Physical activity: a possible determinant of vincristine (NSC-67574) neuropathy.
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Biomedical subjects
Publications and source records attributed to A Sakamoto.
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Human P-glycoprotein (Pgp) encoded by the MDR1 gene confers multidrug resistance to cancer cells. The clinical role of MDR1/Pgp in lung cancer is not fully understood. A total of 87 lung cancer surgical tissue samples, including previously untreated 84 non-small-cell (NSCLC) and three small-cell lung carcinoma (SCLC), were analyzed for levels of MDR1 mRNA determined by Northern blotting and compared with MDR1-positive cell lines. Fifteen percent (13/87) of the tumors were positive for the MDR1 gene, but the level was low in all samples except in one adenocarcinoma which expressed a high level of MDR1. The gene expression in these tumors did not relate with any pathologic factors such as histologic type, pathologic stage and tumor size. The SCLC and only one of the 14 MDR1-negative NSCLC responded to adjuvant chemotherapy after surgery. The present results indicate that the MDR1 gene is not associated in NSCLC with tumor progression and drug resistance.
Metallothioneins (MTs) are induced by various stimuli and probably confer drug resistance in tumor cells in vitro. To investigate whether MT expression in lung cancer is induced by chemotherapy, ninety-seven surgical specimens from patients who had or not received chemotherapy containing cisplatin, were stained immunohistochemically for MT. In untreated tumors, 23% (15/64) of all tumors and 27% (15/56) of non-small-cell carcinoma (NSCLC) stained positive, while all eight small-cell carcinoma (SCLC) were negative. In treated tumors, 52% (17/33) of all tumors, 80% (12/15) of NSCLC and 28% (5/18) of SCLC stained positive. The proportion of positively-stained tumors was significantly higher in treated NSCLC compared with untreated NSCLC (P = 0.0005) and treated SCLC (P < 0.005). Our results indicate that MT expression increases following chemotherapy and that such expression may confer during resistance in lung cancer, especially NSCLC.