Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Relationships among tenascin expression, DNA ploidy, and P-glycoprotein were examined in 81 primary human colon cancers and 61 metastatic lymph nodes. First, the DNA ploidy patterns of colon cancerous tissue surrounded (TN+) and not surrounded (TN-) by tenascin immunoreactivity were investigated. Then the expression of P-glycoprotein, one of two multidrug resistance gene products, was examined in TN+ and TN- colon cancer tissues by immunohistochemistry. Aneuploid DNA patterns were observed at high frequency in TN- colon cancer tissues (37/61) and metastatic lymph nodes (44/52). In contrast, diploid DNA patterns were observed predominantly in TN+ colon cancer tissues (50/56). Although P-glycoprotein expression was observed in primary TN+ and TN- colon cancer (9/81), the level of P-glycoprotein expression was not correlated with DNA aneuploidy in TN- colon cancer tissues. Overall, reduced tenascin expression was correlated well with DNA aneuploidy, but no significant correlation was found between DNA aneuploidy and P-glycoprotein appearing when cancer cells become resistant to several anti-cancer drugs. Thus, tenascin may play an important role in preventing colon cancer cells from invading surrounding tissues.
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PMID:Relationships among tenascin expression, DNA ploidy patterns, and multidrug resistance gene product (P-glycoprotein) in human colon carcinoma. 769 Mar 53

In the wake of recent progress in understanding the genetic pathways involved in the development of brain tumors, a major goal is to correlate molecular data with clinical outcome, survival, and response to treatment modalities. This is of particular importance among the pediatric population. Reliable prognostic factors could potentially permit a tailoring of therapy in that only patients with the most aggressive tumors would receive the most intense treatments. A survey of publications about prognosis-related molecular features among pediatric brain tumors revealed 74 series, of which 46 presented statistically significant outcome-associated parameters as defined by a p value <0.05. Most investigations revealing significant prognosis-related features were performed on medulloblastomas (34 publications), followed by astrocytic tumors (6 publications) and ependymomas (5 publications). Promising approaches and molecular markers include gene expression profiles, DNA ploidy, loss of heterozygosity and chromosomal aberrations as detected by CGH and FISH (1q, 17p, 17q), as well as oncogenes/ tumor suppressor genes and their proteins (TP53, PTEN, c-erbB2, N-myc, c-myc), growth factor and hormonal receptors (PDGFRA, VEGF, EGFR, HER2, HER4, ErbB-2, hTERT, TrkC), cell cycle genes (p27) and cell adhesion molecules, as well as factors potentially related to therapeutic resistance (multi-drug resistance, DNA topoisomerase IIalpha, metallothionein, P-glycoprotein, tenascin). This review discusses the predictive potential of molecular markers for clinical outcome and their influence on therapeutic decision-making among children with brain tumors.
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PMID:Prognosis-related molecular markers in pediatric central nervous system tumors. 1562 58

Brain tumors account for approximately 20% of all childhood cancers, and are the leading cause of cancer morbidity and mortality among children. Although numerous demographic, clinical and therapeutic parameters have been identified over the past few years that have significant prognostic bearing for some pediatric brain tumors, predicting the clinical course and outcome among children with central nervous system tumors is still difficult. A survey of publications on prognosis-related histopathological and immunohistochemical features among pediatric brain tumors revealed 172 series, of which 91 presented statistically significant outcome-associated parameters as defined by a P value of less than 0.05. Most investigations revealing significant prognosis-related markers were performed on medulloblastomas (30 publications), ependymomas (25) and astrocytic tumors (18). In total, 16 cohorts consisted of more than 100 cases (5 on ependymomas, 3 each on medulloblastomas and astrocytic tumors). On the other hand, there were also 13 series with fewer than 20 cases (5 on medulloblastomas). Potentially prognostic histopathological markers vary among different entities and consist of assessment of necroses, mitoses, differentiation, vascular proliferation, and growth pattern, whereas immunohistochemical features include proliferation markers (Ki-67, MIB-1), expression of oncogenes/tumor suppressor genes and their proteins (TP53, c-erbB2), growth factor and hormonal receptors (VEGF, EGFR, HER2, HER4, ErbB-2), cell cycle genes (p27, p14ARF) and cell adhesion molecules, as well as factors potentially related to therapeutic resistance (DNA topoisomerase IIalpha, metallothionein, P-glycoprotein, tenascin). This review discusses the prognostic potential of histopathological and immunohistochemical markers that can be investigated by the practicing neuropathologist as part of the routine diagnostic workload, and scrutinizes their benefit for predicting therapy response and patient outcome among children with brain tumors.
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PMID:Prognosis-related histomorphological and immunohistochemical markers in central nervous system tumors of childhood and adolescence. 1564 46

