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片岡 洋望カタオカ ヒロミ

所属部署医学研究科消化器・代謝内科学分野
職名教授
メールアドレス
ホームページURLhttp://ncu-shotai.ac/
生年月日
Last Updated :2020/06/02

研究者基本情報

学歴

  •  - 2000年03月, 名古屋市立大学大学院医学研究科
  •  - 1989年03月, 名古屋市立大学, 医学部

学位

  • 名古屋市立大学大学院医学研究科/博士(医学)

所属学協会

  • 国際消化器発癌学会(ISGC)
  • 日本内科学会
  • 米国臨床消化器病学会
  • ESMO (European Society for Medical Oncology)
  • 日本癌治療学会
  • 日本臨床腫瘍学会
  • 日本癌学会
  • 日本光線力学学会
  • 日本カプセル内視鏡学会
  • 日本レーザー医学会
  • 日本潰瘍学会
  • 日本消化器癌発生学会
  • 日本消化器内視鏡学会
  • 日本消化管学会
  • 日本消化器病学会

委員歴

  • 日本カプセル内視鏡学会読影トレーニング委員
  • 日本レーザー医学会選奨委員
  • 日本消化管学会総務委員
  • 愛知県生活習慣病対策協議会 胃がん・大腸がん検診精度管理委員会委員

