6-ketoprostaglandin-f1-alpha and Lung-Neoplasms

To explore the role of hypercoagulation in the metastasis of carcinoma.. The effect of Tetramethylpyrazine (TTMP) on platelet functions among the 25 advanced cases of lung carcinoma, and 26 matched control subjects were investigated in the study. Their ages varied from 31-86 years (mean 58.2) in lung carcinoma group (13 male, 12 female) and 36 to 61 (mean 52.9) in the control group (16 male, 10 female). The pathologic types were as follows: 7 cases of squamous cell cancer, 12 adenocarcinoma, 2 small cell carcinoma and 4 undistinguished type. The TNM stage revealed 14 cases in stage IIIa, 3 in stage IIIb and 8 in stage IV. The site of metastasis included mediastinal lymph node, pleura, supraclavicular lymph node, brain, spine, costa, skin and pericardium. The levels of plasma TXB2, 6-keto-PGF1 alpha, VIII:C, vWF, AT-III:a, AT-III:Ag, Fg and blood PAdT, PAgT were measured before and after the intravenous infusion of 80 mg TTMP in patients with lung carcinoma.. The levels of TXB2, 6-keto-PGF1 alpha, VIII:C, vWF and Fg in lung carcinoma group were significantly elevated, while the levels of PAdT was greatly decreased, compared with the control group, no significant differences in levels of PAgT, AT-III:a and AT-III:Ag were found between the two groups. After the infusion of TTMP the levels of PAdT, PagT, VIII:C, dWF and Fg were decreased significantly, while TXB2, 6-keto-PGF1 alpha, AT-III:a and AT-III:Ag remained unchanged.. TTMP inhibits the adhesion and aggregatory functions of blood platelet and the activity of coagulation factors. It might be one of the mechanisms of TTMP's antimetastasis of lung carcinoma.

Topics: 6-Ketoprostaglandin F1 alpha; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Humans; Lung Neoplasms; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Pyrazines; Thromboxane B2

Epidemiological investigations suggest that chronic lung inflammation increases lung cancer risk. Pharmacologic and genetic evidence in mouse models indicates that lipid mediators released during pulmonary inflammation enhance lung tumor formation. Cytosolic phospholipase A2 (cPLA2) catalyzes arachidonic acid (AA) release from membrane phospholipids. AA can then lead to the synthesis of several classes of lipid mediators, including prostaglandin (PG) biosynthesis through the cyclooxygenase (COX) pathway. We investigated a role for cPLA2 in mouse lung tumorigenesis by using mice genetically deficient in cPLA2. After multiple urethane injections into cPLA2 null mice and wild-type littermates, the number of lung tumors was determined. cPLA2 null mice developed 43% fewer tumors (from 16 +/- 2 to 9 +/- 2 tumors/mouse; P < 0.05) than wild-type littermates. cPLA2, COX-1, COX-2 and microsomal prostaglandin E2 synthase (mPGES), examined by immunohistochemistry, are present in alveolar and bronchiolar epithelia and in alveolar macrophages in lungs from naive mice and tumor-bearing mice. Tumors express higher levels of each of these four enzymes than control lungs, as determined by immunoblotting. No differences were detected in the contents of COX-1, COX-2 and mPGES between wild-type and cPLA2 null mice. Although the steady-state levels of prostaglandin E2 and prostaglandin I2 in lung tissue extracts prepared from wild-type or cPLA2 (-/-) mice were not significantly different, both prostaglandins markedly increased in tumors from wild-type mice, an increase that was significantly blunted in tumors from cPLA2 (-/-) mice. These results demonstrate a role for cPLA2 in mouse lung tumorigenesis that may be mediated by decreased prostaglandin synthesis.

Topics: 6-Ketoprostaglandin F1 alpha; Alleles; Animals; Arachidonic Acid; Cyclooxygenase 1; Cyclooxygenase 2; Cytosol; Dinoprostone; Immunoblotting; Immunoenzyme Techniques; Immunohistochemistry; Inflammation; Isoenzymes; Lipid Metabolism; Lung; Lung Neoplasms; Macrophages; Macrophages, Alveolar; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microsomes; Phospholipases A; Phospholipases A2; Prostaglandin-Endoperoxide Synthases; Prostaglandins

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Carcinoma, Non-Small-Cell Lung; Cytochrome P-450 Enzyme System; Dinoprostone; Epoprostenol; Humans; Intramolecular Oxidoreductases; Lung Neoplasms; Neoplasm Proteins

