder an inflamed-intestinal milieu, increased free sialic acids are associated with the overgrowth of some pathogenic bacterial strains. Recently, the protective immunomodulatory activity of gut bacteriophages (phages) has also been highlighted. However, the role of phages in triple reciprocal interactions between pathogenic bacteria, beneficial bacteria, and their host cell sialic acids has not been studied so far. We established a sialidase-explicit model in which beneficial and pathogenic bacteria interact through cross-feeding and competition for free sialic acid using a human triple co-culture cell model incorporating colonocytes (T84 cells), monocytes (THP-1 cells), and hepatocytes (Huh7 cells). Triple co-cultured cells were challenged with Gram-positive Bifidobacterium bifidum (B. bifidum) and Gram-negative Pseudomonas aeruginosa PAO1 (P. a PAO1) in the absence or presence of its KPP22 phage in two different cell culture mediums: 1) standard Dulbecco's Modified Eagle Medium (DMEM) and 2) DMEM with 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA). Changes in physiological, functional, and structural health markers of stimulated cocultured cells were evaluated. The concentrations of sialic acid and pro-inflammatory cytokines in the cell culture supernatants were quantified. P. a PAO1 triggered the release of interleukin 6 and 8 (IL-6 and IL-8), accompanied by increased levels of free sialic acid, reduced viability of co-cultured cells, and disrupted the integrity of the cellular monolayer. These disruptive effects were markedly attenuated by KPP22 phage and B. bifidum. In addition to well-documented differences in the structure and composition of the bacterial cell walls of Gram-negative pathogenic bacteria and bifidobacteria, two distinct factors seem to be pivotal in modulating the pathogen-host interface milieu: (i) the presence of phages and (ii) the utilization of free sialic acids secreted from host cells by bifidobacteria.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1936-52091932025Oregon Wolfe barley genetic stocks – Research and teaching tools for next generation scientistse70004ENMargaret R.KrauseDepartment of Crop and Soil Science, Oregon State UniversityJuan DavidArbelaezDepartment of Crop Sciences, University of Illinois at Urbana-ChampaignÅsmundAsdalNordic Genetic Resource CentreRamziBelkodjaCIHEAM-ZaragozaNancyBouryDepartment of Plant Pathology, Entomology, and Microbiology, Iowa State UniversityVictoria C.BlakeDepartment of Plant Sciences and Plant Pathology, Montana State UniversityPatrick J.BrownDepartment of Plant Sciences, University of California-DavisAnaCasasDepartamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSICLuisCistuéDepartamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSICAlbaFarré‐MartínezAGROTECNIO-CERCA Center, Universidad de LleidaScottFiskDepartment of Crop and Soil Science, Oregon State UniversityGregory S.FuerstU.S. Department of Agriculture-Agricultural Research Service, Corn Insects and Crop Genetics Research Unit, Iowa State UniversityEstelaGiménezDepartment of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de MadridCarlaGuijarro‐RealDepartment of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de MadridKatyGuthrieDepartment of Agronomy and Plant Genetics, University of MinnesotaMargaretHalsteadAardevo North AmericaLauraHelgersonDepartment of Crop and Soil Science, Oregon State UniversityHiroshiHisanoInstitute of Plant Science and Resources, Okayama UniversityErnestoIgartuaDepartamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSICMortenLillemoDepartment of Plant Sciences, Norwegian University of Life SciencesMarinaMartínez‐GarcíaDepartment of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de MadridMarionaMartínez‐SubiràAGROTECNIO-CERCA Center, Universidad de LleidaSusanMcCouchPlant Breeding and Genetics Section, School of Integrative Plant Science, Cornell UniversityLaurieMcGheeColfax-Mingo Community High SchoolTravisNickolsDepartment of Crop and Soil Science, Oregon State UniversityNickPetersDepartment of Plant Pathology, Entomology, and Microbiology, Iowa State UniversityRaymondPorterHaupert Institute for Agricultural Studies, Huntington UniversityIgnacioRomagosaAGROTECNIO-CERCA Center, Universidad de LleidaAnja KarineRuudDepartment of Plant Sciences, Norwegian University of Life SciencesKazuhiroSatoInstitute of Plant Science and Resources, Okayama UniversitySilvioSalviDepartment of Agricultural and Food Sciences, University of BolognaGiuseppeSangiorgiDepartment of Agricultural and Food Sciences, University of BolognaRebekkaSchüllerDepartment of Crop Sciences, University of Illinois at Urbana-ChampaignTaner Z.SenCrop Improvement and Genetics Research Unit, U.S. Department of Agriculture-Agricultural Research ServiceJosé MiguelSorianoAGROTECNIO-CERCA Center, Universidad de LleidaRobert M.StuparDepartment of Agronomy and Plant Genetics, University of MinnesotaTo‐ChiaTingAgronomy Department, Purdue UniversityKellyViningDepartment of Crop and Soil Science, Oregon State UniversityMariavon KorffInstitute of Plant Genetics, Heinrich-Heine-Universität DüsseldorfAgathaWallaInstitute of Plant Genetics, Heinrich-Heine-Universität DüsseldorfDiane R.WangAgronomy Department, Purdue UniversityRobbieWaughDivision of Plant Sciences, School of Life Sciences, University of DundeeRoger P.WiseDepartment of Plant Pathology, Entomology, and Microbiology, Iowa State UniversityRobertWolfeAgriculture and Agri-Food CanadaEricYaoCrop Improvement and Genetics Research Unit, U.S. Department of Agriculture-Agricultural Research ServicePatrick M.HayesDepartment of Crop and Soil Science, Oregon State UniversityThe Oregon Wolfe Barley (OWB) mapping population (Reg. no. MP-4, NSL 554937 MAP) is a resource for genetics research and instruction. The OWBs are a set of doubled haploid barley (Hordeum vulgare L.) lines developed at Oregon State University from the F1 of a cross between Dr. Robert Wolfe's dominant and recessive marker stocks. Exhibiting a high level of genetic and phenotypic diversity, the OWBs are used throughout the world as a research tool for barley genetics. To date, these endeavors have led to 56 peer-reviewed publications, as well as three reports in the Barley Genetics Newsletter. At the same time, the OWBs are widely used as an instructor resource at the K–12, undergraduate, graduate, and professional levels. They are currently used at universities and/or institutes in German, Italy, Norway, Spain, and the United States and are currently being developed further for educational use in other countries. Genotype and phenotype data, lesson plans, and seed availability information are available herein and online.No potential conflict of interest relevant to this article was reported.Elsevier B.V.Acta Medica Okayama0304-41651869122025The F54L mutation of Thioredoxin shows protein instability and increased fluctuations of the catalytic center130860ENTakumiBabaLife Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 CenterGoUenoLife Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 CenterChikaOheLife Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 CenterShukuSajiStructural Biology Division, Japan Synchrotron Radiation Research InstituteSachikoYamamotoStructural Biology Division, Japan Synchrotron Radiation Research InstituteMasakiYamamotoLife Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 CenterHiroshiNakagawaMaterials Sciences Research Center, Japan Atomic Energy AgencyNobuoOkazakiNeutron Science and Technology Center, Comprehensive Research Organization for Science and Society (CROSS)MamoruOuchidaDepartment of Molecular Oncology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIoriKawasaki-OhmoriSection of Developmental Physiology and Pathology, Faculty of Education, Okayama UniversityKoheiTakeshitaLife Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 CenterThioredoxin is a ubiquitous redox protein that acts as an electron donor via its conserved dithiol motif (C32GPC35), catalyzing dithiol–disulfide exchange to regulate the redox state of target proteins. It supports antioxidant defense via peroxiredoxins, facilitates DNA synthesis by donating electrons to ribonucleotide reductase, and regulates redox-sensitive signaling pathways, including those controlling transcription and apoptosis. Neuronal degeneration and chronic kidney disease have been observed in Txn-F54L mutant rats; however, the details of why the Txn mutation causes these phenomena remain unknown. The present study aimed to elucidate the functional and structural changes caused by the F54L mutation. The Thioredoxin-F54L showed less insulin-reducing activity and more thermosensitivity to denaturation in the body temperature range compared to the wild type. The crystal structure revealed that F54 forms hydrophobic interactions with the surrounding hydrophobic amino acids. In addition, molecular dynamics simulation predicts increased fluctuations around the F54L mutation and a tendency for the distance between residues C32 and C35 at the catalytic center to be widened. The increased distance between residues C32 and C35 of the catalytic center may affect the reducing activity of the enzyme on the substrate. The finding that Thioredoxin-F54L is prone to denaturation at normal body temperature may reduce the normally functioning Thioredoxin. These molecular characteristics of Thioredoxin-F54L may be related to brain and kidney disease development in the Txn-F54L rats.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1071-26902025S100A8/A9-MCAM signaling promotes gastric cancer cell progression via ERK-c-Jun activationENYouyiChenDepartment of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of MedicineXuYangDepartment of Pathology, The First Affiliated Hospital, Zhejiang University School of MedicineRieKinoshitaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNahokoTomonobuDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBoPanThe First Affiliated Hospital, Zhejiang University School of MedicineFangpingWuSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical UniversityXuZhangDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of MedicineKazumiSagayamaFaculties of Educational and Research Management Field, Okayama UniversityBeiSunDepartment of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical UniversityMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesS100 protein family members S100A8 and S100A9 function primarily as a heterodimer complex (S100A8/A9) in vivo. This complex has been implicated in various cancers, including gastric cancer (GC). Recent studies suggest that these proteins play significant roles in tumor progression, inflammation, and metastasis. However, the exact mechanisms by which S100A8/A9 contributes to GC pathogenesis remain unclear. This study investigates the role of S100A8/A9 and its receptor in GC. Immunohistochemical analysis was performed on GC tissue samples to assess the expression of the S100A8/A9 receptor melanoma cell adhesion molecule (MCAM). In vitro transwell migration and invasion assays were used to evaluate the motility and invasiveness of GC cells. Cell proliferation was assessed using a growth assay, and Western blotting (WB) was employed to examine downstream signaling pathways, including ERK and the transcription factor c-Jun, in response to S100A8/A9–MCAM interaction. S100A8/A9 stimulation enhanced both proliferation and migration through MCAM binding in GC cell lines. These cellular events were accompanied by ERK activation and c-Jun induction. Downregulation of MCAM suppressed both ERK phosphorylation and c-Jun expression, highlighting the importance of the S100A8/A9‒MCAM‒ERK‒c-Jun axis in promoting GC progression. These findings indicate that S100A8/A9 contributes to GC progression via MCAM, which activates the ERK‒c-Jun pathway. The S100A8/A9‒signaling axis may represent a novel therapeutic target in GC.No potential conflict of interest relevant to this article was reported.American Institute of Mathematical Sciences (AIMS)Acta Medica Okayama2377-90981232025Biophysical regulation of extracellular matrix in systemic lupus erythematosus412437ENQiweiLiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityQiangLiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityZhaoyangXiaoDepartment of Anesthesiology, The Second Affiliated Hospital of Dalian Medical UniversityKeijiNARUSEDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySystemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by immune dysregulation and multi-organ damage. Recent advances have underscored the critical involvement of extracellular matrix (ECM) biophysical properties in shaping immune cell behavior and metabolic states that contribute to disease progression. This review systematically delineates the pathological remodeling of ECM biophysics in SLE, with a focus on their roles in mechanotransduction, immune-metabolic interplay, and organ-specific tissue injury. By integrating current evidence, we highlight how ECM-derived mechanical cues orchestrate aberrant immune responses and propose new perspectives for targeting ECM-immune crosstalk in the development of organ-specific, mechanism-based therapies for SLE.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2077-038314172025Evaluation of the Diagnostic Performance of the Brush/Biopsy Rapid On-Site Evaluation (B-ROSE) in Cases of Bile Duct Stricture: A Prospective, Pilot Study6207ENNaoHattoriDepartment of Gastroenterology, Okayama University HospitalDaisukeUchidaDepartment of Gastroenterology, Okayama University HospitalKeiHaradaDepartment of Gastroenterology, Okayama University HospitalRyosukeSatoDepartment of Gastroenterology, Okayama University HospitalTaisukeObataDepartment of Gastroenterology, Okayama University HospitalAkihiroMatsumiDepartment of Gastroenterology, Okayama University HospitalKazuyaMiyamotoDepartment of Gastroenterology, Okayama University HospitalHiroyukiTerasawaDepartment of Gastroenterology, Okayama University HospitalYukiFujiiDepartment of Gastroenterology, Okayama University HospitalKoichiroTsutsumiDepartment of Gastroenterology, Okayama University HospitalShigeruHoriguchiDepartment of Gastroenterology, Okayama University HospitalKazuyukiMatsumotoDepartment of Gastroenterology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology, Okayama University HospitalsettingsOrder Article Reprints
Open AccessArticle
Evaluation of the Diagnostic Performance of the Brush/Biopsy Rapid On-Site Evaluation (B-ROSE) in Cases of Bile Duct Stricture: A Prospective, Pilot Study
by Nao Hattori 1,Daisuke Uchida 1,2,*,Kei Harada 1,Ryosuke Sato 1ORCID,Taisuke Obata 1,Akihiro Matsumi 1ORCID,Kazuya Miyamoto 1ORCID,Hiroyuki Terasawa 1ORCID,Yuki Fujii 1,Koichiro Tsutsumi 1ORCID,Shigeru Horiguchi 1,Kazuyuki Matsumoto 1ORCID andMotoyuki Otsuka 1
1
Department of Gastroenterology, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
2
Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2025, 14(17), 6207; https://doi.org/10.3390/jcm14176207
Submission received: 23 June 2025 / Revised: 21 August 2025 / Accepted: 26 August 2025 / Published: 2 September 2025
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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Abstract