研究活動情報

研究キーワード

    消化器内視鏡, 化学療法, 大腸癌, 胃癌, 食道癌, 光線力学療法, 分子標的治療, 転写因子

論文

  • Current status of urinary diagnostic biomarkers for colorectal cancer., Iwasaki H, Shimura T, Kataoka H, Clinica chimica acta; international journal of clinical chemistry, 498, 76 - 83,   2019年11月, 査読有り
  • Novel Genetic Rearrangements Termed "Structural Variation Polymorphisms" Contribute to the Genetic Diversity of Orthohepadnaviruses., Kei Fujiwara, Kentaro Matsuura, Kayoko Matsunami, Etsuko Iio, Yoshihito Nagura, Shunsuke Nojiri, Hiromi Kataoka, Viruses, 11, (9) ,   2019年09月17日, 査読有り, The genetic diversity of orthohepadnaviruses is not yet fully understood. This study was conducted to investigate the role of structural variations (SVs) in their diversity. Genetic sequences of orthohepadnaviruses were retrieved from databases. The positions of sequence gaps were investigated, since they were found to be related to SVs, and they were further used to search for SVs. Then, a combination of pair-wise and multiple alignment analyses was performed to analyze the genomic structure. Unique patterns of SVs were observed; genetic sequences at certain genomic positions could be separated into multiple patterns, such as no SV, SV pattern 1, SV pattern 2, and SV pattern 3, which were observed as polymorphic changes. We provisionally referred to these genetic changes as SV polymorphisms. Our data showed that higher frequency of sequence gaps and lower genetic identity were observed in the pre-S1-S2 region of various types of HBVs. Detailed examination of the genetic structure in the pre-S region by a combination of pair-wise and multiple alignment analyses showed that the genetic diversity of orthohepadnaviruses in the pre-S1 region could have been also induced by SV polymorphisms. Our data showed that novel genetic rearrangements provisionally termed SV polymorphisms were observed in various orthohepadnaviruses.
  • Prophylactic technique for preventing inward stent migration during placement of multiple plastic stents in a patient with surgically altered anatomy., Kachi K, Hori Y, Hayashi K, Naitoh I, Yoshida M, Kataoka H, Endoscopy,   2019年09月, 査読有り
  • Antitumor Effect of a Novel Photodynamic Therapy With Acetylated Glucose-conjugated Chlorin for Gastrointestinal Cancers., Ichikawa H, Nishie H, Yano S, Komai Y, Yamaguchi H, Nomoto A, Suzuki T, Tanaka M, Shimura T, Mizoshita T, Kubota E, Tanida S, Kataoka H, Anticancer research, 39, (8) 4199 - 4206,   2019年08月, 査読有り
  • Real-world efficacy of adalimumab and infliximab for refractory intestinal Behçet's disease., Sugimura N, Mizoshita T, Sugiyama T, Togawa S, Miyaki T, Suzuki T, Tanida S, Kataoka H, Sasaki M, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 51, (7) 967 - 971,   2019年07月, 査読有り
  • Endoscopic drainage using a lumen-apposing metal stent under contrast-enhanced harmonic endoscopic ultrasonography guidance., Hori Y, Yoshida M, Hayashi K, Naitoh I, Kato A, Miyabe K, Kataoka H, Endoscopy, 51, (7) E187 - E188,   2019年07月, 査読有り
  • Laterally Spreading Adenocarcinoma Involving the Lower Bile Duct and Duodenum Expressing Heterogeneous Immunohistochemical Phenotypes., Miyabe K, Notohara K, Go A, Kachi K, Kato A, Natsume M, Jinno N, Hori Y, Yoshida M, Naitoh I, Hayashi K, Ohara H, Takahashi S, Kataoka H, Internal medicine (Tokyo, Japan),   2019年07月, 査読有り
  • Placental growth factor is a predictive biomarker for ramucirumab treatment in advanced gastric cancer., Natsume M, Shimura T, Iwasaki H, Okuda Y, Kitagawa M, Okamoto Y, Hayashi K, Kataoka H, Cancer chemotherapy and pharmacology, 83, (6) 1037 - 1046,   2019年06月, 査読有り
  • Successful peroral endoscopic removal of migrated metal stent., Hori Y, Hayashi K, Sobajima Y, Naitoh I, Miyabe K, Yoshida M, Kataoka H, Endoscopy,   2019年06月, 査読有り
  • A novel urinary microRNA biomarker panel for detecting gastric cancer., Iwasaki H, Shimura T, Yamada T, Okuda Y, Natsume M, Kitagawa M, Horike SI, Kataoka H, Journal of gastroenterology,   2019年06月, 査読有り
  • The efficacy of maintenance therapy after remission induction with tacrolimus in ulcerative colitis with and without previous tumor necrosis factor-α inhibitor., Suzuki T, Mizoshita T, Tanida S, Sugimura N, Katano T, Nishie H, Kataoka H, JGH open : an open access journal of gastroenterology and hepatology, 3, (3) 217 - 223,   2019年06月, 査読有り
  • A Basic Study of Photodynamic Therapy with Glucose-Conjugated Chlorin e6 Using Mammary Carcinoma Xenografts., Osaki T, Hibino S, Yokoe I, Yamaguchi H, Nomoto A, Yano S, Mikata Y, Tanaka M, Kataoka H, Okamoto Y, Cancers, 11, (5) ,   2019年05月, 査読有り
  • Long-term Outcomes of One Stage Surgery Using Transanal Colorectal Tube for Acute Colorectal Obstruction of Stage II/III Distal Colon Cancer., Okuda Y, Yamada T, Hirata Y, Shimura T, Yamaguchi R, Sakamoto E, Sobue S, Nakazawa T, Kataoka H, Joh T, Cancer research and treatment : official journal of Korean Cancer Association, 51, (2) 474 - 482,   2019年04月, 査読有り
  • Urinary Cysteine-Rich Protein 61 and Trefoil Factor 3 as Diagnostic Biomarkers for Colorectal Cancer., Shimura T, Iwasaki H, Kitagawa M, Ebi M, Yamada T, Yamada T, Katano T, Nisie H, Okamoto Y, Ozeki K, Mizoshita T, Kataoka H, Translational oncology, 12, (3) 539 - 544,   2019年03月, 査読有り
  • Intestinal obstruction caused by small bowel adenocarcinoma misdiagnosed as psychogenic disorder., Nishie H, Suzuki T, Ichikawa H, Kataoka H, BMJ case reports, 12, (1) ,   2019年01月, 査読有り
  • Adalimumab Dose-Escalation Therapy Is Effective in Refractory Crohn's Disease Patients with Loss of Response to Adalimumab, Especially in Cases without Previous Infliximab Treatment., Suzuki T, Mizoshita T, Sugiyama T, Hirata Y, Kimura Y, Suzuki Y, Yamada T, Tsukamoto H, Mizushima T, Sugimura N, Katano T, Tanida S, Kataoka H, Sasaki M, Case reports in gastroenterology, 13, (1) 37 - 49,   2019年01月, 査読有り