Fludarabine phosphate (FLU), the 2-fluro derivative of Ara-A, 9-beta-D-arabino-furanosyl-2-fluoroadenine, has been shown to display both in vitro and in vivo antiproliferative activity toward a variety of murine tumors and human lymphoid malignancies. In the present study, we have determined the effect of FLU, alone and in combination with recombinant human fibroblast interferon (IFN-B), on in vitro growth, gene expression and the antigenic phenotype of human glioblastoma multiforme (GBM) cells displaying a multidrug sensitive and a multidrug resistant (MDR) phenotype. FLU exhibited a marked differential toxicity toward GBM-MDR cells versus the multidrug sensitive GBM parental cell line. Growth of GBM-MDR cells for seven days in 2.5 to 7.5 muM FLU resulted in a dose-dependent reduction or elimination of growth which persisted after removal of this agent. In contrast, recovery from FLU-induced growth suppression was observed in parental multidrug sensitive GBM cells. Acquisition of increased FLU sensitivity in GBM-MDR cells did not appear to result from selection for a subset of sensitive cells or an artifact associated with the DNA-transfection process. This conclusion is supported by the similar pattern of FLU resistance in GBM-18 clones isolated after transfection with a cloned hygromycin resistance gene and selection for resistance to hygromycin. The antiproliferative and toxic effect of FLU was increased in GBM-MDR cells by simultaneous growth in IFN-B and the toxic effect of FLU could be blocked in a dose-dependent manner by the simultaneous addition of deoxycytidine. In contrast, the toxicity of FLU toward GBM-MDR cells was not altered when cells were grown in the presence or absence of colchicine or by the administration of verapamil, which can reverse the MDR phenotype in GBM-MDR cells. The selective toxicity of FLU toward GBM-MDR versus GBM-18 cells was not associated with a consistent differential change in all of the GBM-18 MDR clones in the steady-state mRNA levels of a number of genes, including mdr-1, c-myc, c-fos, JunB, C-jun, proliferative cell nuclear antigen (PCNA), interferon stimulated gene-15 (ISG-15), fibronectin, tenascin, Class I HLA antigen, intercellular adhesion molecule I (ICAM-1), beta-actin or GAPDH. A common change observed in both parental GBM-18 cells and MDR GBM-18 clones exposed to FLU was an increase in the steady-state mRNA levels of deoxycytidine kinase (DCT). Analysis of the antigenic phenotype in GBM and GBM-MDR cells by fluorescence activated cell sorter (FACS) analysis using specific monoclonal antibodies (MoAbs) recognizing ICAM-1, Class I HLA antigen and a high molecular weight-melanoma associated antigen (HMW-MAA) indicated that FLU was generally more active as an immunomodulating agent in MDR versus non-MDR GBM cells. Although the mechanism underlying the differential effect of FLU toward GBM-MDR versus GBM cells is not presently known, the present findings indicate that the growth inhibitory and immunomodulatory effects of FLU are enhanced in cells expressing an MDR phenotype resulting from overexpression of a cell membrane localized 170,000 M(r) glycoprotein (P-glycoprotein).
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PMID:Fludarabine phosphate selectively inhibits growth and modifies the antigenic phenotype of human glioblastoma-multiforme cells expressing a multidrug resistance phenotype. 2158 36