Search

Purpose: To explore the feasibility and efficacy of interstitial brachytherapy application for nonresectable and chemo-resistant malignant liver and lung lesions. Materials and Methods: Percutaneous high-dose-rate interstitial brachytherapy (HDR ISBT) was applied in nine lesions of seven middle-aged patients with advanced carcinoma (five patients with liver lesion and two patients with lung lesion). All patients were surgically ineligible. All patients had already received systemic chemotherapy. Under computed tomography (CT) guidance (for lung lesion) or ultrasonography (USG) guidance (for liver lesion), a single stainless steel brachytherapy needle was inserted percutaneously in patients with lesion size =4 centimeter (cm) and multiple needles were inserted in patients of lesion size >4cm. A single dose of 15 Gy to 20 Gy with HDR ISBT was prescribed at the periphery of the lesion. The needles were removed just after treatment. Patients were kept under observation for 24 h after treatment. Results: The median size of the lesion was 6.5 cm. In all the cases of liver lesion, more than 75% shrinkage of tumor volume in follow-up at 6 mo was observed. It was more than 50% for lung lesion. None of the patients had developed significant complications as on the median follow up period of 15 mo (ranges 3-27 mo). Conclusions: Percutaneous CT-guided high-dose-rate interstitial brachytherapy is a minimally invasive, safe, and feasible treatment option with minimal complication for inoperable, chemo resistant, advanced cancers with encouraging treatment outcomes. [ABSTRACT FROM AUTHOR]

The N-ribosyldihydronicotinamide (NRH):quinone oxidoreductase 2 (NQO2) gene encodes an enzyme that catalyzes activation of quinones. Blood DNA from 80 control individuals and 118 age-matched Parkinson's disease patients were analyzed for NQO2 gene promoter polymorphisms. The results revealed three allelic variants, designated 1-29, 1-16, and D. These results were confirmed in fibroblast cell lines. In patients with Parkinson's disease, there was a significant increase in the frequency of the D allele, but there was no difference in the frequency of the alleles in familial compared to sporadic Parkinson's disease. The D and 1-16 promoters direct higher NQO2 gene expression that results in higher enzyme activity. Overexpression of NQO2 in the catecholaminergic neuroblastoma SH-SY5Y cells resulted in increased production of reactive oxygen species when exposed to exogenous dopamine. The results suggest that the association of the D promoter with Parkinson's disease may be due to an increase in expression of the NQO2 gene. Key Words: NRH:quinone oxidoreductase 2--Promoter polymorphism--Parkinson's disease.

Twenty-four base pairs of the human anti-oxidant response element (hARE) are required for high basal transcription of the NAD(P)H:quinone [oxidoreductase.sub.1] ([NQO.sub.1]) gene and its induction in response to xenobiotics and antioxidants. hARE is a unique cis-element that contains one perfect and one imperfect AP1 element arranged as inverse repeats separated by 3 bp, followed by a 'GC' box. We report here that Jun, Fos, Fra, and Nrf nuclear transcription factors bind to the hARE. Overexpression of cDNA derived combinations of the nuclear proteins Jun and Fos or Jun and Fra1 repressed hARE-mediated chloramphenicol acetyltransferase (CAT) gene expression in transfected human hepatoblastoma (Hep-G2) cells. Further experiments suggested that this repression was due to overexpression of c-Fos and Fra1, but not due to Jun proteins. The Jun (c-Jun, Jun-B, and Jun-D) proteins in all the possible combinations were more or less ineffective in repression or upregulation of hARE-mediated gene expression. Interestingly, overexpression of Nrf1 and Nrf2 individually in Hep-G2 and monkey kidney (COS1) cells significantly increased CAT gene expression from reporter plasmid hARE-thymidine kinase-CAT in transfected cells that were inducible by [Beta]-naphthoflavone and tert-butyl hydroquinone. These results indicated that hARE-mediated expression of the [NQO.sub.1] gene and its induction by xenobiotics and antioxidants are mediated by Nrf1 and Nrf2. The hARE-mediated basal expression, however, is repressed by overexpression of c-Fos and Fra1.

Use of monkey kidney COS1 cells transfected with cDNAs encoding plasmids pMT2-cytochrome P450 1A1 (CYP1A1), pMT2-cytochrome P450 reductase (P450 reductase) and pMT2-NAD(P)H:quinone oxidoreductase (NQO1) helps examine the influence of these enzymes on the metabolic activation and/or detoxification of benzo(a)pyrene (BP). 32P postlabeling studies show the direct binding between DNA and semiquinones produced by P450 reductase. NQO1 inhibits the binding of DNA and quinone metabolites of BP generated by CYP1A1 and P450 reductase.