研究者業績
基本情報
- 所属
- 藤田医科大学 医学部 医学科 先端光学診療学講座
- 学位
- 博士(医学）
- J-GLOBAL ID
- 200901011108502975
- researchmap会員ID
- 6000005568
患者さんの立場にたって、安全かつ最高の医療を提供できるよう努力します。
研究キーワード
8研究分野
1委員歴
28-
2024年2月 - 現在
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2023年2月 - 現在
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2022年9月 - 現在
受賞
4-
2022年10月
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2019年10月
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2015年10月
論文
270-
The Journal of dermatology 2024年9月30日 査読有り
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JAMA 2024年7月22日 査読有りImportance The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. Objective To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. Design, Setting, and Participants Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. Interventions For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. Main Outcomes and Measures The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. Results Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No adverse event signals were detected in the treatment groups. Conclusion and Relevance Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. Trial Registration ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135
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Journal of gastrointestinal and liver diseases : JGLD 33(2) 164-169 2024年6月29日 査読有りBACKGROUND AND AIMS: Early gastric cancers (EGCs) after Helicobacter pylori (H. pylori) eradication often appear as reddish depressed lesions (RDLs); the same features are also appeared in benign stomachs after eradication. We compared clinic-pathological and endoscopic features of benign and neoplastic RDLs after H. pylori eradication. METHODS: 228 neoplastic RDLs after H. pylori eradication were studied. All lesions were divided into neoplastic RDLs (differentiated carcinoma or adenoma, n=114) and benign RDLs (n=114) according to the histology. Clinical and pathological characteristics were compared in neoplastic and benign groups. Endoscopic diagnostic yields using the white light (WL) endoscopy, chromoendoscopy (CE) using indigo carmine dye and the magnifying endoscopy with narrow-band imaging (ME-NBI) were also evaluated in relation to the pathological diagnosis. RESULTS: Size of neoplastic RDLs was larger than that of benign RDLs (p<0.01). Sensitivity, specificity and accuracy for predicting pathological types of RDLs was 70.1%, 52.6% and 61.4% for the WL, 65.8%, 63.1% and 65.4% for the CE, while the ME-NBI scored better with the 88.6%, 88.6%, 99.1% and 93.9% of sensitivity, specificity and accuracy. The accuracy of the ME-NBI was 99.9% (113/114) in the benign RDLs and 89.4% (101/114) for the neoplastic RDLs. Undiagnosed neoplastic RDLs using the ME-NBI were associated with more differentiated tumors such as adenoma and well-differentiated adenocarcinoma (tub1) and the presence of an unclear demarcation line. CONCLUSIONS: ME-NBI is useful to diagnose RDLs after H. pylori eradiation, while some of neoplastic lesions are difficult to diagnose using the ME-NBI.
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Journal of gastroenterology 59(5) 376-388 2024年5月 査読有りBACKGROUND: The clinicopathological features and prognosis of primary small bowel adenocarcinoma (PSBA), excluding duodenal cancer, remain undetermined due to its rarity in Japan. METHODS: We analyzed 354 patients with 358 PSBAs, between January 2008 and December 2017, at 44 institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum. RESULTS: The median age was 67 years (218 males, 61.6%). The average tumor size was 49.9 (7-100) mm. PSBA sites consisted of jejunum (66.2%) and ileum (30.4%). A total of 219 patients (61.9%) underwent diagnostic small bowel endoscopy, including single-balloon endoscopy, double-balloon endoscopy, and capsule endoscopy before treatment. Nineteen patients (5.4%) had Lynch syndrome, and 272 patients (76.8%) had symptoms at the initial diagnosis. The rates for stages 0, I, II, III, and IV were 5.4%, 2.5%, 27.1%, 26.0%, and 35.6%, respectively. The 5-year overall survival rates at each stage were 92.3%, 60.0%, 75.9%, 61.4%, and 25.5%, respectively, and the 5-year disease-specific survival (DSS) rates were 100%, 75.0%, 84.1%, 59.3%, and 25.6%, respectively. Patients with the PSBA located in the jejunum, with symptoms at the initial diagnosis or advanced clinical stage had a worse prognosis. However, multivariate analysis using Cox-hazard model revealed that clinical stage was the only significant predictor of DSS for patients with PSBA. CONCLUSIONS: Of the patients with PSBA, 76.8% had symptoms at the initial diagnosis, which were often detected at an advanced stage. Detection during the early stages of PSBA is important to ensure a good prognosis.
