dinoprost and Liver-Neoplasms

Chronic inflammation and oxidative stress play pivotal roles in the pathogenesis of hepatocellular carcinoma (HCC). We conducted a nested case-control study of 347 HCC cases and 691 matched controls within a prospective cohort of 18 244 Chinese men in Shanghai, China. The concentrations of 8-epi-prostaglandin F2α (8-epi-PGF2α), a biomarker of oxidative stress, and prostaglandin E2 (PGE2) metabolite (PGE-M), a biomarker of the inflammation mediator PGE2, were determined in baseline urine samples using validated mass spectrometry assays. 8-epi-PGF2α levels were significantly higher in HCC cases than control subjects (geometric means 0.92 versus 0.80 pmol/mg creatinine, P < 0.001). The relative risks of developing HCC for the highest relative to the lowest quartile of 8-epi-PGF2α were 2.55 (95% confidence interval = 1.62-4.01, Ptrend < 0.001). This positive 8-epi-PGF2α-HCC risk association was independent of smoking status, alcohol consumption and hepatitis B or liver cirrhosis and was present 10 years before the clinical manifestation of HCC. This study did not find any significant association between urinary PEG-M and HCC risk. This study provides direct evidence in support of the critical role of oxidative stress in the development of HCC regardless of its underlying causes.

Topics: Biomarkers, Tumor; Body Mass Index; Carcinoma, Hepatocellular; Case-Control Studies; China; Cohort Studies; Dinoprost; Dinoprostone; Female; Humans; Inflammation; Liver Neoplasms; Male; Middle Aged; Oxidative Stress; Risk Factors

Oxidative stress has been hypothesized to affect cancer development via various mechanisms, but the evidence from human is limited and inconclusive. 15-F

Topics: Adult; Aged; Biomarkers; Case-Control Studies; China; Dinoprost; Female; Humans; Liver; Liver Neoplasms; Male; Men's Health; Middle Aged; Odds Ratio; Oxidative Stress; Prospective Studies; Women's Health

To evaluate the role of oxidative stress and aflatoxin exposure on risk of hepatocellular carcinoma (HCC), a case-control study nested within a large community-based cohort was conducted in Taiwan. Baseline urine samples, collected from a total of 74 incident HCC cases and 290 matched controls, were used to determine by enzyme-linked immunosorbent assays the level of urinary 15-F(2t)-isoprostane (15-F(2t)-IsoP), a biomarker of lipid peroxidation. These samples had been previously analyzed for urinary aflatoxin B(1) (AFB(1)) metabolites and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). Pearson partial correlation coefficient analysis showed that urinary AFB(1) metabolites and 8-oxodG were significantly associated with the level of urinary 15-F(2t)-IsoP. After adjustment for potential confounding factors in a conditional logistic regression model, urinary 15-F(2t)-IsoP was significantly associated with risk of HCC [above versus below the mean odds ratio (OR) = 2.53, 95% confidence interval (CI) = 1.30-4.93]. Moreover, when compared with subjects in the lowest tertile of 15-F(2t)-IsoP, there was a trend of increasing risk of HCC (P(trend) = 0.0008), with adjusted ORs (95% CIs) of 3.87 (1.32-11.38) and 6.27 (2.17-18.13) for the second and third tertile, respectively. In addition, the combination of urinary 15-F(2t)-IsoP above the mean and chronic hepatitis B virus (HBV) infection resulted in an OR of 19.01 (95% CI = 6.67-54.17) compared with those with low urinary 15-F(2t)-IsoP and without HBV infection. These results suggest that elevated levels of urinary 15-F(2t)-IsoP may be related to increasing level of aflatoxin exposure and are associated with an increased risk of HCC.

Topics: Aflatoxin B1; Biomarkers; Carcinoma, Hepatocellular; Death Certificates; Dinoprost; Hepatitis B; Humans; Interviews as Topic; Lipid Peroxidation; Liver Neoplasms; Mass Screening; Odds Ratio; Reference Values; Registries; Taiwan