Background: Biliary strictures are diagnosed using endoscopic retrograde cholangiopancreatography (ERCP) with brush cytology and biopsy. However, brush cytology shows a sensitivity of 9–56.1% and a diagnostic accuracy of 43–65.4%, while biopsy demonstrates a sensitivity of 48%. Both methods exhibit high specificity but limited sensitivity. While rapid on-site evaluation (ROSE) is effective in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), its application in ERCP-obtained samples remains underexplored. Methods: This prospective pilot study was conducted at Okayama University Hospital from April 2019 to July 2024. Patients requiring ERCP-guided sampling for bile duct strictures were included. ROSE was applied to brush cytology with up to three additional attempts and to imprint cytology from biopsy samples with up to two attempts. Diagnostic accuracy was assessed based on pathology and clinical course. Results: Among 37 patients (median age: 73 years, add range, and male–female ratio: 27:10), 18 had hilar and 19 had distal bile duct strictures. Brush cytology required one, two, or three attempts in twenty-six, six, and five cases, respectively, whereas biopsy required one or two attempts in thirty-five and two cases, respectively. Among the thirty-seven cases, thirty-five were malignant and two were benign. The B-ROSE group showed a sensitivity, specificity, and accuracy of 71.4%, 100.0%, and 73.0%, respectively, compared to lower accuracy in the conventional group, where single brush cytology attempts yielded a sensitivity of 48.6% and an accuracy of 48.6%, and single biopsy attempts showed a sensitivity of 68.6% and an accuracy of 70.3%. Conclusions: B-ROSE improves diagnostic accuracy, reduces repeat sampling, and minimizes patient burden in ERCP-based diagnosis of bile duct strictures, making it a valuable addition to current diagnostic protocols.No potential conflict of interest relevant to this article was reported.Informa UK LimitedActa Medica Okayama1071-5762598-92025Pseudohypoxia induced by iron chelator activates tumor immune response in lung cancer570582ENYusukeHamadaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiakiOharaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYuehuaChenDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityManatoTeradaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYuzeWangDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHotakaKawaiDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasayoshiFujisawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTeizoYoshimuraDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAkihiroMatsukawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHypoxia-inducible factor (HIF) signaling plays a critical role in immune cell function. Pseudohypoxia is characterized as iron-mediated stabilization of HIF-1α under normoxic conditions, which can be induced by iron chelators. This study explored whether iron chelators exert antitumor effects by enhancing tumor immune responses and elucidating the underlying mechanisms. The iron chelators Super–polyphenol 10 (SP10) and Deferoxamine (DFO) were used to create iron-deficient and pseudohypoxia conditions. Pseudohypoxia induced by iron chelators stimulates IL-2 secretion from T cells and from both human and murine nonsmall cell lung cancer (NSCLC) cell lines (A549, PC-3, and LLC). Administration of SP10 reduced tumor growth when LLC tumors were implanted in C57BL/6 mice; however, this was not observed in immunodeficient RAG1-deficient C57BL/6 mice. SP10 itself did not directly inhibit LLC cells proliferation in vitro, suggesting an activation of the tumor immune response. SP10 synergistically enhanced the efficacy of PD-1 antibody therapy in lung cancer by increasing the number of tumor-infiltrating lymphocytes (TILs). In conclusion, iron chelation-induced pseudohypoxia activates tumor immune responses by directly upregulating HIF-1α, augmenting T cell function, and inducing IL-2 secretion from T cells, and cancer cells, thereby amplifying the immune efficacy of the PD-1 antibody in lung cancer treatment.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Prevalence of Streptococcus mutans harboring the cnm gene encoding cell surface protein Cnm in Japanese children27047ENYutoSuehiroDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaMakotoOkudaDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaMasatoshiOtsuguDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaMarinOchiaiDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaMisatoTakagiDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaFumikazuTojoDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaYusukeMikasaDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaShuheiNakaDepartment of Pediatric Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMichiyoMatsumoto-NakanoDepartment of Pediatric Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJinthanaLapirattanakulDepartment of Oral Microbiology, Faculty of Dentistry, Mahidol UniversityRenaOkawaDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaRyotaNomuraDepartment of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityKazuhikoNakanoDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaDental caries is a highly prevalent infectious disease primarily caused by the pathogenic bacterium Streptococcus mutans, which has also been associated with systemic disease. A 120-kDa collagen-binding protein (Cnm) produced by S. mutans contributes to cardiovascular disease pathogenicity. Few studies have addressed the current prevalence of S. mutans and the cnm gene in Japanese children or examined caries pathology in relation to cnm presence. Here, we investigated the prevalence of S. mutans and the distribution of cnm-positive S. mutans among 490 children who visited two university hospitals in Japan. The caries experience index (dmft/DMFT) was calculated, and the collagen-binding ability of cnm-positive S. mutans strains was assessed. S. mutans was isolated from the oral cavities of 158 patients (36.8%); 10.1% (16/158) harbored cnm-positive S. mutans. When caries experience indices were compared across dentitions, patients harboring cnm-positive strains had significantly higher dmft/DMFT scores than those with cnm-negative strains (P < 0.05). Additionally, a positive correlation was observed between the collagen-binding capacity of cnm-positive S. mutans and the dmft/DMFT score (r = 0.601, P < 0.05). These findings suggest that cnm contributes to caries progression through collagen-mediated adherence to tooth surfaces. The presence of cnm-positive S. mutans may represent a risk factor for increased caries susceptibility in children.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1865-72571912025Metachronic development of cholangiocarcinoma during treatment for IgG4-related sclerosing cholangitis2229ENKosakuMorimotoDepartment of Internal Medicine, Tsuyama Chuo HospitalKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalTakakiOkuyamaDepartment of Internal Medicine, Tsuyama Chuo HospitalShogoKimuraDepartment of Internal Medicine, Tsuyama Chuo HospitalKensukeTakeiDepartment of Internal Medicine, Tsuyama Chuo HospitalTakuyaSatomiDepartment of Internal Medicine, Tsuyama Chuo HospitalTsuyoshiOkadaDepartment of Surgery, Tsuyama Chuo HospitalSusumuShinouraDepartment of Surgery, Tsuyama Chuo HospitalReiShibataDepartment of Diagnostic Pathology, Tsuyama Chuo HospitalRyutaTakenakaDepartment of Internal Medicine, Tsuyama Chuo HospitalWe report a case of obstructive jaundice due to recurrent distal biliary stricture during 3 years of treatment for immunoglobulin G4 (IgG4)-related sclerosing cholangitis (IgG4-SC) associated with autoimmune pancreatitis. Although a relapse of IgG4-SC was initially suspected, imaging findings, laboratory tests, and histopathological examinations led to the diagnosis of metachronous cholangiocarcinoma. The patient underwent pancreaticoduodenectomy, and no cancer recurrence was noted 6 months postoperatively. Distal cholangiocarcinoma and IgG4-SC remission were observed in the resected specimen. In patients with recurrent biliary strictures during IgG4-SC treatment, comprehensive evaluations are essential because of the risk of disease relapse and development of metachronous cholangiocarcinoma.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2692-4609612025Adequacy evaluation of 22‐gauge needle endoscopic ultrasound‐guided tissue acquisition samples and glass slides preparation for successful comprehensive genomic profiling testing: A single institute experiencee70104ENTamiNagataniClinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYojiWaniDepartment of Pathology, Japanese Red Cross Society, Himeji Red Cross HospitalMasahiroTakataniDepartment of Internal Medicine, Japanese Red Cross Society, Himeji Red Cross HospitalSoichiroFushimiDepartment of Pathology, Japanese Red Cross Society, Himeji Red Cross HospitalHirofumiInoueDivision of Medical Support, Dentistry and Pharmaceutical Science, Okayama University Graduate School of MedicineShinichiroHoriDepartment of Internal Medicine, Japanese Red Cross Society, Himeji Red Cross HospitalKyoheiKaiDepartment of Genetic Medicine, Japanese Red Cross Society, Himeji Red Cross HospitalHidekiYamamotoClinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTetsuyaOkazakiClinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMakiTaniokaClinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiOkadaDepartment of Internal Medicine, Japanese Red Cross Society, Himeji Red Cross HospitalAkiraHirasawaClinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesObjectives: This study aimed to evaluate the successful sequencing rate of Foundation One CDx (F1CDx) using small tissue samples obtained with a 22-gauge needle (22G) through endoscopic ultrasound-guided fine needle acquisition (EUS-TA) and to propose guidelines for tissue quantity evaluation criteria and proper slide preparation in clinical practice.<br>
Methods: Between June 2019 and April 2024, 119 samples of 22G EUS-TA collected for F1CDx testing at Himeji Red Cross Hospital were retrospectively reviewed. Tissue adequacy was only assessed based on tumor cell percentage (≥20%). The procedure stopped when white tissue fragments reached 20 mm during macroscopic on-site evaluation. The specimens were prepared using both ‘tissue preserving sectioning’ to retain tissue within formalin-fixed paraffin-embedded blocks and the ‘thin sectioning matched needle gauge and tissue length’ method with calculation to ensure minimal unstained slides for the 1 mm3 sample volume criterion. Tissue area from HE slides and sample volume were measured, and F1CDx reports were analyzed.<br>
Results: Of 119 samples, 108 (90.8%) were suitable for F1CDx. Excluding the cases not submitted for testing, in the 45 cases where F1CDx was done using 22G EUS-TA samples, eight (17.8%) had a sum of tissue area tissue of 25 mm2 or greater in the HE-stained sample. However, all cases met the F1CDx 1 mm3 volume criterion by submitting > 30 unstained slides per sample. As a result, 43 of 45 cases (95.6%) were successfully analyzable.<br>
Conclusions: The 22G EUS-TA needle is an effective tool for providing the sufficient tissue volume required for F1CDx.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841782025Craniofacial Fibrous Dysplasia to Affect or Not the Optic Nerve in Long-Term Follow-Up of Three Casese91072ENToshihikoMatsuoDepartment of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama University HospitalTakehiroTanakaDepartment of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKiyoshiYamadaDepartment of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMitsuhiroOkanoDepartment of Otorhinolaryngology, School of Medicine, International University of Health and WelfareFibrous dysplasia of the bone is characterized by immature fibrous bones of trabeculae and fibrovascular proliferation in the medulla. In this study, we report three consecutive patients with craniofacial fibrous dysplasia with or without optic nerve involvement. In Case 1, a 43-year-old man with blurred vision in the right eye at the first visit was well until the age of 54 years, when he came back with symptoms suggestive of paranasal sinusitis. Computed tomography scans disclosed a mucocele in the right sphenoid sinus and thickened bilateral ethmoid, sphenoid, and frontal bones. He underwent an emergency nasal endoscopic surgery to make a drainage opening to the sphenoid and ethmoid sinuses on the right side with incomplete success. The pathology of the resected tissue confirmed fibrous dysplasia. With intravenous antibiotics, he recovered from blepharoptosis, complete ophthalmoplegia, and visual acuity decrease on the right side. He was well until the age of 71 years when he had a self-limiting episode of visual field cloudiness caused by the right sphenoid sinus mucocele. At the age of 75 years, he developed abrupt vision loss to no light perception in the right eye. He underwent an open skull surgery to extirpate the sphenoid mucocele on the right side and died of an unknown cause two years later. In Case 2, a 29-year-old man had a two-week-long headache, and computed tomography scans revealed fibrous dysplasia in the bilateral sphenoid bones. Nasal biopsy at the spheno-ethmoid recess proved a pathological diagnosis of fibrous dysplasia. Goldmann perimetry showed normal visual fields in both eyes. He was followed every year by magnetic resonance imaging to maintain normal visual fields until the latest visit at the age of 41 years. In Case 3, a 12-year-old girl was referred to an ophthalmologist to check her vision. She had been diagnosed with fibrous dysplasia of the left maxillary bone at the age of six years by a dentist. She had a gingival resection on the left maxilla at the age of 15 years and had a left maxillary bone resection at 18 years at another hospital. One month after the resection, Goldmann perimetry showed superior peripheral field depression in the left eye, in contrast with the normal visual field in the right eye. She maintained the visual acuity of 1.5 in both eyes until the last visit at the age of 21 years. In fibrous dysplasia as a rare disease, functional and cosmetic problems, including vision problems, should be considered in a case-based approach.