Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rectal carcinomas of previously untreated patients were analyzed for oxygen status using a computerized polarographic needle electrode histograph. Microvessel density and expression of c-jun, vascular endothelial growth factor (VEGF) and several resistance-related proteins (glutathione S-transferase-pi, GST; thymidylate synthase, TS; metallothioneine, MT) were determined using immunohistochemistry. To examine whether a relationship exists between intratumoral vessel density and tumor oxygenation, microvessel counts were determined in a 400x field using factor-VIII-related antigen and were correlated with the corresponding pO2 values. Linear regression analysis revealed a significant relationship between vessel density and oxygenation status of the tumors. Expression of c-jun, VEGF and resistance-related proteins was correlated with microvessel counts and pO2 values. Significantly lower vessel counts were found in GST- and MT-positive tumors and in tumors with overexpression of c-jun and VEGF than in negative tumors. In addition, significantly lower pO2 values were found in c-jun- and VEGF-positive tumors as well as a tendency for pO2 values to be lower in tumors where MT, GST and TS were expressed. These data show that expression of c-jun, VEGF, and resistance-related proteins is linked with poor vascularization and low oxygenation status in rectal cancer.
 ...
PMID:Association of resistance-related protein expression with poor vascularization and low levels of oxygen in human rectal cancer. 869 May 19

Lipid peroxide levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione transferase (GST) activities were investigated in mitochondrial fractions obtained from tumorous and nontumorous colorectal tissues of fourteen patients with colon and rectum cancer. Histopathological evaluations, including type, stage, necrosis and lymphocyte infiltration were also performed for each patient. The activities of SOD, GSH-Px and GST were increased significantly, but lipid peroxide levels remained unchanged in mitochondria obtained from tumors compared to adjacent normal tissues of subjects with colorectal cancer. When the patients were grouped according to their histopathological evaluation, such as type, stage, necrosis and lymphocyte infiltration, no relationship was observed between the histopathological results and the mitochondrial lipid peroxidation or antioxidant enzyme activities.
 ...
PMID:Mitochondrial lipid peroxides and antioxidant enzymes in colorectal adenocarcinoma tissues. 1112 24

Oxaliplatin (L-OHP) is a new platinum analogue that has shown antitumour activity against colon cancer both in vitro and in vivo and is now used in the chemotherapeutic treatment of metastatic colon and rectal cancer. L-OHP like cisplatin (CDDP), is detoxified by glutathione (GSH)-related enzymes and forms platinum (Pt)-DNA adducts lesions that are repaired by the nucleotide excision repair system (NER). We investigated the cytotoxicity and the pharmacology of L-OHP and CDDP on a panel of six colon cell lines in vitro. We showed that GSH and glutathione S-transferase (GST) activity were not correlated to oxaliplatin cytotoxicity. Pt-DNA adducts formation and repair were correlated with CDDP, but not with L-OHP cytotoxicity. The determination of ERCC1 and XPA expression, two enzymes of the NER pathway, by reverse transcriptase-polymerase chain reaction (RT-PCR), demonstrated that ERCC1 expression was predictive of L-OHP sensitivity (r(2)=0.67, P=0.02) and XPA level after oxaliplatin exposure was also correlated to L-OHP IC(50) (r(2)=0.5; P=0.04). The knowledge of such correlations could help predict the sensitivity of patients with colon cancer to L-OHP.
 ...
PMID:Cellular determinants of oxaliplatin sensitivity in colon cancer cell lines. 1250 67

Meat consumption, particularly of red and processed meat, is one of the most thoroughly studied dietary factors in relation to colon cancer. However, it is not clear whether meat, red meat, heterocyclic amines (HCA), or polycyclic aromatic hydrocarbons (PAH) are associated with the risk for rectal cancer. Rectal cancer cases (n = 952) and controls (n = 1205) from Utah and Northern California were recruited from a population-based case-control study between September 1997 and February 2002. Detailed in-person interviews regarding lifestyle, medical history, and diet were conducted. DNA was extracted from peripheral lymphocytes obtained from whole-blood samples, and glutathione S-transferase (GST)M1 enzyme and N-acetyl transferase (NAT)2 enzyme genotypes were assessed. Although energy and cholesterol intakes were higher among cases than controls, adjustment for confounders accounted for the differences. Increased consumption of well-done red meat [odds ratio (OR) 1.33 95% CI 0.98, 1.79] was associated with an (P = 0.04) increase in risk for rectal cancer among men. The mutagen index, calculated on the bases of reported amount, doneness, and method of cooking meat, was also positively but not significantly (P = 0.24) associated with risk of rectal cancer for men (OR 1.37 95% CI 0.98, 1.92). NAT2-imputed phenotype and GSTM1 did not consistently modify rectal cancer risk associated with meat intake. These data suggest that mutagens such as HCA that form when meat is cooked may be culpable substances in rectal cancer risk, not red meat itself.
 ...
PMID:Meat consumption patterns and preparation, genetic variants of metabolic enzymes, and their association with rectal cancer in men and women. 1505 25

Neurotoxicity is one of the most frequent side-effects of oxaliplatin. Oxaliplatin-induced cumulative and dose-limiting neurotoxicity either results in dose reduction or decreases the patients' quality of life. However, the symptoms of neurotoxicity often vary among patients. The current study presents the case of a male with rectal cancer, who was administered a cumulative oxaliplatin dose of >5,000 mg/m2 without developing neurotoxicity or allergic reactions. Consequently, this patient continued therapy with modified 5-fluorouracil, leucovorin and oxaliplatin treatment for four years, with stabilization of the disease. This case indicates that if oxaliplatin-containing chemotherapy shows efficacy with no toxicity, the long-term administration of oxaliplatin would be effective and tolerable. Previously, the analysis of genomic polymorphisms in drug target genes has been important for explaining interindividual variations in the efficacy and toxicity of anti-cancer drugs. In the present patient, the glutathione S-transferase P1 (GSTP1) gene polymorphism, which is involved in the detoxification of platinum drugs, was analyzed. The genotype of the present case has been revealed as wild type (Ile/Ile) genotype. In addition, the associations between oxaliplatin-induced neurotoxicity and the GSTP1 polymorphism were also assessed. Certain studies have demonstrated that oxaliplatin-induced neurotoxicity occurs more frequently in patients with the Ile/Ile genotype, while others have demonstrated that those patients with the Val/Val or Ile/Val genotypes are more likely to develop neurotoxicity. Therefore, correlation between the GSTP1 polymorphism and oxaliplatin-induced neurotoxicity remains controversial. Overall, further development of individualized chemotherapy with an analysis of genomic polymorphisms in the drug target genes is required for the prophylaxis oxaliplatin-induced neurotoxicity.
 ...
PMID:Long-term administration and efficacy of oxaliplatin with no neurotoxicity in a patient with rectal cancer: Association between neurotoxicity and the GSTP1 polymorphism. 2476 64