Detail of "204005-46-9"

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Effect of SU5416 on the inhibition of growth and metastasis of human gastric cancer implanted in nude mice

Effect of SU5416 on the inhibition of growth and metastasis of human gastric cancer implanted in nude mice. Zhang, Guo Feng; Wang, Yuan He; Wang, Qiang; Zhang, Min Gao; Han, Ce Ran; Rao, Ying Yang (Department of General Surgery, Changzheng Hospital, Second Military University, Shanghai, Peop.Some chemicals with cas registry numbers like 204005-46-9 and 51-21-8 are also used. Rep. China). Chinese Journal of Digestive Diseases, 4(2), 60-63 (English) 2003 Blackwell Publishing Asia Pty Ltd. CODEN: CJDDA9. ISSN: 1443-9611. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) OBJECTIVE: To study the effects of the angiogenesis inhibitor SU5416 on the growth and liver metastasis of gastric cancer and to investigate its effects on the apoptosis of gastric cancer cells. METHODS: A model simulating the metastasis of human gastric cancer was established by orthotopic implantation of histol. intact human tumor tissue into the gastric wall of nude mice, which were randomly divided into four groups: control group (saline soln.), 5-FU group (fluorouracil 30 mg/kg per day i.p), SU5416 group (SU5416 15 mg/kg per day i.p.), and combined treatment with 5-FU and SU5416. Eight weeks after implantation, the tumor wt., inhibition rate, intratumoral microvessel d. (MVD), apoptotic index (AI), and the status of metastasis were evaluated after the mice were killed. RESULTS: Compared with the control group, the growth of the orthotopically-implanted tumors was significantly inhibited, with reduced wt., and the tumor inhibition rate was 44.5%, 79.3%, and 84.4%, resp., in the mice treated with 5-FU, SU5416 and both. The incidence of liver metastasis was also significantly decreased in the 5-FU, SU5416, and combination groups compared with the control group (36.4%, 25.0%, and 0% vs 90.0%). The MVD of the 5-FU group, the SU5416 group and the combined group was 13.1±4.7, 3.9±1.8 and 2.1±1.5, resp., which was decreased significantly compared with the control group (14.6±5.8). The AI was increased significantly in the treated mice (6.81±4.92%, 9.82±3.76% and 17.65±9.85% vs 3.76±2.25%). The growth of and liver metastasis of the human gastric cancer implanted in the nude mice were both more significantly inhibited in the SU5416 group and the combined group than in the control and 5-FU groups (P < 0.05). CONCLUSIONS: SU5416 can induce apoptosis in gastric cancer by inhibiting tumor angiogenesis and has a strong inhibitory effect on both the growth and liver metastasis of gastric cancer implanted in nude mice. The combination of SU5416 with other cytotoxic agents is more effective. .

SU5416 selectively impairs angiogenesis to induce prostate cancer-specific apoptosis

SU5416 selectively impairs angiogenesis to induce prostate cancer-specific apoptosis. Huss, Wendy J.; Barrios, Roberto J.; Greenberg, Norman M. ( Departments of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA). Molecular Cancer Therapeutics, 2(7), 611-616 (English) 2003 American Association for Cancer Research. CODEN: MCTOCF. 204005-46-9 is the cas registry number. This chemical is also mentioned in this article. ISSN: 1535-7163. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) We have previously demonstrated the differential expression in tumor-assocd. blood vessels of two vascular endothelial growth factor receptors (VEGFRs), VEGFR1 and VEGFR2, during initiation and progression of prostate cancer in the genetically engineered transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model. In our "progression switch" model, expression of VEGFR1 is assocd. with early and more differentiated disease, whereas expression of VEGFR2 is assocd. with advanced and more poorly differentiated disease. To test the hypothesis that stage-specific inhibition of vascular endothelial growth factor signaling could be used as therapy for autochthonous prostate cancer, we initiated a preclin. trial with SU5416, a potent antiangiogenic small mol. inhibitor of VEGFR assocd. tyrosine kinase activity. In our early intervention trial, administration of SU5416 to TRAMP mice did not appear to influence angiogenesis or tumor progression between 10 and 16 wk of age, a time corresponding to high levels of VEGFR1 expression. In our late intervention trial, however, we obsd. a significant decrease in tumor-assocd. mean vessel d., increased apoptotic index, and pronounced regions of cell death when SU5416 was administered to TRAMP mice between 16 and 22 wk of age, a time corresponding to high levels of VEGFR2 expression. These results clearly demonstrate that therapy directed specifically against the VEGFR signaling axis can dramatically impair angiogenesis and induce apoptosis of autochthonous spontaneous and progressive prostate cancer. .