  • Colorectal obstruction is a potential prognostic factor for stage II colorectal cancer., Okuda Y, Shimura T, Yamada T, Hirata Y, Yamaguchi R, Sakamoto E, Kataoka H, International journal of clinical oncology, 23, (6) 1101 - 1111,   2018年12月, 査読有り
  • An Increased Chromosome 7 Copy Number in Endoscopic Bile Duct Biopsy Specimens Is Predictive of a Poor Prognosis in Cholangiocarcinoma., Kato A, Naitoh I, Miyabe K, Hayashi K, Yoshida M, Hori Y, Natsume M, Jinno N, Asano G, Kato H, Kuno T, Takahashi S, Kataoka H, Digestive diseases and sciences, 63, (12) 3376 - 3381,   2018年12月, 査読有り
  • The Successful Treatment of Metastatic Extraosseous Ewing Sarcoma with Pazopanib., Mori Y, Kinoshita S, Kanamori T, Kataoka H, Joh T, Iida S, Takemoto M, Kondo M, Kuroda J, Komatsu H, Internal medicine (Tokyo, Japan), 57, (18) 2753 - 2757,   2018年09月, 査読有り
  • Refractory gastric antral ulcers without Helicobacter pylori infection and non-steroidal anti-inflammatory drugs., Nishie H, Kataoka H, Kato H, Suzuki T, Ichikawa H, Nojiri Y, Kitagawa M, Inagaki Y, Iwasaki H, Tanaka M, Katano T, Okamoto Y, Ozeki K, Mizoshita T, Shimura T, Kubota E, Tanida S, Joh T, Clinical journal of gastroenterology, 11, (3) 251 - 256,   2018年06月, 査読有り
  • Combination Therapy With Intensive Granulocyte and Monocyte Adsorptive Apheresis Plus Ustekinumab in Patients With Refractory Crohn's Disease., Tanida S, Mizoshita T, Ozeki K, Katano T, Tanaka M, Nishie H, Shimura T, Okamoto Y, Kubota E, Kataoka H, Joh T, Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy, 22, (3) 295 - 300,   2018年06月, 査読有り
  • Excellent antitumor effects for gastrointestinal cancers using photodynamic therapy with a novel glucose conjugated chlorin e6., Nishie H, Kataoka H, Yano S, Yamaguchi H, Nomoto A, Tanaka M, Kato A, Shimura T, Mizoshita T, Kubota E, Tanida S, Joh T, Biochemical and biophysical research communications, 496, (4) 1204 - 1209,   2018年02月, 査読有り
  • Glucagon promotes colon cancer cell growth via regulating AMPK and MAPK pathways., Yagi T, Kubota E, Koyama H, Tanaka T, Kataoka H, Imaeda K, Joh T, Oncotarget, 9, (12) 10650 - 10664,   2018年02月, 査読有り
  • Anti-tumor efficacy of oncolytic reovirus against gastrointestinal stromal tumor cells., Inagaki Y, Kubota E, Mori Y, Aoyama M, Kataoka H, Johnston RN, Joh T, Oncotarget, 8, (70) 115632 - 115646,   2017年12月, 査読有り
  • Expression and subcellular localization of AT motif binding factor 1 in colon tumours, Hiromi Kataoka, Yutaka Miura, Makoto Kawaguchi, Shugo Suzuki, Yasuyuki Okamoto, Keiji Ozeki, Takaya Shimura, Tsutomu Mizoshita, Eiji Kubota, Satoshi Tanida, Satoru Takahashi, Kiyofumi Asai, Takashi Joh, MOLECULAR MEDICINE REPORTS, 16, (3) 3095 - 3102,   2017年09月, 査読有り, AT motif binding factor 1 (ATBF1) is a transcriptional regulator that functions as a tumour suppressor to negatively affect cancer cell growth. In the present study four specific polyclonal antibodies against ATBF1 were generated, and the expression and intracellular localization of ATBF1 in colonic mucosae, polyps, adenoma and adenocarcinoma tissue samples were investigated. The four polyclonal antibodies produced were as follows: MB34 and MB49, which recognize the N- and C-terminal fragments of ATBF1, respectively; and D1-120 and MB44, which recognize the middle fragments of ATBF1 that contain three nuclear localization signals (NLS). In total, 191 colon samples were examined by immunohistochemical analysis. In addition, colon cancer cells were transfected with four ATBF1 expression vectors, and the subcellular localization of each fragment was examined. Normal colon mucosal cells were not observed to express ATBF1. However, a small number of hyperplastic polyps, serrated adenomas and tubular adenomas expressed ATBF1. Colon cancer cells were observed to express D1-120- Zand MB44-reactive middle fragments of ATBF1 in their cell nuclei. However, the N- and C-terminal fragments of ATBF1 did not translocate to the nucleus. Transfection of ATBF1 fragments revealed cleavage of the ATBF1 protein and nuclear translocation of the cleaved middle portion containing the NLS. A positive correlation between the cytoplasmic localization of the N- and C-termini of ATBF1, nuclear localization of the middle portion of ATBF1 and malignant cancer cell invasion was observed. In conclusion, the results of the present study suggest that alterations in the expression and subcellular localization of ATBF1, as a result of post-transcriptional modifications, are associated with malignant features of colon tumours.
  • Prospective comparison of preference and efficacy of adalimumab and infliximab for treating ulcerative colitis naive to antitumor necrosis factor therapy, Tsutomu Mizoshita, Takahito Katano, Satoshi Tanida, Atsuyuki Hirano, Tomokatsu Miyaki, Keiji Ozeki, Yuka Suzuki, Naomi Sugimura, Hiromi Kataoka, Takashi Joh, MEDICINE, 96, (32) ,   2017年08月, 査読有り, There have been few reports on 2 tumor necrosis factor alpha inhibitors, infliximab and adalimumab, with respect to patient preference and efficacy in ulcerative colitis (UC). We used questionnaires to evaluate the preference and reasons for drug choice between infliximab and adalimumab in UC patients naive to antitumor necrosis factor alpha therapy. We also analyzed the efficacy of infliximab and adalimumab prospectively and endoscopically before treatment and at 14 and 54 weeks. Of the 25 UC patients, infliximab and adalimumab were chosen by 10 (40%) and 15 (60%), respectively. Patients who favored infliximab considered "fear of syringes" (7/10, 70%) as the most important influencing factor, whereas patients who favored adalimumab considered "ease of administration" (10/15, 66.7%) and "time required for therapy" (10/15, 66.7%) as the most important factors. There were no statistical differences in remission induction and maintenance between the infliximab and adalimumab groups with regard to response, remission, mucosal healing, steroid-free, and steroid-free remission rates at weeks 14 and 54. The efficacy of adalimumab in remission induction and maintenance was equivalent to that of infliximab in UC patients naive to antitumor necrosis factor alpha therapy in this prospective study, but more patients preferred adalimumab.
