1999 Fiscal Year Final Research Report Summary
Development of Antibodies to Angiogenic Factors for Diagnosis and Therapy of Solid Tumors.
| Project/Area Number |
09557129
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Urology
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| Research Institution | Akita University |
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Principal Investigator |
KATO Tetsuro School of Medicine, Akita University, Urology, Professor, 医学部, 教授 (40004642)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUDA Yukihisa School of Medicine, Akita University, Zoology, Subprofessor, 医学部, 助教授 (50157327)
SUZUKI Toshio School of Medicine, Akita University, Pharmacy, Professor, 医学部, 教授 (20108559)
MASUDA Hiroki School of Medicine, Akita University, Pathology, Professor, 医学部, 教授 (60103462)
MIURA Naoyuki Biochemistry, Hamamatsu Medical College, Professor, 医学部, 教授 (40165965)
SASAKI Ryusei School of Medicine, Akita University, Urology, Assistant Prof., 医学部, 助手 (90292375)
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| Project Period (FY) |
1997 – 1999
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| Keywords | angiogenic factor / urogenital cancer / VEGF / bFGF / ELISA / angiogenesis |
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| Research Abstract |
The relationship between tumor angiogenesis and angiogenic factors was evaluated in renal cell carcinoma (RCC) and urinary bladder carcinoma (BCィイD2aィエD2). VEGF genes, VEGFィイD2121ィエD2 and VEGFィイD2165ィエD2, were overexpressed in 60% of RCCs. The Expression level of VEGF genes was significantly correlated with the intratumoral microvessel density. An immunohistologic analysis was done with and anti-VEGF antiserum that had been raised by immunizing a rabbit with an oligopeptide homologous to the N-terminal of VEGF. Cytoplasm of RCC appeared to be positive to the VEGF staining. VEGF genes were also overexpressed in 40% of Bcas. At protein level, VEGF was apparently positive in bladder carcinoma cells. VEGF-receptor genes were expressed in concordance with the VEGF gene expression level in both tumors. Thus, angiogenesis in RCC and Bca is suggested to be facilitated by a paracrine mechanism with VEGF and its receptors.
VEGF-relating genes (VEGF-A,B,C, and D) and their receptor genes have been
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cloned one after another. We studies the expression of these genes in RCCs and found that VEGF-A and the receptors, VEGFR-1 and VEGFR-2, play crucial roles in the angiogenesis of RCC while VEGF-B and VEGF-C do little.
Based on the above results, we compared serum VEGF levels between a RCC patient group and a healthy control group. The mean serum VEGF level was higher in the RCC patient group than in the healthy control group. Postoperative serum VEGF level apparently decreased as compared with the preoperative level. Serum VEGF level was significantly correlated with tumor volume, metastasis, and stage. When the VEGF cut-off value was set at 100pg/ml based on a receiver-operator curve analysis, the sensitivity and the specificity of RCC were 80.0% and 72.5%, respectively. Thus we suggest that RCC releases VEGF into the blood circulation and serum VEGF level would be a marker of malignant potential of RCC.
Taken together, these results would be useful as basic data for the development of anti-angiogenic-factor antibody facilitating diagnosis and therapy of RCC. Less
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