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2227-905912102024Development and Characterization of a Three-Dimensional Organotypic In Vitro Oral Cancer Model with Four Co-Cultured Cell Types, Including Patient-Derived Cancer-Associated Fibroblasts2373ENYukaAizawaDivision of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityKentaHagaDivision of Reconstructive Surgery for Oral and Maxillofacial Region, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityNagakoYoshibaDepartment of Oral Health and Welfare, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityWitsanuYortchanDivision of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityShoTakadaDivision of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityRintaroTanakaDivision of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityErikoNaitoDivision of Oral and Maxillofacial Surgery, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityTatsuyaAbéDivision of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversitySatoshiMaruyamaDivision of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityManabuYamazakiDivision of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityJun-ichiTanumaDivision of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityKazuyoIgawaNeutron Therapy Research Center, Okayama UniversityKeiTomiharaDivision of Oral and Maxillofacial Surgery, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityShinsakuTogoDepartment of Respiratory Medicine, Graduate School of Medicine, Juntendo UniversityKenjiIzumiDivision of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityBackground/Objectives: Cancer organoids have emerged as a valuable tool of three-dimensional (3D) cell cultures to investigate tumor heterogeneity and predict tumor behavior and treatment response. We developed a 3D organotypic culture model of oral squamous cell carcinoma (OSCC) to recapitulate the tumor–stromal interface by co-culturing four cell types, including patient-derived cancer-associated fibroblasts (PD-CAFs). Methods: A stainless-steel ring was used twice to create the horizontal positioning of the cancer stroma (adjoining normal oral mucosa connective tissue) and the OSCC layer (surrounding normal oral mucosa epithelial layer). Combined with a structured bi-layered model of the epithelial component and the underlying stroma, this protocol enabled us to construct four distinct portions mimicking the oral cancer tissue arising in the oral mucosa. Results: In this model, α-smooth muscle actin-positive PD-CAFs were localized in close proximity to the OSCC layer, suggesting a crosstalk between them. Furthermore, a linear laminin-γ2 expression was lacking at the interface between the OSCC layer and the underlying stromal layer, indicating the loss of the basement membrane-like structure. Conclusions: Since the specific 3D architecture and polarity mimicking oral cancer in vivo provides a more accurate milieu of the tumor microenvironment (TME), it could be crucial in elucidating oral cancer TME.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1422-00672692025The Possibility of Plasma Membrane Transporters as Drug Targets in Oral Cancers4310ENChiharuSogawaDepartment of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of TechnologyKatsumitsuShimadaDepartment of Clinical Phathophysiology, Matsumoto Dental UniversityKeisukeNakanoDepartment of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPlasma membrane transporters are increasingly recognized as potential drug targets for oral cancer, particularly oral squamous cell carcinoma (OSCC). These transporters play crucial roles in cancer cell metabolism, drug resistance, and the tumor microenvironment, making them attractive targets for therapeutic intervention. Among the two main families of plasma membrane transporters, ATP-binding cassette (ABC) transporters have long been known to be involved in drug efflux and contribute to chemoresistance in cancer cells. On the other hand, solute carriers (SLCs) are also a family of transporters that facilitate the transport of various substrates, including nutrients and drugs, and have recently been shown to contribute to cancer chemosensitivity, metabolism, and proliferation. SLC transporters have been identified as potential cancer biomarkers and therapeutic targets, and their expression profiles suggest that they could be utilized in precision oncology approaches. We summarize previous reports on the expression and role of ABC and SLC transporters in oral cancer and discuss their potential as therapeutic targets.No potential conflict of interest relevant to this article was reported.岡山大学大学院教育学研究科Acta Medica Okayama1883-24231892025二分脊椎症の病態理解に基づく教育現場での支援6774ENIoriOHMORI (KAWASAKI)Faculty of Education，Okayama UniversityMitsukoYAMANAKAOkayama prefectural Okayama east special needs school/10.18926/bgeou/69238 二分脊椎症のある子どもは、症状の個人差が大きく、肢体不自由特別支援学校だけでなく普通学級にも多く在籍している。本研究の目的は，二分脊椎症の病態に基づき、教育現場での支援の在り方について、先行研究の知見をまとめ、教育上の課題をあきらかにすることである。<br>
二分脊椎症には、下肢の運動障害と感覚障害、排泄障害に加え、水頭症をはじめとした様々な合併症があることから、運動面、生活面、認知面において適切な支援を要する。さらに、思春期以降になると、脊髄係留による疼痛の出現や、歩行能力の低下に注意する必要がある。神経因性膀胱による排尿障害を合併する場合は、清潔間欠導尿を行う。学校生活を楽しいと肯定的に捉えていた子どもたちのほとんどは、清潔間欠導尿を介助無しあるいは一部の介助のみで排尿することができていた。このことから、担任は、身体的、認知的な支援と配慮に加え、多職種と密な連携を取りながら清潔間欠自己導尿を目指した自立活動の指導を進めることと、良好な友人関係を築くための支援を行うことが重要と思われた。No potential conflict of interest relevant to this article was reported.BMJActa Medica Okayama2053-36241212025Clinical impact of combined assessment of myocardial inflammation and fibrosis using myocardial biopsy in patients with dilated cardiomyopathy: a multicentre, retrospective cohort studye003250ENTakafumiNakayamaDepartment of Cardiology, Nagoya City University Graduate School of Medical SciencesKeiko OhtaOgoDepartment of Pathology, National Cerebral and Cardiovascular CenterYasuoSuganoDepartment of Cardiology, Keiyu HospitalTetsuroYokokawaDepartment of Cardiovascular Medicine, Fukushima Medical UniversityHiromitsuKanamoriDepartment of Cardiology, Gifu University Graduate School of MedicineYoshihikoIkedaDepartment of Pathology, National Cerebral and Cardiovascular CenterMichiakiHiroeDepartment of Cardiology, National Center for Global Health and MedicineKintaHatakeyamaDepartment of Pathology, National Cerebral and Cardiovascular CenterHatsueIshibashi-UedaDepartment of Pathology, National Cerebral and Cardiovascular CenterKazufumiNakamuraCenter for Advanced Heart Failure, Okayama University HospitalKaoruDohiDepartment of Cardiology and Nephrology, Mie University Graduate School of MedicineToshihisaAnzaiDepartment of Cardiovascular Medicine, Hokkaido University Graduate School of MedicineYoshihiroSeoDepartment of Cardiology, Nagoya City University Graduate School of Medical SciencesKyokoImanaka-YoshidaDepartment of Pathology and Matrix Biology, Mie University Graduate School of MedicineBackground Among patients with dilated cardiomyopathy (DCM), myocardial inflammation and fibrosis are risk factors for poor clinical outcomes. Here, we investigated the combined prognostic value of these two factors, as evaluated using myocardial biopsy samples.<br>
Methods This retrospective and multicentre study included patients with DCM—defined as LVEF of ≤45% and left diastolic diameter of >112% of predicted value, without evidence of secondary or ischaemic cardiomyopathy. In myocardial biopsy samples, inflammatory cells were counted using immunohistochemistry, and Masson’s Trichrome staining was performed to quantify the myocardial fibrosis as collagen area fraction (CAF). Higher myocardial inflammation was defined as leucocytes of ≥14/mm², including ≤4 monocytes/mm², with CD3+ T lymphocytes of≥7/mm². Greater myocardial fibrosis was defined as CAF of>5.9% by the Youden’s index. The primary endpoint was cardiac death or left ventricular assist device implantation.<br>
Results A total of 255 DCM patients were enrolled (average age, 53.1 years; 78% males). Within this cohort, the mean LVEF was 28.0%, mean CAF was 10.7% and median CD3+ cell count was 8.3/mm2. During the median follow-up period of 2688 days, 46 patients met the primary endpoint. Multivariable Cox proportional hazard analyses revealed that CD3+ cell count and CAF were independent determinants of the primary endpoint. Kaplan–Meier analysis showed that patients with both higher myocardial inflammation and greater fibrosis had the worst prognosis (log-rank p<0.001). When myocardial inflammation was graded as one of three degrees: T lymphocytes of <13/mm² (low); 13 of 13.1–23.9/mm² (moderate); and T lymphocytes of ≥24 /mm² (high), patients with moderate inflammation exhibited a superior survival rate when CAF was ≤5.9%, but a worse survival rate when CAF was >5.9%.<br>
Conclusions Having both biopsy-proven higher myocardial inflammation and greater fibrosis predicted the worst clinical prognosis in patients with DCM.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1071-269060102024NCF-1 plays a pivotal role in the survival of adenocarcinoma cells of pancreatic and gastric origins11511159ENChiemiFuruya-IkudeDivision of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical UniversityAkaneKittaDivision of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical UniversityNaokoTomonobuDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshihiroKawasakiDivision of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical UniversityMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesEisakuKondoDivision of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical UniversityReactive oxygen species (ROS) play a pivotal biological role in cells, with ROS function differing depending on cellular conditions and the extracellular environment. Notably, ROS act as cytotoxic factors to eliminate infectious pathogens or promote cell death under cellular stress, while also facilitating cell growth (via ROS-sensing pathways) by modifying gene expression. Among ROS-related genes, neutrophil cytosolic factor-1 (NCF-1; p47phox) was identified as a ROS generator in neutrophils. This product is a subunit of a cytosolic NADPH oxidase complex activated in response to pathogens such as bacteria and viruses. NCF-1 has been examined primarily in terms of ROS-production pathways in macrophages and neutrophils; however, the expression of this protein and its biological role in cancer cells remain unclear. Here, we report expression of NCF-1 in pancreatic and gastric cancers, and demonstrate its biological significance in these tumor cells. Abundant expression of NCF-1 was observed in pancreatic adenocarcinoma (PDAC) lines and in patient tissues, as well as in gastric adenocarcinomas. Accumulation of the protein was also detected in the invasive/metastatic foci of these tumors. Unexpectedly, BxPC-3 underwent apoptotic cell death when transfected with a small interfering RNA (siRNA) specific to NCF-1, whereas the cells treated with a control siRNA proliferated in a time-dependent manner. A similar phenomenon was observed in HSC-58, a poorly differentiated gastric adenocarcinoma line. Consequently, the tumor cells highly expressing NCF-1 obtained coincident accumulation of ROS and reduced glutathione (GSH) with expression of glutathione peroxidase 4 (GPX4), a quencher involved in ferroptosis. Unlike the conventional role of ROS as a representative cytotoxic factor, these findings suggest that NCF-1-mediated ROS generation may be required for expansive growth of PDAC and gastric cancers.No potential conflict of interest relevant to this article was reported.Japanese Society of Internal MedicineActa Medica Okayama0918-291863122024Gastric Mucosa-associated Lymphoid Tissue Lymphoma That Relapsed after 11 Years Subsequent to Achieving Complete Remission16971702ENShokoInooDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University HospitalYoshiroKawaharaDepartment of Practical Gastrointestinal Endoscopy, Okayama University HospitalMotoyukiOotukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesA 38-year-old Japanese man was diagnosed with extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue in the stomach (gastric MALT lymphoma). Fluorescence in situ hybridization analysis revealed the absence of t (11;18) (q21;q21) translocation but the presence of extra copies of MALT1, indicating tetrasomy 18. Helicobacter pylori eradication led to complete remission (CR). However, the gastric MALT lymphoma relapsed after 11 years old. This case underscores the need for long-term observation (>10 years) of patients with gastric MALT lymphoma. Further investigation is warranted to elucidate the correlation between trisomy/tetrasomy 18 and the recurrence propensity.No potential conflict of interest relevant to this article was reported.Japanese Society of Internal MedicineActa Medica Okayama0918-291863102025Idiopathic Gastric Antral Ulcers13671371ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSeijiKawanoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshiroKawaharaDepartment of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesA Japanese woman presented with gastric antral ulcers accompanied by erosion and edema, demonstrating a chronic pattern of improvement and recurrence for more than six years. The patient had no relevant treatment history, and Helicobacter pylori infection was ruled out. Other potential etiologies contributing to gastric ulcers were eliminated on the basis of endoscopic biopsy and blood laboratory findings. Consequently, the patient was diagnosed with idiopathic gastric antral ulcer. This disease is often overlooked, and the chronological endoscopic images provided in this report can be used as a reference.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7942025A Rare Presentation of Pneumonic-Type Adenocarcinoma Hidden behind Empyema305309ENSatoruSenooDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterEitoNimanDepartment of General Thoracic Surgery, National Hospital Organization Fukuyama Medical CenterRyokoTsujiDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterKoheiTakataDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterShunsukeMatsumoriDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterFumikaMuranoDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterYukaSugisakiDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterHirokiOmoriDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterAkihikoTaniguchiDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterRikaOmoteDepartment of Diagnostic Pathology, National Hospital Organization Fukuyama Medical CenterEikiIchiharaDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterKenjiTakahashiDepartment of General Thoracic Surgery, National Hospital Organization Fukuyama Medical CenterToshiakiOkadaDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterCase Report10.18926/AMO/69158Pneumonic-type adenocarcinoma (P-ADC) can closely mimic pneumonia. We report a P-ADC initially diagnosed as pneumonia which developed into a pulmonary abscess and empyema. A 50-year-old Japanese male diagnosed with pneumonia, pulmonary abscess, and empyema was administered antibiotics and a chest tube for drainage, which improved his symptoms and blood test results. However, chest computed tomography showed an enlarged infiltrative shadow. The patient underwent bronchoscopy and was diagnosed with an adenocarcinoma. This case highlights the importance of considering P-ADC in differential diagnoses when a pneumonia-like shadow enlarges post-empyema treatment. Diagnostic and clinical tests, e.g., bronchoscopy, should be performed in such cases.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7942025Pulmonary Calcium Phosphate Cement Embolism After Percutaneous Vertebroplasty for Thoracic Vertebrae Fractures299303ENRuibinFengDepartment of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical UniversityBikangZhuDepartment of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical UniversityDanyunWeiDepartment of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical UniversityDingjiaoZhuDepartment of Radiology, the Ninth Affiliated Hospital of Guangxi Medical UniversityCairuChenDepartment of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical UniversityCase Report/10.18926/AMO/69157Pulmonary cement embolism (PCE) is a rare but severe complication following percutaneous vertebroplasty (PVP). Calcium phosphate cement (CPC) has emerged as an alternative to traditional materials for vertebral augmentation. There appear to be no established guidelines for managing symptomatic PCE, and there is scarce literature on CPC embolisms. This is a first report of a case of pulmonary CPC embolism following PVP. The patient, a 63-year-old Chinese female, was administered anticoagulant treatment and achieved a satisfactory outcome. Her case highlights the severe potential morbidity associated with CPC leakage and emphasizes the efficacy of anticoagulant treatment for managing pulmonary CPC embolisms.