Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To prospectively assess the role of the MDR1 gene in breast carcinomas, MDR1 RNA levels of breast carcinoma specimens were determined by slot blot analysis. In 59 evaluable patients with primary breast carcinomas, MDR1 RNA levels of the carcinomas were negative in 54%, low in 29% and high in 17% of the patients. No differences in age, menopause status, oestrogen and progesterone receptor levels, tumour size, lymph node involvement and c-erbB-2/neu gene expression were observed between MDR1 RNA negative patients and MDR1 RNA positive patients.
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PMID:MDR1 gene expression and prognostic factors in primary breast carcinomas. 183 47

Of the approximately 18,000 new cases of cancer in Venezuela each year, only half can be treated with surgery and radiation. The remainder must be treated systematically using chemotherapy or biological response modifiers. It has become evident that any drug resistant human tumors express the MDR1 gene, since MDR1 RNA levels are elevated in many cancers that do not respond to chemotherapy. Human mammary carcinomas have multiple oncogene alterations, the most frequently reported being overexpression of the oncogenes c-myc, int-2, neu and c-myb. Thirteen specimens of mammary cancer were obtained by biopsy of untreated patients in stage IIIB. All these patients received three cycles of FAC or CMF-L+GM-CSF after biopsy. In the slot blot analysis of RNA from invasive carcinomas, MDR1 and c-myc transcripts were detectable at a high level in 30% of tumors. Two patients with increased levels of MDR1 before chemotherapy did not respond to the treatment and distant metastasis and death occurred in these patients. Another patient, MDR1-negative before therapy, did not respond to CMF-1 + GM-CSF and showed high levels of MDR1 transcripts in a second biopsy which was obtained during surgery.
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PMID:Expression of the multidrug-resistance (MDR) gene in breast cancer. 859 30

Chemotherapeutic drug resistance is a major clinical problem and cause for failure in the therapy of human cancer. One of the goals of molecular oncology is to identify the underlying mechanisms, with the hope that more effective therapies can be developed. Several mechanisms have been suggested to contribute to chemoresistance: 1) amplification or overexpression of the P-glycoprotein family of membrane transporters (eg, MDR1, MRP, LRP) which decrease the intracellular accumulation of chemotherapy; 2) changes in cellular proteins involved in detoxification (eg, glutathione S-transferase pi, metallothioneins, human MutT homologue, bleomycin hydrolase, dihydrofolate reductase) or activation of the chemotherapeutic drugs (DT-diaphorase, nicotinamide adenine dinucleotide phosphate:cytochrome P-450 reductase); 3) changes in molecules involved in DNA repair (eg, O6-methylguanine-DNA methyltransferase, DNA topoisomerase II, hMLH1, p21WAF1/CIP1; 4) activation of oncogenes such as Her-2/neu, bcl-2, bcl-XL, c-myc, ras, c-jun, c-fos, MDM2, p210 BCR-abl, or mutant p53. An overview of these resistance mechanisms is presented, with a particular focus on the role of oncogenes. Some current strategies attempting to reverse their effects are discussed.
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PMID:Role of oncogenes in resistance and killing by cancer therapeutic agents. 909 Apr 98

Major advances in cellular biology, genetics, pharmacology and immunology in the past decade are beginning to be translated into progress in cancer treatment. This progress is manifested by new cytotoxic drugs which have recently entered clinical practice (taxanes, topoisomerase I inhibitors, gemcitabine, vinorelbine, new purines), as well as the efficacy of monoclonal antibody therapies against the CD-20 antigen of B-cell lymphomas and the Her2/neu oncogene in breast cancer. Several new drugs in development are targeted at reversal or prevention of the multidrug resistance mechanism caused by expression of the MDR1 gene (P-glycoprotein). Tumour angiogenesis as a target is being studied in several early clinical trials. As with many other biological therapies, the evaluation of these compounds and their integration with standard therapies presents a major challenge to clinical investigators. The emerging field of genomics and gene expression micro-arrays will provide enormous information about the biology of cancers. This technology offers great opportunities for the discovery of new therapeutic targets, which should provide a basis for the design and evaluation of many new agents in the coming decade.
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PMID:New approaches in cancer treatment. 1067 67

