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)

Multidrug resistance of cancer (CA) is one of a major problems in CA chemotherapy that is frequently associated with the expression of P-glycoprotein (P-gp) encoded by mdr1 genes. However, the controversial results exist regarding to the significance of mdr1 gene expression on clinical drug resistance to chemotherapy of breast CA cells. Recent evidence reported a strong correlation between the increased P-gp levels and the prognosis in advanced breast CA. The current study investigated whether mdr1 gene expression has any impact on prognosis and response to chemotherapy in breast CA patients. We determined mdr1 expression in 127 primary and 8 locally relapsed breast CA using a sensitive, specific and quantitative technique based on a RT-PCR and Southern blot hybridization detection by non-radioactive labelled-probe. In patients with primary breast CA, mdr1 expression were negative (mdr1-ve), low (< 10 units), high (> or = 10 units) in 63.8, 8.7 and 27.5 per cent of the patients, respectively. No differences in age, menopause status, tumor size, stage, lymph node involvement, estrogen receptor level and p53 level were observed between mdr1-ve and mdr1+ve expression patients. However, mdr1 gene expression is often associated with number of positive lymph nodes and negative estrogen receptors (p = 0.008 and 0.0007, respectively). In locally relapsed cases, mdr1-ve was 62.5 per cent whereas 37.5 per cent were mdr1+ve with high level of mdr1 RNA. No differences in other prognostic factors: lymph nodal involvement, estrogen receptor level and p53 level, were detected in both groups. Response to chemotherapy in primary and recurrent breast CA was not different in mdr1-ve and mdr1+ve patients. Finally, our results show that mdr1 gene expression is frequently present in breast CA both before and after chemotherapy. Association of mdr1 gene overexpression with other two prognostic factors suggests that they may confer a more aggressive nature of the tumor, drug resistance and poor prognosis. Evaluation of these factors may improve the ability to identify and select breast CA patients at high risk for poor prognosis for aggressive treatment. However, in this series response to CMF chemotherapy of primary and locally recurrent breast CA were not affected by the presence or absence of mdr1 gene product.
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PMID:Association of mdr1 gene expression with other prognostic factors and clinical outcome in human breast cancer. 934 65

ELAM is an E-Selectin adhesion molecule involved in the inflammatory process but it is also thought to potentially participate in the development of blood borne metastases, by facilitating tumour cell adhesion to vessels wall. ELAM expression in tumours was immunohistochemically investigated in 203 breast carcinomas. Frozen tissue sections were probed with monoclonal anti ELAM (Clone 1.2B6) using automated and quantitative immunoperoxidase systems. A positive anti-ELAM immunoreaction was observed in 113 tumours (57%). The mean surface of positive tumours varied from 3% to 50% (mean = 11.75%, SD = 8.7) and was correlated with histoprognostic indicators and tumour expression of various antigens detected according to the same method as ELAM. The results showed that ELAM immunoexpression was independent of the tumour size, grade and type and of the nodal status but significantly increased parallel to patients' age (p<0. 01). ELAM expression was independent of Ki-67/MIB1, anti-P53 and anti-Bcl2, anti-CD44v, anti-c-erbB-2, anti-CD31, anti-RE/RP, anti-PS2, and anti-VLA3 immunoreactions. But ELAM expression correlated with that of the VCAM vascular cell adhesion molecule (p=0.0004), VLA2 (p<0.0001), P-glycoprotein (p=0.025), and of Cathepsin D to a lower degree (p=0.06) and inversely correlated with E-cadherin (p=0.03). The results suggest that endothelial cell activation is independent of tumour cell proliferative activity and of stromal angiogenesis and that the precise role and regulation of ELAM in tumours remains to be elucidated. Also the clinical relevance of ELAM immunohistochemical expression requires further investigation and correlation with patients' follow-up.
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PMID:ELAM selectin expression in breast carcinomas detected by automated and quantitative immunohistochemical assays. 953 26

