論文 - 高石　官均

Predicting exacerbation of renal function by DNA methylation clock and DNA damage of urinary shedding cells: a pilot study

Hishikawa A., Nishimura E.S., Yoshimoto N., Nakamichi R., Hama E.Y., Ito W., Maruki T., Nagashima K., Shimizu-Hirota R., Takaishi H., Itoh H., Hayashi K.

Scientific Reports 14 （ 1 ）  2024年12月

　概要を見る

Recent reports have shown the feasibility of measuring biological age from DNA methylation levels in blood cells from specific regions identified by machine learning, collectively known as the epigenetic clock or DNA methylation clock. While extensive research has explored the association of the DNA methylation clock with cardiovascular diseases, cancer, and Alzheimer's disease, its relationship with kidney diseases remains largely unexplored. In particular, it is unclear whether the DNA methylation clock could serve as a predictor of worsening kidney function. In this pilot study involving 20 subjects, we investigated the association between the DNA methylation clock and subsequent deterioration of renal function. Additionally, we noninvasively evaluated DNA damage in urinary shedding cells using a previously reported method to examine the correlation with the DNA methylation clock and worsening kidney function. Our findings revealed that patients with an accelerated DNA methylation clock exhibited increased DNA damage in urinary shedding cells, along with a higher rate of eGFR decline. Moreover, in cases of advanced CKD (G4-5), the DNA damage in urinary shedding cells was significantly increased, highlighting the interplay between elevated DNA damage and eGFR decline. This study suggests the potential role of the DNA methylation clock and urinary DNA damage as predictive markers for the progression of chronic kidney disease.

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Optimal number of images and 2-year interval affect cancer detection in screening esophagogastroduodenoscopy: An observational study

Ksahiwagi K., Yoshida T., Fukuhara K., Bessho R., Ichikawa H., Inoue N., Takaishi H., Iwao Y., Kanai T.

Medicine (United States) 103 （ 26 ）  2024年06月

ISSN  00257974

　概要を見る

We aimed to identify quality indicator for esophagogastroduodenoscopy for detecting upper gastrointestinal (UGI) cancer. Data from 43,526 consecutive health checkups from August 2012 to January 2022 were retrospectively collected. The study ultimately analyzed 42,387 examinations by 12 endoscopists who performed more than 1000 examinations, including all cancers detected. These endoscopists were classified either into fast/slow group based on their mean examination time for a normal finding of esophagogastroduodenoscopy during their first year of the examination, or small/large group based on number of endoscopic images, respectively. The association between UGI cancer detection rate and examination time or the number of images was analyzed, using 5 minutes or 50 images as cutoff values. The detection rate of overall (8 pharyngeal, 39 esophageal, 69 gastric) cancers in the fast, slow, small, and large groups were 0.17%, 0.32%, 0.21%, and 0.31%, respectively. On multivariable analysis, endoscopists in the fast group or the small group were less likely to detect overall UGI cancer (OR: 0.596, 95% CI: 0.373-0.952, P = .030; OR: 0.652, 95% CI: 0.434-0.979, P = .039). Additionally, repeated endoscopy within 2 years had a higher overall cancer detection rate, compared with repeated screening after 2 years. In a sub-analysis, a significant negative relationship was found between the detection rate of gastric cancer and the number of gastric images < 35 (OR: 0.305, 95% CI: 0.189-0.492, P = .000). There was also a negative correlation trend between the detection rate of pharyngeal and esophageal cancers and the number of esophageal images < 11 (OR: 0.395, 95% CI: 0.156-1.001, P = .050). The optimal number of images and screening 2-year interval are considered useful quality indicators for detecting UGI cancer. This study also suggests that a total of 50 images, or 35 images of the stomach are suitable for detecting UGI cancer, or gastric cancer, during screening endoscopy.

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WJOG13219G: The Efficacy and Safety of FOLFOXIRI or Doublet plus Anti-VEGF Therapy in Previously Untreated BRAF^V600E Mutant Metastatic Colorectal Cancer: A Multi-Institutional Registry-Based Study (BRACELET Study)

Shimozaki K., Hirata K., Sato T., Nakamura M., Kato K., Hirano H., Kumekawa Y., Hino K., Kawakami K., Kito Y., Matsumoto T., Kawakami T., Komoda M., Nagashima K., Sato Y., Yamazaki K., Hironaka S., Takaishi H., Hamamoto Y., Muro K.

Clinical Colorectal Cancer 21 （ 4 ） 339 - 346 2022年12月

ISSN  15330028

　概要を見る

Background: The real-world survival benefit of FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus anti-VEGF therapy (Triplet) over doublet chemotherapy (Doublet) remains controversial in patients with BRAFV600E mutant metastatic colorectal cancer (mCRC). Patients and Methods: WJOG13219G was a multicenter, retrospective, registry-based study of patients with BRAFV600E mutant mCRC who received first-line triplet or doublet chemotherapy from January 2014 to December 2019 in Japan. Inverse probability of treatment weighting (IPTW) was used to adjust for patient background. Results: The analysis included 79 and 91 patients in the Triplet and Doublet groups, respectively. The Triplet group was significantly younger and had better performance status. No statistical difference was noted in progression-free survival (PFS; HR, 0.82; 95% CI, 0.60–1.13; P = .22) and overall survival (OS; HR, 0.88; 95% CI, 0.62–1.25; P = .48) between both groups. IPTW analysis also showed no difference between the 2 groups in PFS (HR, 0.86; 95% CI, 0.69–1.08; P = .20) and OS (HR, 0.93; 95% CI, 0.73–1.20; P = .59). The Triplet and Doublet groups had an objective response rate of 53% and 41%, respectively (P = .10). At least one grade 3 or 4 adverse event was seen in 51 (65%) and 43 (47%) patients in the Triplet and Doublet groups, respectively, with the incidence of neutropenia being significantly higher in the former. Conclusion: Triplet therapy had no survival benefit versus doublet therapy in the overall and IPTW cohorts or specific subgroups for real-world patients with BRAFV600E mutant mCRC.

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A significant risk of metabolic dysfunction-associated fatty liver disease plus diabetes on subclinical atherosclerosis

Bessho R., Kashiwagi K., Ikura A., Yamataka K., Inaishi J., Takaishi H., Kanai T.

PLoS ONE 17 （ 5 May ）  2022年05月

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Background This cross-sectional study aims to investigate the association between subclinical atherosclerosis and metabolic dysfunction-associated fatty liver disease (MAFLD) or non-alcoholic fatty liver disease (NAFLD), and a synergistic effect of diabetes mellitus (DM) and MAFLD on subclinical atherosclerosis. Methods Of 977 subjects who underwent health checkups with coronary artery calcification (CAC), carotid intima-media thickness, and brachial-ankle pulse wave velocity (ba-PWV), 890 were included in this study. They were classified as MAFLD, NAFLD, or Neither-FLD, and MAFLD was further categorized into three groups by three metabolic disorders (obesity, lean with metabolic dysregulation, DM), according to its new definition: Obesity-MAFLD, Lean-MAFLD and DM-MAFLD. Results In a multivariable analysis, MAFLD and NAFLD were significantly associated with subclinical atherosclerosis, except for an association between ba-PWV and NAFLD. MAFLD had higher odds for CAC than NAFLD (for CAC score > 100, odds ratio (OR) = 2.599, 95% confidence interval (CI) = 1.625–4.157; OR = 1.795, 95%CI = 1.145–2.814, respectively). In a sub-analysis, DM-MAFLD had higher odds for CAC (for CAC score > 100, OR = 5.833, 95% CI = 3.047–11.164) than the other groups of MAFLD, when compared to Neither FLD as a reference. Moreover, DM-MAFLD had a higher level of homeostasis model assessment of insulin resistance and high sensitive C-reactive protein, compared to the other groups of MAFLD. Conclusions MAFLD was significantly associated with subclinical atherosclerosis in the general population. Additionally, DM-MAFLD could be a significant risk factor for cardiovascular disease through insulin resistance and low-grade inflammation and requires careful follow-up or appropriate intervention.

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Unbiased, comprehensive analysis of Japanese health checkup data reveals a protective effect of light to moderate alcohol consumption on lung function

Makino K., Shimizu-Hirota R., Goda N., Hashimoto M., Kawada I., Kashiwagi K., Hirota Y., Itoh H., Jinzaki M., Iwao Y., Ko M., Ko S., Takaishi H.

