IOS Press Acta Medica Okayama 0926-9630 2025 Assessing the Proportion of Clinical Trial Eligibility Criteria Expressible with Standard EHR Data Elements 1892 1893 EN Risa Okazaki Department of Pharmacy, Okayama University Hospital Kunihisa Kamikawa Center for Innovative Clinical Medicine, Okayama University Hospital Hideki Uno Center for Innovative Clinical Medicine, Okayama University Hospital Hiroto Okuda Division of Clinical Research of New Drugs and Therapeutics, Center for Innovative Clinical Medicine, Okayama University Hospital Shihoko Namba Division of Clinical Research of New Drugs and Therapeutics, Center for Innovative Clinical Medicine, Okayama University Hospital Mitsunobu Kano Graduate School of Interdisciplinary Science and Technology in Health Systems, Okayama University Mizuki Morita Graduate School of Interdisciplinary Science and Technology in Health Systems, Okayama University Patient recruitment for clinical trials often requires substantial human effort and experiences delays, leading to increased drug development costs. Leveraging electronic health records (EHRs) may improve the accuracy of estimates of potentially recruitable patients. We evaluated the feasibility of using EHRs by analyzing the proportion of computable eligibility criteria. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0142-9612 251 2020 Heterotypic 3D pancreatic cancer model with tunable proportion of fibrotic elements 120077 EN Hiroyoshi Y. Tanaka Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsuyoshi Kurihara Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takuya Nakazawa Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Michiya Matsusaki Department of Applied Chemistry, Graduate School of Engineering, Osaka University Atsushi Masamune Division of Gastroenterology, Graduate School of Medicine, Tohoku University Mitsunobu R. Kano Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Pancreatic ductal adenocarcinoma (PDAC) is an often lethal disease characterized by a dense, fibrotic stroma. However, the lack of relevant preclinical models that recapitulate the characteristic histopathology of human PDAC in vitro impedes the development of novel therapies. The amount of stromal elements differ largely within and between patients, but in vitro models of human PDAC often do not account for this heterogeneity. Indeed, analyses of human PDAC histopathology revealed that the proportion of stroma ranged from 40 to 80% across patients. We, therefore, generated a novel 3D model of human PDAC, consisting of co-cultured human PDAC tumor cells and fibroblasts/pancreatic stellate cells, in which the proportion of fibrotic elements can be tuned across the clinically observed range. Using this model, we analyzed the signaling pathways involved in the differentiation of myofibroblasts, a characteristic subpopulation of fibroblasts seen in PDAC. We show that both YAP and SMAD2/3 in fibroblasts are required for myofibroblastic differentiation and that both shared and distinct signaling pathways regulate the nuclear localization of these factors during this process. Our novel model will be useful in promoting the understanding of the complex mechanisms by which the fibrotic stroma develops and how it might be therapeutically targeted. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0142-9612 192 2018 Pancreatic stellate cells derived from human pancreatic cancer demonstrate aberrant SPARC-dependent ECM remodeling in 3D engineered fibrotic tissue of clinically relevant thickness 355 367 EN Hiroyoshi Y. Tanaka Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kentaro Kitahara Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Naoki Sasaki Department of Chemical and Biological Sciences, Japan Women's University Natsumi Nakao Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kae Sato Department of Chemical and Biological Sciences, Japan Women's University Hirokazu Narita Department of Anatomical Science, Hirosaki University Graduate School of Medicine Hiroshi Shimoda Department of Anatomical Science, Hirosaki University Graduate School of Medicine Michiya Matsusaki Department