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001-es BibID:	BIBFORM005190
Első szerző:	Park, John W.
Cím:	Unraveling the biologic and clinical complexities of HER2 / Park, J. W., Neve, R. A., Szollosi, J., Benz, C. C.
Dátum:	2008
Megjegyzések:	It has been over 20 years since the discovery of the human epidermal growth factor receptor 2 (HER2), a tyrosine kinase receptor that is a patent oncoprotein in breast and other cancers and has become an opportune forget for therapy. HER2 plays a critical role in normal development, forming homodimers or heterodimers with other HER family members and triggering downstream signaling cascades controlling proliferation, cell survival, and apoptosis. However, amplification of the HER2 gene in cancer cells results in overexpression of HER2 receptors on the cell surface, leading to excessive and dysregulated signaling. HER2-driven signaling also upregulates transcription factors that act on the HER2 promoter, increasing its expression. In breast cancer, HER2 is gene amplified in 20%-25% of primary tumors and is associated with a more aggressive phenotype and poorer prognosis. The key role HER2 plays In tumorigenesis makes it an ideal target for therapy. Trastuzumab, a monoclonal antibody against HER2, Inhibits downstream signaling and has proven to be effective against HER2-overexpressing metastatic breast cancer both as a single agent and in combination with chemotherapy. Seminal clinical trial data also show that the use of adjuvant trastuzumab in combination with chemotherapy or as a single agent after chemotherapy significantly increases disease-free and overall survival. Lapatinib, a dual tyrosine kinase inhibitor against HER1 and HER2, has been approved in combination with capecitabine for HER2-overexpressing advanced or metastatic breast cancer, which has progressed following previous anthracycline, taxane, and trastuzumab therapy. Other HER2-targeting strategies are also under active investigation.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Antibodies Apoptosis Cell Survival Cells Clinical trial Epidermal Growth Factor Human Phenotype therapy Tyrosine
Megjelenés:	Clinical Breast Cancer. - 8 : 5 (2008), p. 392-401. -
További szerzők:	Neve, Richard A. Szöllősi János (1953-) (biofizikus) Benz, Christopher C.
Internet cím:	DOI elektronikus változat
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001-es BibID:	BIBFORM004934
Első szerző:	Szöllősi János (biofizikus)
Cím:	ERBB-2 (HER2/neu) gene copy number, p185HER-2 overexpression, and intratumor heterogeneity in human breast cancer / Szollosi, J., Balazs, M., Feuerstein, B. G., Benz, C. C., Waldman, F. M.
Dátum:	1995
Megjegyzések:	Amplification of the ERBB-2 (HER-2/neu) gene is accompanied by overexpression of its cell surface receptor product, p185HER-2. Heterogeneity has been observed for both the gene copy number and the level of overexpression of its protein product. To better understand their relationship, correlation between the level of cellular expression of p185HER-2 and ERBB-2 gene amplification was studied in four human breast cancer cell lines (BT-474, SK-BR-3, MDA-453, and MCF-7) and in a primary human breast tumor sample. The relative expression of p185HER-2 was measured by immunofluorescence by using flow and/or image cytometry while correlated DNA analysis was performed on the same cells by fluorescence in situ hybridization to determine ERBB-2 gene and chromosome 17 copy numbers. Marked heterogeneity was observed in both protein expression and ERBB-2 copy number. Despite this heterogeneity, and in accordance with previous studies, the average levels of p185HER-2 expression correlated well with average ERBB-2 gene copy numbers in the four lines examined (r = 0.99). When the relationship between copy number and protein expression was studied on a cell-by-cell basis, p185HER-2 expression correlated with both the absolute number of ERBB-2 gene copies/cell (r = 0.59-0.63) and chromosome 17 copy number (r = 0.45-0.61). It is of interest that there was weak or no correlation between p185HER-2 protein expression and the ERBB-2 copy number:chromosome 17 copy number ratio (r = 0.0-0.25). In more than one-half of cells expressing a high level of p185HER-2, the chromosome 17 copy number was high (two or three times the average copy number), whereas < 2% of an unselected population had a high chromosome 17 copy number. Bromodeoxyuridine incorporation indicated that the S-phase-labeling index was homogeneous across various p185HER-2-expressing subpopulations in the SK-BR-3 cell line. Analysis of the primary breast tumor sample showed results similar to the cell lines, supporting the strong possibility of a mechanistic link among p185HER-2 overexpression, ERBB-2 amplification, and high chromosome 17 copy number.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban analysis biosynthesis Breast Neoplasms Cell Line Chromosomes,Human,Pair 17 Dna Female Fluorescence Gene Amplification Gene Dosage Genes,erbB-2 genetics Human Hybridization Image Cytometry Receptor,erbB-2 Support,Non-U.S.Gov't Support,U.S.Gov't,P.H.S. Tumor Cells,Cultured
Megjelenés:	Cancer Research. - 55 : 22 (1995), p. 5400-5407. -
További szerzők:	Balázs Margit (1952-) (sejtbiológus, molekuláris genetikus) Feuerstein, Burt G. Benz, Christopher C. Waldman, Frederick
Internet cím:	elektronikus változat
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