  • New photodynamic therapy with next-generation photosensitizers., Kataoka H, Nishie H, Hayashi N, Tanaka M, Nomoto A, Yano S, Joh T, Annals of translational medicine, 5, (8) ,   2017年04月, 査読有り
  • Maltotriose conjugation to a chlorin derivative enhances the antitumor effects of photodynamic therapy in peritoneal dissemination of pancreatic cancer., Kato A, Kataoka H, Yano S, Hayashi K, Hayashi N, Tanaka M, Naitoh I, Ban T, Miyabe K, Kondo H, Yoshida M, Fujita Y, Hori Y, Natsume M, Murakami T, Narumi A, Nomoto A, Naiki-Ito A, Takahashi S, Joh T, Mol Cancer Ther.,   2017年
  • A next-generation bifunctional photosensitizer with improved water-solubility for photodynamic therapy and diagnosis, Hirotada Nishie, Hiromi Kataoka, Shigenobu Yano, Jun-ichi Kikuchi, Noriyuki Hayashi, Atsushi Narumi, Akihiro Nomoto, Eiji Kubota, Takashi Joh, ONCOTARGET, 7, (45) 74259 - 74268,   2016年11月, Photodynamic therapy (PDT) exploits light interactions and photosensitizers to induce cytotoxic reactive oxygen species. Photodynamic diagnosis (PDD) uses the phenomenon of photosensitizer emitting fluorescence to distinguish some tumors from normal tissue. The standard photosensitizer used for PDD is 5-aminolevulinic acid (5-ALA), although it is not entirely satisfactory. We previously reported glucose-conjugated chlorin (G-chlorin) as a more effective photosensitizer than another widely used photosensitizer, talaporfin sodium (TS); however, G-chlorin is hydrophobic. We synthesized oligosaccharide-conjugated chlorin (O-chlorin) with improved water-solubility. We report herein on its accumulation and cytotoxicity. O-chlorin was synthesized and examined for solubility. Flow cytometric analysis was performed to evaluate O-chlorin accumulation in cancer cells. To evaluate the intracellular localization of photosensitizer, cells were stained with O-chlorin and organelle-specific fluorescent probes. We then measured the in vitro fluorescence of various photosensitizers and the half-maximal inhibitory concentrations to evaluate effects in PDD and PDT, respectively. Xenograft tumor models were established, and antitumor and visibility effects were analyzed. O-chlorin was first shown to be hydrophilic. Flow cytometry then revealed a 20-to 40-times higher accumulation of O-chlorin in cancer cells than of TS, and a 7- to 23-times greater fluorescence than 5-ALA. In vitro, the cytotoxicity of O-chlorin PDT was stronger than that of TS PDT, and O-chlorin tended to accumulate in lysosomes. In vivo, O-chlorin showed the best effect in PDT and PDD compared to other photosensitizers. O-chlorin was hydrophilic and showed excellent tumor accumulation and fluorescence. O-chlorin is promising as a next-generation bifunctional photosensitizer candidate for both PDT and PDD.
  • Immunogenic cell death due to a new photodynamic therapy (PDT) with glycoconjugated chlorin (G-chlorin), Mamoru Tanaka, Hiromi Kataoka, Shigenobu Yano, Takuya Sawada, Haruo Akashi, Masahiro Inoue, Shugo Suzuki, Yusuke Inagaki, Noriyuki Hayashi, Hirotada Nishie, Takaya Shimura, Tsutomu Mizoshita, Yoshinori Mori, Eiji Kubota, Satoshi Tanida, Satoru Takahashi, Takashi Joh, ONCOTARGET, 7, (30) 47242 - 47251,   2016年07月, Both the pre-apoptotic exposure to calreticulin (CRT) and the post-apoptotic release of high-mobility group box 1 protein (HMGB1) are required for immunogenic cell death. Photodynamic therapy (PDT) uses non-toxic photosensitizers and visible light at a specific wavelength in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumor microvasculature, and stimulate the host immune system. We have previously shown that glycoconjugated chlorin (G-chlorin) has superior cancer cell selectivity and effectively suppresses the growth of xenograft tumors. In the present study, we evaluated the immunogenicity of PDT with G-chlorin treatment in colon cancer cells. PDT with G-chlorin suppressed CT26 (mouse colon cancer cells) tumor growth considerably more efficiently in immunocompetent mice (wild-type mice, allograft model) than in immune-deficient mice (nude mice, xenograft model), although control treatments were not different between the two. This treatment also induced CRT translocation and HMGB1 release in cells, as shown by western blot and immunofluorescence staining. To evaluate the use of PDT-treated cells as a tumor vaccine, we employed a syngeneic mouse tumor model (allograft model). Mice inoculated with PDT-treated CT26 cells were significantly protected against a subsequent challenge with live CT26 cells, and this protection was inhibited by siRNA for CRT or HMGB1. In conclusion, PDT with G-chlorin treatment induced immunogenic cell death in a mouse model, where the immunogenicity of this treatment was directed by CRT expression and HMGB1 release.