of Frontier Biosciences, Osaka University Graduate School of Frontier Biosciences Hiroshi Nishihara Genomics Unit, Keio Cancer Center, Keio University School of Medicine, Institute of Integrated Medical Research Atsushi Masamune Division of Gastroenterology, Tohoku University Graduate School of Medicine Mitsunobu R. Kano Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Desmoplasia is a hallmark of pancreatic cancer and consists of fibrotic cells and secreted extracellular matrix (ECM) components. Various in vitro three-dimensional (3D) models of desmoplasia have been reported, but little is known about the relevant thickness of the engineered fibrotic tissue. We thus measured the thickness of fibrotic tissue in human pancreatic cancer, as defined by the distance from the blood vessel wall to tumor cells. We then generated a 3D fibrosis model with a thickness reaching the clinically observed range using pancreatic stellate cells (PSCs), the main cellular constituent of pancreatic cancer desmoplasia. Using this model, we found that Collagen fiber deposition was increased and Fibronectin fibril orientation drastically remodeled by PSCs, but not normal fibroblasts, in a manner dependent on Transforming Growth Factor (TGF)-ƒÀ/Rho-Associated Kinase (ROCK) signaling and Matrix Metalloproteinase (MMP) activity. Finally, by targeting Secreted Protein, Acidic and Rich in Cysteine (SPARC) by siRNA, we found that SPARC expression in PSCs was necessary for ECM remodeling. Taken together, we developed a 3D fibrosis model of pancreatic cancer with a clinically relevant thickness and observed aberrant SPARC-dependent ECM remodeling in cancer-derived PSCs. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0168-3659 230 2016 Increased fibrosis and impaired intratumoral accumulation of macromolecules in a murine model of pancreatic cancer co-administered with FGF-2 109 115 EN Satoshi Sakai Graduate School of Medicine, The University of Tokyo Caname Iwata Graduate School of Medicine, The University of Tokyo Hiroyoshi Y. Tanaka Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Horacio Cabral Graduate School of Engineering, The University of Tokyo Yasuyuki Morishita Graduate School of Medicine, The University of Tokyo Kohei Miyazon Graduate School of Medicine, The University of Tokyo Mitsunobu R. Kano Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Pancreatic cancer is notorious for its poor prognosis. The histopathologic characteristic of pancreatic ductal adenocarcinoma (PDAC), which is the most common type of pancreatic cancer, is fibrosis within tumor tissue. Although fibrosis within tumor tissue is thought to impede drug therapy by interfering with the intratumoral accumulation of anti-tumor drugs, this hypothesis has yet to be proven directly in preclinical models. Here, we evaluated the effect of enhanced fibrosis on intratumoral accumulation of macromolecular drugs by increasing fibrosis in a murine tumor model of subcutaneously xenografted BxPC-3, a human PDAC cell line. When fibroblast growth factor-2 (FGF-2) was co-administered upon BxPC-3 inoculation, stromal fibrotic area was increased and was characterized by augmented murine collagen accumulation compared to inoculation of BxPC-3 alone, which correlated with increased monocyte/macrophage contents in the tumor tissues. We further discovered that the intratumoral accumulation of intravenously administrated fluorescein isothiocyanate-dextran of 2,000,000 Da (2 MDa) was significantly reduced in the FGF-2 co-administered tumors despite unaltered hyaluronan accumulation and pericyte coverage of the tumor neovasculature and increased lymphangiogenesis. Finally, we found that FGF-2 co-administered tumors are more refractory to macromolecular drug therapy using nab-paclitaxel (Abraxane). The model established and analyzed in this study, characterized by increased fibrotic component, provides a preclinical animal model suited to predict the intratumoral accumulation of macromolecular drugs and to evaluate the efficacy of drugs targeting the tumor stroma. No potential conflict of interest relevant to this article was reported.