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7942025Anterior Uveitis Secondary to an Infected Postoperative Maxillary Cyst283286ENYutaImamuraDepartment of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYusukeShiodeDepartment of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShuheiKimuraDepartment of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMioHosokawaDepartment of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoMatobaDepartment of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiKanzakiDepartment of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyaKindoDepartment of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTetsuroMoritaDepartment of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAyaMuraiDepartment of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMizuoAndoDepartment of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiMorizaneDepartment of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report/10.18926/AMO/69154A 76-year-old man presented with right eyelid swelling and deteriorated vision. Examination revealed anterior uveitis with hypopyon and a visual acuity of 20/2,000 in the right eye, with no abnormalities in the left. Computed tomography revealed enlargement of the right maxillary sinus and internal fluid accumulation, suggesting a postoperative maxillary cyst (POMC). Nasal endoscopic surgery drained the pus by opening the lower wall of the maxillary cyst. Following the procedure, intraocular inflammation resolved, and visual acuity in the right eye improved to 24/20. This is the first reported case of uveitis secondary to POMC.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0387-76044712025Hypotheses of pathophysiological mechanisms in epileptic encephalopathies: A review104318ENKatsuhiroKobayashiDepartment of Pediatrics, Asahigawaso Rehabilitation and Medical CenterTakashiShibataDepartment of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirokiTsuchiyaDepartment of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMariAkiyamaDepartment of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomoyukiAkiyamaDepartment of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIntroduction: Epileptic encephalopathy (EE) is a serious clinical issue that manifests as part of developmental and epileptic encephalopathy (DEE), particularly in childhood epilepsy. In EE, neurocognitive functions and behavior are impaired by intense epileptiform electroencephalogram (EEG) activity. Hypotheses of pathophysiological mechanisms behind EE are reviewed to contribute to an effective solution for EE.<br>
Review: Current hypotheses are as follows: 1) neuronal dysfunction based on genetic abnormalities that may affect neurocognitive functions and epilepsy separately; 2) impairment of synaptic homeostasis during sleep that may be responsible for DEE/EE with spike-and-wave activation in sleep; 3) abnormal subcortical regulation of the cerebral cortex; 4) abnormal cortical metabolism and hemodynamics with impairment of the neural network including default mode network; 5) neurotransmitter imbalance and disordered neural excitability; 6) the effects of neuroinflammation that may be caused by epileptic seizures and in turn aggravate epileptogenesis; 7) the interaction between physiological and pathological high-frequency EEG activity; etc. The causal relationship between epileptiform EEG activity and neurocognitive dysfunctions is small in DEE based on genetic abnormalities and it is largely unestablished in the other hypothetical mechanisms.<br>
Conclusion: We have not yet found answers to the question of whether the single-central or multiple derangements are present and what seizures and intense epileptiform EEG abnormalities mean in EE. We need to continue our best efforts in both aspects to elucidate the pathophysiological mechanisms of DEE/EE and further develop epilepsy treatment and precision medicine.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2045-763414152025Real‐World Data of Comprehensive Cancer Genomic Profiling Tests Performed in the Routine Clinical Setting in Sarcomae71098ENEijiNakataDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDaisukeEnnishiCenter for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTatsunoriOsoneDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakutoItanoDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomohiroFujiwaraDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshiyukiKunisadaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNaoyukiIdaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHidekiYamamotoDepartment of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMashuFutagawaDepartment of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTatsunoriShimoiDepartment of Medical Oncology, National Cancer Center HospitalHiroyukiYanaiDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAkiraHirasawaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShinichiToyookaCenter for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasahiroTabataCenter for Clinical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesIntroduction: Next-generation sequencing-based comprehensive cancer genomic profiling (CGP) tests are beneficial for refining diagnosis and personalized treatment of various cancers. However, the clinical impact of CGP, as covered by public health insurance in the management of sarcomas, remains unknown. Especially, the data on the utility of the newly emerging dual DNA–RNA panel compared to the conventional DNA-only panel in clinical settings is lacking. Therefore, we evaluated the utility of CGP in routine clinical practice for sarcoma treatment.<br>
Patients and Methods: In this study, three types of DNA panel and one DNA–RNA panel, reimbursed by Japanese public health insurance, were utilized. We detected oncogenic and druggable gene mutations and genotype-matched therapies.<br>
Results: One hundred and thirty-six patients were included in this study. Based on the detection of highly histology-specific translocations in the sequencing results, 2.2% of patients were re-classified. In patients with translocation-related sarcomas, a DNA–RNA panel identified more histology-specific fusion genes than DNA panels (p = 0.0035). Specifically, 86.8% and 39.0% of patients had oncogenic and druggable genomic alterations, respectively. Of these, 9.6% underwent genotype-matched therapy, with a 36.3% response rate and an 81.8% disease control rate. Patients who were administered genomically matched therapy had better overall survival (OS) than those who did not in patients with metastatic or advanced sarcoma with no prior chemotherapy (3-year OS: 83.3% vs. 48.0%, p = 0.42). Patients with TP53 and RB1 mutations had worse OS than those without. Germline findings were detected in 11.0% of the patients, one of whom had a truly germline origin.<br>
Conclusions: This study suggests that publicly reimbursed CGP tests, particularly the dual DNA–RNA panel, could be beneficial for refining diagnostic precision in selected sarcoma subtypes, treatment decisions, detecting the germline findings, and prognosis prediction in routine clinical settings for sarcoma. The implementation of genotype-matched therapies showed favorable clinical outcomes and improved the prognosis.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0028-083663880492025Immune evasion through mitochondrial transfer in the tumour microenvironment225236ENHidekiIkedaDivision of Cell Therapy, Chiba Cancer Center Research InstituteKatsushigeKawaseDivision of Cell Therapy, Chiba Cancer Center Research InstituteTatsuyaNishiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomofumiWatanabeDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeizoTakenagaDivision of Innovative Cancer Therapeutics, Chiba Cancer Center Research InstituteTakashiInozumeDivision of Cell Therapy, Chiba Cancer Center Research InstituteTakamasaIshinoDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShoAkiDivision of Nutriomics and Oncology, RCAST, The University of TokyoJasonLinDivision of Cell Therapy, Chiba Cancer Center Research InstituteShusukeKawashimaDivision of Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan Department of Dermatology, Graduate School of Medicine, Chiba UniversityJojiNagasakiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoukiUedaDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShinichiroSuzukiDepartment of Medical Oncology, Kindai University Faculty of MedicineHidekiMakinoshimaTsuruoka Metabolomics Laboratory, National Cancer CenterMakikoItamiDepartment of Surgical Pathology, Chiba Cancer CenterYukiNakamuraDivision of Cell Therapy, Chiba Cancer Center Research InstituteYasutoshiTatsumiDivision of Cell Therapy, Chiba Cancer Center Research InstituteYusukeSuenagaLaboratory of Evolutionary Oncology, Chiba Cancer Center Research InstituteTakaoMorinagaDivision of Cell Therapy, Chiba Cancer Center Research InstituteAkikoHonobe-TabuchiDepartment of Dermatology, Faculty of Medicine, University of YamanashiTakehiroOhnumaDepartment of Dermatology, Faculty of Medicine, University of YamanashiTatsuyoshiKawamuraDepartment of Dermatology, Faculty of Medicine, University of YamanashiYoshiyasuUmedaDepartment of Skin Oncology/Dermatology, Saitama Medical University International Medical CenterYasuhiroNakamuraDepartment of Skin Oncology/Dermatology, Saitama Medical University International Medical CenterYukikoKiniwaDepartment of Dermatology, Shinshu University School of MedicineEikiIchiharaDepartment of Allergy and Respiratory Medicine, Okayama University HospitalHidetoshiHayashiDepartment of Medical Oncology, Kindai University Faculty of MedicineJun-ichiroIkedaDepartment of Diagnostic Pathology, Graduate School of Medicine, Chiba UniversityToyoyukiHanazawaDepartment of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of MedicineShinichiToyookaDepartment of General Thoracic Surgery and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroyukiManoDivision of Cellular Signalling, National Cancer Center Research InstituteTakujiSuzukiDepartment of Respirology, Graduate School of Medicine, Chiba UniversityTsuyoshiOsawaDivision of Nutriomics and Oncology, RCAST, The University of TokyoMasahitoKawazuDivision of Cell Therapy, Chiba Cancer Center Research InstituteYosukeTogashiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityCancer cells in the tumour microenvironment use various mechanisms to evade the immune system, particularly T cell attack1. For example, metabolic reprogramming in the tumour microenvironment and mitochondrial dysfunction in tumour-infiltrating lymphocytes (TILs) impair antitumour immune responses2,3,4. However, detailed mechanisms of such processes remain unclear. Here we analyse clinical specimens and identify mitochondrial DNA (mtDNA) mutations in TILs that are shared with cancer cells. Moreover, mitochondria with mtDNA mutations from cancer cells are able to transfer to TILs. Typically, mitochondria in TILs readily undergo mitophagy through reactive oxygen species. However, mitochondria transferred from cancer cells do not undergo mitophagy, which we find is due to mitophagy-inhibitory molecules. These molecules attach to mitochondria and together are transferred to TILs, which results in homoplasmic replacement. T cells that acquire mtDNA mutations from cancer cells exhibit metabolic abnormalities and senescence, with defects in effector functions and memory formation. This in turn leads to impaired antitumour immunity both in vitro and in vivo. Accordingly, the presence of an mtDNA mutation in tumour tissue is a poor prognostic factor for immune checkpoint inhibitors in patients with melanoma or non-small-cell lung cancer. These findings reveal a previously unknown mechanism of cancer immune evasion through mitochondrial transfer and can contribute to the development of future cancer immunotherapies.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2475-0328862024High risk of multiple gastric cancers in Japanese individuals with Lynch syndrome10081016ENNobuhikoKanayaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThijs A.van SchaikDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical SchoolHidekiAokiDepartment of Surgery, National Hospital Organization Iwakuni Clinical CenterYumikoSatoDepartment of Pathology, National Hospital Organization Iwakuni Clinical CenterFumitakaTaniguchiDepartment of Surgery, National Hospital Organization Iwakuni Clinical CenterKunitoshiShigeyasuDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKokichiSuganoDepartment of Genetic Medicine, Kyoundo Hospital, SSasaki FoundationKiwamuAkagiDivision of Molecular Diagnosis and Cancer Prevention, Saitama Cancer CenterHideyukiIshidaDepartment of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical UniversityKohjiTanakayaDepartment of Surgery, National Hospital Organization Iwakuni Clinical CenterAim: Lynch syndrome (LS) is a dominantly inherited syndrome characterized by an increased risk for LS associated tumors such as colorectal cancer (CRC) and gastric cancer (GC). However, the clinical benefit of surveillance for GC remains unclear while it has already been recommended for CRC. This study aimed to elucidate the clinical features of GC in Japanese individuals with LS, and the risk of developing multiple GCs to build regional-tailored surveillance programs in LS patients with GC.<br>
Methods: Data on Japanese individuals with LS were retrospectively collected from a single institution. The clinical features of GC, including the cumulative risk of multiple GCs, were analyzed.<br>
Results: Among 96 individuals with LS (MLH1/MSH2/MSH6, 75:20:1), 32 GC lesions were detected in 15 individuals with LS (male/female, 11:4). The median age at initial GC diagnosis was 52.7 y (range: 28–71). Histological examination revealed a predominance of intestinal type (19/24: 87.5%). Moreover, the majority of the GC lesions (82%) were determined to have high-frequency of microsatellite instability. The cumulative risk of individuals with LS developing GC at 70 y was 31.3% (MLH1 36.1%, MSH2 18.0%). Notably, the cumulative risk of individuals with LS developing metachronous and/or synchronous GCs at 0, 10 and 20 y after initial diagnosis of GC was 26.7%, 40.7%, and 59.4%, respectively.<br>
