Okayama University Medical SchoolActa Medica Okayama0386-300X7052016A Phase I Trial of 100mg/m2 Docetaxel in Patients with Advanced or Recurrent Breast Cancer425427ENTomokiTamuraDepartment of Allergy and Respiratory Medicine, Okayama University HospitalTaizoHirataDepartment of Medical Oncology, National Hospital Organization Kure Medical CenterMasahiroTabataDepartment of Allergy and Respiratory Medicine, Okayama University HospitalShiroHinotsuCenter for Innovative Clinical Medicine, Okayama University HospitalAkinobuHamadaDivision of Clinical Pharmacology & Translational Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer CenterTakayukiMotokiDepartment of Breast and Endocrinological Surgery, Okayama University HospitalTakayukiIwamotoDepartment of Breast and Endocrinological Surgery, Okayama University HospitalTaekoMizooDepartment of Breast and Endocrinological Surgery, Okayama University HospitalTomohiroNogamiDepartment of Breast and Endocrinological Surgery, Okayama University HospitalTadahikoShienDepartment of Breast and Endocrinological Surgery, Okayama University HospitalNarutoTairaDepartment of Breast and Endocrinological Surgery, Okayama University HospitalJunjiMatsuokaDepartment of Breast and Endocrinological Surgery, Okayama University HospitalHiroyoshiDoiharaDepartment of Breast and Endocrinological Surgery, Okayama University HospitalClinical Study Protocols10.18926/AMO/54607Docetaxel is a standard treatment for patients with advanced or recurrent breast cancer. The recommended dose is 60 to 100 mg/m2. Previous study have shown that the tumor response rates of patients who received docetaxel monotherapy at doses of 60, 75, and 100 mg/m2 were 22.1% , 23.3% , and 36.0% , respectively, and there was a significant relationship between the dose and response. In Europe and the United States, docetaxel is approved at a dose of 100 mg/m2, and Japanese guidelines also recommend a dose of 100 mg/m2. However, the approved dose in Japan is up to 75 mg/m2. We have launched a phase I trial evaluating 100 mg/m2 docetaxel in patients with advanced or relapsed breast cancer. The major eligibility criteria are as follows: age ≥20 years, pathologically diagnosed breast cancer, recurrent or advanced breast cancer, a good performance status, and HER2 [human epidermal growth factor receptor 2] negative. The primary endpoint is demonstrated safety of 100 mg/m2 docetaxel. This study will clarify whether 100mg/m2 docetaxel can be administrated safely in Japanese patients with advanced or recurrent breast cancer.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7042016Study about the Efficacy of Metformin to Immune Function in Cancer Patients327330ENMototsuguWatanabeDepartment of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiromasaYamamotoDepartment of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShingoEikawaDepartment of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoShienDepartment of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTadahikoShienDepartment of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunichiSohDepartment of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShiroHinotsuCenter for Innovative Clinical Medicine, Okayama University HospitalToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiKiuraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyoshiDoiharaDepartment of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiroMiyoshiDepartment of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHeiichiroUdonoDepartment of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiToyookaDepartment of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesClinical Study Protocols10.18926/AMO/54514A study to evaluate the effect of metformin on the immune system was commenced in July 2014. Metformin is one of the most commonly prescribed drugs for type 2 diabetes, and previous studies have reported that metformin has an anti-tumor effect. The aim of this study is to evaluate the efficacy of metformin on the immune system in human cancer patients in vivo. The primary outcome parameter will be the rate change in the population of CD8＋ T cells, which produce multiple cytokines. No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6962015Correlation between 18F-fluorodeoxyglucose Positron Emission Tomography/computed Tomography and Clinicopathological Features in Invasive Ductal Carcinoma of the Breast333338ENMaikoItoTadahikoShienMitsumasaKajiTaekoMizooTakayukiIwamotoTomohiroNogamiTakayukiMotokiNarutoTairaHiroyoshiDoiharaShinichiroMiyoshiOriginal