Scientific Reports 11 （ 1 ）  2021年12月

　概要を見る

The overall effect of lifestyle habits, such as alcohol consumption, on general health remains controversial and it is important to clarify how such habits affect aging-related health impairments. To discover novel impacts of lifestyle on general health, we employed a mathematical approach to perform a comprehensive, unbiased, cross-sectional analysis of data from 6036 subjects who participated in a Japanese health checkup. Notably, we found that moderate alcohol consumption was positively correlated with lung function, muscle mass, and strength. Health checkup data were collected periodically from the same subjects. These people were light to moderate drinkers who had high health awareness and were basically free of major underlying diseases. We next analyzed 5 years of data from 1765 of these subjects. We found that higher baseline alcohol consumption, as well as increased alcohol intake over 5 years attenuated time-related deterioration of forced vital capacity without affecting total lung volume. This effect was independent of smoking. Our study suggests a possible protective effect of moderate amounts of alcohol on lung function, due to increased muscle mass/strength and forced vital capacity.

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Clinical, Endoscopic, and Pathological Characteristics of Immune Checkpoint Inhibitor-Induced Gastroenterocolitis

Hayashi Y., Hosoe N., Takabayashi K., Limpias Kamiya K.J.L., Tsugaru K., Shimozaki K., Hirata K., Fukuhara K., Fukuhara S., Mutaguchi M., Sujino T., Sukawa Y., Hamamoto Y., Naganuma M., Takaishi H., Shimoda M., Ogata H., Kanai T.

Digestive Diseases and Sciences 66 （ 6 ） 2129 - 2134 2021年06月

ISSN  01632116

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Oncogenic KRAS–expressing organoids with biliary epithelial stem cell properties give rise to biliary tract cancer in mice

Kasuga A., Semba T., Sato R., Nobusue H., Sugihara E., Takaishi H., Kanai T., Saya H., Arima Y.

Cancer Science 112 （ 5 ） 1822 - 1838 2021年05月

ISSN  13479032

　概要を見る

Biliary tract cancer (BTC) arises from biliary epithelial cells (BECs) and includes intrahepatic cholangiocarcinoma (IHCC), gallbladder cancer (GC), and extrahepatic cholangiocarcinoma (EHCC). Although frequent KRAS mutations and epigenetic changes at the INK4A/ARF locus have been identified, the molecular pathogenesis of BTC is unclear and the development of corresponding anticancer agents remains inadequate. We isolated epithelial cell adhesion molecule (EpCAM)–positive BECs from the mouse intrahepatic bile duct, gallbladder, and extrahepatic bile duct, and established organoids derived from these cells. Introduction of activated KRAS and homozygous deletion of Ink4a/Arf in the cells of each organoid type conferred the ability to form lethal metastatic adenocarcinoma with differentiated components and a pronounced desmoplastic reaction on cell transplantation into syngeneic mice, indicating that the manipulated cells correspond to BTC–initiating cells. The syngeneic mouse models recapitulate the pathological features of human IHCC, GC, and EHCC, and they should therefore prove useful for the investigation of BTC carcinogenesis and the development of new therapeutic strategies. Tumor cells isolated from primary tumors formed organoids in three-dimensional culture, and serial syngeneic transplantation of these cells revealed that their cancer stem cell properties were supported by organoid culture, but not by adherent culture. Adherent culture thus attenuated tumorigenic activity as well as the expression of both epithelial and stem cell markers, whereas the expression of epithelial-mesenchymal transition (EMT)–related transcription factor genes and mesenchymal cell markers was induced. Our data show that organoid culture is important for maintenance of epithelial cell characteristics, stemness, and tumorigenic activity of BTC–initiating cells.

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A significant association of non-obese non-alcoholic fatty liver disease with osteosarcopenic obesity in females 50 years and older

Kashiwagi K., Takayama M., Ichikawa H., Takaishi H., Iwao Y., Kanai T.

Clinical Nutrition ESPEN 42   166 - 172 2021年04月

ISSN  24054577

　概要を見る

Background & aims: Osteosarcopenic obesity (OSO) encompassing obesity, sarcopenia and osteopenia, is due to redistribution or infiltration of fat into muscle and bone. This cross-sectional study evaluated the association between OSO and non-alcoholic fatty liver disease (NAFLD). Methods: Obesity, sarcopenia and osteopenia was defined using the percentage of body fat mass, reduced muscle mass, and the percentage of young adult mean < 80%, measured by dual-energy x-ray absorptiometry, respectively. Non-obese and obese NAFLD was diagnosed by ultrasound and body mass index cut-off point (25 kg/m2). A total of 619 subjects ≥ 50 years who completed health checkups were divided into obesity group including OSO and sarcopenic obesity (SO) alone phenotype, and non-obesity group that did not belong to any phenotype, including standard (St). Results: Overall osteopenia and OSO were detected in only 10% and 1% in males, compared with 45% and 9% in females, respectively. Multivariate analysis for females demonstrated a significant association of OSO with non-obese NAFLD (odds ratio = 3.737, 95% confidence interval = 1.365–10.233, P = 0.010), while the association between SO alone and non-obese NAFLD was equivocal. The OSO phenotype had a significantly higher proportion of slower walking speed and weaker grip strength, compared to the St phenotype. The proportion of OSO increased with age in contrast to constant prevalence of non-obese NAFLD. Conclusion: Non-obese NAFLD had a significant association with OSO in females, independent of plausible confounders. These results suggest that non-obese NAFLD might be an independent risk factor for OSO.

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Estimating copy number using next-generation sequencing to determine ERBB2 amplification status

Nakamura K., Aimono E., Oba J., Hayashi H., Tanishima S., Hayashida T., Chiyoda T., Kosaka T., Hishida T., Kawakubo H., Kitago M., Okabayashi K., Funakoshi T., Okita H., Ikeda S., Takaishi H., Nishihara H.

Medical Oncology 38 （ 4 ）  2021年04月

ISSN  13570560

　概要を見る

Assessing Erb-b2 receptor tyrosine kinase 2 (ERBB2) amplification status in breast and gastric cancer is necessary for deciding the best therapeutic strategy. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are currently used for assessing protein levels and gene copy number (CN), respectively. The use of next-generation sequencing (NGS) to measure ERBB2 CN in breast cancer is approved by the United States Federal Drug Administration as a companion diagnostic. However, a CN of less than 8 is evaluated as “equivocal”, which means that some ERBB2 amplification cases diagnosed as “HER2 negative” might be false-negative cases. We reviewed the results of gene profiling targeting 160 cancer-related genes in breast (N = 90) and non-breast (N = 19) cancer tissue, and compared the ERBB2 CN results with the IHC/FISH scores. We obtained an estimated CN from the measured CN by factoring in the histological proportion of tumor cells and found that an ERBB2-estimated CN of 3.2 or higher was concordant with the combined IHC/FISH outcome in 98.4% (88/90) of breast cancer cases, while this was not always evident among non-breast cancer cases. Therefore, NGS-estimated ERBB2 CN could be considered a diagnostic test for anti-HER2 therapy after the completion of adequate prospective clinical trials.

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RT-PCR screening tests for SARS-CoV-2 with saliva samples in asymptomatic people: Strategy to maintain social and economic activities while reducing the risk of spreading the virus

Oba J., Taniguchi H., Sato M., Takamatsu R., Morikawa S., Nakagawa T., Takaishi H., Saya H., Matsuo K., Nishihara H.

Keio Journal of Medicine 70 （ 2 ） 35 - 43 2021年

ISSN  00229717

　概要を見る

The year 2020 will be remembered for the coronavirus disease 2019 (COVID-19) pandemic, which continues to affect the whole world. Early and accurate identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is fundamental to combat the disease. Among the current diagnostic tests, real-time reverse transcriptase–polymerase chain reaction (RT-qPCR) is the most reliable and frequently used method. Herein, we discuss the interpretation of RT-qPCR results relative to viral infectivity. Although nasopharyngeal swab samples are often used for RT-qPCR testing, they require collection by trained medical staff. Saliva samples are emerging as an inexpensive and efficient alternative for large-scale screening. Pooled-sample testing of saliva has been applied for mass screening of SARS-CoV-2 infection. Current policies recommend isolating people with borderline cycle threshold (Ct) values (35<Ct <40), despite these Ct values indicating minimal infection risk. We propose the new concept of a “social cut-off” Ct value and risk stratification based on the correlation of Ct with infectivity. We also describe the experience of RT-qPCR screening of saliva samples at our institution. It is important to implement a scientific approach to minimize viral transmission while allowing economic and social activities to continue.

