MOLECULAR BIOLOGICAL RESEARCH ON THE PRECURSOR AND PRECANCEROUS LESIONS OF THE KIDNEY-ANALYSIS WITH LASER CAPTURE MICRODISSECTION AND CHROMOGENIC IN SITU HYBRIDIZATION-

• Project/Area Number: 15590309
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: YOKOHAMA CITY UNIVERSITY
• Principal Investigator: NAGASHIMA Yoji YOKOHAMA CITY UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, DEPARTMENT OF MOLECULAR PATHOLOGY AND ONCOLOGY, ASSOCIATE PROFESSOR, 大学院・医学研究科, 助教授 (10217995)
• Co-Investigator(Kenkyū-buntansha): YAO Masahiro YOKOHAMA CITY UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, DEPARTMENT OF MOLECULAR UROLOGIC MEDICINE, ASSOCIATE PROFESSOR, 大学院・医学研究科, 助教授 (00260787)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: RENAL CELL CARCINOMA (RCC) / PRECURSOR / PRECANCEROUS LESION / VON HIPPEL-LINDAU DISEASE / HEMODIALYSIS / LASER CAPTURE MICRODISSECTION / CHROMOGENIC IN SITU HYBRIDIZATION / cDNA MICROARRAY

Research Abstract

Back ground and aim: It is well known that the kidney of von Hippel-Lindaus (VHL) disease and after persistent hemodialysis contains various precursor and precancerous lesions of renal cell carcinoma (RCC). Here, we aimed to investigate the genetic abnormalities in such lesions using laser capture microdissection (LCM) and chromogenic in situ hybridization (CISH). Materials and methods: On the kidney tissue derived from 2 cases of VHL disease and 7 cases of persistent hemodialysis, LCM was performed to cut out atypical tubules and cysts for RT-PCR followed by cDNA microarray, and CISH for evaluate the cchromosome numbers of #3, 7, 17 and Y, which have been known to be related with pathogenesis of RCCs. Results and discussion: The extracted RNAs were not appropriate for RT-PCR or cDNA microarray in the quality. CISH also failed to reveal the signals. Along with these attempts, we performed LCM study using frozen ovarian cancer tissue to evaluate the expression of the prolactin receptor and to demonstrate the copy numbers of Her2 gene in extramammary Paget disease, both of which were successful (Asai-Sato, Nagashima et al., in press; Ogawa, Nagashima, et al., submitted). Based on these facts, the methods to collect the RCC samples should be reconsidered for future study.

Research Products

• [Journal Article] Gene expression analysis of renal carcinoma : Identification of differentially expressed genes in renal parenchymal tumors using high-density oligonucleotide microarray : Adipophilin as a potential diagnostic and prognostic biomarker for clear-cell renal carcinoma. (2005)
  • Author(s): Yao M et al.
  • Journal Title: J Pathol 205・3 Pages: 377-387
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Renal oncocytosis. (2005)
  • Author(s): Nagashima Y et al.
  • Journal Title: Pathol Int 55・4 Pages: 210-215
  • NAID: 10016475097
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Composite distal nephron-derived renal cell carcinoma with chromophobe and collecting duct carcinomatous elements. (2005)
  • Author(s): Kawano N et al.
  • Journal Title: Pathol Int 55(in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Amelioration of 2,4,6-trinitrobenzene sulfonic acid-induced colitis in angiotensinogen gene knockout mice (2005)
  • Author(s): Inokuchi, Y., Morohashi, T., Kawana, I., Nagashima, Y., Kihara, M., Umemura, S.
  • Journal Title: Gut 54(3) Pages: 349-356
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of differentially expressed genes in renal parenchymal tumors using high-density oligonucleotide microarray: Adipophilin as a potential diagnostic and prognostic biomarker for clear-cell renal carcinoma (2005)
  • Author(s): Yao, M., Tabuchi, H., Nagashima, Y., Baba, M., Nakaigawa, N., Ishiguro, H., Hamada, K., Kobayashi, K., Yoshida, M., Hattori, K., Komiya, A., Kishida, T., Kondo, K-I, Inayama, Y., Yamada-Okabe, H., Kubota, Y.