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日本消化器病学会雑誌 121(臨増総会) A190-A190 2024年3月
MISC
1258-
日本消化器病学会雑誌 100(臨増大会) A397-A397 2003年9月
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日本消化器病学会雑誌 100(臨増大会) A639-A639 2003年9月
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GASTROENTEROLOGY 124(4) A551-A551 2003年4月
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日本消化器病学会雑誌 100(臨増総会) A169-A169 2003年3月
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Journal of gastroenterology and hepatology 17(12) 1283-90 2002年12月 査読有りBackground and Aims: Interferon (IFN)-gamma and tumor necrosis factor (TNF) are predominant cytokines produced in the gastric mucosa of patients with Helicobacter pylori-infected gastritis. Several studies reported that IFN-gamma and TNF induced the synergistic effect on many cell lines. We attempted to clarify the apoptotic activity and the synergistic effect of IFN-gamma and TNF on the gastric epithelial cell, and whether IFN-gamma relates to soluble TNF receptors (sTNF-R) release from the gastric epithelial cell. Methods: On the gastric epithelial cell line MKN45, cytotoxic and apoptotic effects of IFN-gamma and TNF were examined. Next, sTNF-R released in response to IFN-gamma and the protective effect of sTNF-R against the cytotoxic activity of TNF and IFN-gamma were examined by blocking the release of sTNF-R with a serine protease inhibitor such as phenylmethylsulfonyl fluoride. Results: Interferon-gamma significantly decreased cell viability, but TNF decreased it only slightly. Interferon-gamma and TNF did not make a synergistic effect on cell viability and apoptosis. Interferon-gamma and TNF induced sTNF-R release from gastric epithelial cells. Phenylmethylsulfonyl fluoride significantly inhibited shedding of sTNF-R and a synergistic effect of TNF and IFN-gamma on apoptosis was observed. Conclusion: These results suggest that sTNF-R released by IFN-gamma regulate the injury on the gastric epithelial cell line induced by TNF. (C) 2002 Blackwell Publishing Asia Pty Ltd.
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American journal of clinical pathology 118(5) 683-92 2002年11月 査読有りOf 987 cases of gastric adenocarcinoma seen at Nagoya University School of Medicine, we found 6 rare, extremely well-differentiated advanced gastric adenocarcinomas that could not be diagnosed as malignant tumors with only H&E staining, even with repeated biopsies under preoperative endoscopy. The aim of this study was to determine whether an immunohistochemical method using p53 and Ki-67 antibody would be helpful for preoperative pathologic diagnosis. The cancer control cases were 16 cases of ordinary well-differentiated advanced gastric adenocarcinoma, while the gastritis control cases were 22 cases of Helicobacter pylori positive chronic gastritis. The p53 labeling index and the localization of Ki-67+ cells showed that the special adenocarcinomas in biopsy specimens were distinct from the surrounding normal mucosa and chronic gastritis, but not from the cancer control cases. These methods are useful markers for preoperative pathologic diagnosis of extremely well-differentiated gastric adenocarcinoma, which sometimes is confused with regenerative atypical glands before operation.
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Gastroenterological Endoscopy 44(Suppl.2) 1643-1643 2002年9月
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Simultaneous multiple early cancers of esophagus and stomach treated by endoscopic mucosal resectionENDOSCOPY 34(8) 667-669 2002年8月 査読有りEndoscopic mucosal resection (EMR) has been accepted as a completely curative treatment of gastrointestinal mucosal cancers. With advances in diagnostic techniques, the tendency to detect simultaneous multiple primary cancers is increasing. Patients with another cancer coexisting with esophageal cancer have had a poor prognosis, but if both cancers are detected in the early stage, complete treatment consisting only of endoscopic surgery, with a good prognosis, is expected. We describe two cases of simultaneous multiple early cancers of the stomach and esophagus, treated by EMR.