Article10.18926/AMO/53907We evaluated the usefulness of preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) examinations to predict the pathological features in primary breast cancer. In particular, we evaluated the correlation between the maximum standardized uptake values (SUVmax) obtained by 18F-FDG PET/CT and the Ki67 expression in estrogen receptor (ER)-positive invasive ductal carcinoma (IDC). Primary IDC patients operated between March 2009 and July 2013 at Okayama University Hospital were enrolled. We evaluated the correlations between the SUVmax and age, postoperative pT, histological grade, lymph vascular invasion, status of hormone receptor, human epidermal growth factor receptor 2 (HER2), Ki67 expression and node status. The Ki67 expression was classified as high (>14%) versus low (<14%). We enrolled 138 patients with IDC. Their median SUVmax was 3.85 (range:0-52.57). In a univariate analysis, the SUVmax was significantly related to age, pT, histological grade, lymphovascular invasion, hormone receptor status, HER2 status, node status and Ki67. In the 113 patients with ER-positive IDC, there was a significant correlation between Ki67 and SUVmax (p=0.0030). The preoperative 18F-FDG PET/CT results of IDC patients had significant relationships with pathological status parameters. The determination of the preoperative SUVmax might help classify Luminal A and Luminal B patients among luminal-type breast cancer patients.No potential conflict of interest relevant to this article was reported.BioMed Central Ltd.Acta Medica Okayama1471-2407132013Effects of lifestyle and single nucleotide polymorphisms on breast cancer risk: a case-control study in Japanese womenENTaekoMizooNarutoTairaKeikoNishiyamaTomohiroNogamiTakayukiIwamotoTakayukiMotokiTadahikoShienJunjiMatsuokaHiroyoshiDoiharaSetsukoIshiharaHiroshiKawaiKensukeKawasakiYouichiIshibeYutakaOgasawaraYoshifumiKomoikeShinichiroMiyoshiBackground: Lifestyle factors, including food and nutrition, physical activity, body composition and reproductive factors, and single nucleotide polymorphisms (SNPs) are associated with breast cancer risk, but few studies of these factors have been performed in the Japanese population. Thus, the goals of this study were to validate the association between reported SNPs and breast cancer risk in the Japanese population and to evaluate the effects of SNP genotypes and lifestyle factors on breast cancer risk.
Methods: A case-control study in 472 patients and 464 controls was conducted from December 2010 to November 2011. Lifestyle was examined using a self-administered questionnaire. We analyzed 16 breast cancer-associated SNPs based on previous GWAS or candidate-gene association studies. Age or multivariate-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were estimated from logistic regression analyses.
Results: High BMI and current or former smoking were significantly associated with an increased breast cancer risk, while intake of meat, mushrooms, yellow and green vegetables, coffee, and green tea, current leisure-time exercise, and education were significantly associated with a decreased risk. Three SNPs were significantly associated with a breast cancer risk in multivariate analysis: rs2046210 (per allele OR = 1.37 [95% CI: 1.11-1.70]), rs3757318 (OR = 1.33[1.05-1.69]), and rs3803662 (OR = 1.28 [1.07-1.55]). In 2046210 risk allele carriers, leisure-time exercise was associated with a significantly decreased risk for breast cancer, whereas current smoking and high BMI were associated with a significantly decreased risk in non-risk allele carriers.
Conclusion: In Japanese women, rs2046210 and 3757318 located near the ESR1 gene are associated with a risk of breast cancer, as in other Asian women. However, our findings suggest that exercise can decrease this risk in allele carriers.No potential conflict of interest relevant to this article was reported.SpringerActa Medica Okayama0167-680614322014Estrogen receptor (ER) mRNA expression and molecular subtype distribution in ER-negative/progesterone receptor-positive breast cancers403409ENMitsuyaItohTakayukiIwamotoJunjiMatsuokaTomohiroNogamiTakayukiMotokiTadahikoShienNarutoTairaNaokiNiikuraNaokiHayashiShoichiroOhtaniKenjiHigakiToshiyoshiFujiwaraHiroyoshiDoiharaW. FraserSymmansLajosPusztaiWe examined estrogen receptor (ER) mRNA expression and molecular subtypes in stage I-III breast cancers that are progesterone receptor (PR) positive but ER and HER2 negative by immunohistochemistry (IHC) or