6-ketoprostaglandin-f1-alpha and Liver-Neoplasms

To explore the protective effect and mechanism of ligustrazine (LGT) and propofol (PRO) on peri-operational liver ischemia-reperfusion injury (HIRI).. Thirty-six patients scheduled for hepatic surgery were randomly divided into the control group, the LGT group, the PRO group and the LGT + PRO group, 9 patients in each group. Changes of superoxide dismutase (SOD), lipid peroxide (LPO), ratio of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha), alanine aminotransferase (ALT) activity, and the ultrastructure of liver tissue were dynamically observed.. Compared with the control group, SOD activity was significantly higher, LPO concentration, TXB2/6-keto-PGF1alpha ratio and ALT value were significantly lower (P < 0.05 and P < 0.01) in the LGT group, the PRO group and the LGT + PRO group during HIRI, with the abnormal changes of hepatic ultrastructure 25 min after reperfusion significantly alleviated in the three treated group.. Combination of ligustrazine and propofol shows protective effect on liver by decreasing oxygen free radical level, reducing lipid peroxidation and adjusting TXA2/PGI2 imbalance after hepatic ischemia-reperfusion in patients undergoing hepatic cancer surgery.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Drug Therapy, Combination; Female; Humans; Lipid Peroxides; Liver; Liver Neoplasms; Male; Middle Aged; Propofol; Pyrazines; Reperfusion Injury; Superoxide Dismutase

Cyclooxygenase 2 (COX-2) has been suggested to be associated with liver carcinogenesis. Several reports have shown that NSAIDs inhibit the growth of hepatocellular carcinoma cell lines. There is little evidence of how COX-2 inhibitors regulate the proliferation of hepatocellular carcinoma cells or the mechanism involved. In our study, we investigated the growth-inhibitory mechanism of a selective COX-2 inhibitor, NS-398, in 4 hepatocellular carcinoma cell lines by studying cell growth, COX-2 and proliferating cell nuclear antigen (PCNA) expression, cell cycle distribution and the evidence of apoptosis. NS-398 inhibited the growth of all 4 cell lines in a time- and dose-dependent manner and the inhibitory effects were independent of the level of COX-2 protein expression. PCNA expression was downregulated by NS-398 in a dose-independent manner. NS-398 caused cell cycle arrest in the S phase with a reduction in cell numbers and cell accumulation in the G0/G1 phase, for all 4 cell lines. No evidence of apoptosis was observed in our present study. Our findings suggest that a selective COX-2 inhibitor might serve as an effective tool for the chemoprevention and treatment of hepatocellular carcinomas. A reduction in cell number in the S phase may be an important event in cell cycle arrest caused by NS-398 in hepatocellular carcinoma cell lines.

Topics: 6-Ketoprostaglandin F1 alpha; Antineoplastic Agents; Apoptosis; Carcinoma, Hepatocellular; Cell Cycle; Cell Division; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; G1 Phase; Humans; Isoenzymes; Liver Neoplasms; Membrane Proteins; Nitrobenzenes; Proliferating Cell Nuclear Antigen; Prostaglandin-Endoperoxide Synthases; Resting Phase, Cell Cycle; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; S Phase; Sulfonamides; Tumor Cells, Cultured

Arachidonic acid metabolites known to affect platelet function also interfere with tumor growth and metastases. The purpose of this study was to evaluate the anti-metastatic potential of ketoconazole, a thromboxane synthetase and 5-lipoxygenase inhibitor, on hepatic metastasis from a human pancreatic adenocarcinoma in nude mice and its effect on serum prostaglandin levels.. The human pancreatic tumor cells (RWP-2) were injected intrasplenically in nude mice grouped into control, ketoconazole (270 microg), ketoconazole (360 microg), and ketoconazole (540 microg). The agent was administered intraperitoneally 30 min before and every 24 h after the tumor cell inoculation for 8 days. In a separate experiment thromboxane B2 (TxB2), prostaglandin D2 (PGD2), prostaglandin E2 (PGE2) and 6-Keto-F1a (stable prostacyclin derivative) were measured on blood from controls, tumor bearing animals and animals bearing tumors treated with 270 microg of ketoconazole.. Statistically significant differences were observed between the control and three-treatment groups on the reduction of liver tumor nodules (p < 0.001), and in the liver surface areas occupied by tumor (p < 0.001). The TxB2 levels decreased from 150.6 ng/mL in the tumor bearing to 104.8 ng/mL in the ketoconazole treated animals (p < 0.05). PGD2, PGE2 and 6-keto-F1a levels increased to 7.1 ng/mL, 8.3 ng/mL, and 13.6 ng/mL from 3 ng/mL, 5.8 ng/mL, and 0.02 ng/mL respectively (p < 0.001).. These results indicate that ketoconazole significantly reduced hepatic metastases from the human pancreatic carcinoma RWP-2 in the nude mouse model, and inhibited thromboxane B2 formation, potentiating a concomitant redirection of platelet endoperoxide metabolism into PGD2, PGE2, and 6-keto-F1a. It is hypothesized that the changes in the arachidonic acid metabolism mediate the ameliorating effect of ketoconazole on experimental hepatic metastasis.