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Post-progression survival following second-line chemotherapy in patients with advanced pancreatic cancer previously treated with gemcitabine: a meta-analysis

高石 官均

Investigational New Drugs （Investigational New Drugs）  36 （ 5 ） 939 - 948 2018年10月

研究論文（学術雑誌）,  ISSN  0167-6997

　概要を見る

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Background Post-progression survival (PPS) could be a confounding element in interpreting data from clinical trials of second-line chemotherapy in patients with advanced pancreatic cancer (PC) previously treated with gemcitabine (GEM) because a recent meta-analysis of oxaliplatin combination therapy showed statistical heterogeneity for overall survival (OS) but not for progression-free survival (PFS). This study aimed to improve the understanding of the impact of PPS on OS in this setting. Methods Databases were searched to identify randomized controlled trials (RCTs) in the salvage setting. We evaluated relationships between OS and PFS, PPS, and other variables. Results Totally, 17 RCTs with 3253 patients were identified. Median OS was strongly and moderately associated with median PPS and PFS, respectively (r = 0.913; p < 0.001 and 0.780; p < 0.001, respectively). The proportion of patients with good performance status was significantly associated with both PPS and PFS (r = 0.574, p < 0.001 and 0.492, p < 0.001, respectively). The induction rate of subsequent chemotherapy was related to the duration of PPS and OS (r = 0.640, p < 0.001 and 0.647, p < 0.001, respectively). Median PPS and OS were significantly longer in recent trials than those in older trials (3.55 versus 2.78 months, p < 0.001 and 6.29 versus 5.02 months, p < 0.001). Conclusions Median PPS was strongly correlated with median OS. Given the recently increased opportunity for subsequent chemotherapy and supportive care, PPS may serve as an important element to clarify problems in this setting.

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Pancreatic Fat Content Detected by Computed Tomography and Its Significant Relationship with Intraductal Papillary Mucinous Neoplasm

高石 官均

Pancreas （Pancreas）  47 （ 9 ） 1087 - 1092 2018年10月

研究論文（学術雑誌）,  ISSN  0885-3177

　概要を見る

© Wolters Kluwer Health, Inc. All rights reserved. Objectives Intraductal papillary mucinous neoplasms (IPMNs) are premalignant lesions of pancreatic ductal adenocarcinomas (PDACs). Fat accumulation in the pancreas is increasingly recognized as a cause of PDAC. We aimed to identify factors that are relevant between IPMN and metabolic-related factors, including pancreatic fat. Methods The database for 781 subjects who underwent a health checkup and upper abdominal magnetic resonance imaging was searched and computed tomography attenuation indexes (pancreatic and spleen attenuation, pancreas-to-spleen attenuation ratio) were decided by measuring the regions of interest in the pancreas and spleen on nonenhanced images, using Hounsfield units. Eighty-five subjects from each of the IPMN and noncyst groups were matched for age, sex, and glycemic status and statistically compared in clinical characteristics. Results There was no difference in metabolic-related factors except for apolipoprotein A1 and high-density lipoprotein cholesterol between the 2 groups in univariate analysis. Multivariate logistic regression analysis showed that both indexes were significantly associated with IPMN (odds ratio, 0.905 [95% confidence intervals, 0.851-0.963; P = 0.002]; odds ratio, 0.006 [95% confidence intervals, 0.000-0.152; P = 0.002]). Conclusions Pancreatic fat content measured by computed tomography was significantly associated with IPMN. These results suggest that IPMN may develop secondary to pancreatic steatosis that could be an overlapping risk factor for PDAC and IPMN.

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Pilot study of WT1 peptide-pulsed dendritic cell vaccination with docetaxel in esophageal cancer

高石 官均

Oncology Letters （Oncology Letters）  16 （ 1 ） 1348 - 1356 2018年07月

研究論文（学術雑誌）,  ISSN  1792-1074

　概要を見る

© 2018, Spandidos Publications. All rights reserved. In the present study, the immune response to Wilms tumor gene 1 (WT1) peptide-pulsed dendritic cell (DC) vaccination combined with docetaxel (DCDOC) in advanced esophageal cancer patients who had already received first-line chemotherapy was investigated. Ten HLA-A*2402 patients were treated with docetaxel (50 mg/m2) on day 1 and WT1 peptide-pulsed DC vaccination (1x107 cells) on days 15 and 22 (repeated every 4 weeks for 3 cycles). The delayed-type hypersensitivity skin test, HLA tetramer assay and interferon-γ enzyme-linked immunospot (ELISPOT) assay were used to evaluate the induction of a WT1-specific immune response. Median overall survival was 5 months (range, 1.1-11.6). The clinical effect of DCDOC therapy was not observed and only 1 patient could complete the protocol therapy. Disease progression was observed in 9 patients and 1 patient succumbed to fatality during the second cycle of therapy. As a pilot study, it was not possible to evaluate the safety of WT1 peptide-pulsed DCDOC therapy for esophageal squamous cell cancer. However, a WT1-specific response in 6 patients, as indicated by the ELISPOT or HLA/WT1-tetramer assay, was demonstrated. The results suggested that the positive immune response had significant relevance on the low percentage of CD11b+ and CD66b+ granulocytic myeloid-derived suppressor cells in CD15+ cells. Furthermore, DCDOC elicited a WT1-specific immune response regardless of the myelosuppression associated with docetaxel. The present findings support future studies and further work to assess DCDOC as an adjuvant therapy for esophageal cancer will be performed. The present clinical trial was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry on November 11th, 2011, no. UMIN000006704.

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Guidelines for treatment of renal injury during cancer chemotherapy 2016

高石 官均

Clinical and Experimental Nephrology （Clinical and Experimental Nephrology）  22 （ 1 ） 210 - 244 2018年02月

研究論文（学術雑誌）,  ISSN  1342-1751

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Clinical efficacy of immune checkpoint inhibitors in the treatment of unresectable advanced or recurrent gastric cancer: An evidence-based review of therapies

Togasaki K., Sukawa Y., Kanai T., Takaishi H.

OncoTargets and Therapy （OncoTargets and Therapy）  11   8239 - 8250 2018年

　概要を見る

© 2018 Togasaki et al. Standard treatment options for patients with advanced gastric cancer (GC) offer limited efficacy and are associated with some toxicity, which necessitates the development of more effective therapies for improving the treatment outcomes for this disease. Immunotherapy involving immune checkpoint inhibitors (ICIs) which inhibit the programmed death 1 (PD-1)/ programmed death ligand 1 interaction has emerged as a new treatment option. Nivolumab, a human IgG4 monoclonal antibody inhibitor of PD-1, has demonstrated promising clinical activity and induced durable responses in patients with advanced GC. Nivolumab has recently been approved for treating patients with pretreated advanced GC in Japan. In the present review, we summarized current evidence of the clinical efficacy of ICIs in a variety of solid tumors and reported our experience in patients with GC who were treated with nivolumab and the interesting features that were observed in these cases. Certain ICI-specific clinical features such as pseudo-and hyper-progression of tumor and hyper-response to subsequent chemotherapy have been reported in several cancer types. Lastly, we discussed the present scenario regarding research on biomarkers for assessing the clinical benefits of ICI therapies.

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Analysis of sensitivity and cell death pathways mediated by anti-cancer drugs using three-dimensional culture system

Kinoshita T., Higuchi H., Ayano-Kabashima-Niibe, Sakai G., Hamamoto Y., Takaishi H., Kanai T.

International Journal of Cancer Research （International Journal of Cancer Research）  14 （ 1 ） 1 - 12 2018年

ISSN  18119727

　概要を見る

© 2018 Takeshi Kinoshita et al. Objective: The aim of this study was to evaluate the differences of cytotoxicity mediated by anti-cancer drugs between 2D and 3D culture conditions. Methodology: The colon cancer cell line HCT116 was cultured in 2D and 3D conditions. Anti-proliferation effects and cell death pathways of cytotoxic agents, i.e., SN-38 and multi-kinase inhibitors i.e., sorafenib were examined. Data was analyzed by Studentʼs t-test. Results: Although SN-38 induced significant apoptosis associated with caspase-3/7 activation in 2D condition, apoptosis and anti-proliferation effects of SN-38 dramatically diminished in 3D condition. In contrast, anti-proliferation effects mediated by sorafenib unchanged. Interestingly, sorafenib induced significant apoptosis in the cells locating in the center of the 3D spheroids, whereas it did not induce caspase activation in 2D condition. In addition, 2D culture with low glucose concentration, a model mimicking central condition of the spheroids, revealed the significant cell death with caspase activation by sorafenib. Conclusion: 3D culture system provide new findings regarding cytotoxicity of compounds which are not identified by the 2D culture.