BMJ Publishing Group Acta Medica Okayama 2044-6055 9 12 2019 Fall-related mortality trends in older Japanese adults aged >= 65 years: a nationwide observational study e033462 EN Hideharu Hagiya Department of General Internal Medicine, Osaka University Hospital Toshihiro Koyama Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School Yasuhisa Tatebe Department of Pharmacy, Okayama University Hospital Tomoko Funahashi Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kazuaki Shinomiya Department of Pharmaceutical Care and Clinical Pharmacy, Faculty of Pharmaceutical Sciences Tokushima Bunri University Yoshihisa Kitamura Department of Pharmacy, Okayama University Hospital Shiro Hinotsu Department of Biostatistics, Sapporo Medical University Toshiaki Sendo Department of Pharmacy, Okayama University Hospital Hiromi Rakugi Department of General Internal Medicine, Osaka University Hospital Mitsunobu R. Kano Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University OBJECTIVES:<br/> Fall-related mortality among older adults is a major public health issue, especially for ageing societies. This study aimed to investigate current trends in fall-related mortality in Japan using nationwide population-based data covering 1997-2016.<br/> DESIGN:<br/> We analysed fall-related deaths among older persons aged ≥65 years using the data provided by the Japanese Ministry of Health, Labour and Welfare.<br/> RESULTS:<br/> The crude and age-standardised mortality rates were calculated per 100 000 persons by stratifying by age (65-74, 75-84 and ≥85 years) and sex. To identify trend changes, a joinpoint regression model was applied by estimating change points and annual percentage change (APC). The total number of fall-related deaths in Japan increased from 5872 in 1997 to 8030 in 2016, of which 78.8% involved persons aged ≥65 years. The younger population (65-74 years) showed continuous and faster-decreasing trends for both men and women. Average APC among men aged ≥75 years did not decrease. Among middle-aged and older women (75-84 and ≥85 years) decreasing trends were observed. Furthermore, the age-adjusted mortality rate of men was approximately twice that of women, and it showed a faster decrease for women.<br/> CONCLUSIONS:<br/> Although Japanese healthcare has shown improvement in preventing fall-related deaths over the last two decades, the crude mortality for those aged over 85 years remains high, indicating difficulty in reducing fall-related deaths in the super-aged population. Further investigations to uncover causal factors for falls in older populations are required. No potential conflict of interest relevant to this article was reported.

Nature Publishing Group Acta Medica Okayama 2045-2322 9 2019 Place of death trends among patients with dementia in Japan: a population-based observational study 20235 EN Toshihiro Koyama Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Misato Sasaki Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hideharu Hagiya Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School Tomoko Funahashi Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ayako Ohshima Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yasuhisa Tatebe Department of Pharmacy, Okayama University Hospital Naoko Mikami Division of Pharmacy, Chiba University Hospital Kazuaki Shinomiya Department of Pharmaceutical Care and Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Tokushima Bunri University Yoshihisa Kitamura Department of Pharmacy, Okayama University Hospital Toshiaki Sendo Department of Pharmacy, Okayama University Hospital Shiro Hinotsu Department of Biostatistics, Sapporo Medical University Mitsunobu R. Kano Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Dementia is a major public health concern in ageing societies. Although the population of Japan is among the most aged worldwide, long-term trends in the place of death (PoD) among patients with dementia is unknown. In this Japanese nationwide observational study, we analysed trends in PoD using the data of patients with dementia who were aged >= 65 years and died during 1999-2016. Trends in the crude death rates and PoD frequencies were analysed using the Joinpoint regression model. Changes in these trends were assessed using the Joinpoint regression analysis in which significant change points, the annual percentage change (APC) and average APCs (AAPC) in hospitals, homes, or nursing homes were estimated. During 1999-2016, the number of deaths among patients with dementia increased from 3,235 to 23,757 (total: 182,000). A trend analysis revealed increased mortality rates, with an AAPC of 8.2% among men and 9.3% among women. Most patients with dementia died in the hospital, although the prevalence of hospital deaths decreased (AAPC: -1.0%). Moreover, the prevalence of nursing home deaths increased (AAPC: 5.6%), whereas the prevalence of home deaths decreased (AAPC: -5.8%). These findings support a reconsideration of the end-of-life care provided to patients with dementia. No potential conflict of interest relevant to this article was reported.