Conclusion: Due to a higher risk of developing multiple GCs, intensive surveillance might be especially recommended for Japanese individuals with LS associated initial GC.No potential conflict of interest relevant to this article was reported.Spandidos PublicationsActa Medica Okayama2049-94502332025Association of the expression of 5‑FU biomarkers with aging and prognosis in elderly patients with lung cancer treated with S‑1 adjuvant chemotherapy: Follow‑up results of the Setouchi Lung Cancer Group Study 120179ENJunichiSohDepartment of Thoracic Surgery, Okayama University HospitalHiromasaYamamotoDepartment of Thoracic Surgery, Okayama University HospitalNorihitoOkumuraDepartment of Thoracic Surgery, Kurashiki Central HospitalHiroyukiSuzukiDepartment of Chest Surgery, Fukushima Medical University HospitalMasaoNakataDepartment of General Thoracic Surgery, Kawasaki Medical School HospitalToshiyaFujiwaraDepartment of Thoracic Surgery, Hiroshima City Hiroshima Citizens HospitalKenicehiGembaDepartment of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Hiroshima 720‑0001, Japan; 8Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku HospitalIsaoSanoDepartment of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku HospitalTakujiFujinagaDepartment of General Thoracic Surgery, National Hospital Organization Nagara Medical CenterMasafumiKataokaDepartment of Surgery and Respiratory Center, Okayama Saiseikai General HospitalYasuhiroTerasakiDepartment of Respiratory Surgery, Saga Medical Center KoseikanNobukazuFujimotoDepartment of Medical Oncology and Respiratory Medicine, Okayama Rosai HospitalKazuhikoKataokaDepartment of Thoracic Surgery, National Hospital Organization Iwakuni Clinical CenterShinjiKosakaDepartment of Thoracic Surgery, Shimane Prefectural Central HospitalMotohiroYamashitaDepartment of Thoracic Surgery, National Hospital Organization Shikoku Cancer CenterHidetoshiInokawaDepartment of Thoracic Surgery, National Hospital Organization Yamaguchi‑Ube Medical CenterMasaakiInoueDepartment of Thoracic Surgery, Shimonoseki City HospitalHiroshigeNakamuraDivision of General Thoracic Surgery, Tottori University HospitalYoshinoriYamashitaDepartment of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer CenterYutaTakahashiDepartment of Thoracic Surgery, Okayama University HospitalHidejiroTorigoeDepartment of Thoracic Surgery, Okayama University HospitalHirokiSatoDepartment of Thoracic Surgery, Okayama University HospitalShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalHiroshigeYoshiokaDepartment of Thoracic Oncology, Kansai Medical University HospitalSatoshiMoritaDepartment of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of MedicineKeitaroMatsuoDivision of Cancer Epidemiology and Prevention, Aichi Cancer Center Research InstituteJunichiSakamotoTokai Central HospitalHiroshiDateDepartment of Thoracic Surgery, Kyoto University HospitalShinichiToyookaDepartment of Thoracic Surgery, Okayama University HospitalManaging elderly patients presents several challenges because of age‑related declines; however, age should not be the sole determinant for adjuvant treatment decisions in patients with non‑small cell lung cancer (NSCLC). Moreover, age may affect the expression of 5‑fluorouracil (5‑FU) biomarkers. The present study assessed: i) The effect of age on the expression levels of 5‑FU biomarkers by analyzing a public database; and ii) the ability of these biomarkers to predict clinical outcomes in elderly patients with NSCLC who underwent complete resection in the Setouchi Lung Cancer Group Study 1201 (SCLG1201) followed by S‑1 adjuvant chemotherapy. Changes in gene expression levels across age groups were assessed by analyzing The Cancer Genome Atlas (TCGA) database. The expression of 5‑FU biomarkers, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase, epidermal growth factor receptor (EGFR) and excision repair cross‑complementation group 1 (ERCC1), were assessed via quantitative reverse‑transcription PCR assays in 89 elderly patients (≥75 years) with NSCLC who received adjuvant chemotherapy with oral fluoropyrimidine prodrug S‑1 in the SLCG1201 trial. TCGA database analysis (n=955) showed that TS expression decreased significantly with aging, especially in the age group ≥75. In the SCLG1201 trial, univariate analysis revealed that EGFR upregulation and TS downregulation were correlated with favorable recurrence‑free survival (RFS) and overall survival (OS), respectively. Multivariate analysis demonstrated that pathological stage was an independent prognostic factor for both RFS and OS. EGFR mutations were associated with upregulation of DPD and EGFR, and downregulation of TS and ERCC1. In conclusion, although pathological stage is an independent prognostic factor for survival, EGFR upregulation and TS downregulation may be a greater predictor of clinical outcomes in elderly patients with NSCLC treated with S‑1 adjuvant chemotherapy. The age‑related decrease in TS expression supports the potential benefit of 5‑FU therapies in elderly patients. Nonetheless, further research is warranted to validate these results.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0003-497512012025Comparable Clinical Outcomes Between Segmentectomy and Lobectomy for NSCLC With Unsuspected N1/N2: A Multicenter Real-World Data Study8798ENTsuyoshiRyukoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikioOkazakiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Okayama University HospitalKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTsuyoshiUenoOkayama University Thoracic Surgery Study GroupToshiyaFujiwaraOkayama University Thoracic Surgery Study GroupMototsuguWatanabeOkayama University Thoracic Surgery Study GroupHidetoshiInokawaOkayama University Thoracic Surgery Study GroupTakahikoMisaoOkayama University Thoracic Surgery Study GroupHidejiroTorigoeOkayama University Thoracic Surgery Study GroupKazuhiroWashioOkayama University Thoracic Surgery Study GroupHiroyukiTaoOkayama University Thoracic Surgery Study GroupDaisukeOkutaniOkayama University Thoracic Surgery Study GroupMakioHayamaOkayama University Thoracic Surgery Study GroupMasashiUomotoOkayama University Thoracic Surgery Study GroupEijiYamadaOkayama University Thoracic Surgery Study GroupShinjiOtaniOkayama University Thoracic Surgery Study GroupTakeshiKurosakiOkayama University Thoracic Surgery Study GroupYujiYaginumaOkayama University Thoracic Surgery Study GroupEitoNimanOkayama University Thoracic Surgery Study GroupOsamuKawamataOkayama University Thoracic Surgery Study GroupHitoshiNishikawaOkayama University Thoracic Surgery Study GroupTomoakiOtsukaOkayama University Thoracic Surgery Study GroupTakeshiYoshikawaOkayama University Thoracic Surgery Study GroupTatsuroHayashiOkayama University Thoracic Surgery Study GroupShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground Segmentectomy for lung cancer has been increasingly performed. However, evidence regarding the necessity of additional surgical resection after the diagnosis of unsuspected N1 or N2 lymph node metastasis is limited.<br>
Methods We conducted a multicenter, real-world data study of patients with any clinical T and N0 non-small cell lung cancer (NSCLC) who underwent lobectomy or segmentectomy between 2012 and 2021 and who subsequently received a diagnosis of pathologic N1 or N2 lymph node metastasis. Patients were categorized into lobectomy and segmentectomy groups. We analyzed overall survival (OS), recurrence-free survival (RFS), cumulative recurrence rates, and recurrence patterns using both unadjusted and propensity score–adjusted cohorts.<br>
Results A total of 736 patients were in the lobectomy group, and 70 were in the segmentectomy group. In the unadjusted cohort, segmentectomy-treated patients were older, had a lower preoperative percentage of vital capacity, had smaller tumors, and received less postoperative adjuvant chemotherapy. The 5-year OS was significantly worse in the segmentectomy group (P = .011), with no significant differences in 5-year RFS or cumulative recurrence rates. In the propensity score–adjusted cohort, there were no significant differences in OS, RFS, or recurrence rates; however, the segmentectomy group had a higher rate of local recurrence.<br>
Conclusions In patients with unsuspected N1 or N2 NSCLC, analysis using a cohort adjusted for patient background with propensity scores revealed no differences in OS, RFS, or cumulative recurrence rates between segmentectomy and lobectomy. This finding suggests that additional resection of the remaining segments may not be necessary for these patients. However, the higher rate of local recurrence in the segmentectomy group warrants careful consideration.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1071-269060102024Enhanced design of pCMViR-TSC plasmid vector for sustainably high cargo gene expression in mammalian cells12151227ENMasakiyoSakaguchiDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineRieKinoshitaDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineNahokoTomonobuDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYoshihikoSakaguchiDepartment of Microbiology, Tokushima Bunri UniversityJunichiroFutamiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAkiraYamauchiDepartment of Biochemistry, Kawasaki Medical SchoolHitoshiMurataDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKen-ichiYamamotoDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTettaTakahashiDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYumaGoharaDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineToshikiOchiDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineFanJiangDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineNi Luh Gede YoniKomalasariFaculty of Medicine, Udayana UniversityYouyiChenDepartment of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of MedicineI Made WinarsaRumaFaculty of Medicine, Udayana UniversityI WayanSumardikaFaculty of Medicine, Udayana UniversityJinZhouMedical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of TechnologyTomokoHonjoDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityFutoshiKuribayashiDepartment of Biochemistry, Kawasaki Medical SchoolKazumiSagayamaOrganization for Research and Innovation Strategy, Okayama UniversityShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineEisakuKondoDivision of Tumor Pathology, Near InfraRed Photo-Immuno-Therapy Research Institute, Kansai Medical UniversityYusukeInoueFaculty of Science and Technology, Division of Molecular Science, Gunma UniversityThe first-generation pCMViR-TSC, implemented through the promoter sandwich rule, yields 10- to 100-fold higher gene expression than the standard plasmid used with the CMV (cytomegalovirus) or CAG promoter. However, the vector’s shortcomings limit its utility to transient expression only, as it is not suitable for establishing stable transformants in mammalian cells. To overcome this weakness, we here introduce the improved plasmid vector pSAKA-4B, derived from pCMViR-TSC as a second-generation chromosome-insertable vector. This vector facilitates the linear entry of the expression unit into the TTAA site of DNA universally with transposase assistance. The vector is helpful for the indefinite expression of our target gene. The new vector system is proven here to be efficient in establishing stable transformants with a high likelihood of positive clones that exhibit significantly elevated expression levels of the delivered foreign gene. This system, alongside the first-generation vector, is therefore instrumental for diverse basic research endeavors concerning genes, proteins, cells, and animals, and potentially for clinical applications such as gene therapy.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1432-053315012025Biallelic variants in DNAJC7 cause familial amyotrophic lateral sclerosis with the TDP-43 pathology19ENToruYamashitaDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOsamuYokotaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaikiOusakaDepartment of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHongmingSunDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiHaraguchiDepartment of Neurology, National Hospital Organisation Minami-Okayama Medical CentreRicardo SatoshiOta-ElliottDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChikaMatsuokaDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomohitoKawanoDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHanaeNakashima-YasudaDepartment of Psychiatry, Zikei HospitalYusukeFukuiDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYumikoNakanoDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyutaMoriharaDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatoHasegawaDepartment of Brain and Neurosciences, Tokyo Metropolitan Institute of Medical ScienceYasuyukiHosonoDepartment of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeishiTeradaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesManabuTakakiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiIshiuraDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons. ALS pathology primarily involves the failure of protein quality control mechanisms, leading to the accumulation of misfolded proteins, particularly TAR DNA-binding protein 43 (TDP-43). TDP-43 aggregation is a central pathological feature of ALS. Maintaining protein homeostasis is critical and facilitated by heat shock proteins (HSPs), particularly the HSP40 family, which includes co-chaperones such as DNAJC7. Here, we report a family with three siblings affected by ALS who carry a homozygous c.518dupC frameshift variant in DNAJC7, a member of the HSP40 family. All three patients exhibited progressive muscle weakness, limb atrophy, bulbar palsy, and respiratory failure. Pathological examination revealed degeneration of both upper and lower motor neurons, with phosphorylated TDP-43-positive neuronal cytoplasmic inclusions in the frontal and temporal cortices. Immunoblot analysis were consistent with a type B pattern of phosphorylated TDP-43 in the precentral gyrus. Immunohistochemistry and RNA sequencing analyses demonstrated a substantial reduction in DNAJC7 expression at both the protein and RNA levels in affected brain regions. In a TDP-43 cell model, DNAJC7 knockdown impaired the disassembly of TDP-43 following arsenite-induced stress, whereas DNAJC7 overexpression suppressed the assembly and promoted the disassembly of arsenite-induced TDP-43 condensates. Furthermore, in a zebrafish ALS model, dnajc7 knockdown resulted in increased TDP-43 aggregation in motor neurons and reduced survival. To the best of our knowledge, this study provides the first evidence linking biallelic loss-of-function variants in DNAJC7 to familial ALS with TDP-43 pathology.No potential conflict of interest relevant to this article was reported.American Society for MicrobiologyActa Medica Okayama2379-50421062025Mycobacterium tuberculosis bacillus induces pyroptosis in human lung fibroblastse00110-25ENTakemasaTakiiDepartment of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis AssociationHiroyukiYamadaDepartment of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis AssociationChihiroMotozonoDepartment of Molecular Immunology, Research Institute for Microbial Diseases, The University of OsakaShoYamasakiDepartment of Molecular Immunology, Research Institute for Microbial Diseases, The University of OsakaJordi B.TorrellesTexas Biomedical Research Institute and International Center for the Advancement of Research & Education (I•CARE)JoanneTurnerTexas Biomedical Research Institute and International Center for the Advancement of Research & Education (I•CARE)AoiKimishimaLaboratory of Applied Microbial Chemistry, Ōmura Satoshi Memorial Institute, Kitasato UniversityYukihiroAsamiLaboratory of Applied Microbial Chemistry, Ōmura Satoshi Memorial Institute, Kitasato UniversityNaoyaOharaDepartment of Oral Microbiology, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama UniversityShigeakiHidaDepartment of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City UniversityHidetoshiHayashiDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City UniversityKikuoOnozakiDepartment of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City UniversityWe previously reported that live, but not dead, virulent Mycobacterium tuberculosis (Mtb) H37Rv bacilli induce cell death in human lung fibroblast cell lines, MRC-5, MRC-9, and TIG-1. Here, using two distinct Mtb strains from two different lineages (HN878 lineage 2 and H37Rv lineage 4), we confirmed cell death at day 2 after infection with a device that measures cell growth/cytotoxicity in real time (Maestro-Z [AXION]). Mtb bacilli uptake by the fibroblast was confirmed with a transmission electron microscope on day 2. Expressions of inflammatory cytokines and interleukin (IL)−1β, IL-6, and IL-8 were observed when exposed to live, but not dead bacteria. The cell death of fibroblasts induced by both Mtb strains tested was prevented by caspase-1/4 and NLRP3 inflammasome inhibitors, but not by caspase-3 and caspase-9 inhibitors. Therefore, we classified the fibroblast cell death by Mtb infection as pyroptosis. To investigate the biological and pathological relevance of fibroblast cell death by Mtb infection, we performed dual RNA-Seq analysis on Mtb within fibroblasts and Mtb-infected fibroblasts at day 2. In Mtb bacilli tcrR, secE2, ahpD, and mazF8 genes were highly induced during infection. These genes play roles in survival in a hypoxic environment, production of a calcium-binding protein-inducing cytokine, and regulation of transcription in a toxin-antitoxin system. The gene expressions of IL-1β, IL-6, and IL-8, caspase-4, and NLRP3, but not of caspase-3 and caspase-9, were augmented in Mtb bacilli-infected fibroblasts. Taken together, our study suggests that Mtb bacilli attempt to survive in lung fibroblasts and that pyroptosis of the host fibroblasts activates the immune system against the infection.