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Comprehensive genomic sequencing detects important genetic differences between right-sided and left-sided colorectal cancer

高石 官均

ONCOTARGET 8 （ 55 ） 93567 - 93579 2017年11月

研究論文（学術雑誌）,  ISSN  1949-2553

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Curative resectability of gastrointestinal cancer identified from iron deficiency anemia

高石 官均

ONCOLOGY LETTERS 14 （ 4 ） 4301 - 4304 2017年10月

研究論文（学術雑誌）,  ISSN  1792-1074

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Safety and efficacy of gemcitabine plus nab-paclitaxel therapy in elderly patients with advanced pancreatic cancer

高石 官均

ANNALS OF ONCOLOGY 28   210 - 244 2017年10月

研究論文（学術雑誌）,  ISSN  0923-7534

Inter-evaluator heterogeneity of clinical diagnosis for locally advanced esophageal squamous cell carcinoma

高石 官均

ESOPHAGUS 14 （ 4 ） 324 - 332 2017年10月

研究論文（学術雑誌）,  ISSN  1612-9059

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Benefit of rebiopsy for deciding treatment strategy in rectal cancer: A case report

高石 官均

ONCOLOGY LETTERS 14 （ 3 ） 3697 - 3700 2017年09月

研究論文（学術雑誌）,  ISSN  1792-1074

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ELF3 modulates mesenchymal to epithelial transition through regulation of CD44 variant isoform expression in pancreatic cancer cells

高石 官均

CANCER RESEARCH 77   A3 - A3 2017年07月

研究論文（学術雑誌）,  ISSN  0008-5472

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A systemic review and meta-analysis to evaluate the efficacy and postprogression survival of second-line chemotherapy for gemcitabine-refractory pancreatic cancer.

高石 官均

JOURNAL OF CLINICAL ONCOLOGY 35   93567 - 93579 2017年05月

研究論文（学術雑誌）,  ISSN  0732-183X

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Positive relationship between subsequent chemotherapy and overall survival in pancreatic cancer: meta-analysis of postprogression survival for first-line chemotherapy

高石 官均

CANCER CHEMOTHERAPY AND PHARMACOLOGY 79 （ 3 ） 595 - 602 2017年03月

研究論文（学術雑誌）,  ISSN  0344-5704

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Phase II study of the effectiveness and safety of trastuzumab and paclitaxel for taxane- and trastuzumab-naive patients with HER2-positive, previously treated, advanced, or recurrent gastric cancer (JFMC45-1102)

高石 官均

INTERNATIONAL JOURNAL OF CANCER 140 （ 1 ） 188 - 196 2017年01月

研究論文（学術雑誌）,  ISSN  0020-7136

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Meta-analysis of postprogression survival for first-line gemcitabine monotherapy in patients with advanced pancreatic cancer: Positive relationship between subsequent anti-cancer therapy and overall survival.

高石 官均

JOURNAL OF CLINICAL ONCOLOGY 34 （ 15 ） 3697 - 3700 2016年05月

研究論文（学術雑誌）,  ISSN  0732-183X

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Fatal hemorrhage in a patient with advanced soft tissue sarcoma following radiation and pazopanib treatment: A case report

高石 官均

ONCOLOGY LETTERS 11 （ 4 ） 2408 - 2410 2016年04月

研究論文（学術雑誌）,  ISSN  1792-1074

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Early tumor cavitation with regorafenib in metastatic colorectal cancer: A case report

高石 官均

ONCOLOGY LETTERS 11 （ 1 ） 231 - 233 2016年01月

研究論文（学術雑誌）,  ISSN  1792-1074

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外来化学療法中の消化器がん患者の身体活動量についての検討

岩越めぐみ、辻哲也、高石官均、 浜本康夫、 高橋常浩、遠藤高志、北川雄光、里宇明元

癌と化学療法 11 （ 43 ） 1367 - 1373 2016年

研究論文（学術雑誌）

Phase I/II trial of chemoradiotherapy with concurrent S-1 and cisplatin for clinical stage II/III esophageal carcinoma (JCOG 0604)

高石 官均

CANCER SCIENCE 106 （ 10 ） 1414 - 1420 2015年10月

研究論文（学術雑誌）,  ISSN  1347-9032

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Phase I pilot study of Wilms tumor gene 1 peptide-pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer

高石 官均

CANCER SCIENCE 106 （ 4 ） 397 - 406 2015年04月

研究論文（学術雑誌）,  ISSN  1347-9032

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Phase I Study of S-1 plus Fractional Cisplatin as Adjuvant Chemotherapy for Advanced Gastric Cancer in an Outpatient Setting (KOGC-03)

高石 官均

ANTICANCER RESEARCH 35 （ 1 ） 467 - 471 2015年01月

研究論文（学術雑誌）,  ISSN  0250-7005

Rac1 accumulates in the nucleus at the invasive front of colorectal cancer through promoting cell motility

高石 官均

CANCER RESEARCH 74 （ 19 ） 467 - 471 2014年10月

研究論文（学術雑誌）,  ISSN  0008-5472

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NEUROENDOCRINE TUMOR EVALUATED AS PR BY TREATING 14 MONTHS BY EVEROLIMUS

高石 官均

ANNALS OF ONCOLOGY 25   3847 - 3853 2014年10月

研究論文（学術雑誌）,  ISSN  0923-7534

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Continuous low-dose irradiation by I-125 seeds induces apoptosis of gastric cancer cells regardless of histological origin

高石 官均

CANCER BIOLOGY &amp; THERAPY 15 （ 1 ） 81 - 88 2014年01月

研究論文（学術雑誌）, 共著,  ISSN  1538-4047

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TGF-beta 1 in Tumor Microenvironments Induces Immunosuppression in the Tumors and Sentinel Lymph Nodes and Promotes Tumor Progression

高石 官均

JOURNAL OF IMMUNOTHERAPY 37 （ 2 ） 63 - 72 2014年01月

研究論文（学術雑誌）, 共著,  ISSN  1524-9557

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Symptomatic Pericardial Effusion After Chemoradiation Therapy in Esophageal Cancer Patients

高石 官均

INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 87 （ 3 ） 487 - 493 2013年11月

研究論文（学術雑誌）,  ISSN  0360-3016

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Mesenchymal stem cells regulate epithelial-mesenchymal transition and tumor progression of pancreatic cancer cells

高石 官均

CANCER SCIENCE 104 （ 2 ） 157 - 164 2013年02月

研究論文（学術雑誌）,  ISSN  1347-9032

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Phase I study of neoadjuvant chemoradiotherapy as an outpatient setting for patients with resectable advanced gastric cancer

高石 官均

JOURNAL OF CLINICAL ONCOLOGY 31 （ 4 ） 3759 - 3762 2013年02月

研究論文（学術雑誌）, 共著,  ISSN  0732-183X

Suppression of myeloid cell leukemia-1 (Mcl-1) enhances chemotherapy-associated apoptosis in gastric cancer cells

高石 官均

GASTRIC CANCER 16 （ 1 ） 100 - 110 2013年01月

研究論文（学術雑誌）,  ISSN  1436-3291

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Second-line chemotherapy for refractory small cell neuroendocrine carcinoma of the esophagus that relapsed after complete remission with irinotecan plus cisplatin therapy: Case report and review of the literature

高石 官均

ONCOLOGY LETTERS 5 （ 1 ） 117 - 122 2013年01月

研究論文（学術雑誌）,  ISSN  1792-1074

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Phase I Study of Combination Chemotherapy Consisting of Paclitaxel, Cisplatin, and S-1 in Patients with Unresectable Gastric Cancer (KOGC-02)

高石 官均

ANTICANCER RESEARCH 32 （ 12 ） 5401 - 5406 2012年12月

研究論文（学術雑誌）,  ISSN  0250-7005

T-helper 17 and Interleukin-17-Producing Lymphoid Tissue Inducer-Like Cells Make Different Contributions to Colitis in Mice

高石 官均

GASTROENTEROLOGY 143 （ 5 ） 1288 - 1297 2012年11月

研究論文（学術雑誌）,  ISSN  0016-5085

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Single Strain of Clostridium butyricum Promotes IL-10-Producing CD11b(+)F4/80(+) Regulatory Macrophages in Inflammatory Conditions

高石 官均

DIGESTIVE DISEASES AND SCIENCES 57 （ 11 ） 2731 - 2732 2012年11月

研究論文（学術雑誌）,  ISSN  0163-2116

Chemoresistance Is Associated with Cancer Stem Cell-like Properties and Epithelial-to-Mesenchymal Transition in Pancreatic Cancer Cells