Topics: 6-Ketoprostaglandin F1 alpha; Adenocarcinoma; Animals; Antineoplastic Agents; Dinoprostone; Humans; Injections, Intraperitoneal; Ketoconazole; Liver Neoplasms; Mice; Mice, Nude; Neoplasm Metastasis; Pancreatic Neoplasms; Prostaglandin Antagonists; Prostaglandin D2; Prostaglandins; Thromboxane B2; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Eicosanoid production and the compositions of precursor fatty acids were determined in human cancerous and reference liver tissues. Seventeen hepatectomized cases (12 cases of hepatocellular carcinoma (HCC) and 5 cases of metastatic liver cancer) were evaluated. The cancerous tissues and the noncancerous reference tissues were separated, lipids were extracted, and the fatty acids were determined as methyl esters by gas chromatography. Prostanoids (6-keto PGF1 alpha and TXB2) were measured by radioimmunoassay. In HCC, the levels of alpha-linolenic acid (omega-3) (0.41 +/- 0.38 x 100 micrograms/g) and docosahexaenoic acid (10.41 +/- 4.96 x 100 micrograms/g) in liver cancer tissue were significantly less than those in the reference tissues. In HCC, the levels of TXB2 reference (1.86 +/- 2.77 pg/mg wet weight) and 6-keto PGF1 alpha were 10-fold higher than those in reference tissues. We speculate that in HCC higher prostanoid levels in the liver are related in part to tumor metabolism.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; alpha-Linolenic Acid; Carcinoma, Hepatocellular; Docosahexaenoic Acids; Eicosanoids; Fatty Acids; Female; Hepatectomy; Humans; Linolenic Acids; Liver Neoplasms; Male; Middle Aged; Thromboxane B2

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

We measured blood platelet count and plasma beta-thromboglobulin concentration in 67 patients with acute or chronic liver diseases. Plasma TXB2 and 6-keto-PGF1a concentration were also measured in these patients. The results showed that blood platelet count of less than 100 x 10(9)/L was found in 14% of the patients with acute hepatitis, 23% with chronic hepatitis, 67% with hepatic cirrhosis but without splenectomy and 40% with primary liver carcinoma. Platelet count is lowest in patients with hepatic cirrhosis without splenectomy but normal in patients with hepatic cirrhosis after splenectomy. Plasma beta-TG concentration increased in patients with acute or chronic liver diseases. A negative correlation was found between beta-TG concentration and platelet count in chronic liver diseases. It is suggested that platelet is in activated state in vivo and this may be one of the important reasons for both decrease of platelet count and impairment of platelet function. Plasma TXB2 concentration increased in chronic liver diseases, while plasma 6-keto-PGF1a concentration decreased. The balance between TXA2 and PGI2 is upset; this may be an important mechanism for activation of platelets in vivo.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; beta-Thromboglobulin; Female; Hepatitis, Viral, Human; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Platelet Count; Thromboxane B2

Following hepatectomy, arterial concentrations of thromboxane B2(TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), which are stable metabolites of thromboxane A2(TXA2) and prostaglandin I2(PGI2), were measured by radioimmunoassay in 17 cirrhotic and 9 non-cirrhotic patients to assess the role of TXB2 and PGI2 in patients with liver dysfunction during hepatectomy. In both cirrhotic and non-cirrhotic patients, arterial TXB2 and 6-keto-PGF1 alpha levels significantly increased during hepatectomy and decreased to preoperative levels at the 1st postoperative day (1-POD). The TXB2/6-keto-PGF1 alpha ratio significantly decreased during hepatectomy and at 1-POD. There were no significant differences in changes of TXB2 and PGI2 levels between cirrhotic and non-cirrhotic patients. In cirrhotic patients with poor hepatic reserve, whose ICG K values were less than 0.08, arterial 6-keto-PGF1 alpha levels were significantly higher and the ratio were significantly lower than in cirrhotic patients with good hepatic reserve and non-cirrhotic patients before and after operation. Based on these results, it is concluded that the TXA2/PGI2 ratio becomes low after hepatectomy and the ratio is lower in cirrhotic patients with poor hepatic reserve.

Topics: 6-Ketoprostaglandin F1 alpha; Female; Hepatectomy; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Postoperative Period; Thromboxane B2