An inflammatory response accompanies the reversible pneumotoxicity caused by butylated hydroxytoluene (BHT) administration to mice. Lung tumor formation is promoted by BHT administration following an initiating agent in BALB/cByJ mice, but not in CXB4 mice. To assess the contribution of inflammation to this differential susceptibility, we quantitatively characterized inflammation after one 150 mg/kg body weight, followed by three weekly 200 mg/kg ip injections of BHT into male mice of both strains. This examination included inflammatory cell infiltrate and protein contents in bronchoalveolar lavage (BAL) fluid, cyclooxygenase (COX)-1 and COX-2 expression in lung extracts, and PGE(2) and PGI(2) production by isolated bronchiolar Clara cells. BAL macrophage and lymphocyte numbers increased in BALB mice (P<0.0007 and 0.02, respectively), as did BAL protein content (P<0.05), COX-1 and COX-2 expression (P<0.05 for each), and PGI(2) production (P<0.05); conversely, these indices were not perturbed by BHT in CXB4 mice. BALB mice fed aspirin (400 mg/kg of chow) for two weeks prior to BHT treatment had reduced inflammatory cell infiltration. Our results support a hypothesis that resistance to BHT-induced inflammation in CXB4 mice accounts, at least in part, for the lack of effect of BHT on lung tumor multiplicity in this strain.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Aspirin; Bronchoalveolar Lavage Fluid; Butylated Hydroxytoluene; Carcinogens; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprostone; Immunoblotting; Immunoenzyme Techniques; Immunohistochemistry; Isoenzymes; Lung; Lung Neoplasms; Male; Membrane Proteins; Mice; Mice, Inbred BALB C; Pneumonia; Prostaglandin-Endoperoxide Synthases; Statistics, Nonparametric

108 cases of advanced non-small cell lung cancer (NSCLC) with Qi deficiency and blood stasis syndrome (QDBS) had been studied in this paper. It has been found that: (1) QDBS existed commonly in 60.2% of NSCLC patients. (2) QDBS patients had lowered immune function and blood hypercoagulating function, as compared with healthy persons. (3) The abnormal change of immunological indexes such as TC subgroup. TXB2, 6-keto-PGF1 alpha, fibrinogen and plasmin activity as well as hemorheological indices are important pathophysiological manifestation of QDBS. Thus, the principle of supplementing Qi and activating blood circulation combined with reducing phlegm and resolving masses should be emphasized in future research.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Carcinoma, Non-Small-Cell Lung; Diagnosis, Differential; Female; Fibrinogen; Humans; Immunity, Cellular; Lung Neoplasms; Male; Medicine, Chinese Traditional; Middle Aged; T-Lymphocyte Subsets; Thromboxane B2

Polyactin A (PAA) is a home-made immunomodulator, isolated from submerged culture broths of alpha-hemolytic streptococci. The effect of PAA on the metastasis of B16-F10 melanoma cells in the syngeneic C57BL/6J mice and its antimetastatic mechanism have been studied. The results showed that: PAA inhibited the experimental pulmonary metastasis nodules at a dose of 100 mg.kg-1.d-1 for 18 d. The number of pulmonary metastasis nodules were significantly decreased from 137 to 95 as compared with those in the control; The plasma concentration of TXB2 in B16 bearing mice was higher than that in normal mice. After treatment with PAA, a decreased content of TXB2 and 6-keto-PGF1 alpha was found without change of the ratio TXB2 to 6-keto-PGF1 alpha. The cellular immunities were evidently decreased in the B16 bearing mice. The restoration of lymphocyte proliferation response and augmentation of the NK cell activity of the splenocytes were found in vivo in normal mice and B16 bearing mice after treated with PAA. PAA was also shown to antagonize the suppressing effect of cyclophosphamide on murine NK cells; PAA at the concentration of 10-5000 micrograms.ml-1 was found to inhibit the biosynthesis of DNA, RNA and protein in the B16-F10 melanoma cells to different degrees and the effect was dose-dependent. It is evident that PAA is effective in preventing the pulmonary metastasis of B16-F10 melanoma and the antimetastatic action may be related not only to promoting the effect the antitumor immunities, but also to inhibiting the growth of B16-F10 melanoma cells.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Female; Glycopeptides; Immunologic Factors; Killer Cells, Natural; Lung Neoplasms; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Thromboxane B2