To evaluate the clinical significance of drug resistance mechanisms in breast cancer, we examined the expression of MDR1 and MRP in primary breast carcinoma and normal adjacent tissue using a highly quantitative and reproducible reverse transcription-PCR assay. Expression of both genes was observed in all specimens examined, both tumor (n = 74) and normal adjacent tissue (n = 55). The expression of MDR1, however, was low, with the level of expression being 25 times less than the drug-resistant control cell line KB 8-5. Immunohistochemical analysis of P-glycoprotein corroborated the PCR results; only 6% (2 of 31) were positive for JSB1 staining, and 0 of 32 were positive for for UIC2. MRP expression did not exceed control cell line levels, and immunohistochemistry detected moderate levels of expression. MDR1 expression was independent of grade, stage, tumor size, nodal status, metastasis, and estrogen receptor and progesterone receptor status. There was, however, a significant correlation of MDR1 expression with age and histology. Approximately twice the expression of MDR1 was observed in the < 50 age group compared to the > 50 age group, and lobular carcinoma had 4 times the expression of MDR1 of other histological types. MRP expression was independent of all other clinical parameters. Thus, these results show that although MDR1 expression is detectable in primary breast carcinoma by PCR, this expression as measured by quantitative reverse transcriptase-PCR is extremely low. The significance of these low levels is yet to be determined. MDR1 expression was higher in < 50 age group and lobular carcinoma, which may contribute to poor prognosis associated with young age and lobular histology.
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PMID:Quantitative reverse transcriptase-polymerase chain reaction measured expression of MDR1 and MRP in primary breast carcinoma. 962 74

VLA2 is thought to be involved in the metastatic process in malignant tumours, in particular in carcinomatous cell adhesion to vessel basement membrane. VLA2 expression was immunohistochemically investigated in 204 breast carcinomas. Frozen tissue sections were probed with monoclonal anti-VLA2 using automated (Ventana ES 320 System) and quantitative (SAMBA 2005 image processor) immunoperoxidase. A positive anti-VLA2 immunoreaction was observed in 48 tumours (23.5%), within epithelial carcinomatous cells. The VLA2-positive surface in tumours varied from 3% to 20% (mean 8.75, S.D. 7.17) and was correlated with histoprognostic indicators and tumour expression of various antigens detected using the same method as that for VLA2. The results show that VLA2 immunoexpression was independent of the tumour size, grade, type and aneuploidy, and of the nodal status. VLA2 significantly correlated with ELAM, VCAM, VLA3 and P-glycoprotein (P-gp) (P < 0.01) and inversely correlated with cathepsin D (P < 0.001), but was independent of Ki67/MIB1, p53, bcl-2, c-erbB-2, E cadherin, CD44v, CD31, oestrogen and progesterone receptors' (ER, PR) antigenic sites and pS2. The exact role, if any, of VLA2 in tumour cell dissemination remains to be elucidated and the clinical relevance of VLA2 immunodetection in breast carcinomas requires further investigation of the correlation between VLA2 immunocytochemical expression and patients' outcome and response to chemotherapy.
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PMID:VLA2 integrin expression in breast carcinomas evaluated by automated and quantitative immunohistochemistry. 964 45

T-cell lymphomas are a biologically heterogeneous group of diseases with varying clinical presentations and outcomes. We tried to understand the effect of Epstein-Barr virus (EBV) on lymphogenesis, prognostic factors and drug resistance of T-cell lymphomas, and to establish their relationship with international prognostic factors. Formalin-fixed paraffin-embedded tissue sections from 35 patients (12 women and 23 men) with T-cell lymphomas were examined to detect the presence of EBV using RNA in situ hybridization for EBV-encoded small nuclear RNA (EBER) 1/2 and immunohistochemical stain for latent membrane protein (LMP)-1. We also tried to establish the expression of p53 and P-glycoprotein (P-gp) using immunohistochemistry. The distribution according to the subgroup was: two T-lymphoblastic lymphomas, 13 NK/T-cell lymphomas, one angioimmunoblastic T-cell lymphoma, 17 peripheral T-cell lymphomas, unspecified, and two anaplastic large cell lymphomas. The EBER was detected in 15 of 35 T-cell lymphomas (42.9%) and among these it was detected in five of 17 nodal lymphomas (29.4%) and 10 of 18 extranodal lymphomas (55.6%). There was close correlation between EBER positivity and NK/T-cell lymphoma (P = 0.032). Expression of LMP was found in a proportion of tumor cells in seven of the 15 EBER-positive cases (46.7%). There was no correlation between EBER expression and complete response (CR rate), but coexpression of EBER and p53 was associated with treatment failure (P = 0.047). The 18 patients (51.4%) with p53 expression had significantly poorer outcomes compared with the 17 patients without p53 expression (CR rate, P < 0.0005; overall survival, P = 0.0102). Twenty of 35 patients (57.1%) were positive for P-gp expression. P-gp expression was significantly associated with treatment failure (P = 0.001) and overall survival (P = 0.0089). Seventeen of 35 patients (48.6%) treated with systemic chemotherapy or radiation therapy achieved a CR after initial treatment. When the prognostic factors were grouped using the international prognostic index, the CR rate was 58.8% for the low risk group, 50.0% for the low-intermediate risk group, 14.3% for the high-intermediate risk group, and 0% for the high risk group. In conclusion, high incidence of EBV was detected among Korean patients with T-cell lymphomas. Our study supports the prediction that patients who express p53 and P-gp have a poorer prognosis than those who do not and this should be considered when treatment strategies for individual patients are selected.
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PMID:Epstein-Barr virus infection, drug resistance and prognosis in Korean T- and NK-cell lymphomas. 1142 93