Type and composition of polyunsaturated fatty acids (PUFAs) are suspected to play an important role in carcinogenesis. Thus we investigated the effects of n-3, n-6 and n-9 PUFAs on tumour growth, liver metastasis and concentration of prostaglandins (PG) and leukotrienes (LT) in experimental ductal pancreatic adenocarcinoma. Ninety male hamsters were randomised into six groups (Gr.) (n=15). While Gr. 1-3 were healthy control groups, Gr. 4-6 weekly received subcutaneous injections of 10mg N-nitrosobis-2-oxypropylamine (BOP)/kg body weight for 12 weeks in order to induce ductal pancreatic adenocarcinoma. Between week 1 and 16 all animals were fed with a standard diet with a raw fat content of 2.9%. In week 17 Gr. 1-6 were allocated to three types of diets: Gr. 1: standard high fat (=SHF diet, rich in n-6 PUFAs)/Gr. 2: FISH-OIL (rich in n-3 PUFAs)/Gr. 3: SMOF (=mixture of n-3, n-6 and n-9 PUFAs)/Gr. 4: BOP+SHF/Gr. 5: BOP+SMOF/Gr. 6: BOP+FISH-OIL. After 32 weeks all animals were sacrificed and pancreas as well as liver were analysed histologically. Furthermore pancreatic and hepatic concentrations of prostaglandins (PGF1alpha, PGE(2)) and LT were measured. FISH-OIL decreased number of macroscopically visible pancreatic tumours (Gr. 4-6: 54.5% vs. 45.5% vs. 9.1%, P<0.05) as well as incidence of liver metastasis (Gr. 4-6: 90.9% vs. 72.7% vs. 36.4%, P<0.05). Furthermore concentration of PGF(1)(alpha), PGE(2) and LT were significantly increased in pancreatic carcinoma compared to tumour-free tissue. Moreover levels of PGF(1)(alpha) and PGE(2) were higher in liver metastasis than in extrametastatic hepatic tissue. However, in Gr. 6 (FISH-OIL) intrametastatic concentration of LT was significantly lower than in non-metastatic hepatic tissue as well as in Gr. 4 and Gr. 5. FISH-OIL decreased number of visible pancreatic tumours and incidence of histological proven liver metastasis. This effect might be caused by a decrease of intrametastatic concentration of LT compared to extrametastatic hepatic tissue.

Topics: Adenocarcinoma; Animals; Cricetinae; Dietary Fats, Unsaturated; Dinoprost; Dinoprostone; Fatty Acids, Unsaturated; Leukotrienes; Liver; Liver Neoplasms; Male; Pancreas; Pancreatic Neoplasms; Prostaglandins

The effect of vitamin E on gamma-glutamyl transpeptidase-positive foci, with or without phenobarbital, was investigated. Groups of six female Sprague-Dawley rats were initiated with diethylnitrosamine (15 mg/kg) at 24 hours of age. After weaning, they were fed diets with 10% (wt/wt) fish oil; the diets contained 0, 5,000 or 15,000 ppm vitamin E supplementation with or without phenobarbital (500 ppm) for six months. Phenobarbital significantly increased liver weight and liver weight as a percentage of body weight (p < 0.05), suggesting a liver hypertrophic effect of phenobarbital. Phenobarbital significantly decreased hepatic phospholipid arachidonate, eicosapentaenoate, and docosahexaenoate (p < 0.05); this may indicate that phenobarbital stimulates phospholipase A2 activity and results in the increased release of polyunsaturated fatty acids from phospholipids and the decrease of hepatic phospholipid polyunsaturated-to-saturated fat ratio. In rats fed phenobarbital, hepatic vitamin E content was lower than in rats fed no phenobarbital; this suggests that phenobarbital causes oxidative stress or induces enzymes that metabolize the vitamin. Phenobarbital exposure significantly increased hepatic prostaglandin F2 alpha and glutathione S-transferase activity (p < 0.05). Vitamin E did not influence hepatic gamma-glutamyl transpeptidase-positive foci area and number with or without phenobarbital, and phenobarbital showed a strong promoting action on enzyme-altered hepatic foci.

Topics: Animals; Dinoprost; Fatty Acids; Female; Fish Oils; gamma-Glutamyltransferase; Glutathione Transferase; Lipid Peroxidation; Liver; Liver Neoplasms; Organ Size; Phenobarbital; Phospholipids; Pregnancy; Rats; Rats, Sprague-Dawley; Vitamin E

In order to study the mechanism of cancer metastasis, AH100B cells, an ascitic hepatoma cell line, were transplanted into the small intestine of male Donryu rats. Each metastatic nodule in the liver was collected with the respective intestinal lesion. Each sample thus obtained was injected into the peritoneal cavity of male Donryu rats to make free cancer cells. Then, the cancer cells, having an intact cell surface, of the metastatic and primary intestinal lesion were collected respectively. After washing in Dolbecco's PBS (Ca2+ and Mg(2+)-free, pH 7.2), the definite numbers of cancer cells of the metastatic and primary intestinal lesion were incubated in the PBS containing [1-14C]-AA at 25 degrees C for 30 min, respectively. AA metabolites formed during the incubation period were extracted and subjected to TLC, followed by autoradiography. Each radioactive part was scraped off the plate and measured for its radioactivity. The pattern of the ability to synthesize PGs was different between the cancer cells which metastasized to the liver and those of the primary lesion, that is, percentage values of PGE2 and PGF2 alpha were higher (p < 0.01) in the cancer cells which metastasized to liver as compared with those of the primary intestinal lesion. These results suggest that PGs produced by hepatic metastatic cancer cells might play an important role in cancer metastasis.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Carcinoma, Hepatocellular; Cell Line; Dinoprost; Dinoprostone; Intestinal Neoplasms; Liver Neoplasms; Male; Prostaglandin D2; Prostaglandins; Rats; Rats, Inbred Strains; Thromboxane B2; Tumor Cells, Cultured