The sensitivity of cancer patient macrophages from different anatomical sites to arachidonic acid metabolism was investigated in tumor cell cytotoxicity assays. Alveolar macrophages and peripheral blood monocytes from 13 non-small cell lung cancer patients, peritoneal macrophages and peripheral blood monocytes from 13 ovarian cancer patients, and comparable macrophages from control patients with nonmalignant lung or gynecological diseases were tested. Inhibitors of either the cyclooxygenase pathway or the lipoxygenase pathway together with specific metabolites of each pathway were used to evaluate how these different macrophage populations are regulated by eicosanoids. In addition, metabolic studies were performed to compare directly the arachidonic acid metabolism of macrophages obtained from these different anatomical locations. The results demonstrate that the peripheral blood monocytes from lung cancer and ovarian cancer patients and the peritoneal macrophages from ovarian cancer patients are sensitive to cyclooxygenase inhibition; this was not seen with comparable macrophages from the relevant control patients. Sensitivity to modulation by cyclooxygenase inhibition correlated with increased cyclooxygenase metabolism and with the capacity of prostaglandin to mediate suppression of tumoricidal function in these populations of cancer patient macrophages. In contrast, alveolar macrophages from cancer patients were not sensitive to either cyclooxygenase inhibition or to prostaglandin-mediated suppression. No such differential influences were revealed for the lipoxygenase pathway of arachidonic acid metabolism in any macrophage population tested. Thus, eicosanoids, particularly those of the cyclooxygenase pathway, can be a critical immunoregulatory feature of certain tumor microenvironments.

Topics: 6-Ketoprostaglandin F1 alpha; Arachidonic Acid; Carcinoma, Non-Small-Cell Lung; Dinoprostone; Humans; Indomethacin; Lung Neoplasms; Macrophages; Masoprocol; Monocytes; SRS-A

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Blood Platelets; Female; Humans; Lipid Peroxides; Lung Neoplasms; Male; Middle Aged; Neoplastic Cells, Circulating; Thromboxane B2

Plasma levels of three stable prostaglandin (PG) metabolites were measured in 29 patients with lung cancer. The mean level of 6-keto-PGF1 alpha, the hydrolysis product of prostacyclin, was significantly elevated in cancer patients compared to a control group with non-malignant respiratory disorders, although an overlap in values between the groups was seen. Levels correlated inversely with survival and showed a significant fall in 14 patients with tumour regression. The mean level of 11-deoxy-3,14-dihydro-15-keto-11,16-cyclo-prostaglandin E2 was also significantly elevated in cancer patients, but did not correlate with tumour response. 13,14-Dihydro-15-keto prostaglandin F2 alpha levels did not differ in lung cancer patients and controls. Contrary to previous reports we could not support a role for the metabolites of PGE2 and PGF2 alpha as tumour markers in lung cancer but plasma 6-keto-PGF1 alpha should be further evaluated in this regard.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Biomarkers, Tumor; Dinoprost; Dinoprostone; Female; Humans; Lung Neoplasms; Male; Middle Aged; Prostaglandins; Prostaglandins E; Prostaglandins F

Plasma calcitonin and 6-oxo-Prostaglandin-F1 alpha (6-oxo-PGF1 alpha), one of the stable metabolite of prostacyclin, were determined in patients with malignant and non-malignant diseases of the lung. 11 out of 14 patients with small cell carcinoma and only 3 out of 17 patients with other histological types of lung cancer had abnormally elevated plasma calcitonin levels. 6-oxo-PGF1 alpha levels were significantly higher in patients with different types of lung cancer, compared to a control group with non-malignant lung disease. Combining the results of calcitonin and 6-oxo-PGF1 alpha measurements led to improved specificity and efficiency for the correct differentiation between small cell and non-small cell carcinoma of the lung; the predictive value for the diagnosis of small cell carcinoma approached 90%.

Topics: 6-Ketoprostaglandin F1 alpha; Calcitonin; Carcinoma, Small Cell; Cell Transformation, Neoplastic; Female; Humans; Lung Neoplasms; Male

Topics: 6-Ketoprostaglandin F1 alpha; Adenocarcinoma; Adult; Aged; Carcinoma, Squamous Cell; Epoprostenol; Female; Humans; Lung Neoplasms; Male; Middle Aged; Platelet Aggregation; Pneumonectomy; Thromboxane B2; Thromboxanes