2001 Fiscal Year Final Research Report Summary
Investigation for Mechanism of Cancer Metastasis Utilizing Green
| Project/Area Number |
11671260
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | YOKOHAMA CITY UNIVERSITY, SCHOOL OF MEDICINE |
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Principal Investigator |
OOKI Shigeo YOKOHAMA CITY UNIVERSITY, SCHOOL OF MEDICINE, ASISTANT PROFESSOR, 医学部, 助教授 (40160436)
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| Co-Investigator(Kenkyū-buntansha) |
ICHIKAWA Yasushi YOKOHAMA CITY UNIVERSITY, SCHOOL OF MEDICINE, ASISTANT PROFESSOR, 医学部, 助教授 (70254208)
TOGO Sginji YOKOHAMA CITY UNIVERSITY, SCHOOL OF MEDICINE, ASISTANT PROFESSOR, 医学部, 助教授 (10244477)
SHIMADA Hiroshi YOKOHAMA CITY UNIVERSITY, SCHOOL OF MEDICINE, CHAIRMAN, 医学部, 助教授 (90117747)
MIYAGI Yohei YOKOHAMA CITY UNIVERSITY, SCHOOL OF MEDICINE, ASISTANT PROFESSOR, 医学部, 助教授 (00254194)
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| Project Period (FY) |
1999 – 2001
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| Keywords | green fluorescence protein / micrometastasis / inhibition of tumor angiogenesis / KDR / Flk-1 |
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| Research Abstract |
We have successfully transfecfed green fluorescence protein (GFP) into human colon cancer cell line ; WiDr, and gastric cancer cell line ; NUGC-4, and then confirmed those cells constantly emitting fluorescence. Using these fluorescent cells, very small metastasis including single cancer cell could be easily detected in vivo as liver metastasis or peritoneal dissemination. Moreover, neovascularization in such micrometastases could be clearly identified.
Using these in vivo fluorescent micrometastases models, we clarified effect of suppression of angiogenesis on growth inhibition of micrometastases using antisense (AS) oligonucleotides for VEGF receptor ; KDR/Flk-1. The AS inhibited expression of KDR/Flk-1 on human prostate cancer cell line ; PC-3, and also inhibited growth of the cell in vitro. On the other hands, growth inhibition of NUGC-4, not expressing KDR/Flk-1 was not induced by the AS in vitro. Administration of the AS to the in vivo fluorescent micrometastases models using NUGC-4 inhibited numbers and growth of micrometastatic nodules of NUGC-4 on peritoneum by reduction of tumor angiogenesis.
Our in vivo fluorescent micrometastases models are useful for investigation of actual and real time dynamism of metastatic cancer cells and for development of a new technology to treatment for cancer metastasis.
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[Publications] Kamiyama M, Ichikawa Y, Ishikawa T, Chishima T, Hasegawa S, Hamaguchi Y, Nagashima Y, Miyagi Y, Mitsuhashi M, Hyndman D, Hoffman RM, Ohki S, Shimada H: "VEGF receptor antisense therapy inhibits angiogenesis and peritoneal dissemination of human gastric cancer in nude mice"Cancer Gene Ther.. 9 (2). 197-201 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Yang M, Baranov E, Jiang P, Sun FX, Li XM, Li L, Hasegawa S, Bouvet M, Al-Tuwaijri M, Chishima T, Shimada H, Moossa AR, Penman S, Hoffman RM.: "Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases"Proc Natl Acad Sci U S A. 97(3). 1206-11 (2000)
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[Publications] Masako: Kamiyama, Yasushi Ichikawa, Yoji Nagashima, Satoshi Hasegawa, Takashi Chishima, David Hyndman, Kaoru Miyazaki, Hiroshi Shimada: "VEGF-Recepter (KDR/Flk-1) Antisense Oligonucleotide Inhibits Peritoneal Dissemination of Human Grastric Carcinoma, NUGC-4, in Nude Mouse"92nd Annual Meeting American Association for Cancer Research, 2001.3.24, New Orleans.
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