Epidemiological studies have demonstrated that oxidative stress associated with a variety of pathological conditions is one of the major causes of carcinogenesis. Reactive oxygen and nitrogen species contribute to genomic alterations, presumably followed by selection of the best-adapted proliferating cells in a given environment. Recent data suggest that there exist common signaling pathways for oxidative stress-associated carcinogenesis. So far, oxidative DNA damage has been assumed to be randomly distributed based on in vitro experiments, and localization of oxidative DNA damage in the genome in vivo has rarely been studied. However, by the use of novel techniques in combination with constructed genome databases, it was found that the localization of oxidative DNA appears to be not random in vivo. We propose to call this rather novel research area "oxygenomics". Not a few signaling pathways start from the recognition of DNA damage. Possible underlying principles should be elucidated in association with cell type, the function of each genomic location, and its transcriptional activity as well as chromatin status determining epigenetic information. Furthermore, this concept may contribute to the development of novel oxidative stress biomarkers. Thus, oxygenomics is a promising research area.
Breast cancer is the most common malignancy among women in India. It is the second most frequent cancer occuring in females. Studies have suggested that breast cancer is directly associated with increased dietary fat intake. The levels of lipids and lipoproteins were studied in postmenopausal women with breast cancer and after cyclophosphamide, methotrexate, & 5-flurouracil (CMF) treatment. The levels of cholesterol, triglyceride (TG) and free fatty acids increased in breast cancer patients as compared to healthy controls. The levels of malondialdehyde, lipid hydroperoxides and conjugated dienes increased in breast cancer patients and CMF treated subjects as compared to controls. The levels of reduced glutathione (GSH), vitamin E and vitamin C decreased in breast cancer patients as compared to healthy controls. The activities of catalase, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and glutathione S-transferase decreased in breast cancer patients and CMF treated subjects as compared to controls. These results are discussed with reference to CMF treatment.
Wound infection and abscess are the common post operative complications in pancreatic cancer patients. The aim of this study was to evaluate the status of immunity in patients with cancer in the head of pancreas by analyzing the levels of immunoglobulins, compliments, acute phase reactants and the efficiency of neutrophils for phagocytosis. The study was conducted on 89 patients with cancer in the pancreatic acini/pancreatic duct/head of pancreas/periampullary region and on equal number of age and sex matched normal healthy volunteers. All the patients were in a need to undergo either pancreaticoduodenectomy or duodenal preserving resection of head of the pancreas. The levels of IgM, IgA, IgE, C3, C4, C-reactive proteins, haptaglobin, α2 macroglobulin were assayed in the blood samples. The level of phagocytosis and bactericidal activity were evaluated in neutrophils. The level of IgM was significantly low and the levels of IgA and IgE were significantly high in pancreatic cancer patients. The levels of C-reactive protein, haptaglobin, α2 macroglobulin , C3 and C4 were elevated significantly. The phagocytic efficiency and the bactericidal action of polymorphonuclear lymphocytes and mononuclear cells were low in pancreatic cancer patients when compared to normal control subjects. In pancreatic cancer patients the antibody mediated immunity is disturbed and the acute phase response is stimulated to counteract the infection and the abnormal metabolites released from malignant cells. The functional impairment of phagocytes might be responsible for the post operative complications in pancreatic cancer patients.
Single-nucleotide polymorphisms (SNPs) of the β3-adrenergic receptor (BAR-3) and mitochondrial NADH dehydrogenase subunit-2 (ND2) genes are well established to be associated with obesity or other lifestyle-related diseases. We previously reported that the BAR-3 normal (Trp64Trp) + ND2 variant (Mt5178A) group preferred much more carbohydrate and less animal protein than the other genetic groups. In the present study, cross-sectional analysis of these genotypes was conducted with a much greater number of participants. The BAR-3 normal (Trp64Trp) + ND2 variant (Mt5178A) group was confirmed to have the significantly higher carbohydrate energy ratio and lower animal protein intake than the others. The statistical significance was greater than that obtained previously. In addition, an association of low intake of vitamin B2 intake and calcium with this genetic group was newly found in this expanded study.
Endogenous antioxidative potential was examined in rats given green tea as daily drinking water for 4 weeks. Rats ingested 196 μmol/kg body weight/day of catechins (sum total of 8 kinds of catechins), and plasma levels were around 0.24 μM. The green tea also contained 2.1 mM ascorbic acid, but the plasma level was similar to that in control rats drinking water, about 30 μM. The tea-drinking rats had significantly lower levels of lipid peroxidation in the small intestines and kidneys, 30% and 40% lower, respectively, than the controls, and their erythrocytes showed significant resistance to aqueous peroxyl radicals generated from azo initiator. Then, the effects of 8 catechins were examined on the antioxidative potency of ascorbic acid in in vitro. Catechins suppressed the oxidation of deoxyguanosine after the immediate exhaustion of ascorbic acid. Thus, frequent daily drinking of green tea improved the antioxidative potential of ascorbic acid.
We hypothesized a suppressive mechanism for dietary docosahexaenoic acid (DHA)-induced tissue lipid peroxidation in which the degradation products, especially aldehydic compounds, are conjugated with glutathione (GSH) through catalysis by glutathione S-transferases (GSTs), and then excreted into urine as mercapturic acids. Sprague-Dawley rats were fed a diet containing DHA (8.4 % of total energy) for 31 days. Lipid peroxides in the liver and kidney, liver GST and urinary excretion of mercapturic acid were measured. The lipid peroxide levels in the liver and kidney except the liver aldehydic compounds were higher, and the urinary excretion of mercapturic acid also tended to be higher in the DHA-fed rats although the activity of GST was not increased after DHA intake. We presume from our results that a proportion of the lipid peroxidation-derived aldehydic degradation products might be excreted into urine as mercapturic acid after intake of DHA, thus suppressing the accumulation of aldehydic products in tissues, particularly in the liver.
Objective: A number of clinical trials have reported that proton-pump inhibitors are efficacious in the treatment of upper abdominal symptoms, but most of these trials have been carried out in Caucasians. This study investigated the type of upper abdominal symptoms reported by Japanese patients with reflux esophagitis and the efficacy of omeprazole for treating their symptoms. Methods: A total of 234 patients aged ≥20 years with grade A to D reflux esophagitis were enrolled in this multicenter, open study. Patients received omeprazole 10 or 20 mg/day for 4 weeks. Symptom and quality of life questionnaires were administered at baseline, week 2 and week 4. Results: Among the 221 evaluable patients, almost 70% reported reflux-type symptoms (e.g. regurgitation and heartburn). Ulcer- and dysmotility-type symptoms (e.g. stomach pain and belching) were also common, occurring in 38-62% of patients. After 4 weeks of omeprazole treatment, all symptoms (except anorexia) were improved in approximately 90% of patients. Quality of life was also improved following omeprazole treatment. Conclusion: Reflux-type symptoms as well as ulcer- and dysmotility-type symptoms were seen frequently in Japanese patients with reflux esophagitis. However, omeprazole improved all symptom types and quality of life in this patient population.