高石 官均

ANTICANCER RESEARCH 32 （ 9 ） 3847 - 3853 2012年09月

研究論文（学術雑誌）,  ISSN  0250-7005

Anti-high mobility group box 1 and box 2 non-histone chromosomal proteins (HMGB1/HMGB2)antibodies and anti-Saccharomyces cerevisiae antibodies(ASCA): accuracy in differentially diagnosing UC and CD and correlation with inflammatory bowel disease phenotype

高石 官均

JOURNAL OF GASTROENTEROLOGY 47 （ 9 ） 969 - 977 2012年09月

研究論文（学術雑誌）,  ISSN  0944-1174

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Colon Neoplastic Cells Do Not Originate from Bone Marrow-derived Cells after Sex-mismatched Bone Marrow Transplantation

高石 官均

ANTICANCER RESEARCH 32 （ 9 ） 4097 - 4103 2012年09月

研究論文（学術雑誌）,  ISSN  0250-7005

CCR9(+) plasmacytoid dendritic cells in the small intestine suppress development of intestinal inflammation in mice

高石 官均

IMMUNOLOGY LETTERS 146 （ 1-2 ） 64 - 69 2012年08月

研究論文（学術雑誌）,  ISSN  0165-2478

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The use of infliximab in the prevention of postsurgical recurrence in polysurgery Crohn's disease patients: a pilot open-labeled prospective study

高石 官均

INTERNATIONAL JOURNAL OF COLORECTAL DISEASE 27 （ 7 ） 947 - 952 2012年07月

研究論文（学術雑誌）, 共著,  ISSN  0179-1958

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Intermittent Granulocyte and Monocyte Apheresis Versus Mercaptopurine for Maintaining Remission of Ulcerative Colitis: A Pilot Study

高石 官均

THERAPEUTIC APHERESIS AND DIALYSIS 16 （ 3 ） 213 - 218 2012年06月

研究論文（学術雑誌）,  ISSN  1744-9979

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CCL2-Induced Migration and SOCS3-Mediated Activation of Macrophages Are Involved in Cerulein-Induced Pancreatitis in Mice

高石 官均

GASTROENTEROLOGY 142 （ 4 ） 1010 - U526 2012年04月

研究論文（学術雑誌）,  ISSN  0016-5085

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5-Aminosalicylic Acid Mediates Expression of Cyclooxygenase-2 and 15-Hydroxyprostaglandin Dehydrogenase to Suppress Colorectal Tumorigenesis

高石 官均

ANTICANCER RESEARCH 32 （ 4 ） 1193 - 1202 2012年04月

研究論文（学術雑誌）,  ISSN  0250-7005

HEPATITIS C VIRUS INFECTION INCREASES THE CANCER STEM CELL-LIKE POPULATIONS IN HEPATOCELLULAR CARCINOMA CELL LINE

高石 官均

HEPATOLOGY 54   960A - 960A 2011年10月

研究論文（学術雑誌）,  ISSN  0270-9139

Phase I Study of Neoadjuvant Chemoradiotherapy Consisting of S-1 and Cisplatin for Patients with Resectable Advanced Gastric Cancer (KOGC-01)

高石 官均

ANTICANCER RESEARCH 31 （ 9 ） 3079 - 3083 2011年09月

研究論文（学術雑誌）,  ISSN  0250-7005

Regulatory T Cells Suppress Development of Colitis, Blocking Differentiation of T-Helper 17 Into Alternative T-Helper 1 Cells

高石 官均

GASTROENTEROLOGY 141 （ 3 ） 1014 - 1023 2011年09月

研究論文（学術雑誌）,  ISSN  0016-5085

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SOCS3 Promotes the Activation of CCR2-Dependent Migratory Cd11b+GR-1lowly6chigh Macrophages in Murine Cerulcin Pancreatitis

高石 官均

GASTROENTEROLOGY 140 （ 5 ） S127 - S127 2011年05月

研究論文（学術雑誌）, 共著,  ISSN  0016-5085

【膵癌診療と研究の最先端】切除不能局所進行膵癌に対するS-1/CDDP併用化学放射線療法の検討

栗田聡、樋口肇、中村公子、船越信介、足立雅之、山岸由幸、高石官均、朴沢重成、日比紀文

胆と膵 7 （ 38 ） 1167 - 1170 2011年

研究論文（学術雑誌）

gemcitabine、S-1併用療法が著効し、治癒切除にいたった巨大な進行胆嚢癌の1例

瀧田麻衣子、岩崎栄典、鳩貝健、岸野竜平、関恵理、泉谷幹子、前田憲男、中澤敦、水城啓、半田寛、下山豊、向井清、樋口肇、高石官均、日比紀文、塚田信廣

日本消化器病学会雑誌 7 （ 108 ） 1263 - 1270 2011年

研究論文（学術雑誌）

5-FU/CDDP併用化学療法にて肝転移が消失し原発巣の内視鏡的切除後長期無再発生存中の食道癌の1例

泉谷幹子、山岸由幸、中村公子、酒井元、船越信介、足立雅之、樋口肇、高石官均、杉浦仁、入江理恵、大森泰、日比紀文

癌と化学療法 7 （ 38 ） 1167 - 1170 2011年

研究論文（学術雑誌）

Gemcitabine as first-line chemotherapy in elderly patients with unresectable pancreatic carcinoma

高石 官均

JOURNAL OF GASTROENTEROLOGY 45 （ 11 ） 1146 - 1154 2010年11月

研究論文（学術雑誌）, 共著,  ISSN  0944-1174

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MyD88-dependent pathway accelerates the liver damage of Concanavalin A-induced hepatitis

高石 官均

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 399 （ 4 ） 744 - 749 2010年09月

研究論文（学術雑誌）,  ISSN  0006-291X

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Feasibility and Efficacy of Combination Chemotherapy with S-1 and Fractional Cisplatin for Advanced Gastric Cancer

高石 官均

ANTICANCER RESEARCH 30 （ 9 ） 3759 - 3762 2010年09月

研究論文（学術雑誌）, 共著,  ISSN  0250-7005

Competition between colitogenic Th1 and Th17 cells contributes to the amelioration of colitis

高石 官均

EUROPEAN JOURNAL OF IMMUNOLOGY 40 （ 9 ） 2409 - 2422 2010年09月

研究論文（学術雑誌）,  ISSN  0014-2980

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DNMT1 and DNMT3b silencing sensitizes human hepatoma cells to TRAIL-mediated apoptosis via up-regulation of TRAIL-R2/DR5 and caspase-8

Kurita S, Higuchi H, Saito Y, Nakamoto N, Takaishi H, Tada S, Saito H, Gores GJ, Hibi T

Cancer Sci 101 （ 6 ） 1431 - 1439 2010年06月

研究論文（学術雑誌）, 共著

Octreotide acetate enables the administration of chemoradiotherapy, including the oral anticancer drug S-1, in gastric cancer patients with malignant gastrointestinal obstruction

高石 官均

ONCOLOGY LETTERS 1 （ 4 ） 673 - 677 2010年01月

研究論文（学術雑誌）,  ISSN  1792-1074

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Side population of pancreatic cancer cells predominates in TGF-beta-mediated epithelial to mesenchymal transition and invasion

高石 官均

INTERNATIONAL JOURNAL OF CANCER 124 （ 12 ） 2771 - 2779 2009年06月

研究論文（学術雑誌）, 共著,  ISSN  0020-7136

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Imbalance in intestinal microflora constitution could be involved in the pathogenesis of inflammatory bowel disease

Takaishi H, Matsuki T, Nakazawa A, Takada T, Kado S, Asahara T, Kamada N, Sakuraba A, Yajima T, Higuchi H, Inoue N, Ogata H, Iwao Y, Nomoto K Tanaka R, Hibi T

Int J Med Microbiol 298 （ 5-6 ） 463 - 472 2008年09月

研究論文（学術雑誌）, 共著

Bone marrow-derived cells were not identified in colonic cancer of patients after sex-mismatched bone marrow transplantation

高石 官均

AMERICAN JOURNAL OF GASTROENTEROLOGY 103   S196 - S196 2008年09月

研究論文（学術雑誌）,  ISSN  0002-9270

Efficacy and safety of S-1-based chemotherapy in patients with advanced gastric adenocarcinoma: a single institute retrospective study

高石 官均

AMERICAN JOURNAL OF GASTROENTEROLOGY 103   S47 - S48 2008年09月

研究論文（学術雑誌）,  ISSN  0002-9270

A pilot open-labeled prospective randomized study between weekly and intensive treatment of granulocyte and monocyte adsorption apheresis for active ulcerative colitis

