Research for molecular mechanisms of lymphangiogenesis and lymph node metastasis
Project/Area Number |
16390378
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
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Research Institution | Kyoto University |
Principal Investigator |
KUBO Hajime Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 科学技術振興助教授 (50362520)
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Project Period (FY) |
2004 – 2005
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Project Status |
Completed (Fiscal Year 2005)
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Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2005: ¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 2004: ¥7,400,000 (Direct Cost: ¥7,400,000)
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Keywords | Lymphangiogensis / Lymph node metastasis / ES cells / tumor suppressor gene / RNA editing / 血管新生 |
Research Abstract |
1.The expression of lymphatic marker, podoplanin by cancer were associated with the frequency of lymph node metastasis. We established novel anti-human podoplanin antibodies, and found the expression by several cancer cells using tissue microarrays. We also found that podoplanin was the specific marker for mesothelioma. 2.Homeobox gene, prox1 as a novel tumor suppressor gene. We found that there was a significant correlation between prox1 expression and the differentiation scores of the tumors. Subsequently, we also showed that low expression of prox1 in tumors was closely associated with a poor prognosis. The specific knockdown of prox1 by RNA interference strongly accelerated in vitro cell growth, while the over-expression of prox1 greatly suppressed the growth. 3.Two populations of Thy1-positive mesenchymal cells regulate the in vitro maturation of hepatic progenitor cells We determined that the mucin-type transmembrane glycoprotein gp38 could distinguish the cuboidal cells from the spin
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dle cells by immunocytochemistry. In vitro maturation of hepatic progenitor cells promoted by gp38-positive cells may be opposed by an inhibitory effect of gp38-negative cells, which likely maintain the immature, proliferative state of CD49f-positive cells. 4.Differentiation of lymphatic endothelial cells from Embryonic Stem cells on OP9 stromal cells VEGFR-2^+ cells derived from ES cells differentiated into LECs at day3 on OP9 stromal cells defined by the expression of prox1, VEGFR-3 and another lymphatic marker podoplanin. VEGFR-2^+ cells gave rise to LYVE-1^+ embryonic ECs, which were negative for prox1 on day1 but turned to prox1^+ LECs by day3. VEGFR3-Fc or Tie2-Fc, sequestering VEGF-C or angiopoietin 1 (Ang1), suppressed colony formation of LECs on OP9 cells. However, addition of VEGF-C and Ang1 in combination with VEGF to the culture of VEGFR-2^+ cells on collagen-coated dishes failed to induce LECs. LEC inducing activity of OP9 cells was fully reproduced on PFA-fixed OP9 cells with the conditioned medium. Less
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Report
(3 results)
Research Products
(13 results)
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[Journal Article] Lymphangiogenesis-Mediated Shedding of LAM Cell Clusters as a Mechanism for Dissemination in Lymphangioleiomyomatosis.2005
Author(s)
Kumasaka T, Seyama K, Mitani K, Souma S, Kashiwagi S, Hebisawa A, Sato T, Kubo H, Gomi K, Shibuya K, Fukuchi Y, Suda K
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Journal Title
Am J Surg Pathol. 29
Pages: 1356-1366
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[Journal Article] Suppression of VEGFR-3 signaling inhibits lymph node metastasis in gastric cancer.2004
Author(s)
Shimizu K, Kubo H, Yamaguchi K, Kawashima K, Ueda Y, Matsuo K, Awane M, Shimahara Y, Takabayashi A, Yamaoka Y, Satoh S.
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Journal Title
Cancer Sci. 95
Pages: 328-333
NAID
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