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Clinical and experimental pharmacology & physiology 29(7) 544-8 2002年7月 査読有り1. Liposome-mediated transfection is useful due to no DNA constraints, lower immunogenicity and easy preparation. However, it has the disadvantage of low transfection efficiency. We aimed to test whether lipofection efficiency could be enhanced in gastrointestinal cell lines by the growth-promoting effect of insulin. 2. To assess the effect of insulin on lipofection efficiency and the cell cycle, expression of green fluorescent protein (GFP) and DNA distribution in gastric (MKN1), colonic (HT29) and pancreatic (BxPC3) carcinoma cell lines was analysed using flow cytometry. 3. The percentage of positive cells with GFP was significantly higher in MKN1 cells in culture medium with 5 mg/mL insulin than without insulin, whereas the percentage was the same in HT29 and BxPC3 cells with insulin as without insulin. The percentage of S phase fraction MKN1 cells with insulin was greater than without insulin, whereas the percentage of S phase fractions of HT29 and BxPC3 cells was the same with or without insulin. Lipofection efficiency correlated with the percentage of S phase fraction. 4. Insulin has the potential to enhance efficiency of lipofection into a sensitive cell line by increasing cellular proliferation.
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Gastrointestinal endoscopy 55(1) 37-43 2002年1月 査読有りBackground: With the advent of immunohistochemical analysis, the term "gastrointestinal stromal tumor" (GIST) was proposed to designate the largest category of primary nonepithelial neoplasms. EUS-guided fine needle aspiration (EUS-FNA) is useful for diagnosis of GISTs. The aim of this study was to evaluate the phenotyping of GISTs and diagnosis of malignant GISTs by using EUS-FNA with immunohistochemical analysis. Methods: A diagnosis of GIST was made in 23 patients by using EUS-FNA with immunohistochemical analysis. The accuracy of EUS-FNA diagnosis compared with the EUS imaging alone was analyzed. Additionally, immunophenotyping of specimens obtained by EUS-FNA and surgical resection specimens was compared. Factors that were diagnostic for malignant GISTs were also analyzed. Results: The overall accuracy for the diagnosis of malignant GIST was 78% (18/23) by EUS imaging alone and 91% (21/23) by histopathologic evaluation (H&E staining) of specimens obtained by EUS-FNA. In 21 of 23 cases (91%) the immunohistochemical expressions of c-kit, CD34, muscle actin, and S-100 coincided for the FNA and surgical specimens. The presence of mitotic cells (p = 0.011) and the Ki-67 labeling Index (p < 0.0001) with respect to the FNA specimens were significant predictive factors for malignant GIST. For the diagnosis of malignant GIST, the accuracy, sensitivity, and specificity of EUS-FNA with the addition of Ki-67 immunohistochemical staining were 100%. Conclusions. EUS-FNA with immunohistochemical analysis is useful in the preoperative diagnosis of GIST. It provides abundant information on immunohistochemical subtyping and on the capacity of the tumor for cellular progression.
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Progress in Medicine 22(8) 1985-1991 2002年Interleukin(IL)-1多型と慢性萎縮性胃炎,胃癌の関係を明らかにする目的で,胃癌患者116名と,非胃癌の450名を対象に,血漿ペプシノーゲン(PG)I,II,ガストリン値,抗H.pylori IgG抗体を測定した.IL-1β-31,-511,+3954の多型はTaqMan PCR assay,IL-1RNのVNTRはPCR後に電気泳動にて検討した.その結果,IL-1β-31T/T型は,H.pylori感染により慢性萎縮性胃炎,高ガストリン血症を生じやすく,遠位側に発生するペプシノーゲン法陽性胃癌との関連が示唆され,IL-1β-31C/C型は,近位側に発生するペプシノーゲン法陰性胃癌との関連が示唆された
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CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY 28(8) 659-662 2001年8月 査読有り1. The present study was designed to investigate whether or not ageing affects the development of water immersion stress-induced gastric lesions in rats. Effects of cetraxate, an anti-ulcer drug, were also examined. 2. Gastric lesions were induced by 6 h water immersion stress in rats. Gastric mucosal blood flow was determined by the hydrogen gas clearance technique and nitric oxide synthase (NOS) activity was measured enzymatically. 3. Early development of gastric lesions was observed in aged rats and exacerbation of gastric lesions was also found. Lowering of gastric mucosal blood flow and reduced NOS activity were observed in aged rats. 4. Cetraxate mitigated the development of gastric lesions in young rats and also increased gastric mucosal blood flow and NOS activity. However, these favourable effects were diminished in aged rats. 5. Decreased NOS activity may be an important exacerbatory factor to the development of gastric lesions in aged rats. 6. Effects of cetraxate differed between young rats and aged rats. 7. These results may explain the refractoriness and drug resistance in gastric ulcers encountered by elderly individuals.
