Molecular genetics and molecular biology advances in brain tumors

Cd, James; Jj, Olson

doi:10.1097/00001622-199605000-00004

Cited by 27 publications

(17 citation statements)

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“…[1][2][3][4][5]. However, the most common genetic alteration is loss of heterozygosity on chromosome 10, which occurs late in tumor development and at a frequency of Ϸ70-90% (6)(7)(8).…”

mentioning

confidence: 99%

Growth suppression of glioma cells by PTEN requires a functional phosphatase catalytic domain

Furnari

Lin

Huang

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

384

299

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Deletions of all or part of chromosome 10 are the most common genetic alterations in high-grade gliomas. The PTEN gene (also called MMAC1 and TEP1) maps to chromosome region 10q23 and has been implicated as a target of alteration in gliomas and also in other cancers such as those of the breast, prostate, and kidney. Here we sought to provide a functional test of its candidacy as a growth suppressor in glioma cells. We used a combination of Northern blot analysis, protein truncation assays, and sequence analysis to determine the types and frequency of PTEN mutations in glioma cell lines so that we could define appropriate recipients to assess the growth suppressive function of PTEN by gene transfer. Introduction of wild-type PTEN into glioma cells containing endogenous mutant alleles caused growth suppression, but was without effect in cells containing endogenous wild-type PTEN. The ectopic expression of PTEN alleles, which carried mutations found in primary tumors and have been shown or are expected to inactivate its phosphatase activity, caused little growth suppression. These data strongly suggest that PTEN is a protein phosphatase that exhibits functional and specific growth-suppressing activity.The best characterized genetic alterations found in the malignant progression of human gliomas are inactivation of the genes for p53, p16, and RB as well as amplification of CDK4 and the epidermal growth factor receptor genes (for reviews see refs.

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“…[1][2][3][4][5]. However, the most common genetic alteration is loss of heterozygosity on chromosome 10, which occurs late in tumor development and at a frequency of Ϸ70-90% (6)(7)(8).…”

mentioning

confidence: 99%

Growth suppression of glioma cells by PTEN requires a functional phosphatase catalytic domain

Furnari

Lin

Huang

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

384

299

View full text Add to dashboard Cite

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“…However, several genetic alterations are frequently encountered in such tumors, including loss of the tumor suppressor genes p53, p16, RB, or PTEN; increased expression of the protooncogenes bFGF, VEGF, or cdk4; and amplification or mutation of the EGFR gene (4)(5)(6)(7)(8)(9).…”

mentioning

confidence: 99%

Basic fibroblast growth factor induces cell migration and proliferation after glia-specific gene transfer in mice

Holland

Varmus

1998

Proc. Natl. Acad. Sci. U.S.A.

271

194

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Basic fibroblast growth factor (bFGF) is overexpressed in most high-grade human gliomas, implying that it is involved in the pathogenesis of these tumors. To assess the biological effect of inappropriate production of bFGF in normal astrocytes, we developed a system for gliaspecific gene transfer in transgenic mice. A transgene encoding the receptor for subgroup A avian leukosis virus and controlled by the astrocyte-specific glial fibrillary acidic protein promoter permits efficient glia-specific transfer of genes carried by subgroup A avian leukosis virus vectors. With this system, we have demonstrated that bFGF induces proliferation and migration of glial cells in vivo, without the induction of tumors.

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“…Recent advance in the molecular biological analysis of gliomas has revealed that histologically-identical tumours possess heterogeneous gene alterations and thus exhibit heterogeneous sensitivity to anticancer agents (James and Olson, 1995;Iwadate et al, 1996Iwadate et al, , 1998Iwadate et al, , 2000. In vitro DST would provide a rationale for the selection of therapy for individual patient on the basis of biological characteristics of the patient's tumour (Kimmel et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

“…Genetic alterations and gene expression patterns, however, are heterogeneous even in the same histological type of tumours, which leads to heterogeneous responses to the cancer therapies (James and Olson, 1995;Iwadate et al, 1996Iwadate et al, , 1998Iwadate et al, , 2000Rickman et al, 2001). This heterogeneity in drug sensitivity would partly account for the relative lack of success with uniform and conventional chemotherapy regimens obtained by such a clinical trial (Shapiro, 1999).…”

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confidence: 99%

Promising survival for patients with glioblastoma multiforme treated with individualised chemotherapy based on in vitro drug sensitivity testing

et al. 2003

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We retrospectively investigated the efficacy and feasibility of individualised chemotherapy based on in vitro drug sensitivity testing (DST) for patients with glioblastoma multiforme. A total of 40 consecutive patients with glioblastoma multiforme (GM) were enrolled into this study between January 1995 and December 2000. The flow cytometric (FCM) detection of apoptosis was used to determine the in vitro sensitivity of tumour cells obtained at surgery to 30 different kinds of anticancer agents. From the results of FCM assay, an in vitro best regimen was prospectively selected. All the patients concurrently received the individualised chemotherapy with the in vitro best regimen and 60 Gy of conventional radiation therapy. Of the 31 assessable patients, eight patients (26%) achieved partial response, and 20 patients (65%) had stable disease. The median survival time was 20.5 months. The individualised chemotherapy based on in vitro DST was associated with favourable survival time for the patients with GM compared with the reported results of conventional therapy regimens. The present result suggests that the currently available anticancer agents could be effective against GM when used in individualised chemotherapy.

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Molecular genetics and molecular biology advances in brain tumors

Cited by 27 publications

References 0 publications

Growth suppression of glioma cells by PTEN requires a functional phosphatase catalytic domain

Growth suppression of glioma cells by PTEN requires a functional phosphatase catalytic domain

Basic fibroblast growth factor induces cell migration and proliferation after glia-specific gene transfer in mice

Promising survival for patients with glioblastoma multiforme treated with individualised chemotherapy based on in vitro drug sensitivity testing

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