Growth factor receptor inhibitor

About: Growth factor receptor inhibitor is a research topic. Over the lifetime, 4730 publications have been published within this topic receiving 297500 citations.

Activation and function of the epidermal growth factor receptor and erbB-2 during mammary gland morphogenesis

Abstract: The hormonal stimulation of mammary gland morphogenesis is believed to occur through growth factor receptor signaling pathways. To determine the importance of the epidermal growth factor receptor (EGFR) pathway, we examined extracts of inguinal mammary glands from prepubertal and pubertal mice for tyrosine-phosphorylated EGFR and other erbB receptors. Tyrosine phosphorylation of both EGFR and erbB-2 was detected in normal female BALB/c mice at 5-6 weeks of age, but not during the prepubertal stage, e.g., 24 days of age. Treatment of mice with estradiol or epidermal growth factor also stimulated the formation of mammary EGFR/erbB-2

Inhibition of malignant ascites and growth of human ovarian carcinoma by oral administration of a potent inhibitor of the vascular endothelial growth factor receptor tyrosine kinases.

Abstract: We determined whether inhibition of the catalytic tyrosine kinase activity of the receptors for vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) inhibits the formation of malignant ascites and the progressive growth of human ovarian carcinoma cells implanted into the peritoneal cavity of nude mice. The novel protein tyrosine inhibitor PTK 787 was evaluated in two models of human ovarian cancer: Hey-A8 cells, which express low levels of VEGF/VPF and grow as solid tumor foci on the surface of peritoneal organs, and SKOV3 i.p.1 cells, which express high levels of VEGF/VPF and grow as solid peritoneal tumors and ascites. Treatment of nude mice by daily oral administration of 50 mg/kg PTK 787 was not effective against Hey-A8 tumors. In sharp contrast, it significantly inhibited growth of SKOV3 i.p.1 cells and formation of ascites, significantly increasing survival of mice with the implants. Tumor-induced vascular hyperpermeability in the peritoneum of tumor-bearing mice was inhibited by PTK 787, which accounted for its inhibition of ascites formation. Our results suggest that blockade of the VEGF/VPF receptor may be an efficient strategy to inhibit formation of malignant ascites and growth of VEGF/VPF-dependent human ovarian carcinomas.

Lymphocyte activating factor promotes T-cell growth factor production by cloned murine lymphoma cells.

Abstract: Evidence has indicated that two soluble factors are essential for a T-cell proliferative response to antigen or lectin1–3. One such factor, thought to be of T-cell origin, is distinguished by its ability to initiate and maintain continuous T-cell growth (T-cell growth factor, TCGF)4–6. A second activity of macrophage origin augments lectin-initiated proliferative responses of thy-mocytes or adherent cell-depleted splenocytes (lymphocyte activating factor, LAF)7. Although it has been suggested that LAF promotes T-cell proliferation by facilitating the production of TCGF by T-cells1–3, direct evidence supporting this hypothesis has been lacking. We describe here experiments with a murine thymic lymphoma which releases TCGF in response to lectin. In serum-free, defined medium, highly purified LAF promotes a concentration-dependent increase in TCGF release. Because the proliferation of T cells depends on the concentration of TCGF available8,9, these results indicate that LAF and TCGF constitute an essential bimodal amplification system which ultimately determines the extent of T-cell clonal expansion.