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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.


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Journal ArticleDOI
TL;DR: Serum‐free medium has been used to analyse the response of Schwann cell to previously identified Schwann Cell mitogens.
Abstract: Most previous studies on Schwann cell proliferation in vitro have used serum-containing media. This complicates the analysis of agents required for cell division since serum contains an ill-defined mixture of hormones and growth factors. Serum-free medium has therefore been used to analyse the response of Schwann cell to previously identified Schwann cell mitogens. Serum factors were not necessary for DNA synthesis in response to platelet-derived growth factor, basic fibroblast growth factor, or glial growth factor, provided they were used in combination with forskolin to elevate intracellular cAMP. Transforming growth factor beta 1, a Schwann cell mitogen in serum, was not mitogenic under these conditions. Neither the growth factors nor forskolin were effective when used alone. Growth control was analysed further using long-term cultured Schwann cells that had spontaneously immortalized. Measurements of endogenous cAMP levels in short- and long-term Schwann cells revealed that long-term cells had two to three times higher basal cAMP levels. As predicted by these findings, platelet-derived growth factor, basic fibroblast growth factor, and glial growth factor stimulated DNA synthesis in long-term cells without requiring costimulation by agents which elevate cAMP (while transforming growth factor beta 1 had no effect).(ABSTRACT TRUNCATED AT 250 WORDS)

109 citations

Book ChapterDOI
TL;DR: In addition to the use of anti-growth factor antibodies, other strategies for the inhibition of autocrine growth stimulation include mAbs to growth factor receptors, soluble receptors, receptor-mimicking antiidiotype antibodies, and active immunization against growth factors.
Abstract: Normal human cells, cells from nonmalignant proliferative lesions, and primary and metastatic tumor cells can be maintained in vitro and analyzed for requirements for growth in chemically defined media. The human melanocytic cell system with normal melanocytes, precursor nevus cells, and primary and metastatic melanoma cells has been extensively studied for the phenotypic properties of the cells, including their requirements for exogenous growth factors and other mitogens. In high calcium-containing W489 medium, normal melanocytes require four supplements: IGF-I (or insulin); bFGF, TPA, and alpha-MSH. Nevus cells are largely independent of bFGF. Depletion of TPA from medium is not as detrimental to nevus cells as it is to melanocytes, but the phorbol ester is still essential for maintenance of the typical nevic phenotype. Primary melanoma cells require at least one growth factor, IGF-I (or insulin), for continuous proliferation. On the other hand, metastatic cells of melanoma as well as of carcinomas of colon and rectum, bladder, ovary, and cervix are able to proliferate after a short adaptation period in medium depleted of any growth factors and other proteins. Doubling times of metastatic tumor cells in protein-free medium are only 30-60% longer than in FCS-containing medium. The growth autonomy of human tumor cells is apparently due to the endogenous production of growth factors. Likely candidates for autocrine growth stimulation of human tumor cells are TGF-alpha, TGF-beta, and PDGF. Melanoma and colorectal carcinoma cells express functional EGF/TGF-alpha receptors, and produce TGF-alpha, indicating that this growth factor is produced for autocrine stimulation. In addition to the use of anti-growth factor antibodies, other strategies for the inhibition of autocrine growth stimulation include mAbs to growth factor receptors, soluble receptors, receptor-mimicking antiidiotype antibodies, and active immunization against growth factors. Whether any of these therapeutic approaches is clinically feasible will need to be determined in extensive preclinical investigations.

109 citations

Journal ArticleDOI
TL;DR: The findings support a novel tumor suppressor function of BRCA1 that is relevant to breast cancer and identify a potential interactive risk factor for women with B RCA1 mutations.
Abstract: BRCA1 mutations and estrogen use are risk factors for the development of breast cancer. Recent work has identified estrogen receptors localized at the plasma membrane that signal to cell biology. We examined the impact of BRCA1 on membrane estrogen and growth factor receptor signaling to breast cancer cell proliferation. MCF-7 and ZR-75-1 cells showed a rapid and sustained activation of extracellular signal-related kinase (ERK) in response to estradiol (E2) that was substantially prevented by wild-type (wt) but not mutant BRCA1. The proliferation of MCF-7 cells induced by E2 was significantly inhibited by PD98059, a specific ERK inhibitor, or by dominant negative ERK2 expression and by expression of wt BRCA1 (but not mutant BRCA1). E2 induced the synthesis of cyclins D1 and B1, the activity of cyclin-dependent kinases Cdk4 and CDK1, and G(1)/S and G(2)/M cell cycle progression. The intact tumor suppressor inhibited all of these. wt BRCA1 also inhibited epidermal growth factor and insulin-like growth factor I-induced ERK and cell proliferation. The inhibition of ERK and cell proliferation by BRCA1 was prevented by phosphatase inhibitors and by interfering RNA knockdown of the ERK phosphatase, mitogen-activated kinase phosphatase 1. Our findings support a novel tumor suppressor function of BRCA1 that is relevant to breast cancer and identify a potential interactive risk factor for women with BRCA1 mutations.

109 citations

Journal ArticleDOI
TL;DR: This study provides the first experimental evidence that IL-13 can initiate a proliferative response of human airway epithelium in the absence of inflammatory cells or other cell types.
Abstract: Remodeling of the airways, as occurs in asthmatic patients, is associated with the continual presence of inflammatory mediators and Th2 cytokines, especially interleukin (IL)-13, during cycles of epithelial injury and repair. In this study, we examined the effect of IL-13 on well-differentiated normal human bronchial epithelial (NHBE) cells maintained in air–liquid interface culture. IL-13 induced proliferation of NHBE cells after 24 h exposure, as reflected by [3H]thymidine uptake and cell counts. The effects of IL-13 were mediated through the epidermal growth factor receptor (EGFR), as proliferation was attenuated by AG1478, an EGFR tyrosine kinase inhibitor. Proliferation appeared to be mediated by transforming growth factor (TGF)- α , a potent ligand for EGFR, which was released rapidly from NHBE cells in response to IL-13. Neutralizing antibody to TGF- α , but not antibodies against other potentially important growth factors (EGF, heparin binding epidermal growth factor–like growth factor [HB-EGF], p...

109 citations

Journal ArticleDOI
TL;DR: Although as cultures senesced, they became progressively less responsive to mitogenic stimulation, the concentration of epidermal growth factor, insulin, transferrin, and dexamethasone that elicited the maximum proliferative response did not change as a function of age.
Abstract: Normal human diploid cell lines such as WI-38 display a progressive loss of responsiveness to the mitogenic components in serum. Using a serum-free, hormone-growth factor supplemented medium for WI-38 cells (Phillips & Cristofalo, 1980, 1981), we examined the dose-response relationships of cells to the individual growth factor at various in vitro ages. Although as cultures senesced, they became progressively less responsive to mitogenic stimulation, the concentration of epidermal growth factor (25 ng/ml), insulin (5 micrograms/ml), transferrin (5 micrograms/ml), and dexamethasone (55 ng/ml) that elicited the maximum proliferative response did not change as a function of age. As cultures age they may require increasing amounts of platelet-derived growth factor to elicit the maximum mitogenic response.

108 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202352
20225
20211
20201
20191
201811