  • A phase II prospective study of the trastuzumab combined with 5-weekly S-1 and CDDP therapy for HER2-positive advanced gastric cancer, Hiromi Kataoka, Yoshinori Mori, Takaya Shimura, Hirotada Nishie, Makoto Natsume, Hisato Mochizuki, Yoshikazu Hirata, Satoshi Sobue, Takashi Mizushima, Hitoshi Sano, Yusuke Mizuno, Makoto Nakamura, Atsuyuki Hirano, Kenji Tsuchida, Kazunori Adachi, Kyoji Seno, Mika Kitagawa, Takashi Kawai, Takashi Joh, CANCER CHEMOTHERAPY AND PHARMACOLOGY, 77, (5) 957 - 962,   2016年05月, Background We evaluated the efficacy and safety of 5-weekly S-1 and cisplatin combined with trastuzumab, a monoclonal antibody against human epidermal growth factor receptor type 2 (HER2) for HER2-positive advanced gastric cancer (AGC). Methods This phase II study treatment consisted of S-1 (80-120 mg per day) orally on day 1-21, cisplatin (60 mg/m(2)) intravenously on day 8, and trastuzumab (8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks) intravenously. The primary end point was 1-year survival rate. The secondary end points included overall survival, progression-free survival (PFS), response rate (RR), and safety. Results A total 22 patients from seven centers were enrolled. In the 20 patients evaluable for analysis, the 1-year survival rate was 70 % (95 % confidence interval (CI) 49.9-90.1 %), and median survival time, PFS, and RR were 15.3, 7.5 months and 41.2 %, respectively. Major grade 3/4 adverse events were neutropenia (30 %), anorexia (30 %), leukopenia (25 %), fatigue (20 %), and anemia (15 %). Conclusions Five-weekly S-1 and cisplatin combined with trastuzumab showed effective with favorable safety profile in patients with HER2-positive AGC.
  • A novel photodynamic therapy targeting cancer cells and tumor-associated macrophages., Hayashi N, Kataoka H, Yano S, Tanaka M, Moriwaki K, Akashi H, Suzuki S, Mori Y, Kubota E, Tanida S, Takahashi S, Joh T, Mol Cancer Ther., 14(2), 452 - 60,   2015年
  • Antitumor Effects in Gastrointestinal Stromal Tumors Using Photodynamic Therapy with a Novel Glucose-Conjugated Chlorin, Mamoru Tanaka, Hiromi Kataoka, Shigenobu Yano, Hiromi Ohi, Kazuhiro Moriwaki, Haruo Akashi, Takahiro Taguchi, Noriyuki Hayashi, Shingo Hamano, Yoshinori Mori, Eiji Kubota, Satoshi Tanida, Takashi Joh, MOLECULAR CANCER THERAPEUTICS, 13, (4) 767 - 775,   2014年04月, Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Except for surgical resection, no effective treatment strategies have been established. Photodynamic therapy (PDT) consists of intravenous administration of a photosensitizer, activated by a specific wavelength of light, which produces reactive oxygen species that directly kill tumor cells. We analyzed the efficacy of PDT using a newly developed photosensitizer, 5,10,15,20-tetrakis [ 4-[beta-D-glucopyranosylthio-2,3,5,6-tetrafluorophenyl]-2, 3,[ methano[N-methyl] iminomethano] chlorin (H2TFPC-SGlc), for the GIST treatment. Various photosensitizers were administered in vitro to GIST (GIST-T1) and fibroblast (WI-38) cells, followed by irradiation, after which cell death was compared. We additionally established xenograft mouse models with GIST-T1 tumors and examined the accumulation and antitumor effects of these photosensitizers in vivo. In vitro, the expression of the glucose transporters GLUT1, GLUT3, and GLUT4, the cellular uptake of H2TFPC-SGlc, and apoptosis mediated by PDT with H2TFPC-SGlc were significantly higher in GIST-T1 than in WI-38 cells. In vivo, H2TFPC-SGlc accumulation was higher in xenograft tumors of GIST-T1 cells than in the adjacent normal tissue, and tumor growth was significantly suppressed following PDT. PDT with novel H2TFPC-SGlc is potentially useful for clinical applications about the treatment of GIST. Mol Cancer Ther; 13(4); 767-75. (C) 2014 AACR.
  • Telmisartan Inhibits Cell Proliferation by Blocking Nuclear Translocation of ProHB-EGF C-Terminal Fragment in Colon Cancer Cells, Keiji Ozeki, Satoshi Tanida, Chie Morimoto, Yoshimasa Inoue, Tsutomu Mizoshita, Hironobu Tsukamoto, Takaya Shimura, Hiromi Kataoka, Takeshi Kamiya, Eiji Nishiwaki, Hiroshi Ishiguro, Shigeki Higashiyama, Takashi Joh, PLOS ONE, 8, (2) ,   2013年02月, Background & Aims: Current treatment target toward advanced colorectal cancers is mainly focused on the epidermal growth factor receptor (EGFR) signaling, but its additive effects with chemotherapy are still limited. A disintegrin and metalloproteinase (ADAM) cleaves the proheparin-binding epidermal growth factor like growth factor (proHB-EGF). And soluble HB-EGF activates EGFR. In parallel, the carboxy-terminal fragment of proHB-EGF (HB-EGF-CTF) translocates into the inner nuclear membrane, and subsequently exerts on the regulation of cell proliferation by binding nuclear promyelocytic leukemia zinc finger (PLZF) protein, a transcriptional repressor, thereby causing its nuclear export. We hypothesized that the inhibition of HB-EGF-CTF nuclear translocation may be a new strategy in preventing cell proliferation. Methods: 12-O-tetradecanoylphorbor-13-acetate (TPA) was treated to activate ADAM. Nine-thousand chemical compounds were screened for their efficacies in blocking the binding of HB-EGF-CTF to promyelocytic leukemia zinc finger (PLZF) with Alphascreen system. The obtained candidates were then used to block the binding of HB-EGF-CTF to PLZF in colon cancer cells, HT29 and HCT116. Cell proliferation was investigated with a growth curve assay. The intracellular localization, and association between HB-EGF-CTF and PLZF, was assessed with immunofluorescent staining, and immunoprecipitation and Western blotting, respectively. The effects of obtained candidates on EGFR phosphorylation and on nuclear translocation of HB-EGF-CTF and export of PLZF during the angiotensin II type1 receptor (AT1R) knockdown were also investigated. Results: Telmisartan and candesartan were found to be potential candidates. Telmisartan inhibited TPA-induced cell proliferation stronger than candesartan. Telmisartan, but not candesartan blocked the nuclear translocation of HB-EGF-CTF, and binding of HB-EGF-CTF to PLZF, during TPA stimulation. Both telmisartan and candesartan did not inhibit TPA-induced EGFR phosphorylation, and telmisartan, but not candesartan, inhibited TPA-induced nuclear translocation of HB-EGF-CTF after knockdown of AT1R. Conclusions: The inhibition of HB-EGF-CTF nuclear translocation with telmisartan may be a novel strategy in preventing cell proliferation.