  • Journal Title: J Pathol 205(3) Pages: 377-387
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Adenovirus-mediated transfer and overexpression of heme oxygenase 1 cDNA in lungs attenuates elastase-induced pulmonary emphysema in mice (2005)
  • Author(s): Shinohara, T., Kaneko, T., Nagashima, Y., Ueda, A., Tagawa, A., Ishigatsubo, Y.
  • Journal Title: Hum Gene Ther 16(3) Pages: 318-327
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A Src family inhibitor (PP1) potentiates tumor-suppressive effect of connexin 32 gene in renal cancer cells (2005)
  • Author(s): Fujimoto, E., Sato, H., Nagashima, Y., Negishi, E., Shirai, S., Fukumoto, K., Hagiwara, H., Hagiwara, K., Ueno, K., Yano, T.
  • Journal Title: Life Sciences 76(23) Pages: 2711-2720
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Lung pathology of pale ear mouse (a model of Hermansky-Pudlak syndrome 1) and beige mouse (a model of Chediak-Higashi syndrome): Severity of giant lamellar body degeneration of type II pneumocytes correlates with interstitial inflammation (2005)
  • Author(s): Tang, X-Y., Yamanaka, S., Miyagi, Y., Nagashima, Y., Nakatani, Y.
  • Journal Title: Pathol Int 55(3) Pages: 137-143
  • NAID: 10016474826
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Renal oncocytosis (2005)
  • Author(s): Nagashima, Y., Mitsuya, T., Shioi.K-i., Noguchi, S., Kishida, T., Hamano, A., Ohgo, Y., Tsuura, Y., Ogawa, T., Aoki, I., Yao, M.
  • Journal Title: Pathol Int 53(4) Pages: 210-215
  • NAID: 10016475097
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Composite distal nephron-derived renal cell carcinoma with chromophobe and collecting duct carcinomatous elements. A case report (2005)
  • Author(s): Kawano, N., Inayama, Y., Nakaigawa, N., Yao, M., Ogawa, T., Yazawa, T., Aoki, I., Kitamura, H., Nakatani, Y., Nagashima, Y.
  • Journal Title: Pathol Int 55(6) Pages: 360-367
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Role of transforming growth factor-beta1 (TGF beta1) in endotoxin-induced hepatic failure after extensive hepatectomy in rats (2005)
  • Author(s): Yoshimoto, N., Togo, S., Kubota, T., Kamimukai, N., Saito, S., Nagano, Y., Endo, I., Sekido, H., Nagashima, Y., Shimada, H.
  • Journal Title: J Endotoxin Res 11(1) Pages: 33-39
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A good model of hepatic failure after excessive hepatectomy in mice (2005)
  • Author(s): Makino, H., Togo, S., Kubota, T., Morioka, D., Morita, T., Kobayashi, T., Tanaka, K., Shimizu, T., Matsuo, K., Nagashima, Y., Shimada, H.
  • Journal Title: J Surg Res[Epub ahead of print] 21
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Composite distal nephron-derived renal cell carcinoma with chromophobe and collectine duct carcinomatous elements. (2005)
  • Author(s): Kawano N et al.
  • Journal Title: Pathol Int 55(in press)
• [Journal Article] Negative growth control of renal cell carcinoma cell by connexin 32 ; possible involvement of Her-2. (2004)
  • Author(s): Fujimoto E et al.
  • Journal Title: Mol Carcinogenesis 40・3 Pages: 135-142
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The expression of vascular endothelial growth factor-A and -C, and receptors 1 and 3 : Correlation with lymph node metastasis and prognosis in tongue (2004)
  • Author(s): Tanigaki Y et al.