高石 官均

JOURNAL OF GASTROENTEROLOGY 43 （ 1 ） 51 - 56 2008年

研究論文（学術雑誌）,  ISSN  0944-1174

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Clinical significance of serum p53 antibodies in patients with ulcerative colitis and its carcinogenesis

高石 官均

INFLAMMATORY BOWEL DISEASES 13 （ 7 ） 865 - 873 2007年07月

研究論文（学術雑誌）,  ISSN  1078-0998

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Clinical significance of serum p53 antibodies in patients with ulcerative colitis and its carcinogenesis

高石 官均

INFLAMMATORY BOWEL DISEASES 13 （ 7 ） 865 - 873 2007年07月

研究論文（学術雑誌）,  ISSN  1078-0998

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Clinical significance of serum P53 antibodies in patients with ulcerative colitis and its carcinogenesis

高石 官均

GASTROENTEROLOGY 132 （ 4 ） A178 - A178 2007年04月

研究論文（学術雑誌）,  ISSN  0016-5085

プロバイオティクスと炎症性腸疾患

日比紀文、中澤敦、高石官均、鎌田信彦、久松理一、岡本晋、井上詠

無菌生物 1 （ 37 ） 58 - 61 2007年

研究論文（学術雑誌）

腸結核に合併し特異な形態を呈した大腸癌の1例

小林拓、岩男泰、杉野吉則、鳥居幸夫、井上詠、高石官均、金井隆典、緒方晴彦、日比紀文、向井萬起男

胃と腸 6 （ 42 ） 1033 - 1040 2007年

研究論文（学術雑誌）

Mcl-1 depletion enhances anti-cancer drug-induced apoptosis in gastroenteric cancer cells

高石 官均

AMERICAN JOURNAL OF GASTROENTEROLOGY 101 （ 9 ） S142 - S142 2006年09月

研究論文（学術雑誌）,  ISSN  0002-9270

Gemcitabin in elderly patients with unresectable pancreatic carcinoma

高石 官均

AMERICAN JOURNAL OF GASTROENTEROLOGY 101 （ 9 ） S110 - S110 2006年09月

研究論文（学術雑誌）, 共著,  ISSN  0002-9270

Cyclooxygenase-2 inhibitor and interferon-beta synergistically induce apoptosis in human hepatoma cells in vitro and in vivo

高石 官均

INTERNATIONAL JOURNAL OF ONCOLOGY 29 （ 3 ） 625 - 635 2006年09月

研究論文（学術雑誌）,  ISSN  1019-6439

Inhibition of neutrophil elastase prevents the development of murine dextran sulfate sodium-induced colitis

Morohoshi Y, Matsuoka K, Chinen H, Kamada N, Sato T, Hisamatsu T, Okamoto S, Inoue N, Takaishi H, Ogata H, Iwao Y, Hibi T

J Gastroenterol 41 （ 4 ） 318 - 324 2006年04月

研究論文（学術雑誌）, 共著

The constitution and distribution of intestinal bacterial flora in patients with inflammatory bowel disease: Genus or species specific analysis based on 16s rRNA gene sequences of intestinal bacterial flora in human feces and colonic mucosa

高石 官均

GASTROENTEROLOGY 130 （ 4 ） A356 - A357 2006年04月

研究論文（学術雑誌）,  ISSN  0016-5085

Serum p53 antibodies (ABS) in patients with ulcerative colitis (UC) are associated with the development of colorectal cancer and screening of p53 ABS by ELISA is useful in cancer surveillance program for UC patients

高石 官均

GASTROENTEROLOGY 130 （ 4 ） A3 - A3 2006年04月

研究論文（学術雑誌）,  ISSN  0016-5085

肝動注化学療法が有効であった肝内胆管癌の1例

西澤俊宏、樋口肇、高石官均、飯塚秀子、泉谷幹子、山岸由幸、久松理一、鈴木秀和、正岡建洋、岩崎栄典、永田博司、日比紀文

癌と化学療法 11 （ 33 ） 1657 - 1659 2006年

研究論文（学術雑誌）

【非定型的炎症性腸疾患　診断と経過】非定型的Crohn病の診断と経過　内視鏡所見を中心に

岩男泰、杉野吉則、井上詠、高石官均、桜庭篤、矢島知治、久松理一、岡本晋、今枝博之、緒方晴彦、日比紀文、向井萬起男

胃と腸 6 （ 41 ） 925 - 938 2006年

研究論文（学術雑誌）

自然軽快したcap polyposisの1例

船越信介、岩男泰、芳沢茂雄、久松理一、岡本晋、高石官均、井上詠、今枝博之、緒方晴彦、杉野吉則、向井万起男、日比紀文

Progress of Digestive Endoscopy 2 （ 68 ） 140 - 141 2006年

研究論文（学術雑誌）

A novel apoptosis-inducing monoclonal antibody (anti-LHK) against a cell surface antigen on colon cancer cells

Matsukawa H, Kanai T, Naganuma M, Kamada N, Hisamatsu T, Takaishi H, Ogata H, Mukai M, Ishii H, Mimori T, Watanabe M, Hibi T

J Gastroenterol 40 （ 10 ） 945 - 955 2005年10月

研究論文（学術雑誌）, 共著

Clinical significance of microsatellite instability in the inflamed mucosa for the prediction of colonic neoplasms in patients with ulcerative colitis

Tahara T, Inoue N, Hisamatsu T, Kashiwagi K, Takaishi H, Kanai T, Watanabe M, Ishii H, Hibi T

J Gastroenterol Hepatol 20 （ 5 ） 710 - 715 2005年05月

研究論文（学術雑誌）, 共著

Third-LineとしてTS-1，CPT-11併用化学療法を施行し長期生存が得られたKrukenberg腫瘍術後4型胃癌再発性癌性リンパ管症の1症例

山岸由幸、秋葉保忠、泉谷幹子、樋口肇、飯塚秀子、高石官均、永田博司、日比紀文

癌と化学療法 8 （ 32 ） 1167 - 1170 2005年

研究論文（学術雑誌）

胃癌化学療法後再発性胸水にTS-1-Based Sequential TherapyとしてのTS-1，Taxane併用化学療法が奏効した1症例

秋葉保忠、山岸由幸、森朱夏、上田智基、鈴木淳司、細江直樹、泉谷幹子、高石官均、永田博司、日比紀文、石井裕正

癌と化学療法 3 （ 31 ） 453 - 456 2004年

研究論文（学術雑誌）

【Crohn病経過例における新しい治療の位置づけ】Crohn病経過例における免疫抑制剤の効果

岩男泰、諸星雄一、松岡克善、久松理一、岩上祐子、泉谷幹子、桜庭篤、芳沢茂雄、佐藤俊朗、一松収、岡本晋、高石官均、井上詠、緒方晴彦、日比紀文、杉野吉則

胃と腸 2 （ 39 ） 185 - 199 2004年

研究論文（学術雑誌）

Contrasting action of IL-12 and IL-18 in the development of dextran sodium sulfate colitis in mice

Takagi T, Kanai T, Okazawa A, Sato T, Takaishi H, Inoue N, Ogata H, Iwao Y, Hoshino K, Takeda K, Akira S, Watanabe M, Ishii H, Hibi T

Scand J Gastroenterol 38 （ 8 ） 837 - 844 2003年08月

研究論文（学術雑誌）, 共著

腸疾患とプロバイオテックス

日比紀文，高石官均

アレルギー・免疫 10 （ 4 ） 478-482 2003年

研究論文（学術雑誌）, 共著

Oxidative stress induces the expression of Fas and Fas ligand and apoptosis in murine intestinal epithelial cells

Denning TL, Takaishi H, Crowe SE, Boldogh I, Jevnikar A, Ernst PB

Free Radic Biol Med 33 （ 12 ） 1641 - 1650 2002年12月

研究論文（学術雑誌）, 共著

特集：アポトーシスと疾患―最近の展開―炎症性腸疾患とアポートシス

日比紀文，高石官均

最新医学 57 （ 11 ） 2471-2475 2002年12月

研究論文（学術雑誌）, 共著

特集：アポトーシスと疾患―最近の展開―炎症性腸疾患とアポートシス

日比紀文，高石官均

最新医学 57 （ 11 ） 2471-2475 2002年12月

研究論文（学術雑誌）, 共著

潰瘍性大腸炎に対するスターリーミルクの有用性

長沼誠、日比紀文、高石官均、緒方晴彦、井上詠、岩男泰、石井裕正

消化器と免疫  （ 39 ） 26 - 28 2002年

研究論文（学術雑誌）

Staphylococcal enterotoxin B stimulates expansion of autoreactive T cells that induce apoptosis in intestinal epithelial cells: regulation of autoreactive responses by IL-10