  • Aberrant DNA methylation associated with aggressiveness of gastrointestinal stromal tumour, Yasuyuki Okamoto, Akira Sawaki, Seiji Ito, Toshirou Nishida, Tsuyoshi Takahashi, Minoru Toyota, Hiromu Suzuki, Yasuhisa Shinomura, Ichiro Takeuchi, Keiko Shinjo, Byonggu An, Hidemi Ito, Kenji Yamao, Makiko Fujii, Hideki Murakami, Hirotaka Osada, Hiromi Kataoka, Takashi Joh, Yoshitaka Sekido, Yutaka Kondo, GUT, 61, (3) 392 - 401,   2012年03月, Background and aims The majority of gastrointestinal stromal tumors (GISTs) have KIT mutations; however, epigenetic abnormalities that could conceivably potentiate the aggressiveness of GISTs are largely unidentified. Our aim was to establish epigenetic profiles associated with the malignant transformation of GISTs. Methods Methylation of four tumor suppressor genes, RASSF1A, p16, CDH1, and MGMT was analyzed in GISTs. Additionally, genome-wide DNA methylation profiles were compared between small, malignant-prone, and malignant GISTs using methylated GpG island amplification microarrays (MCAM) in a training set (n=40). Relationships between the methylation status of genes identified by MCAM and clinical features of the disease were tested in a validation set (n=75). Results Methylation of RASSF1A progressively increased from small to malignant GISTs. p16 was specifically methylated in malignant-prone and malignant GISTs. MCAM analysis showed that more genes were methylated in advanced than in small GISTs (average of 473 genes vs 360 genes, respectively, P=0.012). Interestingly, the methylation profile of malignant GISTs was prominently affected by their location. Two genes, REC8 and PAX3, which were newly-identified via MCAM analysis, were differentially methylated in small and malignant GISTs in the training and validation sets. Patients with methylation of at least REC8, PAX3, or p16 had a significantly poorer prognosis (P=0.034). Conclusion Our results suggest that GIST is not, in epigenetic terms, a uniform disease and that DNA methylation in a set of genes is associated with aggressive clinical behavior and unfavorable prognosis. The genes identified may potentially serve as biomarkers for predicting aggressive GISTs with poor survivability.
  • Role of ES Cell-Expressed Ras (ERas) in Tumorigenicity of Gastric Cancer, Eiji Kubota, Hiromi Kataoka, Mineyoshi Aoyama, Tsutomu Mizoshita, Yoshinori Mori, Takaya Shimura, Mamoru Tanaka, Makoto Sasaki, Satoru Takahashi, Kiyofumi Asai, Takashi Joh, AMERICAN JOURNAL OF PATHOLOGY, 177, (2) 955 - 963,   2010年08月, ERas, a unique member of the Ras family, was initially found only in embryonic stem (ES) cells, where it plays a crucial role in the transformation of transplanted ES cells to teratomas. ERas is involved in ES cell survival, and unlike other Ras family members, is constitutively active without any mutations. The aim of this study was to investigate the expression and role of ERas in human gastric cancer. To test whether ERas played a significant role in human cancer cells, we examined its expression and function in gastric cancer. ERas was expressed in gastric cancer cell lines at different levels. Induction of ERas expression activated the phosphatidylinositol 3 kinase (PI3K)/Akt axis and then enhanced anchorage-independent growth and ERas knockdown by siRNA suppressed cell invasion. Immunohistochemical analyses revealed that ERas was expressed in 38.7% (55/142) of human gastric carcinoma tissues, and its expression was significantly associated with metastasis to the liver (P < 0.0001) and lymph nodes (P < 0.05). ERas up-regulated transcription regulatory factors including ZFHX1A, ZFHX1B, and TCF3, which repress E-cadherin. These data suggest that ERas is activated in a significant population of gastric cancer, where it may play a crucial role in gastric cancer cell survival and metastases to liver via down-regulation of E-cadherin. (Am J Pathol 2010, 177:955-963; DOI: 10.2353/ajpath.2010.091056)
  • Suppression of proHB-EGF carboxy-terminal fragment nuclear translocation: a new molecular target therapy for gastric cancer., Shimura T, Kataoka H, Ogasawara N, Kubota E, Sasaki M, Tanida S, Joh T, Clin Cancer Res., /14(12),, 3956 - 65,   2008年
  • ING2 as a novel mediator of TGF-beta -dependent responses in epithelial cells., Sarker KP, Kataoka H, Chan A, These authors contributed equally to this work, Netherton SJ, Pot I, Huynh MA, Feng X, Bonni A, Riabowol K, Bonni S, J Biol Chem., /283(19),, 13269 - 79,   2008年
  • Subcellular localization of ATBF1 regulates MUC5AC transcription in gastric cancer, Yoshinori Mori, Hiromi Kataoka, Yutaka Miura, Makoto Kawaguchi, Eiji Kubota, Naotaka Ogasawara, Tadayuki Oshima, Satoshi Tanida, Makoto Sasaki, Hirotaka Ohara, Tsutomu Mizoshita, Masae Tatematsu, Kiyofumi Asai, Takashi Joh, INTERNATIONAL JOURNAL OF CANCER, 121, (2) 241 - 247,   2007年07月, Human gastric epithelium has a unique mucin gene expression pattern, which becomes markedly altered in gastrointestinal disorder. This alteration in mucin expression, including the mucin MUC5AC, may be related to the development and prognosis of gastric cancers, and MUC5AC-positive gastric cancer has been reported to be poor prognosis. However, the molecular mechanism of MUC5AC transcriptional regulation has not been fully elucidated. AT motif-binding factor 1 (ATBF1) is a homeotic transcriptional regulatory factor recently identified as a tumor suppressor gene, and its subcellular localization suggests a link to cell proliferation and differentiation. We investigated the mechanism of MUC5AC transcriptional regulation by ATBF1. In 123 gastric cancer lesions, ATBF1 expressed in the nucleus significantly suppressed MUC5AC expression, as determined by immunohistochemistry. In addition, analysis of the MUC5AC promoter region revealed an AT motif-like element. This element was found to be essential for ATBF1 suppression of MUC5AC promoter activity as shown in a dual luciferase-reporter assay. Over-expressed ATBF1 also significantly suppressed enclogenous MUC5AC protein expression in gastric cancer cells. Chromatin immunoprecipitation demonstrated that ATBF1 binds to the AT motif-like element in the MUC5AC promoter. These results indicate that ATBF1 in the nucleus negatively regulates the MUC5AC gene in gastric cancer by binding to an AT motif-like element in the MUC5AC promoter. (c) 2007 Wiley-Liss, Inc.
