| Co-Investigator(Kenkyū-buntansha) |
DOI Ryuchiro Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 講師 (20301236)
SHIMADA Yutaka Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 講師 (30216072)
ONODERA Hisashi Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (50240825)
ARII Shigeki Tokyo Medical & Dental University, Graduate School of Medicine & Dentistry, Professor, 医歯学総合研究科, 教授 (50151171)
YAMASAKI Seiji Kyoto University, Graduate School of Medicine, Instructor, 医学研究科, 助手 (50303839)
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| Research Abstract |
To elucidate mechanisms of cancer development and progression in intractable gastrointestinal malignancies such as pancreatic cancer, esophageal cancer, rectal cancer and hepatocellular carcinoma and moreover to develop appropriate multimodality therapies in patients with surgically unresectable cancers are extremely difficult tasks, yet they are recognized as one of the fundamental roles of the graduate school of medicine. We have developed the new localization method for pancreatic endocrine tumors, that is, Selective Arterial Secretagogue Injection test (SASH test), that has been used already worldwide. The mechanism of hormone release from the endocrine tumors has been studied, and we found that hormone secretion is the consequence of cytoplasmic calcium increase following ER via IP3 after stimulation of calcium sensing receptor or secretin receptor. However, we have yet to delineate methods to change constitutive secretory pathway in gastrointestinal cancers. Establishment of perm
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anent gastrointestinal cancer cell lines, molecular and biochemical analyses of surgically resected specimens, and postoperative prognostic surveillance of patients in the outpatient clinic have provided us with much information. Likewise, we have had opportunities to present many significant findings from studies in molecular biological aspects of cancer proliferation, invasion, and metastasis. With regard to the development of possible new therapies, we have reported in vivo inhibition of tumor growth by several methods including endostatin gene transfection, interferon r therapy, and injection of the chimeric fusion protein of active p16 peptide and antennapedia into the nucleus. Although clinical application is still hindered by their costs and lack f clinical studies, our findings shall contribute to the improvement in cancer therapies. Presence of micrometastasis is known to be closely related to cancer recurrences after surgical resection. Our work, centering on, but not limited to esophageal cancer, has come to the stage in which the existence of micrometastasis can be detected at the genetic level. Clinically, this will be reflected as a broadened indication for postoperative chemotherapy. Thus, we are still in the process of stepping up the ladder of our research work. Less
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