Ito K, Takaishi H, Jin Y, Song F, Denning TL, Ernst PB

J Immunol 164 （ 6 ） 2994 - 3001 2000年03月

研究論文（学術雑誌）, 共著

Induction of hepatic stellate cell proliferation by LPS-stimulated peripheral blood mononuclear cells from patients with liver cirrhosis

Toda Kyoko, Kumagai Naoki, Tsuchimoto Kanji, Inagaki Hiroyuki, Suzuki Tatsuo, Oishi Tazuko, Atsukawa Kazuhiro, Saito Hidetsugu, Morizane Toshio, Hibi Toshifumi, Ishii Hiromasa

Journal of Gastroenterology 35 （ 3 ） 214-220 2000年

研究論文（学術雑誌）, 共著

Circulating autoantibodies against purified colonic mucin in ulcerative colitis

Takaishi Hiromasa, Ohara Susumu, Hotta Kyoko, Yajima Tomoharu, Kanai Takanori, Inoue Nagamu, Iwao Yasushi, Watanabe Mamoru, Ishii Hiromasa, Hibi Toshifumi

Journal of Gastroenterology 35 （ 1 ） 20-27 2000年

研究論文（学術雑誌）, 共著

シクロスポリンA持続静注療法が著効したステロイド抵抗性潰瘍性大腸炎の1例

宮崎敬子，久松理一，海老名浩利，柏木和弘，矢島知治，高石官均，岩男泰，渡辺守，日比紀文，石井裕正

日本消化器病学会雑誌 96 （ 11 ） 1290-1294 1999年11月

研究論文（学術雑誌）, 共著

シクロスポリンA持続静注療法が著効したステロイド抵抗性潰瘍性大腸炎の1例

宮崎敬子，久松理一，海老名浩利，柏木和弘，矢島知治，高石官均，岩男泰，渡辺守，日比紀文，石井裕正

日本消化器病学会雑誌 96 （ 11 ） 1290-1294 1999年11月

研究論文（学術雑誌）, 共著

虫垂口近傍に限局性病変を呈した無症候性赤痢アメーバ大腸炎の1例

岡田裕美，芹澤宏，熊谷直樹，高石官均，渡辺憲明，濱田慶城，土本寛二，倉持茂，日比紀文，石井裕正

Progress of Digestive Endoscopy 54   126-127 1999年08月

研究論文（学術雑誌）, 共著

シクロスポリンA持続静注療法が著効したステロイド抵抗性潰瘍性大腸炎の1例

宮崎敬子、久松理一、海老沼浩利、柏木和弘、矢島知治、高石官均、岩男泰、渡辺守、日比紀文、石井裕正

日本消化器病学会雑誌 11 （ 96 ） 1290 - 1294 1999年

研究論文（学術雑誌）

虫垂口近傍に限局性病変を呈した無症候性赤痢アメーバ大腸炎の１例

岡田裕美、芹沢宏、熊谷直樹、高石官均、渡辺憲明、濱田慶城、土本寛二、倉持茂、日比紀文、石井裕正

Progress of Digestive Endoscopy  （ 54 ） 126 - 127 1999年

研究論文（学術雑誌）

インターフェロン治療著効後約三年で肝細胞癌が認められたC型慢性肝炎の1例

宮尾直樹、芹澤宏、熊谷直樹、高石官均、渡辺憲明、濱田慶城、土本寛二、竹内修、豊田元、倉持茂、石井裕正

日本消化器病学会雑誌 5 （ 96 ） 535 - 539 1999年

研究論文（学術雑誌）

十二指腸と上行・横行結腸に多発したhepatoid adenocarcinomaの1例

宮尾直樹，芹澤宏，高石官均，渡辺憲明，熊谷直樹，浜田慶城，土本寛二，倉持茂，三浦総一郎，日比紀文，石井裕正

消化器内視鏡の進歩 52   74-77 1998年07月

研究論文（学術雑誌）, 共著

CD45RCHIGHCD4+ intestinal mucosal lymphocytes infiltrating in the inflamed colonic mucosa of a novel rat colotis model induced by TNB immunization

Watanabe M, Hosoda Y, Okamoto S, Yamazaki M, Inoue N, Ueno Y, Iwao Y, Ishii H, Watanabe N, Hamada Y, Yamada T, Suzuki T, Hibi T

Clinical Immunology and Immunopathology 88 （ 1 ） 46-55 1998年07月

研究論文（学術雑誌）, 共著

十二指腸と上行・横行結腸に多発したhepatoid adenocarcinomaの1例

宮尾直樹、芹澤宏、高石官均、渡辺憲明、熊谷直樹、濱田慶城、土本寛二、倉持茂、三浦総一郎、日比紀文、石井裕正

Progress of Digestive Endoscopy（消化器内視鏡の進歩)  （ 52 ） 74 - 77 1998年

研究論文（学術雑誌）

Predicitive factors of response to leukocytapheresis therapy for ulcerative colitis

Yajima T, Takaishi H, Kanai T, Iwao Y, Watanabe M, Ishii H, Hibi T

Therapeutic Apheresis 2 （ 2 ） 115-119 1998年

研究論文（学術雑誌）, 共著

抗生剤多剤併用療法でのHelicobacter pylori除菌効果と内視鏡所見の検討

濱田慶城、芹沢宏、渡辺憲明、高石官均、能谷直樹、土本寛二、日比紀文、石井裕正

Therapeutic Research 10 （ 19 ） 3293 - 3297 1998年

研究論文（学術雑誌）

術前診断が困難であった後腹膜由来Castleman's diseaseの2例

海老根泰子、芹澤宏、高石官均、渡辺憲明、濱田慶城、熊谷直樹、土本寛二、山田好則、豊田元、渡辺賢治、森永正二郎、石井裕正

日本消化器病学会雑誌 3 （ 95 ） 250 - 256 1998年

研究論文（学術雑誌）

長期観察にて増大傾向を認め外科的切除に至った大腸血管腫の1例

富田裕，芹澤宏，渡辺憲明，浜田慶城，高石官均，岩渕直人，熊谷直樹，土本寛二，宮川健，倉持茂，日比紀文，石井裕正

Gastroenterol Endosc 39 （ 12 ） 2409-2414 1997年12月

研究論文（学術雑誌）, 共著

蛋白漏出を来し炎症性ポリポーシスに大腸癌を合併した若年者全結腸型潰瘍性大腸炎の1症例

小林一雄，浜田慶城，芹澤宏，渡辺憲明，高石官均，岩渕直人，熊谷直樹，土本寛二，山田好則，三浦総一郎，日比紀文，石井裕正，倉持茂

日消病会誌 94 （ 11 ） 772-777 1997年11月

研究論文（学術雑誌）, 共著

長期観察にて増大傾向を認め外科的切除に至った大腸血管腫の1例

富田裕、芹澤宏、渡辺憲明、浜田慶城、高石官均、岩渕直人、熊谷直樹、土本寛二、宮川健、倉持茂、日比紀文、石井裕正

Gastroenterological Endoscopy  （ 39 ） 2409 - 2414 1997年

研究論文（学術雑誌）

蛋白漏出を来し炎症性ポリポーシスに大腸癌を合併した若年者全結腸型潰瘍性大腸炎の1症例

小林一雄、浜田慶城、芹澤宏、渡辺憲明、高石官均、岩渕直人、熊谷直樹、土本寛二、山田好則、三浦総一郎、日比紀文、石井裕正、倉持茂

日本消化器病学会雑誌 11 （ 94 ） 772 - 777 1997年

研究論文（学術雑誌）

Differential displayを用いた潰瘍性大腸炎発癌関連遺伝子の研究

久松理一，江崎俊彦，山崎元美，中澤敦，岡本晋，矢島知治，高石官均，与那嶺吉正，岩男泰，渡辺守，加々谷重英，口野嘉幸，日比紀文，土屋雅春，石井裕正

消化器と免疫 32   93-96 1996年08月

研究論文（学術雑誌）, 共著

クローン病に対する栄養療法による暖解導入とその後の腹鏡下切除術

中澤敦，矢島知治，与那嶺吉正，坪内友，久松理一，岡本晋，高石官均，上野義隆，井上詠，石井裕正，岩男泰，渡辺守，渡邊昌彦，大上正裕，日比紀文

JJPEN 18 （ 6 ） 481-482 1996年06月

研究論文（学術雑誌）, 共著

腸管上皮細胞による粘膜免疫制御

日比紀文，高石官均，上野義隆，岩男泰，渡辺守，石井裕正

化学療法の領域 12 （ 5 ） 818-824 1996年05月

研究論文（学術雑誌）, 共著

炎症性腸疾患における免疫抑制の適応

日比紀文，矢島知治，岩男泰，高石官均，渡辺守，石井裕正

治療学 30 （ 3 ） 39-41 1996年03月

研究論文（学術雑誌）, 共著

クローン病肛門病変の治療方針

日比紀文，岩男泰，久松理一，矢島知治，与那嶺吉正，中澤敦，岡本晋，高石官均，上野義隆，井上詠，寺本龍生，石井裕正

消化器科 22 （ 2 ） 162-169 1996年02月

研究論文（学術雑誌）, 共著

Immunosuppressive agents in the treatment of Crohn's disease and ulcerative colitis