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2304-676712112024Coronal Cementum and Reduced Enamel Epithelium on Occlusal Surface of Impacted Wisdom Tooth in a Human348ENNaohiroHorieDivision of Reconstructive Surgery for Oral and Maxillofacial Region, School of Dentistry, Health Sciences University of HokkaidoMasaruMurataDivision of Regenerative Medicine, School of Dentistry, Health Sciences University of HokkaidoYasuhitoMinamidaDivision of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of HokkaidoHirokiNagayasuDivision of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of HokkaidoTsuyoshiShimoDivision of Reconstructive Surgery for Oral and Maxillofacial Region, School of Dentistry, Health Sciences University of HokkaidoToshiyukiAkazawaIndustrial Technology and Environment Research Development, Hokkaido Research OrganizationHidetsuguTsujigiwaDepartment of Life Science, Faculty of Science, Okayama University of ScienceYoussefHaikelDepartment of Biomaterials and Bioengineering, Institut National de la Santé et de la Recherche médicale Unité Mixte de Recherche (INSERM UMR) _S 1121, University of StrasbourgHitoshiNagatsukaDepartment of Oral Pathology and Medicine Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground: There is only limited research on the coronal cementum of a tooth, and the mechanisms of its forming process are not well-defined. This report presents a coronal cementum on the occlusal surfaces of enamel in an impacted wisdom tooth in a human, which is not nearly the cervical portion. Materials and Methods: The tooth (Tooth #1) was derived from a 46-year-old female. Histological analysis, including hematoxylin and eosin (HE) and toluidine blue (TB) staining, and Scanning Electron Microscopy and Energy Dispersive X-ray Spectrometer (SEM-EDS) analysis of the extracted tooth were conducted. Radiographic examination showed that Tooth #1 was horizontally impacted in the maxilla and had the apex of a single root placed between the buccal and palatal roots of Tooth #2. Results: Coronal cementum was distributed widely on the enamel, and reduced enamel epithelium was also found with enamel matrix proteins histologically. The formation of acellular cementum was observed to be more predominant than that of the cellular cementum in Tooth #1. SEM showed that the occlusal cementum connected directly with enamel. Calcium mapping revealed an almost similar occlusal cementum and enamel. In addition, the spectrum of elements in coronal cementum resembled the primary cementum according to SEM-EDS. Discussion: Thus, coronal cementogenesis in impacted human teeth might be related to the existence of reduced enamel epithelium.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0168-01022182025Alteration of perineuronal nets and parvalbumin interneurons in prefrontal cortex and hippocampus, and correlation with blood corticosterone in activity-based anorexia model mice104922ENHoang DuyNguyenDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHarukoMiyazakiDepartment of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHirokiKawaiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesZiyiWangDepartment of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesShinjiSakamotoDepartment of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesManabuTakakiDepartment of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesToshitakaOohashiDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAnorexia nervosa (AN) is an eating disorder characterized by restricted energy intake, severely underweight status, and frequent hyperactivity. Previous research has shown structural and functional alterations in the medial prefrontal cortex (mPFC) and hippocampus of AN patients. To investigate the pathological mechanism of AN, we analyzed the expression and distribution of parvalbumin (PV) interneurons and perineuronal nets (PNNs), which are implicated in the pathology of neuropsychiatric disorders, in the mPFC and hippocampus dorsal (HPCd) and ventral (HPCv) using an activity-based anorexia (ABA) mouse model. We found that PNN expression and density increased in the mPFC, with minor alterations in the HPCd and HPCv of ABA mice. The expression and distribution of PV neurons were unchanged in the brains of ABA mice, except for a regional decrease in PV-expressing neuron density in the HPCd. Co-localization analysis showed an increased number of PNNs enwrapping PV-negative neurons in the mPFC of ABA mice. Furthermore, the upregulation of PNN expression in the mPFC was positively correlated with elevated blood corticosterone levels, a well-known stress indicator, in ABA mice. Our findings suggest that the increased expression and distribution of PNNs surrounding PV-negative neurons in the mPFC may indicate the pathological mechanisms of AN.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2692-4609612025A Case of Gastric Atypical Lipomatous Tumor/Well‐Differentiated Liposarcoma With Endoscopic Morphological Changese70146ENRikaOmoteDepartment of Diagnostic Pathology, NHO Fukuyama Medical CenterShizumaOmoteDepartment of Internal Medicine, Fukuyama Minami HospitalHiroshiSonobeDepartment of Diagnostic Pathology, NHO Fukuyama Medical CenterRyosukeHamanoDepartment of Surgery, NHO Fukuyama Medical CenterTatsuyaToyokawaDepartment of Gastroenterology, NHO Fukuyama Medical CenterShinyaOtsukaDepartment of Surgery, NHO Fukuyama Medical CenterTakehiroTanakaDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiYanaiDepartment of Pathology, Okayama University HospitalMasaruInagakiDepartment of Surgery, NHO Fukuyama Medical CenterHidetakaYamamotoDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtypical lipomatous tumor/well-differentiated liposarcoma is a locally aggressive mesenchymal neoplasm composed of adipocytes and stromal cells. Gastric cases are exceedingly rare, and their malignant potential remains unclear. We report a case of a woman in her 60s who was found to have multiple submucosal tumor-like lesions of the stomach. Over time, the tumors increased in size, requiring a laparoscopic partial gastrectomy. Histological examination revealed a tumor composed of both fatty tissue and fibrous stroma with nuclear atypia. Immunohistochemistry showed positivity for CDK4 and MDM2, and fluorescence in situ hybridization confirmed MDM2 amplification, leading to a diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma. This case presented an unusual gastric manifestation, with multiple submucosal tumor-like lesions on endoscopy and exhibiting progressive morphological changes over several years.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0169-50021992025Real-world status of multimodal treatment of Stage IIIA-N2 non-small cell lung cancer in Japan: Results from the SOLUTION study, a non-interventional, multicenter cohort study108027ENHidehitoHorinouchiDepartment of Thoracic Oncology, National Cancer Center HospitalHaruyasuMurakamiDepartment of Thoracic Oncology, Shizuoka Cancer CenterHideyukiHaradaDivision of Radiation Therapy, Shizuoka Cancer CenterTomotakaSobueDivision of Environmental Medicine and Population Sciences, Graduate School of Medicine, Osaka UniversityTomohiroKatoDepartment of Respiratory Medicine, National Hospital Organization Himeji Medical CenteShinjiAtagiDepartment of Thoracic Oncology, National Hospital Organization Kinki-Chuo Chest Medical CenterToshiyukiKozukiDepartment of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer CenterTakaakiTokitoDivision of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University HospitalSatoshiOizumiDepartment of Respiratory Medicine, National Hospital Organization Hokkaido Cancer CenterMasahiroSeikeDepartment of Pulmonary Medicine and Oncology, Nippon Medical School HospitalKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalTadashiMioDepartment of Respiratory Medicine, National Hospital Organization Kyoto Medical CenterTakashiSoneDepartment of Respiratory Medicine, Kanazawa University HospitalChikakoIwaoDepartment of Medical, AstraZeneca K.K.TakeshiIwaneDepartment of Medical, AstraZeneca K.K.RyoKotoDepartment of Medical, AstraZeneca K.K.MasahiroTsuboiDepartment of Thoracic Surgery, National Cancer Center Hospital EastObjectives: There is limited consensus on resectability criteria for Stage IIIA-N2 non-small cell lung cancer (NSCLC). We examined the patient characteristics, N2 status, treatment decisions, and clinical outcomes according to the treatment modality for Stage IIIA-N2 NSCLC in Japan.<br>
Materials and methods: Patients with Stage IIIA-N2 NSCLC in Japan were consecutively registered in the SOLUTION study between 2013 and 2014. Patients were divided according to treatment (chemoradiotherapy [CRT], surgery + perioperative therapy [neoadjuvant and/or adjuvant therapy], surgery alone). Demographic characteristics, N2 status (number and morphological features), pathological information, and treatments were analyzed descriptively. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) were estimated using the Kaplan–Meier method.<br>
Results: Of 227 patients registered, 133 underwent CRT, 56 underwent surgery + perioperative therapy, and 38 underwent surgery alone. The physicians reported the following reasons for unresectability for 116 of 133 CRT patients: large number of metastatic lymph nodes (70.7 %), extranodal infiltration (25.0 %), poor surgical tolerance (19.0 %), or other reasons (18.1 %). CRT was more frequently performed in patients whose lymph nodes had an infiltrative appearance (64.3 %) and was the predominant treatment in patients with multiple involved stations (discrete: 60.0 %; infiltrative: 80.4 %). Distant metastasis with/without local progression was found in 50.4 %, 50.0 %, and 36.8 % of patients in the CRT, surgery + perioperative therapy, and surgery alone groups, respectively. The respective 3-year OS and DFS/PFS rates (median values) were as follows: surgery + perioperative therapy—61.9 % (not reached) and 37.1 % (22.4 months; DFS); CRT group—42.2 % (31.9 months) and 26.8 % (12.0 months; PFS); surgery alone group—37.7 % (26.5 months) and 28.7 % (12.6 months; DFS).<br>
Conclusion: This study has illuminated the real-world decision rules for choosing between surgical and non-surgical approaches in patients with Stage IIIA-N2 NSCLC. Our landmark data could support treatment decision making for using immune checkpoint inhibitors and targeted therapy for driver oncogenes in the perioperative therapy era.
No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2075-44181552025Review Article: Diagnostic Paradigm Shift in Spine Surgery594ENAras EfeLeventDepartment of Orthopedic Surgery, Okayama Rosai HospitalMasatoTanakaDepartment of Orthopedic Surgery, Okayama Rosai HospitalChetanKumawatDepartment of Orthopedic Surgery, Okayama Rosai HospitalChristianHengDepartment of Orthopedic Surgery, Okayama Rosai HospitalSalamalikisNikolaosDepartment of Orthopedic Surgery, Okayama Rosai HospitalKajetanLatkaDepartment of Orthopedic Surgery, Okayama Rosai HospitalAkiyoshiMiyamotoDepartment of Orthopedic Surgery, Okayama Rosai HospitalTadashiKomatsubaraDepartment of Orthopedic Surgery, Okayama Rosai HospitalShinyaAratakiDepartment of Orthopedic Surgery, Okayama Rosai HospitalYoshiakiOdaDepartment of Orthopedic Surgery, Okayama University HospitalKensukeShinoharaDepartment of Orthopedic Surgery, Okayama University HospitalKojiUotaniDepartment of Orthopedic Surgery, Okayama University HospitalMeticulous clinical examination is essential for spinal disorders to utilize the diagnostic methods and technologies that strongly support physicians and enhance clinical practice. A significant change in the approach to diagnosing spinal disorders has occurred in the last three decades, which has enhanced a more nuanced understanding of spine pathology. Traditional radiographic methods such as conventional and functional X-rays and CT scans are still the first line in the diagnosis of spinal disorders due to their low cost and accessibility. As more advanced imaging technologies become increasingly available worldwide, there is a constantly increasing trend in MRI scans for detecting spinal pathologies and making treatment decisions. Not only do MRI scans have superior diagnostic capabilities, but they also assist surgeons in performing meticulous preoperative planning, making them currently the most widely used diagnostic tool for spinal disorders. Positron Emission Tomography (PET) can help detect inflammatory lesions, infections, and tumors. Other advanced diagnostic tools such as CT/MRI fusion image, Functional Magnetic Resonance Imaging (fMRI), Upright and Kinetic MRI, magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI) could play an important role when it comes to detecting more special pathologies. However, some technical difficulties in the daily praxis and their high costs act as obstacles to their further spread. Integrating artificial intelligence and advancements in data analytics and virtual reality promises to enhance spinal procedures’ precision, safety, and efficacy. As these technologies continue to develop, they will play a critical role in transforming spinal surgery. This paradigm shift emphasizes the importance of continuous innovation and adaptability in improving the diagnosis and treatment of spinal disorders.No potential conflict of interest relevant to this article was reported.Microbiology SocietyActa Medica Okayama0022-131710672025Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses (ICTV) from the Animal dsRNA and ssRNA(−) Viruses Subcommittee, 2025002112ENHolly R.HughesCenters for Disease Control and PreventionMatthew J.BallingerBiological Sciences, Mississippi State UniversityYimingBaoNational Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of SciencesNicolasBejermanConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and Instituto Nacional de Tecnología Agropecuaria (INTA)Kim R.BlasdellCSIRO Health and BiosecurityThomasBrieseCenter for Infection and Immunity, and Department of Epidemiology, Mailman