  • Journal Title: Int J Mol Med 14・3 Pages: 389-395
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Inostamycin suppresses vascular endothelial growth factor-stimulated growth and migration of human umbilical vein endothelial cells. (2004)
  • Author(s): Baba Y et al.
  • Journal Title: Clin Exp Metastasis 21・6 Pages: 419-425
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Pathological and molecular biological aspects of renal epithelial neoplasms. Up-to-date. (2004)
  • Author(s): Nagashima Y et al.
  • Journal Title: Pathol Int 54・6 Pages: 377-386
  • NAID: 10020555909
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Pseudomonas aeruginosa-induced neutrophilic lung inflammation is attenuated by adenovirus-mediated transfer of hemeoxygenase 1 cDNA in mice (2004)
  • Author(s): Tsuburai, T., Kaneko, T., Nagashima, Y., Ueda, A., Tagawa, A., Shinohara, T., Ishigatsubo, Y.
  • Journal Title: Hum Gene Ther 15(3) Pages: 273-285
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The effect of lung-protective ventilation on severe Pseudomonas aeruginosa pneumonia and sepsis in rats (2004)
  • Author(s): Kurahashi, K., Ota, S., Nakamura, K., Nagashima, Y., Yazawa, T., Satoh, M., Fujita, A., Kamiya, R., Fujita, B., Baba, Y., Uchida, K., Morimura, N., Andoh, T., Yamada, Y.
  • Journal Title: Am J Physiol Lung Cell Mol Physiol 287(2)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Negative growth control of renal cell carcinoma cell by connexin 32; possible involvement of Her-2 (2004)
  • Author(s): Fujimoto, E., Satoh, H., Negishi, E., Ueno, K., Nagashima, Y., Hagiwara, K., Yamasaki, H., Yano, T.
  • Journal Title: Mol Carcinogenesis 40(3) Pages: 135-142
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The expression of vascular endothelial growth factor-A and -C, and receptors 1 and 3: Correlation with lymph node metastasis and prognosis in tongue squamous cell carcinoma (2004)
  • Author(s): Tanigaki, Y., Nagashima, Y., Kitamura, Y., Matsuda, H., Mikami, Y., Tsukuda, M.
  • Journal Title: lnt J Mot Med 14(3) Pages: 389-395
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Beneficial effect of hyperbaric oxygen therapy on liver regeneration after 90% hepatectomy in rats (2004)
  • Author(s): Nagamine, K., Kubota, T., Togo, S., Nagashima, Y., Mori, M., Shimada, H.
  • Journal Title: Eur Surg Res 36(6) Pages: 350-356
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inostamycin suppresses vascular endothelial growth factor-stimulated growth and migration of human umbilical vein endothelial cells (2004)
  • Author(s): Baba, Y., Kato, Y., Mochimatsu, I., Nagashima, Y., Kurihara, M., Kawano, T., Taguchi, T., Hata, R-I., Tsukuda, M.
  • Journal Title: Clin Exp Metastasi 21(6) Pages: 419-425
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Pathological and molecular biological aspects of the renal epithelial neoplasms, up-to-date (2004)
  • Author(s): Nagashima, Y., Inayama, Y., Kato, Y., Sakai, N., Kanno, H., Aoki, I., Yao, M.
  • Journal Title: Pathol Int 54(6) Pages: 377-368
  • NAID: 10020555909
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inostamycin suppresses vascular endothelial growth factor-stimulated growth and migration of human umbilical vein endothelial cells. (2004)
  • Author(s): Baba Y et al.
  • Journal Title: Clip Exp Metastasis 21・6 Pages: 419-425
• [Journal Article] Gene expression analysis of renal carcinoma : Identification of differentially expressed genes in renal parenchymal tumors using high-density oligonucleotide microarray : Adipophilin as a potential diagnostic and prognostic biomarker for clear-cell renal carcinoma. (2004)
  • Author(s): Yao M et al.