fluorescent in situ hybridization. The ER, PR, and HER2 status was determined by IHC as part of routine clinical assessment (N = 501). Gene expression profiling was done with the Affymetrix U133A gene chip. We compared expressions of ESR1 and MKI67 mRNA, distribution of molecular subtypes by the PAM50 classifier, the sensitivity to endocrine therapy index, and the DLDA30 chemotherapy response predictor signature among ER/PR-positive (n = 223), ER-positive/PR-negative (<Emphasis Type="ItalicUnderline">n = 73), ER-negative/PR-positive (n = 20), and triple-negative (n = 185) cancers. All patients received neoadjuvant chemotherapy with an anthracycline and taxane and had adjuvant endocrine therapy only if ER or PR > 10 % positive. ESR1 expression was high in 25 % of ER-negative/PR-positive, in 79 % of ER-positive/PR-negative, in 96 % of ER/PR-positive, and in 12 % of triple-negative cancers by IHC. The average MKI67 expression was significantly higher in the ER-negative/PR-positive and triple-negative cohorts. Among the ER-negative/PR-positive patients, 15 % were luminal A, 5 % were Luminal B, and 65 % were basal like. The relapse-free survival rate of ER-negative/PR-positive patients was equivalent to ER-positive cancers and better than the triple-negative cohort. Only 20-25 % of the ER-negative/PR-positive tumors show molecular features of ER-positive cancers. In this rare subset of patients (i) a second RNA-based assessment may help identifying the minority of ESR1 mRNA-positive, luminal-type cancers and (ii) the safest clinical approach may be to consider both adjuvant endocrine and chemotherapy.No potential conflict of interest relevant to this article was reported.SpringerActa Medica Okayama0171-521613852012DNA methylation status of REIC/Dkk-3 gene in human malignancies799809ENTatsuroHayashiHiroakiAsanoShinichiToyookaKazunoriTsukudaJunichiSohTadahikoShienNarutoTairaYuhoMakiNorimitsuTanakaHiroyoshiDoiharaYasutomoNasuNam-hoHuhShinichiroMiyoshiThe REIC (reduced expression in immortalized cells)/Dkk-3 is down-regulated in various cancers and considered to be a tumor suppressor gene. REIC/Dkk-3 mRNA has two isoforms (type-a,b). REIC type-a mRNA has shown to be a major transcript in various cancer cells, and its promoter activity was much stronger than that of type-b. In this study, we examined the methylation status of REIC/Dkk-3 type-a in a broad range of human malignancies.
We examined REIC/Dkk-3 type-a methylation in breast cancers, non-small-cell lung cancers, gastric cancers, colorectal cancers, and malignant pleural mesotheliomas using a quantitative combined bisulfite restriction analysis assay and bisulfate sequencing. REIC/Dkk-3 type-a and type-b expression was examined using reverse transcriptional PCR. The relationships between the methylation and clinicopathological factors were analyzed.
The rate of REIC/Dkk-3 type-a methylation ranged from 26.2 to 50.0% in the various primary tumors that were examined. REIC/Dkk-3 type-a methylation in breast cancer cells was significantly heavier than that in the other cell lines that we tested. REIC/Dkk-3 type-a methylation was inversely correlated with REIC/Dkk-3 type-a expression. There was a correlation between REIC/Dkk-3 type-a and type-b mRNA expression. REIC/Dkk-3 type-a expression was restored in MDA-MB-231 cells using 5-aza-2'-deoxycytidine treatment. We found that estrogen receptor-positive breast cancers were significantly more common among the methylated group than among the non-methylated group.
REIC/Dkk-3 type-a methylation was frequently detected in a broad range of cancers and appeared to play a key role in silencing REIC/Dkk-3 type-a expression in these malignancies.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812612014早期乳癌におけるOne-step Nucleic Acid Amplification(OSNA)法によるセンチネルリンパ節転移診断の検討2530ENTaekoMizooTadahikoShienMaikoItoTomohiroNogamiTakayukiIwamotoTakayukiMotokiNarutoTairaJunjiMatsuokaHiroyoshiDoihara Introduction: The one-step nucleic acid amplification (OSNA) assay is a new method to detect sentinel lymph node (SLN) metastases using cytokeratin 19 (CK19) mRNA in early breast cancer. Here we retrospectively analyzed the advantages and disadvantages of the OSNA assay.
Methods: In a trial period, SLNs were divided into two sections, and we examined one side using the OSNA assay. The other side was examined by pathologists. After this period, we examined whole SLNs using only the OSNA assay. The patients with positive nodes by OSNA assay and/or pathology required axillary dissection.
