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.

Differential Expression of Transforming Growth Factor-α during Prenatal Development of the Mouse

Abstract: Transforming growth factors (TGFs) are differentially expressed in the mouse during neonatal development. Highest levels are seen early at Day 7, and lower levels, at Day 13. Both small- and large-molecular-weight forms of TGF are found; they share many biochemical properties with rat TGF-alpha, including a similar high-pressure liquid chromatography elution profile. Although the embryo-derived activities compete with epidermal growth factor for binding to epidermal growth factor membrane receptors, they are immunologically distinct from epidermal growth factor. These embryonic polypeptides, however, do cross-react in a competitive radioimmunoassay developed using a synthetic peptide corresponding to the carboxy-17 amino acids of rat TGF-alpha as the immunogen. The highly conserved TGF-alpha family of peptides produced by some tumor cells may therefore represent derepressed forms of these embryonic growth factors. A functional role in neonatal development is proposed.

Inhibitors of type 2 vascular endothelial growth factor receptors

Abstract: The present disclosure relates to novel vascular endothelial growth factor receptor (VEGFR)-binding polypeptides and methods for using these polypeptides to inhibit biological activities mediated by vascular endothelial growth factors (VEGFs). The present disclosure also provides various improvements relating to single domain binding polypeptides.

Growth factor-mediated proliferation and differentiation of insulin-producing INS-1 and RINm5F cells: identification of betacellulin as a novel beta-cell mitogen.

Abstract: It is not clear which growth factors are crucial for the survival, proliferation, and differentiation of pancreatic beta-cells. We used the relatively differentiated rat insulinoma cell line INS-1 to elucidate this issue. Responsiveness of the DNA synthesis of serum-starved cells was studied to a wide variety of growth factors. The most potent stimulators were PRL, GH, and betacellulin, a member of the epidermal growth factor (EGF) family that has not previously been shown to be mitogenic for beta-cells. In addition to these, only vascular endothelial growth factor, insulin-like growth factor-1 and -2, had significant mitogenic activity, whereas hepatocyte growth factor, nerve growth factor-beta, platelet-derived growth factors, basic fibroblast growth factor, EGF, transforming growth factor-alpha (TGF-alpha), neu differentiation factor, and TGF-beta were inactive. None of these factors affected the insulin content of INS-1 cells. In contrast, certain differentiation factors, including nicotinamide, sodium butyrate, activin A, and 1,25-dihydroxyvitamin D3 inhibited the DNA synthesis and increased the insulin content. Also all-trans-retinoic acid had an inhibitory effect on cell DNA synthesis but no effect on insulin content. From these findings betacellulin emerges as a novel growth factor for the beta-cell. Half-maximal stimulation of INS-1 DNA synthesis was obtained with 25 pM betacellulin. Interestingly, betacellulin had no effect on RINm5F cells, whereas both EGF and TGF-alpha were slightly mitogenic. These effects may possibly be explained by differential expression of the erbB receptor tyrosine kinases. In RINm5F cells a spectrum of erbB gene expression was detected (EGF receptor/erbB-1, erbB-2/neu, and erbB-3), whereas INS-1 cells showed only expression of EGF receptor. Expression of the erbB-4 gene was undetectable in these cell lines. In summary, our results suggest that the INS-1 cell line is a suitable model for the study of beta-cell growth and differentiation because the responses to previously identified beta-cell mitogens were essentially similar to those reported in primary cells. In addition, we have identified betacellulin as a possible modulator of beta-cell growth.

Cell cycle-independent death of prostate adenocarcinoma is induced by the trk tyrosine kinase inhibitor CEP-751 (KT6587).

Abstract: Advanced prostate cancer remains largely incurable, primarily because the very low growth fraction present in these tumors makes them generally resistant to treatment with standard chemotherapeutic agents that target cell division. Effective therapies should therefore induce death of prostate cancer cells, independent of their growth rate. trkA, the high-affinity tyrosine kinase-linked receptor for nerve growth factor, has been implicated in prostatic cancer growth and may represent a molecular target for therapeutic agents. At low mg/kg doses, the trk tyrosine kinase inhibitor CEP-751 (KT6587) inhibits prostatic cancer growth in nine different animal models independent of the tumor growth rate, androgen sensitivity, metastatic ability, or state of tumor differentiation. CEP-751 is selective for cancerous versus normal prostate cells and affects the growth of only a limited number of nonprostate tumors. Importantly, CEP-751 induces cell death of prostate cancer cells in a cell cycle-independent fashion and, therefore, represents a novel therapeutic approach to the management of both hormone-dependent and hormone-independent prostate cancer.