  • Journal Title: J Pathol 205・3 Pages: 2005-2005
• [Journal Article] Loss of von Hippel-Lindau protein causes cell density dependent deregulation of cyclinD1 expression through hypoxia-inducible factor. (2003)
  • Author(s): Baba M et al.
  • Journal Title: Oncogene 22・18 Pages: 2728-2738
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Forced expression of antisense 14-3-3β RNA suppresses tumor cell growth in vitro and in vivo. (2003)
  • Author(s): Sugiyama A et al.
  • Journal Title: Carcinogenesis 24・9 Pages: 1549-1559
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Angiotensin II receptor blocker shows antiproliferative activity in prostate cancer cells : A possibility of tyrosine kinase inhibitor of growth factor. (2003)
  • Author(s): Uemura H et al.
  • Journal Title: Mol Cancer Ther 2・11 Pages: 1139-1147
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Loss of von Hippel-Lindau protein causes cell density dependent deregulation of cyclinD1 expression through hypoxia-inducible factor (2003)
  • Author(s): Baba, M., Hirai, S., Yamada-Okabe, H., Hamada, K., Tabuchi, H., Kobayashi, K., Kondo, K., Yoshida, M., Yamashita, A., Kishida, T., Nakaigawa, N., Nagashima, Y., Kubota, Y., Yao, M., Ohno, S.
  • Journal Title: Oncogene 22(18) Pages: 2728-2738
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Forced expression of antisense 14-3-3β RNA suppresses tumor cell growth in vitro and in vivo (2003)
  • Author(s): Sugiyama, A., Miyagi, Y., Komiya, Y., Kurabe, N., Kitanaka, C., Koto, K., Nagashima, Y, Kuchino, Y., Tashiro, F.
  • Journal Title: Carcinogenesis 24 Pages: 1549-1559
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Angiotensin II receptor blocker shows antiproliferative activity in prostate cancer cells: A possibility of tyrosine kinase inhibitor of growth factor (2003)
  • Author(s): Uemura, H., Ishiguro, H., Nakaigawa, N., Nagashima, Y., Miyoshi, Y., Fujinami, K., Sakaguchi, A., Kubota, Y.
  • Journal Title: Mot Cancer Ther 2(11) Pages: 1139-1147
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Loss of von Hippel-Lmdau protein causes cell density dependent deregulation of cyclinD1 expression through hypoxia-inducible factor. (2003)
  • Author(s): Baba M et al.
  • Journal Title: Oncogene 22・18 Pages: 2728-2738
• [Journal Article] Prolactin inhibits apoptosis of ovarian carcinoma cells induced by serum starvation and cisplatin treatment.
  • Author(s): Asai-Sato M et al.
  • Journal Title: Int J Cance in press
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Connexin 32 as a tumor suppressor gene in a metastatic renal cell carcinoma cell line.
  • Author(s): Fujimoto E et al.
  • Journal Title: Oncogene in press
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A Src family inhibitor (PP1) potentiates tumor-suppressive effect of connexin 32 gene in renal cancer cells.
  • Author(s): Fujimoto E et al.
  • Journal Title: Life Sciences in press
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Contribution of the Src family of kinases to the appearance of malignant phenotypes in renal cancer cells.
  • Author(s): Yonezawa Y et al.
  • Journal Title: Mol Carcinogenesis in press
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Prolactin inhibits apoptosis of ovarian carcinoma cells induced by serum starvation or cisplatin treatment
  • Author(s): Asai-Sato, M., Nagashima, Y., Miyagi, E., Sato, K., Ohta, I., Vonderhaar, B.K., Hirahara, F.
  • Journal Title: Int J Cancer (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Connexin 32 as a tumor suppressor gene in a metastatic renal cell carcinoma cell line
  • Author(s): Fujimoto, E., Sato, H., Shirai, S., Nagashima, Y., Fukumoto, K., Hagiwara, H., Negishi, E., Ueno, K., Omori, Y., Yamasaki, H., Hagiwara, K., Yano, T.