Hibi T, Iwao Y, Yajima T, Inoue N, Ueno Y, Takaishi H, Watanabe M, Ishii H

J Gastroenterol 30 （ 8 ） 121-123 1996年01月

研究論文（学術雑誌）, 共著

内視鏡的止血術が奏功した十二指腸憩室内潰瘍出血の1例

大石温子、日比紀文、芹澤宏、渡辺守、高石官均、細田泰雄、濱田慶城、三浦総一郎、土屋雅春、石井裕正

Gastroenterological Endoscopy  （ 32 ） 337 - 341 1996年

研究論文（学術雑誌）

拡大電子内視鏡を用いた炎症性腸疾患における微細病変の検討

井上詠、矢島知治、中澤敦、久松理一、岡本晋、高石官均、上野義隆、細田泰雄、石井裕正、岩男泰、渡辺守、日比紀文

Progress of Digestive Endoscopy  （ 49 ） 164 - 165 1996年

研究論文（学術雑誌）

CD4+ intestinal mucosal lymphocytes in the pathogenesis of Crohn's disease

Watanabe M, Takaishi H, Hosoda Y, Ezaki T, Yajima T, Inoue N, Ueno Y, Iwao Y, Ishii H, Ishikawa H, Hibi T

J Gastroenterol 30 （ 8 ） 121 - 123 1995年11月

研究論文（学術雑誌）, 共著

潰瘍性大腸炎病変局所における抗大腸抗体産生B細胞の免疫グロブリンH鎖可変領域遺伝子再構成の検討

久松理一，井上詠，矢島知治，高石官均，上野義隆，大原信，岩男泰，渡辺守，土屋雅春，相磯貞和，渡辺憲明，浜田慶城，日比紀文，石井裕正

消化器と免疫 31 （ 1 ） 123-127 1995年08月

研究論文（学術雑誌）, 共著

潰瘍性大腸炎難治化の免疫学的要因

岩男泰，日比紀文，矢島知治，高石官均，井上詠，上野義隆，渡辺憲明，渡辺守，小林研介，石井裕正

消化器科 20 （ 5 ） 337-345 1995年05月

研究論文（学術雑誌）, 共著

潰瘍性大腸炎

岩男泰，日比紀文，矢島知治，高石官均，上野義隆，井上詠，渡辺憲明，渡辺守，小林研介，石井裕正

リウマチ科 14 （ 4 ） 329-337 1995年04月

研究論文（学術雑誌）, 共著

Immunoglobulin G subclass distribution of human anticolon antibodies in ulcerative colitis

Ohara M, Hibi T, Watanabe N, Kobayashi K, Takaishi H, Hayashi A, Hosoda Y, Toda K, Iwao Y, Watanabe M, Aiso S, Tsuchiya M, Ishii H

J Gastroenterol Hepatol 10 （ 2 ） 158-164 1995年03月

研究論文（学術雑誌）, 共著

経皮経肝血栓除去術を施行した上腸間膜静脈血栓症の1例

長沼誠、井上詠、細田泰雄、高山美智代、北村祐子、高石官均、上野義隆、木村裕之、折井正博、中塚誠之、小川建二、岩男泰、渡辺守、日比紀文、石井裕正

日本消化器病学会雑誌 2 （ 92 ） 158 - 163 1995年

研究論文（学術雑誌）

抗CD4抗体投与によるTNB免疫大腸炎の抑制

高石官均、日比紀文、細田泰雄、矢島知治、井上詠、上野義隆、岩男泰、渡辺憲明、浜田慶城、戸田京子、山田高也、鈴木達夫、相磯貞和、土屋雅春、渡辺守、石井裕正

消化器と免疫  （ 30 ） 128 - 133 1995年

研究論文（学術雑誌）

潰瘍性大腸炎病変局所における抗大腸抗体産生B細胞の免疫グロブリンH鎖可変領域遺伝子再構成の検討

久松理一、井上詠、矢島知治、高石官均、上野義隆、大原信、岩男泰、渡辺守、土屋雅春、相磯貞和、渡辺憲明、浜田慶城、日比紀文、石井裕正

消化器と免疫  （ 31 ） 123 - 127 1995年

研究論文（学術雑誌）

典型的皮疹を欠いたCowden病の1例

井上卓、井上詠、日比紀文、林篤、高石官均、上野義隆、細田泰雄、渡辺守、石井裕正、向井万起男

Gastroenterological Endoscopy  （ 37 ） 65 - 17 1995年

研究論文（学術雑誌）

Enzyme linked immunosorbent assay(ELISA) and immunoprecipitation studies on anti-goblet cell antibody using a mucin producing cell line in patients with inflammatory bowel disease

Hibi T, Ohara M, Kobayashi K, Brown WR, Toda K, Takaishi H, Hosoda Y, Hayashi A, Iwao Y, Watanabe M, Aiso S, Kawai Y, Tsuchiya M

Gut 35 （ 2 ） 224 - 230 1994年02月

研究論文（学術雑誌）, 共著

潰瘍性大腸炎における自己抗体と臨床経過およびHLA-DR2との関連性

高石官均、日比紀文、小林研介、井上詠、上野義隆、矢島知治、渡辺守、大原信、福村大、岩男泰、杉村一仁、朝倉均、戸田京子、浜田慶城、相磯貞和、土屋雅春、石井裕正

消化器と免疫 29   112 - 116 1994年

研究論文（学術雑誌）

一過性に非乾酪性肉芽腫が確認されたリンパ濾胞過形成を伴う"アフタ様大腸炎"の1例

芹澤宏、日比紀文、高石官均、杉野吉則、土屋雅春

胃と腸 29 （ 6 ） 583 - 588 1994年

研究論文（学術雑誌）

消化器外科領域におけるサイトカインとその周辺 炎症性腸疾患におけるサイトカインの発現

渡辺守、日比紀文、上野義隆、矢島知治、高石官均、井上詠、岩男泰、石井裕正、相磯貞和

臨床外科 49 （ 9 ） 1193 - 1198 1994年

研究論文（学術雑誌）

Interleukin 2 and interferon-gamma augment anticolon antibody dependent cellular cytotoxicity in ulcerative colitis

Hibi T, Ohara M, Watanabe M, Kanai T, Takaishi H, Hayashi A, Hosoda Y, Ogata H, Iwao Y, Aiso S, Watanabe N, Toda K, Tsuchiya M

Gut 34 （ 6 ） 788 - 793 1993年06月

研究論文（学術雑誌）

実験大腸炎における免疫担当細胞の動態 [第2報]

細田泰雄、日比紀文、渡辺守、高石官均、井上詠、上野義隆、浜田慶城、土本寛二、山田高也、稲垣宏之、戸田京子、鈴木達夫、岩男泰、相磯貞和、秦順一、土屋雅春

消化器と免疫 28   137 - 141 1993年

研究論文（学術雑誌）

潰瘍性大腸炎におけるADCC活性のサイトカインによる増強．消化器と免疫

高石官均、日比紀文、大原信、戸田京子、金井隆典、細田泰雄、林篤、原歩、渡辺守、相磯貞和、土屋雅春

消化器と免疫 27   155 - 159 1992年

研究論文（学術雑誌）

The mechanism of action of serum immunosuppressive factor in Crohn's disease: it blocks the growth of mitogen-stimulated lymphocytes early G1 phase through an inhibition of transferrin receptor expression

Iwao Y, Hibi T, Watanabe M, Takaishi H, Hosoda Y, Hayashi A, Ohara M, Ogata H, Aiso S, Toda K, Tsuchiya M

J Clin Lab Immunol 38 （ 1 ） 15 - 17 1992年

研究論文（学術雑誌）