School of Public Health, Columbia UniversityJuliaBrignoneInstituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLISJean PaulCarreraInstituto Conmemorativo Gorgas de Estudios de la SaludLanderDe ConinckDivision of Clinical and Epidemiological Virology, KU LeuvenWilliam Marcielde SouzaDepartment of Microbiology, Immunology and Molecular Genetics, University of KentuckyHumbertoDebatInstituto Nacional de Tecnología Agropecuaria (INTA)Ralf G.DietzgenQAAFI, The University of QueenslandRalfDürrwaldRobert Koch InstitutMertErdinDepartment of Virology, University of HelsinkiAnthony R.FooksAnimal and Plant Health Agency (APHA)Kristian M.ForbesDepartment of Biological Sciences, University of ArkansasJulianaFreitas-AstúaEmbrapa Cassava and FruitsJorge B.GarciaInstituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLISJemma L.GeogheganDepartment of Microbiology and Immunology, University of OtagoRebecca M.GrimwoodDepartment of Microbiology and Immunology, University of OtagoMasayukiHorieOsaka International Research Center for Infectious Diseases, Osaka Metropolitan UniversityTimothy H.HyndmanSchool of Veterinary Medicine, Murdoch UniversityReimarJohneGerman Federal Institute for Risk AssessmentJohn D.KlenaViral Special Pathogens Branch, The Centers for Disease Control and PreventionHidekiKondoInstitute of Plant Science and Resources, Okayama UniversityEugene V.KooninComputational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of HealthAlexei Y.KostygovUniversity of OstravaMartKrupovicInstitut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology UnitJens H.KuhnIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of HealthMichaelLetkoPaul G. Allen School for Global Health, Washington State UniversityJun-MinLiInstitute of Plant Virology, Ningbo UniversityYiyunLiuNational Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of SciencesMaria LauraMartinInstituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLISNathanielMullDepartment of Natural Sciences, Shawnee State UniversityYaelNazarInstituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLISNorbertNowotnyCollege of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai HealthMárcio Roberto TeixeiraNunesUniversidade Federal do ParáArnfinn LoddenØklandPharmaq AnalytiqDennisRubbenstrothInstitute of Diagnostic Virology, Friedrich-Loeffler-InstitutBrandy J.RussellCenters for Disease Control and PreventionEricSchottInstitute of Marine and Environmental Technology, University of Maryland Center for Environmental ScienceStephanieSeifertPaul G. Allen School for Global Health, Washington State UniversityCarinaSenInstituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLISElizabethShedroffViral Special Pathogens Branch, The Centers for Disease Control and PreventionTarjaSironenDepartment of Virology, University of HelsinkiTeemuSmuraDepartment of Virology, University of HelsinkiCamila Prestes Dos SantosTavaresIntegrated Group of Aquaculture and Environmental Studies, Federal University of ParanáRobert B.TeshDepartment of Pathology, The University of Texas Medical BranchNatasha L.TilstonDepartment of Microbiology and Immunology, Indiana University School of MedicineNoëlTordoInstitut PasteurNikosVasilakisDepartment of Pathology, The University of Texas Medical BranchPeter J.WalkerUniversity of QueenslandFeiWangWuhan Institute of Virology, Chinese Academy of SciencesAnna E.WhitfieldNorth Carolina State UniversityShannon L.M.WhitmerViral Special Pathogens Branch, The Centers for Disease Control and PreventionYuri I.WolfComputational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of HealthHanXiaWuhan Institute of Virology, Chinese Academy of SciencesGong-YinYeInstitute of Insect Sciences, Zhejiang UniversityZhuangxinYeInstitute of Plant Virology, Ningbo UniversityVyacheslavYurchenkoUniversity of OstravaMingliZhaoDepartment of Pathobiology and Population Sciences, Royal Veterinary CollegeRNA viruses are ubiquitous in the environment and are important pathogens of humans, animals and plants. In 2024, the International Committee on Taxonomy of Viruses Animal dsRNA and ssRNA(−) Viruses Subcommittee submitted 18 taxonomic proposals for consideration. These proposals expanded the known virosphere by classifying 9 new genera and 88 species for newly detected virus genomes. Of note, newly established species expand the large family of Rhabdoviridae to 580 species. A new species in the family Arenaviridae includes a virus detected in Antarctic fish with a unique split nucleoprotein ORF. Additionally, four new species were established for historically isolated viruses with previously unsequenced genomes. Furthermore, three species were abolished due to incomplete genome sequence information, and one family was moved from being unassigned in the phylum Negarnaviricota into a subphylum and order. Herein, we summarize the 18 ratified taxonomic proposals and the general features of the current taxonomy, thereby supporting public and animal health responses.No potential conflict of interest relevant to this article was reported.Microbiology SocietyActa Medica Okayama0022-131710672025Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses from the Plant Viruses Subcommittee, 2025002114ENLuisaRubinoIstituto per la Protezione Sostenibile delle Piante, CNRPeterAbrahamianUSDA-ARS, BARC, National Germplasm Resources LaboratoryWenxiaAnLiaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang UniversityMiguel A.ArandaCentro de Edafología y Biología Aplicada del Segura-CSICJosé T.Ascencio-IbañezDepartment of Molecular and Structural Biochemistry, North Carolina State UniversityNicolasBejermanUnidad de Fitopatología y Modelización Agrícola (UFYMA) INTA-CONICETArnaud G.BlouinPlant Protection DepartmentThierryCandresseUMR 1332 Biologie du Fruit et Pathologie, University of Bordeaux, INRAETomasCantoMargarita Salas Center for Biological Research (CIB-CSIC) Spanish Council for Scientific Research (CSIC)MengjiCaoNational Citrus Engineering and Technology Research Center, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Citrus Research Institute, Southwest UniversityJohn P.CarrDepartment of Plant Sciences, University of CambridgeWon KyongChoAgriculture and Life Sciences Research Institute, Kangwon National UniversityFionaConstableAgriculture Victoria Research, Department of Energy, Environment and Climate Action and School of Applied Systems Biology, La Trobe UniversityIndranilDasguptaUniversity of Delhi South CampuHumbertoDebatUnidad de Fitopatología y Modelización Agrícola (UFYMA) INTA-CONICETRalf G.DietzgenQueensland Alliance for Agriculture and Food Innovation, The University of QueenslandMicheleDigiaroCIHEAM, Istituto Agronomico Mediterraneo of BariLiviaDonaireCentro de Edafología y Biología Aplicada del Segura-CSICTouficElbeainoCIHEAM, Istituto Agronomico Mediterraneo of BariDenisFargetteVirus South DataFionaFilardoQueensland Department of Primary IndustriesMatthias G.FischerMax Planck Institute for Marine MicrobiologyNuriaFontdevilaPlant Protection DepartmentAdrianFoxFera Science Ltd (Fera), York Biotech CampusJulianaFreitas-AstuaEmbrapa Cassava and Fruits, Brazilian Agricultural Research CorporationMarcFuchsPlant Pathology, Cornell UniversityAndrew D.W.GeeringQueensland Alliance for Agriculture and Food Innovation, The University of QueenslandMahanGhafariDepartment of Biology, University of OxfordAndersHafrénSwedish University of AgricultureJohnHammondUSDA-ARS, USNA, Floral and Nursery Plants Research UnitRosemarieHammondUSDA-ARS, BARC, Molecular Plant Pathology LaboratoryBeataHasiów-JaroszewskaInstitute of Plant Protection-NRIEugenieHebrardPHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute AgroCarmenHernándezInstituto de Biología Molecular y Celular de Plantas (IBMCP), Universitat Politècnica de Valencia-CSICJean-MichelHilyInstitut Français de la Vigne et du VinAhmedHosseiniVali-e-Asr University of Rafsanjan, Department of Plant ProtectionRogerHullRetired from John Innes CentreAlice K.Inoue-NagataEmbrapa HortaliçasRamonJordanUSDA-ARS, USNA, Floral and Nursery Plants Research UnitHidekiKondoInstitute of Plant Science and Resources, Okayama UniversityJan F.KreuzeInternational Potato Center (CIP)MartKrupovicInstitut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology UnitKenjiKubotaInstitute for Plant Protection, NAROJens H.KuhnIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of HealthScottLeisnerDepartment of Biological Sciences, University of ToledoJean-MichelLettCIRAD, UMR PVBMTChengyuLiLiaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang UniversityFanLiState Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural UniversityJun MinLiInstitute of Plant Virology, Ningbo UniversityPaola M.López-LambertiniInstituto de Patología Vegetal (IPAVE), INTA, Unidad de Fitopatología y Modelización Agrícola (UFYMA) INTA-CONICETJuan J.Lopez-MoyaCentre for Research in Agricultural Genomics, CRAG (CSIC-IRTA-UAB-UB)FrancoisMaclotUMR 1332 Biologie du Fruit et Pathologie, University of Bordeaux, INRAEKristiinaMäkinenDepartment of Agricultural Sciences, University of HelsinkiDarrenMartinInstitute of Infectious Disease and Molecular Medicine, University of Cape TownSebastienMassartPlant Pathology Laboratory, TERRA Gembloux Agro-Bio Tech, University of LiegeW. AllenMillerDepartment of Plant Pathology, Entomology and Microbiology, Iowa State UniversityMusaMohammadiDepartment of Plant Protection, Gorgan University of Agricultural Sciences and Natural ResourcesDimitreMollovUSDA-APHIS, Plant Protection and QuarantineEmmanuelleMullerCIRAD, AGAP Institut; AGAP Institut, University of Montpellier; CIRAD, INRAETatsuyaNagataInstituto de Ciências Biológicas, Universidade de BrasíliaJesúsNavas-CastilloInstituto de Hortofruticultura Subtropical y Mediterránea “La Mayora” (IHSM-UMA-CSIC), Consejo Superior de Investigaciones CientíficasYutaroNeriyaUtsunomiya UniversityFrancisco M.Ochoa-CoronaOklahoma State University, Institute for Biosecurity & Microbial ForensicsKazusatoOhshimaSaga UniversityVicentePallásInstituto de Biología Molecular y Celular de Plantas (IBMCP), Universitat Politècnica de Valencia-CSICHanuPappuDepartment of Plant Pathology, Washington State UniversityKarelPetrzikInstitute of Plant Molecular BiologyMikhailPoogginPHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRDMaria IsabellaPrigigalloIstituto per la Protezione Sostenibile delle Piante, CNRPedro L.Ramos-GonzálezApplied Molecular Biology Laboratory, Instituto Biológico de São PauloSimoneRibeiroEmbrapa Recursos Genéticos e BiotecnologiaKatja R.Richert-PöggelerJulius Kühn Institute, Federal Research Centre for Cultivated Plants, Institute for Epidemiology and Pathogen DiagnosticsPhilippeRoumagnacCIRAD, UMR PHIMAvijitRoyUSDA-ARS, BARC, Molecular Plant Pathology Laboratory, Beltsville, MD, USASeadSabanadzovicDepartment of Agricultural Science and Plant Protection, Mississippi State UniversityDanaŠafářováDepartment of Cell Biology and Genetics, Faculty of Science, Palacký University OlomoucPasqualeSaldarelliIstituto per la Protezione Sostenibile delle Piante, CNRHélèneSanfaçonSummerland Research and Development Centre, Agriculture and Agri-Food CanadaCeciliaSarmientoDepartment of Chemistry and Biotechnology, Tallinn University of TechnologyTakahideSasayaStrategic Planning Headquarters, NAROKayScheetsDepartment of Plant Pathology, Ecology and Evolution, Oklahoma State UniversityWillem E.W.SchravesandeMolecular Plant Pathology, University of AmsterdamSusanSealNatural Resources Institute, University of GreenwichYoshifumiShimomotoKochi Agricultural Research CenterMerikeSõmeraDepartment of Chemistry and Biotechnology, Tallinn University of TechnologyLiviaStavoloneIstituto per la Protezione Sostenibile delle Piante, CNRLucy R.StewartCurrently unaffiliatedPierre-YvesTeycheneyCIRAD, UMR PVBMT & UMR PVBMT, Université de la RéunionJohn E.ThomasQueensland Alliance for Agriculture and Food Innovation, The University of QueenslandJeremy R.ThompsonPlant Health and Environment LaboratoryAntonioTiberiniCouncil for Agricultural Research and Economics, Research Centre for Plant Protection and CertificationYasuhiroTomitakaInstitute for Plant Protection, NAROIoannisTzanetakisDepartment of Entomology and Plant Pathology, Division of Agriculture, University of Arkansas SystemMarieUmberINRAE, UR ASTROCicaUrbinoPHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute AgroHarrold A.van den BurgMolecular Plant Pathology, University of AmsterdamRené A.A.Van der VlugtWageningen University and ResearchArvindVarsaniThe Biodesign Center for Fundamental and Applied Microbiomics, Center for Evolution and Medicine, School of Life Sciences, Arizona State UniversityAdriaanVerhageRijk Zwaan Breeding B.V.DanVillamorDepartment of Entomology and Plant Pathology, Division of Agriculture, University of Arkansas SystemSusannevon BargenHumboldt-Universität zu Berlin, Thaer-Institute of Agricultural and Horticultural SciencesPeter J.WalkerThe University of QueenslandThierryWetzelDienstleistungszentrum Ländlicher Raum RheinpfalzAnna E.WhitfieldNorth Carolina State UniversityStephen J.WylieFood Futures Institute, Murdoch UniversityCaixiaYangLiaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang UniversityF. MuriloZerbiniDep. de Fitopatologia/BIOAGRO, Universidade Federal de ViçosaSongZhangNational Citrus Engineering and Technology Research Center, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Citrus Research Institute, Southwest UniversityIn March 2025, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote, newly proposed taxa were added to those under the mandate of the Plant Viruses Subcommittee. In brief, 1 new order, 3 new families, 6 new genera, 2 new subgenera and 206 new species were created. Some taxa were reorganized. Genus Cytorhabdovirus in the family Rhabdoviridae was abolished and its taxa were redistributed into three new genera Alphacytorhabdovirus, Betacytorhabdovirus and Gammacytorhabdovirus. Genus Waikavirus in the family Secoviridae was reorganized into two subgenera (Actinidivirus and Ritunrivirus). One family and four previously unaffiliated genera were moved to the newly established order Tombendovirales. Twelve species not assigned to a genus were abolished. To comply with the ICTV mandate of a binomial format for virus species, eight species were renamed. Demarcation criteria in the absence of biological information were defined in the genus Ilarvirus (family Bromoviridae). This article presents the updated taxonomy put forth by the Plant Viruses Subcommittee and ratified by the ICTV.