Expresión de proteínas relacionadas con resistencia a múltiples fármacos y resistencia a la quimioterapia en el cáncer de pulmón

Lario, A. Paredes; García, C. Blanco; Elizondo, M. Echenique; Lobo, Carmen

doi:10.1157/13109467

Cited by 8 publications

(1 citation statement)

References 19 publications

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“… 16 29 30 31 Previous studies have reported that P-gp is expressed in 35-52% of NSCLCs and LRP is expressed in 65-88% of NSCLCs. 29 32 33 The expression of P-gp/LRP could be regarded as a biomarker of primary MDR in NSCLCs. In this study, we found that the frequencies of positive expression of P-gp and LRP detected by immunohistochemistry were 44.1% and 66.1% respectively, which was consistent with the frequencies reported previously, thus the expressions of them were reliable for used as biomarkers to indicate primary MDR of the patients in this study.…”

Section: Discussionmentioning

confidence: 99%

Concomitance of P-gp/LRP Expression with EGFR Mutations in Exons 19 and 21 in Non-Small Cell Lung Cancers

Hong

et al. 2016

Yonsei Med J

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PurposeTraditional chemotherapy is the main adjuvant therapy for the treatment of non-small cell lung cancer (NSCLC). However, the emergence of multi-drug resistance (MDR) has greatly restricted the curative effect of chemotherapy. Therefore, it is necessary to find a method to treat MDR NSCLC clinically. It is worth investigating whether NSCLCs that are resistant to traditional chemotherapy can be effectively treated with tyrosine kinase inhibitors targeting epidermal growth factor receptor (EGFR).Materials and MethodsThe expression of P-glycoprotein (P-gp) and lung resistance-related protein (LRP) was detected by immunohistochemistry, and mutations in EGFR (exons 19 and 21) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (exon 2) were detected by high-resolution melting analysis (HRMA) of surgical NSCLC specimens from 127 patients who did not undergo traditional chemotherapy or radiotherapy. A Pearson chi-square test was performed to analyze the correlations between the expression of P-gp and LRP and mutations in EGFR and KRAS.ResultsThe expression frequencies of P-gp and LRP were significantly higher in adenocarcinomas from non-smoking patients; the expression frequency of LRP was significantly higher in cancer tissue from female patients. The frequency of EGFR mutations was significantly higher in well to moderately differentiated adenocarcinomas from non-smoking female patients. The frequency of EGFR mutations in the cancers that expressed P-gp, LRP, or both P-gp and LRP was significantly higher than that in cancers that did not express P-gp or LRP.ConclusionNSCLCs expressing P-gp/LRP bear the EGFR mutation in exon 19 or 21 easily.

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Section: Discussionmentioning

confidence: 99%

Concomitance of P-gp/LRP Expression with EGFR Mutations in Exons 19 and 21 in Non-Small Cell Lung Cancers

Hong

et al. 2016

Yonsei Med J

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MDM2 antagonist Nutlin-3a protects wild-type p53 cancer cells from paclitaxel

et al. 2012

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The p53 pathway has an important role in cell cycle arrest and apoptosis. Downregulated levels of p53 have been shown to increase resistance to the cytotoxic effects of chemotherapy or radiotherapy. MDM2 (murine double minute 2) is able to bind p53 and modulate its transcriptional activity and stability. We studied the effect of Nutlin-3a, an MDM2 antagonist, on the response of non-small cell lung cancer cell lines, A549 (p53+/+) and H1299 (p53/), to paclitaxel (Taxol). A549 cells treated with Nutlin-3a plus paclitaxel showed a significant increase in MDM2 and wild-type p53 protein, a marked increase in the number of cells in the G0-G1 and G2-M phases, and a significant decrease in the percentage of cells in the S phase. The percentage of apoptotic A549 cells treated with 10 mol/L Nutlin-3a plus 10 nmol/L paclitaxel was significantly lower than those treated with paclitaxel alone, and was also lower than that observed in H1299 cells. MTT assays demonstrated that Nutlin-3a plus paclitaxel also significantly reduced the sensitivity of A549 cells to paclitaxel compared with that of H1299 cells. In conclusion, Nutlin-3a mediates the cytotoxic effect of paclitaxel depending on p53 status. It may also protect wild-type p53 cells from mitotic chemotherapeutics.non-small cell lung carcinoma, p53, MDM2 antagonist, paclitaxel Citation:Shen H C, Dong W, Gao D W, et al. MDM2 antagonist Nutlin-3a protects wild-type p53 cancer cells from paclitaxel.

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Targeting MDR in breast and lung cancer: Discriminating its potential importance from the failure of drug resistance reversal studies

Amiri‐Kordestani

Basseville

Kurdziel

et al. 2012

Drug Resistance Updates

199

128

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This special issue of Drug Resistance Updates is dedicated to multidrug resistance protein 1 (MDR-1), 35 years after its discovery. While enormous progress has been made and our understanding of drug resistance has become more sophisticated and nuanced, after 35 years the role of MDR-1 in clinical oncology remains a work in progress. Despite clear in vitro evidence that P-glycoprotein (Pgp), encoded by MDR-1, is able to dramatically reduce drug concentrations in cultured cells, and that drug accumulation can be increased by small molecule inhibitors, clinical trials testing this paradigm have mostly failed. Some have argued that it is no longer worthy of study. However, repeated analyses have demonstrated MDR-1 expression in a tumor is a poor prognostic indicator leading some to conclude MDR-1 is a marker of a more aggressive phenotype, rather than a mechanism of drug resistance. In this review we will re-evaluate the MDR-1 story in light of our new understanding of molecular targeted therapy, using breast and lung cancer as examples. In the end we will reconcile the data available and the knowledge gained in support of a thesis that we understand far more than we realize, and that we can use this knowledge to improve future therapies.

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Expresión de proteínas relacionadas con resistencia a múltiples fármacos y resistencia a la quimioterapia en el cáncer de pulmón

Cited by 8 publications

References 19 publications

Concomitance of P-gp/LRP Expression with EGFR Mutations in Exons 19 and 21 in Non-Small Cell Lung Cancers

Concomitance of P-gp/LRP Expression with EGFR Mutations in Exons 19 and 21 in Non-Small Cell Lung Cancers

MDM2 antagonist Nutlin-3a protects wild-type p53 cancer cells from paclitaxel

Targeting MDR in breast and lung cancer: Discriminating its potential importance from the failure of drug resistance reversal studies

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