  • The mechanism of cleavage of EGFR ligands induced by inflammatory cytokines in gastric cancer cells, S Tanida, T Joh, K Itoh, H Kataoka, M Sasaki, H Ohara, T Nakazawa, T Nomura, Y Kinugasa, H Ohmoto, H Ishiguro, K Yoshino, S Higashiyama, M Itoh, GASTROENTEROLOGY, 127, (2) 559 - 569,   2004年08月, Background & Aims: The epidermal growth factor (EGF) receptor (EGFR) can be transactivated by many factors including G-protein-coupled receptor agonists and cytokines. Although this EGFR transactivation reportedly requires a disintegrin and metalloproteinase (ADAM) that sheds the ectodomain of EGFR ligands, the detailed mechanisms are still unknown. This study evaluated the mechanism of interleukin (IL)-8- and IL-1beta-dependent shedding of the EGFR ligand in KATO III cells. Methods: We established transfectants stably expressing alkaline phosphatase-tagged heparin-binding EGF-like growth factor (HB-EGF), transforming growth factor alpha, or amphiregulin precursors, and depleted ADAM proteins, using short interfering RNA against ADAM10, 12, or 17. We assessed shedding of EGFR ligands by measuring AP activities in the conditioned media after IL-1beta or IL-8 stimulation. EGFR activation was examined by immuno-precipitation and Western blotting using antiphosphotyrosine antibody. KB-R7785 and anti-IL-8 neutralizing antibody were used to inhibit activities of ADAMs and IL-8 action, respectively. Results: IL-8 dose dependently released the EGFR ligands and transiently phosphorylated EGFR, with a peak at 15 minutes. KB-R7785 completely blocked IL-8-induced shedding and EGFR transactivation. Depletion of ADAM10 also dramatically reduced IL-8-induced shedding and EGFR transactivation, but depletion of ADAM12 and 17 did not. IL-1beta dose dependently enhanced shedding of HB-EGF, which was not blocked by KB-R7785 in the early phase. In the late phase, however, the EGFR transactivation was blocked by Kbeta-R7785 and abrogated by anti-IL-8 neutralizing antibody. Conclusion : IL-8 induces shedding of EGFR ligands because of an ADAM10-dependent pathway in gastric cancer cells, whereas IL-1beta acts principally by an ADAM-independent pathway. IL-1beta-dependent prolonged EGFR transactivation involves multiple pathways, including an IL-8-dependent pathway.
  • ING1 represses transcription by direct DNA binding and through effects on p53, H Kataoka, P Bonnefin, D Vieyra, XL Feng, Y Hara, Y Miura, T Joh, H Nakabayashi, H Vaziri, CC Harris, K Riabowol, CANCER RESEARCH, 63, (18) 5785 - 5792,   2003年09月, The ING family of proteins is involved in the regulation of diverse processes ranging from cell cycle and cellular senescence to apoptosis. These effects are most likely through activation of acetylation-dependent pathways that ultimately alter gene expression. Despite reports linking ING to p53 activation, the molecular basis of how ING activates p53 function has not been elucidated. In this study, we found that a subset of ING family members strongly repressed human a-fetoprotein (AFP) promoter activity but stimulated the p21(WAF1) promoter in parallel experiments in the same cell type, similar to the effects of p53. The p47(ING1a) isoform also repressed AFP promoter activity, but in contrast to other ING isoforms, it repressed the p21(WAF1) promoter. p47(ING3) up-regulated p21(WAF1) promoter activity, but it did not have any effect on the AFP promoter. ING1b and ING2 also repressed the AFP promoter in Hep3B p53-null cell lines, and p53 coexpression enhanced this transcriptional repression. Suppression of AFP gene transcription by ING was strongly dependent on AT-motifs that bind to the hepatocyte nuclear factor 1 (HNF1) transcription factor. Indeed, electrophoretic mobility shift assays confirmed that HNF1 binds to AT-motifs, but we found, surprisingly, that the ING1 complexes binding to these AT-motifs were devoid of HNF1 protein. Both ING1 and p53 were able to suppress AFP transcription and cause p21 induction; hSIR2, a negative regulator of the p53 protein, showed the opposite effects on the AFP promoter and, like HDAC1, repressed p21 promoter activity. In addition, we found that p33(ING1b) physically interacts with hSIR2, reverses its ability to induce the AFP promoter, and induces acetylation of p53 residues at Lys(373) and/or Lys(382). These findings provide novel evidence that p33(ING1b) represses AFP transcription by at least two mechanisms, one of which includes p53. The first is by binding to the AT-motif and excluding HNF1 binding while possibly targeting HAT activity to promoter regions, and the second is by increasing the levels of active, acetylated p53 via binding and inhibiting the ability of hSIR2 to deacetylate p53 protein.
  • Alpha-fetoprotein producing gastric cancer lacks transcription factor ATBF1., Kataoka H, Miura Y, Joh T, Seno K, Tada T, Tamaoki T, Nakabayashi H, Kawaguchi M, Asai K, Kato T, Itoh M, Oncogene, /20,, 869 - 873,   2001年