  • Journal Title: Oncogene (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Contribution of the Src family of kinases to the appearance of malignant phenotypes in renal cancer cells
  • Author(s): Yonezawa, Y., Nagashima, Y., Sato, H., Virgona, N., Fukumoto, K., Shirai, S., Hagiwara, H., Seki, T., Ariga, T., Senba, H., Suzuki, K., Asano, R., Hagiwara, K., Yano, T.
  • Journal Title: Mol Carcinogenesis (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression of SPARC in tongue carcinoma of stage II is associated with poor prognosis. An immunohistochemical study of 86 cases
  • Author(s): Kato, Y., Nagashima, Y., Baba, Y., Kawano, T., Furukawa, M., Kubota, A., Yanoma, S., Imagawa-Ishiguro, Satake, K., Taguchi, T., Hata, R-i., Mochimatsu, I., Aoki, I., Kameda, Y., Inayama, Y., Tsukuda, M.
  • Journal Title: Int J Mol Med (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Reduced excision repair cross-complementing 1 expression associates with enhanced papilloma formation and fibroblast transformation after genetic disruption of secreted protein acidic and rich in cysteine
  • Author(s): Kato, Y., Tsukuda, M., Nagashima, Y., Koshika, S., Sakai, N., Yao, M., Kubota, Y., Aoki, I., Colledge, W.H., Foidart, J-M., Hata, R-I., Thompson, E.W.
  • Journal Title: Int J Oncol (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prolactin inhibits apoptosis of ovarian carcinoma cells induced by serum starvation and cisplatin treatment.
  • Author(s): Asai-Sato M et al.
  • Journal Title: Int J Cancer (in press)
• [Journal Article] Connexin 32 as a tumor suppressor gene in a metastatic renal cell carcinoma cell line.
  • Author(s): Fujimoto E et al.
  • Journal Title: Oncogene (in press)
• [Journal Article] A Src family inhibitor (PP1) potentiates tumor-suppressive effect of connexin 32 gene in renal cancer cells.
  • Author(s): Fujimoto E et al.
  • Journal Title: Life Sciences (in press)
• [Journal Article] Contribution of the Src family of kinases to the appearance of malignant phenotypes in renal cancer cells.
  • Author(s): Yonezawa Y et al.
  • Journal Title: Mol Carcinogenesis (in press)
• [Book] 病理診断における分子生物学 (2004)
  • Author(s): 長嶋洋治 他(分担)
  • Total Pages: 427
  • Publisher: 文光堂(東京)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Baba M et al.: "Loss of von Hippel-Lindau protein causes cell density dependent deregulation of cyclinD1 expression through hypoxia-inducible factor"Oncogene. 22・18. 2728-2738 (2003)
• [Publications] Sugiyama A et al.: "Forced expression of antisense 14-3-3 β RNA suppresses tumor cell growth in vitro and in vivo"Carcinogenesis. 24・9. 1549-1559 (2003)
• [Publications] Uemura H et al.: "Angiotensin II receptor blocker shows antiproliferative activity in prostate cancer cells : A possibility of tyrosine kinase inhibitor of growth factor"Mol Gene Ther. 2・11. 1139-1147 (2003)
• [Publications] Yano T et al.: "Negative growth control of renal cell carcinoma cell by connexin 32 ; possible involvement of Her-2"Mol Carcinogenesis. (in press).
• [Publications] Nagashima Y et al.: "Pathological and molecular biological aspects of the renal epithelial neoplasms, up-to-date"Pathol Int. (in press).
• [Publications] 長嶋洋治 他: "『病理と臨床』2004年臨時増刊号『病理診断における分子生物学』第2部 診断への応用と展望 11.腎癌"文光堂(東京)(印刷中).