| Co-Investigator(Kenkyū-buntansha) |
HOSOTANI Ryo Graduate School of Hedicine, Kyoto University, Associate Professor, 医学研究科, 講師 (00139908)
ARII Shigeki Graduate School of Hedicine, Kyoto University, Associate Professor, 医学研究科, 助教授 (50151171)
SHIOTA Kohei Graduate School of Hedicine, Kyoto University, Professor, 医学研究科, 教授 (80109529)
DOI Ryuichiro Graduate School of Hedicine, Kyoto University, Instructor, 医学研究科, 助手 (20301236)
SHIMADA Yutaka Graduate School of Hedicine, Kyoto University, Lecturer, 医学研究科, 講師 (30216072)
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| Research Abstract |
1. Development of new and specific diagnostic modalities for pancreatic cancer : (1) Six human pancreatic cancer cell lines were established from ductal adenocarcinoma. Several secretory and membrane proteins were newly identified and cloned from these cell lines with the use of SST method. (2) In order to identify pancreatic progenitor cells which might develop oncogenesis, PDX-1 expression was examined in experimental pancreatic duct ligation model. PDX-1 cells were identified in hyperplastic ductal cells and were differentiated into endocrine cells. Expression of PDX-1 was further examined in cells with ductal dysplasia.
2. Differentiation and proliferation of embryonic pancreas : (1) Expression of apoptosis-related molecules including Bcl-XL, Mcl-1, Bax, and Bcl-2 were examined. There was a similar fashion of the expression of these molecules between two tissues; i. e. pancreatic cancer that shows chaotic growth and embryonic pancreas where well-organized differentiation and prolife
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ration were taken place. (2) Three-dimensional culture system of mouse embryonic pancreas was developed. i) No differentiation was observed when pancreatic epithelium (PE) was incubated alone, ii) Full pancreas was developed from PE when incubated with surrounding matrix tissue, iii) Ductal structure was developed when incubated in Matrigel, and iv) Endocrine structure was observed when incubated in Matrigel in the presence of Activin A. Differential display analysis for mRNA are undertaken in order to identify new molecules which are involved in the ductal differentiation steps.
3. Tumor angiogenesis in pancreatic cancer and the development of the antiangiogenic therapy : (1) Analysis of the pancreatic cancer tissue showed that molecules such as MT-MMP-1, activated form MMP-2, VEGF, PD-ECGF and CXCR-4 were angiogenic factors and METH-1 was inhibitory factor, both of which were involved in the control mechanism of the tumor angiogenesis. (2) In experimental liver metastasis model, CXCR-4 antagonist showed no inhibitory effect, but inhibitor of MMP activation caused significant inhibition in liver metastasis. Less
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