Inhibition of tumor growth through suppression of angiogenesis by brain-specific angiogenesis inhibitor 1 gene transfer in murine renal cell carcinoma. 2007

Shigetaka Kudo, and Ryuichiro Konda, and Wataru Obara, and Daisuke Kudo, and Kenzaburo Tani, and Yusuke Nakamura, and Tomoaki Fujioka
Department of Urology, Iwate Medical University School of Medicine, Morioka 020-8505, Japan.

This study was designed to elucidate the therapeutic effect of transfering the brain-specific angiogenesis inhibitor 1 (BAI1) gene to a mouse renal cell carcinoma cell line (Renca). Female BALB/c mice were inoculated subcutaneously with wild-type Renca (Renca/Wild) cells or Renca cells transfected with the BAI-1 (Renca/BAI-1) or LacZ (Renca/LacZ) gene. Tumor growth was observed every other day from 3 to 35 days after implantation. Moreover, the intratumoral injection of the adenovirus vector containing the gene encoding BAI1 was conducted at two-day intervals from 11 to 31 days after implantation of the Renca/Wild or Renca/BAI1 tumor. Tumor blood flow was measured by colorimetric angiogenesis assay (CAA). The concentration of the vascular endothelial growth factor (VEGF) in the cell culture supernatants was determined by enzyme-linked immunoassay. The size of the Renca/BAI1 tumor was significantly (p<0.01) suppressed compared to the Renca/Wild and Renca/LacZ tumors 21 days after tumor implantation. The injection of the BAI1 viral vector at 2-day intervals significantly inhibited the growth of both the Renca/Wild and Renca/BAI1 tumors. The blood volume measured by CAA and microvessel density was significantly lower in the Renca/BAI1 than in the Renca/Wild and Renca/LacZ tumors (p<0.01 and p<0.05, respectively). A significant (p<0.01) reduction in VEGF concentration in the supernatant was demonstrated in the Renca/BAI1 compared with the Renca/Wild and Renca/LacZ cell cultures. These observations suggest that the transfer of the BAI1 gene to Renca can suppress the tumor growth via the inhibition of angiogenesis. The down-regulation of VEGF production in tumor cells contributes to this anti-tumor effect.

UI MeSH Term Description Entries
D007680 Kidney Neoplasms Tumors or cancers of the KIDNEY. Cancer of Kidney,Kidney Cancer,Renal Cancer,Cancer of the Kidney,Neoplasms, Kidney,Renal Neoplasms,Cancer, Kidney,Cancer, Renal,Cancers, Kidney,Cancers, Renal,Kidney Cancers,Kidney Neoplasm,Neoplasm, Kidney,Neoplasm, Renal,Neoplasms, Renal,Renal Cancers,Renal Neoplasm
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D009389 Neovascularization, Pathologic A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions. Angiogenesis, Pathologic,Angiogenesis, Pathological,Neovascularization, Pathological,Pathologic Angiogenesis,Pathologic Neovascularization,Pathological Angiogenesis,Pathological Neovascularization
D002292 Carcinoma, Renal Cell A heterogeneous group of sporadic or hereditary carcinoma derived from cells of the KIDNEYS. There are several subtypes including the clear cells, the papillary, the chromophobe, the collecting duct, the spindle cells (sarcomatoid), or mixed cell-type carcinoma. Adenocarcinoma, Renal Cell,Carcinoma, Hypernephroid,Grawitz Tumor,Hypernephroma,Renal Carcinoma,Adenocarcinoma Of Kidney,Adenocarcinoma, Renal,Chromophil Renal Cell Carcinoma,Chromophobe Renal Cell Carcinoma,Clear Cell Renal Carcinoma,Clear Cell Renal Cell Carcinoma,Collecting Duct Carcinoma,Collecting Duct Carcinoma (Kidney),Collecting Duct Carcinoma of the Kidney,Nephroid Carcinoma,Papillary Renal Cell Carcinoma,Renal Cell Cancer,Renal Cell Carcinoma,Renal Cell Carcinoma, Papillary,Renal Collecting Duct Carcinoma,Sarcomatoid Renal Cell Carcinoma,Adenocarcinoma Of Kidneys,Adenocarcinomas, Renal Cell,Cancer, Renal Cell,Carcinoma, Collecting Duct,Carcinoma, Collecting Duct (Kidney),Carcinoma, Nephroid,Carcinoma, Renal,Carcinomas, Collecting Duct,Carcinomas, Collecting Duct (Kidney),Carcinomas, Renal Cell,Collecting Duct Carcinomas,Collecting Duct Carcinomas (Kidney),Hypernephroid Carcinoma,Hypernephroid Carcinomas,Hypernephromas,Kidney, Adenocarcinoma Of,Nephroid Carcinomas,Renal Adenocarcinoma,Renal Adenocarcinomas,Renal Carcinomas,Renal Cell Adenocarcinoma,Renal Cell Adenocarcinomas,Renal Cell Cancers,Renal Cell Carcinomas,Tumor, Grawitz
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D015316 Genetic Therapy Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions. Gene Therapy,Somatic Gene Therapy,DNA Therapy,Gene Therapy, Somatic,Genetic Therapy, Gametic,Genetic Therapy, Somatic,Therapy, DNA,Therapy, Gene,Therapy, Somatic Gene,Gametic Genetic Therapies,Gametic Genetic Therapy,Genetic Therapies,Genetic Therapies, Gametic,Genetic Therapies, Somatic,Somatic Genetic Therapies,Somatic Genetic Therapy,Therapies, Gametic Genetic,Therapies, Genetic,Therapies, Somatic Genetic,Therapy, Gametic Genetic,Therapy, Genetic,Therapy, Somatic Genetic
D042461 Vascular Endothelial Growth Factor A The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced. Vascular Endothelial Growth Factor,Vascular Endothelial Growth Factor-A,GD-VEGF,Glioma-Derived Vascular Endothelial Cell Growth Factor,VEGF,VEGF-A,Vascular Permeability Factor,Vasculotropin,Glioma Derived Vascular Endothelial Cell Growth Factor,Permeability Factor, Vascular

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