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GENE 272(1-2) 301-313 2001年7月 査読有りHereditary and sporadic gastrointestinal cancer of the microsatellite mutator phenotype (MMP) is characterized by a remarkable genomic instability at simple repeated sequences. The genomic instability is often caused by germline and somatic mutations in DNA mismatch repair (MMR) genes hMSH2 and hMLH1. The MMP can be also caused by epigenetic inactivation of hMLH1. The MMP generates many somatic frameshift mutations in genes containing mononucleotide repeats. We previously reported that in MMP tumors the hMSH6 and hMSH3 MMR genes often carry frameshift mutations in their (C)(8) and (A)(8) tracks. respectively. We proposed that these 'secondary mutator mutations' contribute to a gradual manifestation of the MMP. Here we report the detection of other frameshift. nonsense. and missense mutations in these genes in colon and gastric cancers of the MMP. A germline frameshift mutation was found in hMSH6 in a colon tumor harboring another somatic frameshift mutation. Several germline sequence variants and somatic missense mutations at conserved residues were detected in hMSH6 and only one was detected in hMSH3. Of the three hMSH6 germline variants in conserved residues, one coexisted with a somatic mutation at the (C)(8) track and another had a somatic missense mutation. We suggest that some of these germline and somatic missense variants are pathogenic. While biallelic hMSH6 and hMSH3 frameshift mutations were found in some tumors, many tumors seemed to contain only monoallelic mutations. In some tumors, these somatic monoallelic frameshift mutations at the (C)(8) and (A),., tracks were found to coexist with other somatic mutations in the other allele, supporting their functionality during tumorigenesis. However, the low incidence of these additional somatic mutations in hMSH6 and hMSH3 leaves many tumors with only monoallelic mutations. The impact of the frameshift mutations in gene expression was studied by comparative analysis of RNA and protein expression in different tumor cell clones with different genotypes. The results show that the hMSH6 (C)(8) frameshift mutation abolishes protein expression. ruling out a dominant negative effect by a truncated protein. We suggest the functionality of these secondary monoallelic mutator mutations in the context of an accumulative haploinsufficiency model. (C) 2001 Elsevier Science B.V. All rights reserved.
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AMERICAN JOURNAL OF GASTROENTEROLOGY 96(3) 735-739 2001年3月 査読有りOBJECTIVE: We examined cases of asymptomatic inflammatory bowel diseases, particularly asymptomatic ulcerative colitis, which were found in apparently healthy Japanese persons who underwent general health screening. METHODS: Patients with positive immunological fecal occult blood test (IFOBT) among approximately 236,000 persons participating in the health screening program at the Aichi Prefectural Center for Health Care for the past 9 yr underwent total colonoscopy. In patients with ulcerative colitis, we investigated the sex and age distributions, extent of lesion, endoscopic activity, incidence rate, and clinical course. RESULTS: In ail, 35 cases of inflammatory bowel disease were detected, and 274 cases of colorectal cancer (not discussed here) were detected in the same population. The 35 cases of inflammatory bowel disease consisted of 19 cases of ulcerative colitis (12 Of asymptomatic and minimally symptomatic ulcerative colitis, and seven of symptomatic or with past history of ulcerative colitis); five of intestinal tuberculosis; two of Crohn's disease; two of amebic colitis; and seven of endoscopic colitis. The 12 patients with asymptomatic and minimally symptomatic ulcerative colitis consisted of 11 men and one woman aged 36-63 yr (mean 46.2 yr). We classified these cases into three grades of severity according to endoscopic findings: four cases were mild, eight moderate, and none severe. Of these 12 cases, three were found endoscopically because of positive IFOBT, although barium enema was normal. Anatomic types of colitis cases included three of total colitis, three left-sided colitis, two proctitis, and four right-sided or segmental colitis. In one case, the disease extended proximally during the course of observation. CONCLUSIONS: We found 35 cases of inflammatory bowel disease because of positive IFOBT performed as part of a general health screening. Of these, 19 cases were ulcerative colitis. These included many asymptomatic and minimally symptomatic cases, which could be very important in helping to elucidate the natural history of ulcerative colitis; thus, long-term follow up is necessary. (C) 2001 by Am. Cell. of Gastroenterology.
