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Titolo:
Prognostic and pathologic significance of quantitative protein expression profiling in human gliomas
Autore:
Chakravarti, A; Delaney, MA; Noll, E; Black, PM; Loffler, JS; Muzikansky, A; Dyson, NJ;
Indirizzi:
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Oncol Mol Lab,Dept Radiat Oncol, Charlestown, MA 02129 USA Harvard Univ Charlestown MA USA 02129 at Oncol, Charlestown, MA 02129 USA Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Charlestown, MA 02129 USA Harvard Univ Charlestown MA USA 02129 Biostat, Charlestown, MA 02129 USA Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Oncol, Charlestown, MA 02129 USA Harvard Univ Charlestown MA USA 02129 ol Oncol, Charlestown, MA 02129 USA Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA Harvard Univ Boston MA USA 02114 ed, Dept Neurosurg, Boston, MA 02114 USA
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 8, volume: 7, anno: 2001,
pagine: 2387 - 2395
SICI:
1078-0432(200108)7:8<2387:PAPSOQ>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
HIGH-GRADE ASTROCYTOMAS; BRAIN-TUMORS; TELOMERASE EXPRESSION; SECONDARY GLIOBLASTOMAS; CELL-PROLIFERATION; MALIGNANT GLIOMAS; DE-NOVO; P53; GENE; MUTATIONS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Chakravarti, A Harvard Univ, Massachusetts Gen Hosp, Sch Med, Oncol Mol Lab,Dept Radiat Oncol, 13th St,Bldg 149,Room 7330, Charlestown, MA 02129 USA Harvard Univ 13th St,Bldg 149,Room 7330 Charlestown MA USA 02129
Citazione:
A. Chakravarti et al., "Prognostic and pathologic significance of quantitative protein expression profiling in human gliomas", CLIN CANC R, 7(8), 2001, pp. 2387-2395

Abstract

Purpose: Analysis of tumor-derived genetic lesions has provided insights into molecular pathogenesis of human gliomas. Because these changes represent only one of several mechanisms that alter gene expression during tumorigenesis, it is likely that further information will be obtained from a careful analysis of important regulatory proteins present in these tumors. Experimental Design: We have quantified the levels of key cell cycle/signaling proteins in 94 prospectively collected, meticulously preserved, "snap frozen" glioma specimens and have compared these levels with histopathological data and patient outcome. Results: The results of these experiments confirm that the levels of wild-type tumor suppressor proteins, such as p53, pRB, PTEN, p14(ARF), and p16(INK4), are lost or severely reduced in most gliomas, and that epidermal growth factor receptor, human telomerase reverse transcriptase, and cyclin-dependent kinase 4 are overexpressed frequently and with a few exceptions, almost exclusively, in glioblastomas. In addition, we report frequent underexpression of E2F-1 (in 55% of gliomas) and cyclin E overexpression (in 26% of gliomas), which have not yet been reported on the genomic level. Several ofthese markers significantly correlated with histopathological grade, and the levels of five proteins showed significant association with patient outcome. In particular, overexpression of epidermal growth factor receptor, human telomerase reverse transcriptase, cyclin-dependent kinase 4, and cyclin E was largely restricted to glioblastomas and was significantly associated with reduced patient survivals. Conclusions: We conclude that the quantitation of cell cycle/signaling proteins from meticulously preserved glioma specimens provides further insights into the molecular pathogenesis of human gliomas and yields valuable prognostic information.

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Documento generato il 07/07/20 alle ore 11:54:37