The aim of this work was to determine the expression of the multidrug resistance (MDR) proteins, namely MDR1 (P-glycoprotein), MRP1 (multidrug resistance-related protein) and LRP (lung resistance-related protein), in 87 samples of breast carcinoma. Detection of these proteins was provided by using indirect enzymatic immunohistochemistry. Our findings were compared with the other clinical and pathological parameters: expression of Her2/neu, estrogen receptor status (ER), progesteron receptor status (PR), histological grade and regional lymph node status. For statistical analysis, non-parametric two sided Mann-Whitney-U test was used. Majority of breast carcinoma specimens show positivity for these proteins. The MDR1 and MRP1 signal was found in the cytoplasm of cancer cells. The expression of LRP was detected in the cytoplasm close to the nuclear membrane. The samples were positive for MDR1 protein in 57%, for MRP1 in 84% and for LRP in 79%. Comparing our results with other clinical and pathological parameters, negative correlation between ER, PR and MDR1 expressions and histological grading status was found. No associations were observed between the MRP1 and LRP proteins and histological grading, as well as between the expression of three MDR proteins and the other clinically relevant parameters. In conclusion, high frequency of expression of MDR proteins in breast carcinoma cells suggests, that these proteins might be an important factor of drug resistance in breast carcinoma. Nevertheless, the negative correlation between the histological grade of malignancy of tumor and the expression of ER, PR and MDR1 indicates possible influence of progressive tumor cell de-differentiation. However, this finding has to be confirmed in additional evaluations.
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PMID:Expression of MDR proteins in breast cancer and its correlation with some clinical and pathological parameters. 1657 68

The potential of gene expression profiles to predict the response to neoadjuvant chemotherapy in patients with advanced adenocarcinoma of the esophagus was analyzed. Paraffin-embedded endoscopic esophageal tumor biopsies of 38 patients with advanced esophageal adenocarcinoma (Barrett's adenocarcinoma) were included. All patients underwent two cycles of cisplatin and fluorouracil (5-FU) therapy with or without additional paclitaxel (taxol) followed by abdominothoracal esophagectomy. RNA expression levels of 5-FU-metabolism associated genes thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), MAP7, ELF3, as well as of platinum and taxane associated related genes caldesmon, excision cross-complementing genes (ERCC1 and ERCC4) HER2-neu, DNA damage-inducible gene 45 (GADD45) and multidrug resistance genes (MDR1, MRP1) were determined using real-time RT-PCR. Expression levels were correlated with the histopathological response to chemotherapy assessed in surgically resected specimens. Responding patients showed significantly higher pretherapeutic expression levels of MTHFR (p = 0.012), Caldesmon (p = 0.016), MRP1 (p = 0.007) and MDR1 (p = 0.025). In addition, patients with high pretherapeutic MTHFR and MRP1 levels had a survival benefit after surgery (p = 0.013 and p = 0.015, respectively). Additionally, intratumoral heterogeneity of gene expression of selected genes (TP, DPD, MTHFR, HER2-neu, Caldesmon, ERCC4, MRP1) was additionally verified in 9 untreated Barrett's adenocarcinoma by examination of 5 distinct tumor areas and was observed in 12.7% (5.6%-23.5%, CI 95%) of all cases analyzed. Our results indicate that determination of mRNA levels of a few genes may be useful for the prediction of the success of neoadjuvant chemotherapy in individual cancer patients with advanced adenocarcinoma of the esophagus.
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PMID:[Prediction of response to neoadjuvant chemotherapy in Barrett's carcinoma by quantitative gene expression analysis]. 1689 54