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CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY 28(1-2) 9-12 2001年1月 査読有り1. The present study was designed to investigate the role of nitric oxide (NO) in modulating 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. 2. Damage scores and NO synthase (NOS) activity were measured. 3. The damage scores and NOS activity reached a peak on the 4th day after administration of TNBS solution (day 0), thereafter gradually decreasing, and were significantly higher than in the group treated with saline throughout the experimental period. 4. Subsequently, we divided the stage of colitis into two groups, one from day 0 to day 3 after induction of colitis, and the other from day 4 onwards, We evaluated the effects of the NOS inhibitor N-G-monotnethyl-L-arginine (L-NMMA), on TNBS-hapten-induced colitis and colonic mucosal blood flow. Two different methods of L-NMMA administration, from day 0 to day 3, and from day 4 onwards, were undertaken. 5. The damage score in the early L-NMMA treatment group was significantly higher than in the group without L-NMMA on day 14. In contrast, the damage score in the late L-NMMA treatment group was not significantly different from the group without L-NMMA. Colonic mucosal blood how in the early LMMA treatment group was not significantly different from that in the tate L-NMMA treatment group, 6. These data suggest that NO is important for inhibiting inflammation during the early stages.
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ENDOSCOPY 33(1) 65-69 2001年1月 査読有りBackground and Study Aims: This study was designed to assess the usefulness of variable-stiffness video colonoscopes, compared with conventional videoscopes. Patients and Methods: The first prototype XCF-QAY1 and the latter prototype XCF-Q240AI used in this study can be varied to 4 levels of stiffness of tube insertion during examination. In 352 consecutive colonoscopic examinations performed using these and two conventional scopes, the following data were recorded: time for intubation to the cecum, frequency of changes in the patients' posture, frequency of abdominal pressure attempts, and pain score. The degree of stiffness of the insertion tube and the examiners' impressions score were recorded only in procedures where the variable-stiffness scopes were used. Results: There was no significant difference between colonoscopes in the pain score. Total colonoscopy rate was 97.4 %. The frequency of usage of the varying stiffness control in the colon according to site was as follows: descending colon, 57.3 %; transverse colon, 32.8 %, sigmoid colon, 7.6 %; and ascending colon, 2.3 %. A significant difference in the mean time for intubation to the cecum between the XCF-Q240AI and conventional scopes was observed. Moreover, there were significant differences in the frequency of abdominal pressure attempts and changes in the patient's posture between conventional scopes and the new scopes. Conclusions: These results suggest that only one scope, the XCF-Q240AI, is needed for any colonic examination by any examiner.
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Progress in Medicine 21(3) 633-635 2001年胃癌培養細胞株MKN45において,IFN-γはsTNFRを放出することにより,TNFによる細胞傷害を制御している可能性があると考えられた
書籍等出版物
46講演・口頭発表等
430-
JDDW2024 第108回日本消化器内視鏡学会 2024年11月1日
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第62回日本小腸学会学術集会 2024年10月19日
担当経験のある科目(授業)
7所属学協会
12共同研究・競争的資金等の研究課題
31-
日本学術振興会 科学研究費助成事業 2022年4月 - 2025年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2022年4月 - 2025年3月
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厚生労働省 先進医療B 2021年2月 - 2024年6月
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国立研究開発法人日本医療研究開発機構（AMED) 令和6年度 医療機器等研究成果展開事業（開発実践タイプ） 2024年6月
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国立研究開発法人日本医療研究開発機構（AMED) 令和３年度難治性疾患実用化研究事業 2021年5月 - 2024年3月