The aim of this study is to investigate the correlations among Y-box binding protein-1 (YB-1) and P-glycoprotein(P-gp) and their prognostic significance in diffuse large B-cell lymphoma (DLBCL). The expression of YB-1 and P-gp was examined immunohistochemically on 68 patients with DLBCL who were treated from 2003 to 2005. Samples were paraffin-embedded newly diagnosed DLBCL tissues taken from the surgical specimens before adjuvant chemotherapy. We determined the prognostic significance of YB-1 and its relationship with P-gp in patients with DLBCL. Of the 68 tumors examined, 42 (61.8%) were positive for YB-1 expression in the nucleus. The nuclear expression of YB-1 was significantly associated with clinical stages, bone marrow involvement, extra nodal involvement, and poor response to chemotherapy. No associations were observed between P-gp and clinical features, in context of the poor response to chemotherapy. Nuclear expression of YB-1 was correlated significantly with increased expression of P-gp patients with a nuclear YB-1 tumor had a poorer prognosis than did those with a cytoplasmic YB-1 tumor in all of the DLBCL patients (P = 0.035). Thus, correlation of YB-1 and P-gp emerged as a possible biomarker for unfavorable prognosis in DLBCL. It may provide useful information for clinicians to determine the appropriate therapy for each type of DLBCL.
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PMID:Nuclear expression of YB-1 in diffuse large B-cell lymphoma: correlation with disease activity and patient outcome. 1950 Jan 33

Epstein-Barr virus (EBV)-associated natural killer (NK)/T-cell lymphomas show a geographical predilection for Asian and South American populations and are rare in Western countries. They predominantly occur in extranodal sites, including the nasal or paranasal areas, and less frequently in the localized nodal lesion. Most of the tumor cells exhibit a cytotoxic phenotype, characterized primarily by the expression of granzyme B and perforin. EBV is usually detected in tumor cells by using EBV-encoded small RNA in situ hybridization (EBER), suggesting that EBV plays an important role in lymphomagenesis. In this chapter, we have described 2 diseases: 1) extranodal NK/T-cell lymphoma, nasal type (ENKL), representative of extranodal EBV-associated NK/T-cell lymphoma; and 2) nodal cytotoxic molecule-positive EBV-positive peripheral T-cell lymphoma, not specified type (CM + EBV + PTCL-N), representative of nodal lymphoma. Both ENKL and nodal CM + EBV + PTCL-N are intractable to standard chemotherapy. Although ENKL is sensitive to radiotherapy, it shows a poorer response to chemotherapeutic agents than other lymphomas because of P-glycoprotein expression. P-glycoprotein is a product of the multidrug resistance (MDR1) gene, which is a major cause of the refractoriness of malignant lymphomas to conventional chemotherapeutic regimens containing anthracycline. l-asparaginase-containing regimens such as SMILE (steroid, methotrexate, ifosfamide, l-asparaginase, and etoposide) are effective for ENKL. Evaluation of effective chemotherapy for nodal CM + EBV + PTCL-N is ongoing.
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PMID:Epstein-Barr virus-associated natural killer/T-cell lymphomas. 2376 37

Here we review prognostic and predictive aspects of mutated TP53 in Wilms' tumor biology on the basis of the morphological report and molecular analysis of adult nephroblastoma (diffuse blastemal pattern) of a 37-year-old man. Among quite different proteins, TP53 affects expression of several genes such as hypoxia inducible proteins GLUT1 and EPO as well as multidrug resistance (MDR) mediated by P-glycoprotein (Pgp/MDR1) and multidrug-resistant related protein (MRP1), with certain clinical implications. TP53 mutation was found both in our primary tumor (c.746G>T p.R249M frequency 92%) and in nodal metastasis (c.746G>T p.R249M frequency 90%), and the common polymorphism p.P72R in the same gene was revealed with frequency of about 97% in both primary tumor and metastatic disease with appliance of NGS technology (IonTorrent - LifeTechnology) using Ion AmpliSeq Cancer Hotspot Panel v2.
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PMID:Review of prognostic and predictive aspects of mutated TP53 in Wilms' tumor biology with morphological report and molecular analysis of 37-year-old man's nephroblastoma. 2854 57