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Biomedical subjects

Yasuo Saijo

Publications and source records attributed to Yasuo Saijo.

21 records · Page 2Linked to original sources
PubMed2002

Targeting angiogenesis and HGF function using an adenoviral vector expressing the HGF antagonist NK4 for cancer therapy.

Hepatocyte growth factor (HGF) affects tumor growth/invasion and tumor neovascularization. A proposed HGF antagonist, NK4 (an amino-terminal kringle-domain peptide of HGF), inhibits tumor growth/invasion through the competition of HGF binding to its receptor, c-Met, and acts as an angiogenesis inhibitor. To investigate the in vivo effect of NK4 gene transfer, we constructed an adenovirus vector expressing human NK4 (AdCMV.NK4). Human lung cancer cell lines (A549 and H358) infected in vitro with AdCMV.NK4 yielded NK4 protein without a change in the cell growth rate. In contrast, direct injection of AdCMV.NK4 (1 x 10(9) pfu, twice) into established subcutaneous tumors in BALB/c nu/nu mice resulted in suppression of the tumors by 64% for A549 or by 91% for H358 compared with controls (P<0.02 or P<0.01, respectively). Counting of the tumor vessels revealed suppressed vascularity by 57% in H358 tumors when using AdCMV.NK4 (P<0.0001). Furthermore, systemic NK4 delivery by intraperitoneal injection of AdCMV.NK4 effectively suppressed both angiogenesis in the Matrigel assay (86% reduction, P<0.032), subcutaneous tumor growth in vivo (by 65% for H358, P<0.001), and hematogenous lung metastases without obvious side effects. These results indicate that NK4 elicits tumor-growth suppression in vivo through its anti-angiogenic activity and anti-HGF activity and that NK4 gene transfer can be an effective tool in the treatment of cancer.

Adenoviridae↗
PubMed2002

High level of vascular endothelial growth factor in hemorrhagic pleural effusion of cancer.

Angiogenic cytokines, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and angiogenin, are candidates for the induction of pleural effusions because they have been implicated in the induction of neovascularization, vascular permeability, and hemorrhage both in the inflammatory process and in tumor progression. Thus, we hypothesized that these angiogenic factors in effusion might be involved in the clinical manifestation of malignant pleural disease. We measured the levels of VEGF, bFGF, and angiogenin in pleural effusions and sera from 40 patients. Pleural effusions due to malignancy (1,350 pg/ml) contained significantly higher levels of VEGF than effusions due to inflammatory diseases (102 pg/ml; p = 0.034). Furthermore, hemorrhagic effusions showed significantly higher VEGF levels (1,942 pg/ml) than non-hemorrhagic effusions (202 pg/ml; p = 0.016) in malignant patients. In contrast, neither bFGF nor angiogenin were correlated with any clinical manifestation of pleural effusion. Immunohistochemical study revealed that malignant cells in the pleura were stained with anti-VEGF antibody. Our data suggest that VEGF secreted from tumor cells may be involved in the accumulation of pleural effusion in malignancy, and that increased levels of VEGF may induce hemorrhagic effusion.

Adult↗