Results: We examined 27 primary breast cancer patients (36 SLNs) during the trial period. The overall concordance rate between the OSNA assay and pathology results was 91%. In the later period, 157 patients (217 SLNs) were examined. The CK19-positive rate obtained by the OSNA assay was 16.5% (macrometastases OSNA (++) : 7.2%, micrometastases OSNA (+) : 9.2%). The non-SLN positive rate among the CK19-positivecases was 23%. The OSNA assay's false negative was one case in which the expression of CK-19 on the primary tumor and lymph node was not detected.
Conclusions: Our OSNA assay results were comparable to those obtained using a conventional pathological technique. Pathologists and laboratory technicians could save time and effort by using the OSNA assay when seeking the precise diagnosis during surgery.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812532013乳癌と分子標的薬243250ENHiroyoshiDoiharaNo potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6732013p53 Expression in Pretreatment Specimen Predicts Response to Neoadjuvant Chemotherapy Including Anthracycline and Taxane in Patients with Primary Breast Cancer.165170ENTadahikoShienTakayukiKinoshitaKunihikoSekiMiwaYoshidaTakashiHojoChikakoShimizuNarutoTairaHiroyoshiDoiharaSadakoAkashi-TanakaHitoshiTsudaYasuhiroFujiwaraOriginal Article10.18926/AMO/50409While clinical and pathologic responses are important prognostic parameters, biological markers from core needle biopsy (CNB) are needed to predict neoadjuvant chemotherapy (NAC) response, to individualize treatment, and to achieve maximal efficacy. We retrospectively evaluated the cases of 183 patients with primary breast cancer who underwent surgery after NAC (anthracycline and taxane) at the National Cancer Center Hospital (NCCH). We analyzed EGFR, HER2, and p53 expression and common clinicopathological features from the CNB and surgical specimens of these patients. These biological markers were compared between sensitive patients (pathological complete response;pCR) and insensitive patients (clinical no change;cNC and clinical progressinve disease;cPD). In a comparison between the 9 (5%) sensitive patients and 30 (16%) insensitive patients, overexpression of p53 but not overexpression of either HER2 or EGFR was associated with a good response to NAC. p53 (p＝0.045) and histological grade 3 (p＝0.011) were important and significant predictors of the response to NAC. The correspondence rates for histological type, histological grade 3, ER, PgR, HER2, p53, and EGFR in insensitive patients between CNB and surgical specimens were 70%, 73%, 67%, 70%, 80%, 93%, and 73%. The pathologic response was significantly associated with p53 expression and histological grade 3. The correspondence rate of p53 expression between CNB and surgical specimens was higher than that of other factors. We conclude that the level of p53 expression in the CNB was an effective and reliable predictor of treatment response to NAC.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6732013Association between Mammographic Breast Density and Lifestyle in Japanese Women145151ENSetsukoIshiharaNarutoTairaKensukeKawasakiYouichiIshibeTaekoMizooKeikoNishiyamaTakayukiIwamotoTomohiroNogamiTakayukiMotokiTadahikoShienJunjiMatsuokaHiroyoshiDoiharaYoshifumiKomoikeShuheiSatoSusumuKanazawaOriginal Article10.18926/AMO/50407A high mammographic breast density is considered to be a risk factor for breast cancer. However, only a small number of studies on the association between breast density and lifestyle have been performed. A cross-sectional study was performed using a survey with 29 questions on life history and lifestyle. The breast density on mammography was classified into 4 categories following the BI-RADS criteria. The subjects were 522 women with no medical history of breast cancer. The mean age was 53.3 years old. On multivariate analysis, only BMI was a significant factor determining breast density in premenopausal women (parameter estimate, －0.403;p value, 0.0005), and the density decreased as BMI rose. In postmenopausal women, BMI (parameter estimate, －0.196;p value, 0.0143) and number of deliveries (parameter estimate, －0.388;p value, 0.0186) were significant factors determining breast density;breast density decreased as BMI and number of deliveries increased. Only BMI and number of deliveries were identified as factors significantly influencing breast density. BMI was inversely correlated with breast density before and after menopause, whereas the influence of number of deliveries on breast density was significant only in postmenopausal women in their 50 and 60s.No potential conflict of interest relevant to this article was reported.Springer JapanActa Medica Okayama1880-42332012Expression of ALDH1 in axillary lymph node metastases is a prognostic factor of poor clinical outcome in breast cancer patients with 1–3 lymph node metastasesENTomohiroNogamiTadahikoShienTakehiroTanakaKeikoNishiyamaTaekoMizooTakayukiIwamtoHirokuniIkedaNarutoTairaHiroyoshiDoiharaShinichiroMiyoshiBackground
Recently, evidence in support of the cancer stem cell (CSC) hypothesis has been accumulating. On the other hand, it has been reported that the expression of aldehyde dehydrogenase 1 (ALDH1) in primary breast cancer is a powerful predictor of a poor clinical outcome, and that breast cancer stem cells express ALDH1. According to the CSC hypothesis, development of metastases requires the dissemination of CSC that may remain dormant and be reactivated to cause tumor recurrence. In this study, we investigated whether the detection of CSC in axillary lymph node metastases (ALNM) might be a significant prognostic factor in patients with breast cancer.