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1467-30454762025Artificial Intelligence Approach in Machine Learning-Based Modeling and Networking of the Coronavirus Pathogenesis Pathway466ENShihoriTanabeDivision of Risk Assessment, Center for Biological Safety and Research, National Institute of Health SciencesSabinaQuaderInnovation Centre of NanoMedicine (iCONM), Kawasaki Institute of Industrial PromotionRyuichiOnoDivision of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health SciencesHiroyoshi Y.TanakaDepartment of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAkihisaYamamotoDepartment of Mechanical Systems Engineering, Graduate School of Systems Design Tokyo Metropolitan UniversityMotohiroKojimaDepartment of Surgical Pathology, Kyoto Prefecture University of MedicineEdward J.PerkinsUS Army Engineer Research and Development CenterHoracioCabralDepartment of Bioengineering, Graduate School of Engineering, The University of TokyoThe coronavirus pathogenesis pathway, which consists of severe acute respiratory syndrome (SARS) coronavirus infection and signaling pathways, including the interferon pathway, the transforming growth factor beta pathway, the mitogen-activated protein kinase pathway, the apoptosis pathway, and the inflammation pathway, is activated upon coronaviral infection. An artificial intelligence approach based on machine learning was utilized to develop models with images of the coronavirus pathogenesis pathway to predict the activation states. Data on coronaviral infection held in a database were analyzed with Ingenuity Pathway Analysis (IPA), a network pathway analysis tool. Data related to SARS coronavirus 2 (SARS-CoV-2) were extracted from more than 100,000 analyses and datasets in the IPA database. A total of 27 analyses, including nine analyses of SARS-CoV-2-infected human-induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes and fibroblasts, and a total of 22 analyses of SARS-CoV-2-infected lung adenocarcinoma (LUAD), were identified as being related to “human” and “SARS coronavirus 2” in the database. The coronavirus pathogenesis pathway was activated in SARS-CoV-2-infected iPSC-derived cells and LUAD cells. A prediction model was developed in Python 3.11 using images of the coronavirus pathogenesis pathway under different conditions. The prediction model of activation states of the coronavirus pathogenesis pathway may aid in treatment identification.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1422-006726112025Induced Pluripotent Stem Cells in Cardiomyopathy: Advancing Disease Modeling, Therapeutic Development, and Regenerative Therapy4984ENQuan DuyVoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukihiroSaitoDepartment of Cardiovascular Medicine, Okayama University HospitalSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinsukeYuasaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCardiomyopathies are a heterogeneous group of heart muscle diseases that can lead to heart failure, arrhythmias, and sudden cardiac death. Traditional animal models and in vitro systems have limitations in replicating the complex pathology of human cardiomyopathies. Induced pluripotent stem cells (iPSCs) offer a transformative platform by enabling the generation of patient-specific cardiomyocytes, thus opening new avenues for disease modeling, drug discovery, and regenerative therapy. This process involves reprogramming somatic cells into iPSCs and subsequently differentiating them into functional cardiomyocytes, which can be characterized using techniques such as electrophysiology, contractility assays, and gene expression profiling. iPSC-derived cardiomyocyte (iPSC-CM) platforms are also being explored for drug screening and personalized medicine, including high-throughput testing for cardiotoxicity and the identification of patient-tailored therapies. While iPSC-CMs already serve as valuable models for understanding disease mechanisms and screening drugs, ongoing advances in maturation and bioengineering are bringing iPSC-based therapies closer to clinical application. Furthermore, the integration of multi-omics approaches and artificial intelligence (AI) is enhancing the predictive power of iPSC models. iPSC-based technologies are paving the way for a new era of personalized cardiology, with the potential to revolutionize the management of cardiomyopathies through patient-specific insights and regenerative strategies.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2076-261515102025A Canine c-kit Novel Mutation Isolated from a Gastrointestinal Stromal Tumor (GIST) Retains the Ability to Form Dimers but Lacks Autophosphorylation1444ENKeiShimakawaLaboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science UniversitySoDogeLaboratory of Veterinary Pathology, School of Veterinary Science, Nippon Veterinary and Life Science UniversityMasakiMichishitaLaboratory of Veterinary Pathology, School of Veterinary Science, Nippon Veterinary and Life Science UniversityEriTanabeLaboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science UniversityTsuyoshiTajimaLaboratory of Veterinary Pharmacology, School of Veterinary Science, Nippon Veterinary and Life Science UniversityMasatoKobayashiLaboratory of Veterinary Reproduction, School of Veterinary Science, Nippon Veterinary and Life Science UniversityMakotoBonkobaraLaboratory of Veterinary Clinical Pathology, School of Veterinary Science, Nippon Veterinary and Life Science UniversityMasamiWatanabeLaboratory of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhikoOchiaiLaboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science UniversityYoshikazuTanakaLaboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science UniversityGastrointestinal stromal tumors (GISTs) are mesenchymal tumors that develop in the gastrointestinal tract; KIT mutations are present in both canine and human GISTs. In this study, genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) sections of 55 canine GIST cases, and mutation searches were performed for exons 8, 9, and 11. The results revealed novel mutations, A434T and F436S, in exon 8. In contrast to the A434T mutation without functional changes, the F436S mutant retained its dimerization ability, but lost its phosphorylation function and attenuated downstream Akt signaling, which is reflected in wound healing and migration activities. A comparison of the subcellular localization of WT KIT and the F436S mutant revealed no differences. In silico simulations indicated that the F436S mutation alters the structure of the near-membrane region and that its effects may extend to the transmembrane and intracellular domains compared to the WT. F436S is a point mutation that affects the entire molecule because co-mutation with the F436S mutation and the known autophosphorylation mutation reduces the autophosphorylation abilities.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841772025Six-Year Remission With No Relapse After Four-Time Weekly Rituximab Only for Bilateral Ocular Adnexal Follicular Lymphomae88945ENToshihikoMatsuoOphthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, and Okayama University HospitalTakehiroTanakaDepartment of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityNobuharuFujiiDivision of Transfusion and Cell Therapy, Department of Hematology and Oncology, Okayama University HospitalFollicular lymphoma mostly takes an indolent course, and thus, observation with watchful waiting is a main therapeutic strategy. Recent long-term studies suggest earlier treatment with rituximab monotherapy may benefit patients by delaying the need for treatment in the later phase of exacerbation. In this study, we reported a patient with bilateral orbital follicular lymphoma who received four-time weekly rituximab monotherapy as an induction therapy only and maintained the remission for 5 years with no treatment. The patient was a 51-year-old woman who developed a right upper orbital mass and was diagnosed with follicular lymphoma grade 1 by the excisional biopsy. Two years later, at the age of 53 years, she developed a left lacrimal gland mass and underwent excision. The pathological diagnosis was follicular lymphoma grade 1. She did not have any other systemic lesions by fluorodeoxyglucose positron emission tomography. At the age of 54 years, she developed a new mass on the nasal side of the right orbit and underwent weekly rituximab monotherapy (375 mg/m2) four times a month, leading to the reduction of the mass in 3 months. Two high uptake sites on the temporal and nasal side of the right superior orbit by fluorodeoxyglucose positron emission tomography disappeared one year later at the age of 55 years. She was followed with no treatment for 6 years until the age of 60 years at the latest visit. In case of a local orbital relapse, local radiotherapy would be the standard, but rituximab monotherapy as an induction therapy only was chosen in the present patient. Rituximab monotherapy in place of local radiotherapy would be a treatment option for orbital follicular lymphoma.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1068-92652025Tumor Microvessels with Specific Morphology as a Prognostic Factor in Esophageal Squamous Cell CarcinomaENHnin ThidaTunDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasayoshiFujisawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiakiOharaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySeitaroNishimuraDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomoyoshiKunitomoDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroNomaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAkihiroMatsukawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground Angiogenesis is essential for tumor progression. Microvessel density (MVD) is a widely used histological method to assess angiogenesis using immunostained sections, but its prognostic significance in esophageal cancer remains controversial. Recently, the evaluation of microvascular architecture has gained importance as a method to assess tumor aggressiveness. The present study aimed to identify the histological characteristics of tumor microvessels that are associated with the aggressiveness of esophageal squamous cell carcinoma.<br>
Patients and Methods A total of 108 esophageal squamous cell carcinoma tissues were immunohistochemically stained with blood vessel markers and angiogenesis-related markers, including CD31, alpha smooth muscle actin, vascular endothelial growth factor A (VEGF-A), CD206, and D2-40. MVD, microvessel pericyte coverage index (MPI), and tumor vascular morphology were evaluated by microscopy.<br>
Results MVD was significantly associated with patient outcomes, whereas neither MPI nor VEGF-A expression throughout the tumor showed a significant correlation. In addition, the presence of blood vessels encircling clusters of tumor cells, termed C-shaped microvessels, and excessively branching microvessels, termed X-shaped microvessels, was significantly associated with poor prognosis. These vessel types were also correlated with clinicopathological parameters, including deeper invasion of the primary tumor, presence of lymph node metastasis, advanced pathological stage, and distant metastasis. Focal VEGF-A immunoexpression in tumor cells was higher in areas containing C-shaped or X-shaped microvessels compared with areas lacking these vessel morphologies.<br>
Conclusions The data suggest that tumor microvessels with specific morphologies (C-shaped and X-shaped microvessels) may serve as a promising prognostic factor in esophageal squamous cell carcinoma.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2198-384412182025Cryo-EM Analysis of a Tri-Heme Cytochrome-Associated RC-LH1 Complex from the Marine Photoheterotrophic Bacterium Dinoroseobacter Shibae2413456ENWeiweiWangCollege of Life Sciences, Zhejiang UniversityYantingLiuState Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen UniversityJiayiGuCollege of Life Sciences, Zhejiang UniversityShaoyaAnDepartment of Pathology of Sir Run Run Shaw Hospital, Department of Biophysics, Zhejiang University School of MedicineChengMaDepartment of Pathology of Sir Run Run Shaw Hospital, Department of Biophysics, Zhejiang University School of MedicineHaichunGaoCollege of Life Sciences, Zhejiang UniversityNianzhiJiaoState Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen UniversityJian‐RenShenResearch Institute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama UniversityJohn ThomasBeattyDepartment of Microbiology & Immunology, University of British ColumbiaMichalKoblížekLaboratory of Anoxygenic Phototrophs, Institute of Microbiology, Czech Academy of ScienceXingZhangDepartment of Pathology of Sir Run Run Shaw Hospital, Department of Biophysics, Zhejiang University School of MedicineQiangZhengState Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen UniversityJing‐HuaChenCollege of Life Sciences, Zhejiang UniversityThe reaction center-light harvesting 1 (RC-LH1) complex converts solar energy into electrical energy, driving the initiation of photosynthesis. The authors present a cryo-electron microscopy structure of the RC-LH1 isolated from a marine photoheterotrophic bacterium Dinoroseobacter shibae. The RC comprises four subunits, including a three-heme cytochrome (Cyt) c protein, and is surrounded by a closed LH ring composed of 17 pairs of antenna subunits. Notably, a novel subunit with an N-terminal “helix-turn-helix” motif embedded in the gap between the RC and the LH ring is identified. The purified RC-LH1 complex exhibits high stability in solutions containing Mg2+ or Ca2+. The periplasmic Cyt c2 is predicted to bind at the junction between the Cyt subunit and the membrane plane, enabling electron transfer from Cyt c2 to the proximal heme of the tri-heme Cyt, and subsequently to the special pair of bacteriochlorophylls. These findings provide structural insights into the efficient energy and electron transfer processes within a distinct type of RC-LH1, and shed light on evolutionary adaptations of photosynthesis.No potential conflict of interest relevant to this article was reported.International Institute of Anticancer ResearchActa Medica Okayama1109-65352242025C1orf50 Drives Malignant Melanoma Progression Through the Regulation of Stemness510524ENYUSUKEOTANIDepartment of Pathology, Beth Israel Deaconess Medical CenterMASAKIMAEKAWADepartment of Pathology, Beth Israel Deaconess Medical CenterATSUSHITANAKADepartment of Pathology, Beth Israel Deaconess Medical CenterTIRSOPEÑADepartment of Pathology, Beth Israel Deaconess Medical CenterVANESSA D.CHINUMass Chan Medical School, UMass Memorial Medical CenterANNAROGACHEVSKAYADepartment of Pathology, Beth Israel Deaconess Medical CenterSHINICHITOYOOKADepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMICHAEL H.ROEHRLDepartment of Pathology, Beth Israel Deaconess Medical CenterATSUSHIFUJIMURADepartment of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground/Aim: Recent advancements in omics analysis have significantly enhanced our understanding of the molecular pathology of malignant melanoma, leading to the development of novel therapeutic strategies that target specific vulnerabilities within the disease. Despite these improvements, the factors contributing to the poor prognosis of patients with malignant melanoma remain incompletely understood. The aim of this study was to investigate the role of C1orf50 (Chromosome 1 open reading frame 50), a gene previously of unknown function, as a prognostic biomarker in melanoma.<br>
Materials and Methods: We performed comprehensive transcriptome data analysis and subsequent functional validation of the human Skin Cutaneous Melanoma project from The Cancer Genome Atlas (TCGA).<br>
Results: Elevated expression levels of C1orf50 correlated with worse survival outcomes. Mechanistically, we revealed that C1orf50 plays a significant role in the regulation of cell cycle processes and cancer cell stemness, providing a potential avenue for novel therapeutic interventions in melanoma.<br>
Conclusion: This study is the first to identify C1orf50 as a prognostic biomarker in melanoma. The clinical relevance of our results sheds light on the importance of further investigation into the biological mechanisms underpinning C1orf50’s impact on melanoma progression and patient prognosis.No potential conflict of interest relevant to this article was reported.