Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-small cell lung cancer (N-SCLC) is generally unresponsive to chemotherapy even without previous drug treatment, as opposed to small cell lung cancer (SCLC), which is initially responsive to chemotherapy. The mechanisms of this intrinsic resistance are unknown. This study was designed to investigate the role of DNA repair in intrinsic resistance of N-SCLC to cisplatin. A panel of primary N-SCLC cell cultures and established cell lines were examined and compared to SCLC cell lines established previously from untreated patients. The overall DNA repair capacity was estimated by the ability of cells to reactivate the pRSV-CAT plasmid damaged by cisplatin ("host cell reactivation" assay). Cytotoxicity was determined for cisplatin in vitro. N-SCLC cells were found to be significantly more resistant to cisplatin than SCLC cell lines isolated from untreated patients (P < 0.01). The capacity of N-SCLC cells to reactivate pRSV-CAT plasmid damaged with cisplatin and transfected into cells was higher in N-SCLC cells than in SCLC cells originating from patients who were untreated previously (P < 0.05). Correlation was also observed between chloramphenicol acetyltransferase activity and intrinsic resistance to cisplatin. However, no significant difference was observed between primary N-SCLC cultures and established cell lines. This study indicates that elevated DNA repair capacity is associated with drug resistance in lung cancer and suggests that modulation of DNA repair mechanism(s), such as the incorporation of specific DNA repair inhibitor(s) in therapeutic regimens, may help to improve therapeutic strategies of N-SCLC.
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PMID:Elevated DNA repair capacity is associated with intrinsic resistance of lung cancer to chemotherapy. 758

Herpes simplex virus thymidine kinase (HSV-TK) gene was ligated with four repeats of the Myc-Max response elements (a core nucleotide sequence CACGTG), and its utility for gene therapy was examined by the treatment of either c-, L- or N-myc-overexpressing the small cell lung cancer (SCLC) cell line with ganciclovir (GCV). The chloramphenicol acetyltransferase assay demonstrated that the overexpression of any myc genes activated transcription from the CAT gene depending on the Myc-Max binding sites. The transduction of the HSV-TK gene ligated with the CACGTG core rendered all three SCLC lines to be more sensitive to GCV than parental ones in vitro. In addition, the growth of c- or L-myc-overexpressing SCLC cells containing the hybrid HSV-TK gene were significantly suppressed by GCV in vivo. When parental SCLC cells were mixed with HSV-TK-expressing tumor cells at a ratio of 1:3, GCV treatment inhibited tumor growth by 90% compared with parental cells only, indicating the existence of the "bystander effect." These data suggest that the CACGTG-driven HSV-TK gene may be useful for the treatment of SCLC overexpressing any type of myc family oncogenes.
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PMID:Eradication of Myc-overexpressing small cell lung cancer cells transfected with herpes simplex virus thymidine kinase gene containing Myc-Max response elements. 854 91