Methods
From 1998 to 2006, 40 primary breast cancer patients with ALNM, the number of metastatic nodes varying in number from 1 to 3, underwent surgery at Okayama University; of these, 15 patients developed tumor recurrence. We retrospectively evaluated the common clinicopathological features and the expression of ER, HER2, ALDH1, and Ki67 in both the primary lesions and the ALNM, and analyzed the correlations between the expression of these biological markers and the disease-free survival (DFS).
Results
Expression of ALDH1 in the ALNM was significantly associated with the DFS (P = 0.037).
Conclusion
Evaluation of biomarker expression in ALNM could be useful for prognosis in breast cancer patients with 1–3 metastatic lymph nodes.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6642012Ectopic Cervical Thymoma:A Case Report with 18F-fluorodeoxyglucose Positron Emission Tomography Findings357361ENKazuhikoShienTadahikoShienJunichiSohHirokuniIkedaTomohiroNogamiNarutoTairaHiroyoshiDoiharaShinichiroMiyoshiCase Report10.18926/AMO/48691Ectopic thymoma is considered to arise from ectopic thymus tissue deposited as a result of the abnormal
mislocalization of thymus tissue during the embryonic stage. An 86-year-old man visited our hospital
with chief complaints of hoarseness and a mass in his anterior neck. A preoperative needle biopsy of the mass did not yield a definitive diagnosis. A positron emission tomography (PET) study revealed heterogeneous accumulation of <sup>18</sup>F-fluorodeoxyglucose (FDG) in the tumor. The tumor, affecting the left sternocleidomastoid muscle, the recurrent laryngeal nerve, the internal carotid vein, and the brachiocephalic vein, was resected using a combination of a collar incision in the neck and a median incision in the sternum. Immunohistochemically, the tumor was diagnosed as an ectopic thymoma
of the neck. To date, only a few cases of ectopic thymoma presenting with FDG accumulation have been reported. Our experience indicates that ectopic thymoma should be kept in mind during the differential diagnosis of neck tumors with FDG accumulation appearing on PET images.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812422012早期乳がんに対する手術療法―乳房切除から乳房再建まで―119123ENHiroyoshiDoiharaNo potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6542011Clinical Efficacy of Capecitabine and Cyclophosphamide (XC) in Patients with Metastatic Breast Cancer231237ENTadahikoShienHiroyoshiDoiharaKeikoNishiyamaHirokoMasudaTomohiroNogamiHirokuniIkedaNarutoTairaOriginal Article10.18926/AMO/46848Combined low-dose therapy of oral capecitabine (Xeloda) and cyclophosphamide (XC) has been demonstrated to be useful for long-term control of lesions in patients with metastatic breast cancer (MBC) and is aimed at symptomatic alleviation and prolongation of survival. Here, a retrospective review was conducted of MBC patients administered XC at the Okayama University Hospital (OUH), to evaluate responses to XC, adverse events and time to progression (TTP). Twenty patients with MBC received XC between 2006 and 2009. With the exception of 2 elderly patients who were over the age of 70 at the initial examination, all of the patients had received prior treatment with an anthracycline and/or a taxane. No complete response (CR) cases were observed, but partial response (PR) was achieved in 6 patients (30%) and SD in 9 (45%), of whom 5 (20%) sustained SD status for >12 months. The median TTP was 6 months (range:3-27 mo.). Three patients developed Grade 3 adverse events (diarrhea, nausea and stomatitis), but no other patients developed adverse reactions causing interruption of the therapy. XC was safe even in previously treated and elderly MBC patients;moreover, it yielded remarkable clinical responses.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6122007Effects of adenoviral-mediated hepatocyte growth factor on liver regeneration after massive hepatectomy in rats8188ENIchiroYuasaKazunoriTsukudaRyujiHiraiTetsuyaOtaMasakazuMurakamiMinoruNaitoHiroyoshiDoiharaHiroshiDateNobuyoshiShimizuOriginal Article10.18926/AMO/32891<p>Resection is the only curative treatment for liver metastasis of colorectal cancers. Despite the supreme regenerative potential of the liver, major hepatectomy sometimes leads to liver failure, and the limitation of resectable liver volumes makes advanced tumors inoperable. This study was attempted to promote liver regeneration using hepatocyte growth factor (HGF) gene