特許

  • グリコシル化クロリンe6誘導体,または,その薬学的に許容される塩,医薬組成物標的を破壊する方法,および,グリコシル化クロリンe6誘導体,またはその薬学的に許容される塩の製造方法, 矢野重信, 片岡洋望, 西江裕忠, 城 卓志, 福本圭介, 仲野靖浩, 特願PCT/JP2017/43144
  • 光線力学療法のための新規糖連結光感受性物質, 片岡洋望, 林 則之, 城 卓志, 矢野重信, 特願2013-161518, 特開2015-030703, 特許6177044

受賞

  •   2015年, 消化器とフリーラジカル研究会, Best Panelist賞
  •   2011年, 平成23年度 日本消化器内視鏡学会学会賞
  •   2002年, Alberta Cancer Board Award, Canada.
  •   2001年, 名古屋市立大学医学会賞

競争的資金

  • 癌細胞超選択的光線力学診断法・治療法の開発, 日本医療研究開発機構, 産学連携医療イノベーション創出プロジェクト,   2018年10月 - 2020年03月
  • 大腸癌に対する PARP 阻害剤による抗癌剤 増感の関連遺伝子の 解明と治療への応用,   2017年04月 - 2020年03月
  • 糖鎖結合光感受性物質による癌細胞超選択的光線力療法の開発, 文部科学省, 科学研究費補助金(基盤C),   2017年04月 - 2020年03月
  • DNA修復機構を標的とした新規消化器癌治療の開発,   2016年04月 - 2019年03月
  • 臨床応用のための新規光感受性糖鎖連結クロリンを用いた癌細胞超選択的次世代光線力学療法の開発, 日本医療研究開発機構, 日本医療研究開発機構革新的医療技術創出拠点プロジェクト,   2015年04月 - 2017年03月
  • 癌間質の腫瘍会合性マクロファージを標的とした糖連結光機能分子による光治療法の開発, 文部科学省, 科学研究費補助金(基盤C),   2014年04月 - 2017年03月
  • 癌診断と治療の両機能を有する先端医療用バイファンクショナル糖連結光機能分子の創出, 文部科学省, 科学研究費補助金(基盤B),   2013年04月 - 2016年03月
  • 胃癌,GISTに対する糖鎖連結クロリンを用いた新規光線力学的治療法の開発, 文部科学省, 科学研究費補助金(基盤C),   2011年04月 - 2014年03月
  • 胃癌の悪性度における転写因子型癌抑制因子ATBF1の核・細胞質移行の意義, 文部科学省, 科学研究費補助金(基盤C),   2008年04月 - 2011年03月
  • 胃癌におけるES細胞特異的Ras,ERasの機能解析および新規抗癌剤治療への応用, 文部科学省, 科学研究費補助金(基盤C),   2005年04月 - 2007年03月
  • 消化器癌におけるATM発現とPARP阻害剤感受性の検討, 名古屋市立大学
  • 胃癌の胃型腸型形質,抗癌剤感受性におけるATBF1の核・細胞質移行の意義, 名古屋市立大学
  • 胃癌の新規診断,化学療法を目指したES細胞特異的Ras,Erasの機能解析, 名古屋市立大学
  • 上皮増殖因子前駆体細胞内ドメインをターゲットとした新規薬剤開発, 名古屋市立大学
  • 消化器癌におけるEGF様増殖因子の放出に連動した核内転写抑制の解除機構, 名古屋市立大学
  • ES細胞特異的Ras、ERasを標的とした新規胃癌治療の基礎的解析, 名古屋市立大学
  • 腫瘍溶解性ウイルスによる新規消化管癌治療法の開発, 名古屋市立大学
  • ヘテロ原子の廃位特性を利用した抗癌性糖連結キノリノール白金・パラジウム錯体の合成
  • 消化管腫瘍に対する腫瘍溶解性レオウイルスによる新規内視鏡的治療法の開発

社会貢献活動情報

社会貢献活動

  • 愛知県生活習慣病対策協議がん対策部会 胃がん検診精度管理委員会委員として検討会参加, 行政,   2012年04月01日 - 現在, 愛知県生活習慣病対策協議がん対策部会 胃がん検診精度管理委員会委員として検討会参加
  • 日本カプセル内視鏡学会読影トレーニング委員, 一般社団法人日本カプセル内視鏡学会, 日本カプセル内視鏡学会読影トレーニング活動


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