transfection by venous-administered adenovirus and to improve the survival of rats after massive hepatectomy. The adenovirus that encodes HGF was administered to rats before 85%-hepatectomy. The administration of HGF gene improved the survival of rats after massive hepatectomy, while the administration of control adenovirus deteriorated their survival. Gene transfection of HGF showed up-regulation of serum HGF, stimulation of hepatocellular proliferation and rapid liver regeneration. Moreover, HGF administration reduced apoptosis of hepatocytes. The administration of HGF gene prevented liver dysfunction after major hepatectomy and may be a new assist for surgery.</p>No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X5432000Prognostic value of vascular endothelial growth factor expression in primary lung carcinoma.119126ENHaiyunShengMotoiAoeHiroyoshiDoiharaAkioAndouNobuyoshiShimizuArticle10.18926/AMO/32302<p>To investigate whether an association exists between vascular endothelial growth factor (VEGF) expression and tumor prognosis in primary lung carcinoma, we used immunohistochemical techniques to analyze microvessel density and VEGF expression in lung carcinoma tissue from 98 patients. Tissue had been fresh-frozen at the time of operation and preserved for more than 5 years. The results indicated that VEGF expression was positive for 50 of the 98 patients (51.0%), with 27 (27.6%) being weakly positive and 23 (23.5%) being strongly positive. The microvessel density in tissue showing weakly positive and strongly positive VEGF expression was significantly higher than that in VEGF-negative tumor tissue (P < 0.05: negative vs. weakly positive, P < 0.01: negative vs. strongly positive), we showed demonstrating that VEGF expression was significantly associated with intratumoral microvessel density. The 5-year survival rates were 8.7% for strongly VEGF-positive patients, 43.9% for weakly VEGF-positive patients and 79.2% for VEGF-negative patients, respectively (P < 0.01: negative vs. weakly positive or strongly positive). Furthermore, multivariate analysis employing multiple regression analysis indicated that VEGF expression correlates highly with the overall survival rates of patients with primary lung carcinoma. Two variables, N status and VEGF expression, were found to be significant prognostic factors (P < 0.01). The results of this study suggest that VEGF expression is associated with intratumoral microvessel density. VEGF expression may constitute important independent prognostic evidence that can help us in predicting the outcomes of patients with primary lung carcinomas.</p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6012006Gefitinib, an epidermal growth factor receptor blockade agent, shows additional or synergistic effects on the radiosensitivity of esophageal cancer cells in vitro.2534ENNarutoTairaHiroyoshiDoiharaTetsuyaOotaFumikataHaraTadahikoShienHirotoshiTakahashiSeijiYoshitomiYouichiIshibeNobuyoshiShimizuArticle10.18926/AMO/30755<p>Human esophageal cancers have been shown to express high levels of epidermal growth factor receptor (EGFR) and a relationship between high EGFR expression and local advance, the number of lymph node metastases, life expectancy, and sensitivity to chemo-radiotherapy has been demonstrated. We examined the use of gefitinib, an orally active EGFR-selective tyrosine kinase inhibitor, as a new strategy for treatment of esophageal carcinoma. The effects of gefitinib were evaluated in monotherapy and in combination with radiotherapy in human esophageal carcinoma cell lines. Gefitinib produced a dose-dependent inhibition of cellular proliferation in all of the 8 esophageal carcinoma cell lines examined, with IC50 values ranging from 5.7 microM to 36.9 microM. In combination, gefitinib and radiotherapy showed a synergistic effect in 2 human esophageal carcinoma cell lines and an additive effect in 5 cell lines. Western blotting demonstrated that gefitinib blocked activation of the EGFR-extracellular signal-regulated kinase (Erk) pathway and the EGFR-phosphoinositide-3 kinase (PI3K)-Akt pathway after irradiation. These results suggest that further evaluation of EGFR blockade as a treatment for esophageal cancer should be performed, and that radiotherapy combined with EGFR blockade may enhance the response of esophageal carcinoma to therapy.</p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6022006Intraatrial extension of thyroid cancer: a case report.135140ENSeiichiroSugimotoHiroyoshiDoiharaYutakaOgasawaraMotoiAoeShunjiSanoNobuyoshiShimizuArticle10.18926/AMO/30734<p>A 61-year-old man, who was diagnosed with superior vena cava syndrome by papillary thyroid carcinoma, was referred to our hospital. A bulky thyroid tumor with tracheal invasion extended from the left neck to the right atrium without distant metastases. The risk of sudden death due to airway occlusion, tumor embolism or obstruction of the tricuspid valve led us to elect surgery. Extended resection of thyroid cancer was performed with cardiopulmonary bypass. Peritoneal dissemination was found via laparotomy. A histological diagnosis of anaplastic carcinoma arising from transformation of papillary carcinoma was made. After the operation, bilateral ureteral occlusion by peritoneal dissemination and multiple lung metastases were detected. The patient died with acute renal failure on postoperative day 12. Intraatrial extension of thyroid cancer is rare, and only 12 cases have been reported in the literature. We present a case of thyroid cancer with intraatrial extension.</p>No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6022006Utility of vessel-sealing systems in thyroid surgery.9398ENTakeoFujitaHiroyoshiDoiharaYutakaOgasawaraNobuyoshiShimizuArticle10.18926/AMO/30732<p>The LigaSure TM vessel-sealing system (VSS) represents a new approach to intraoperative ligation. This clinical study retrospectively examined the utility of the VSS in thyroid surgery. In this study, we analyzed 56 consecutive patients who underwent thyroid surgery. Characteristics such as operative duration, the volume of intraoperative hemorrhage, and postoperative course were analyzed and compared between thyroid surgery using the VSS or conventional handtie methods. The present results indicate no significant differences in operative duration, volume of intraoperative hemorrhage, postoperative course, or duration of postoperative drainage between surgeries using the VSS or conventional methods. However, the postoperative hospital stay was found to be significantly shorter (p<0.05) with the VSS. No serious postoperative complications were encountered, and no significant differences were observed in the frequency of postoperative complications between methods. The VSS may simplify procedures for thyroid surgery, and hemostasis is effective for both thyroid vessels and thyroid parenchyma. However, further evaluation is warranted to adequately determine the relative merits of the VSS compared to conventional handtie methods.</p>No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581021-21990核 DNA 量による乳癌の悪性度判定ならびに内分泌療法の作用機序の研究―Flow cytometry による解析―3749ENHiroyoshiDoiharaTo evaluate for primary breast cancer, flow cytometric DNA analysis has been performed on 105 paraffin-embedded tissues. The S-phase fraction and proliferation index correlated significantly with clincopathological factors, sunh as n-number, tumor size, histological stage and hormone receptors. However, there was no correlation between the level of ploidy and the clinicopathological factors. DNA analysis using flow cytometry was found to be useful for the estimation of prognosis and evaluation of malignancy of breast cancer. The effect of medroxyprogesterone acetate (MPA) on primary breast cancer cell kinetics was investigated by flow cytometry. Nuclear DNA contents were measured in 67 cases. MPA, 1,200mg/day, was orally administered for two weeks in 12 cases (MPA group) and the remain-ing cases (n-MPA group) served as the controls, until the day before operatopn. The DNA histograms were compared between both groups. The mean percentage of G0 + G1 phase was higher and that of S-phase and G2 + M phase, lower, in the MPA group than in the n-MPA group. Especially in estorogen receptor-positive and premenopausal cases, significant differ-ences were present between both groups. These results suggest that MPA could inhibit DNA synthesis with a delay of the cell cycle progression in human breast cancer.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030155811932008I 乳がんの診断と治療273283ENHiroyoshiDoiharaNarutoTairaNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030155811922007I 外来化学療法における医師の役割173176ENHiroyoshiDoiharaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama1990核DNA量による乳癌の悪性度判定ならびに内分泌療法の作用機序の研究 Flow cytometryによる解析ENNo potential conflict of interest relevant to this article was reported.