6-ketoprostaglandin-f1-alpha and Carcinoma--Squamous-Cell

Our previous study showed that aspirin induced apoptosis of esophageal cancer cells in vitro by inhibiting the pathway of NF-kappaB downstream regulation of cyclooxygenase-2. The purpose of this study was to determine if similar changes occurred in vivo in the tumors of patients with SCC of the esophagus who were given a preferential COX-2 inhibitor, meloxicam. Fifty-three patients who had an esophagectomy for SCC were allocated randomly to either a Treatment group (n = 25) or a control group (n = 28). Patients in the Treatment group were given 7.5 mg/day of meloxicam, for between 10 and 14 days before surgery. Patients in the control group did not take any type of NSAID during this time interval. Samples of the tumor taken from the resected specimens were collected. Proliferation and apoptosis were measured by flow cytometry. The concentration of 6-keto-prostaglandin F(1)alpha in cancer tissue was determined by radio-immuno-assay. Expression of COX-2 mRNA was measured with RT-PCR and COX-2 protein levels with Western blot analysis. Nuclear NF-kappaB and cytoplasmic I kappaB protein levels were determined by electrophoretic mobility shift assay and Western blot, respectively. There were significantly more apoptotic cells in the tumors of patients who were using meloxicam. It also decreased the levels of COX-2 mRNA, COX-2 protein and nuclear NF-kappaB protein and increased the cytoplasmic I kappaB protein in the cancer. We conclude that meloxicam induces apoptosis in SCC of the esophagus in vivo by inhibiting the pathway of NF-kappaB downstream regulation of COX-2.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Blotting, Western; Carcinoma, Squamous Cell; Cell Proliferation; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Electrophoretic Mobility Shift Assay; Esophageal Neoplasms; Esophagectomy; Female; Flow Cytometry; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; I-kappa B Proteins; Male; Meloxicam; Middle Aged; NF-kappa B; NF-KappaB Inhibitor alpha; Radioimmunoassay; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Thiazines; Thiazoles

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

In order to evaluate the possible role of prostaglandins (PG) in invasion and metastasis of malignant cells in larynx carcinoma, arachidonic acid (AA) metabolite production by tumor tissue, peritumor tissue and node metastasis was investigated in comparison to that by healthy mucosa and unaffected lymph nodes. The study was performed by evaluating PGE2, 6ketoPGF1 alpha and thromboxane B2 (TXB2) production by radioimmunoassay in specimens from eight patients who underwent surgical treatment. The highest rate of AA metabolism was observed in peritumor tissue. PGE2 was the main metabolite produced in all tissues and its levels were significantly higher than those of 6ketoPGF1 alpha and TXB2 (p < 0.05). 6ketoPGF1 alpha production was higher (p < 0.01) than that of TXB2 and did not significantly change among the different tissues. TXB2 production was significantly increased (p < 0.05) by peritumor tissue as compared to healthy mucosa. The ratio between TXB2 and 6ketoPGF1 alpha production was found to be almost twofold higher in tumor tissue, peritumor tissue, metastatic and non-metastatic lymph nodes as compared to control tissue. The lowest AA metabolism was found in affected lymph nodes. These findings demonstrate a different AA metabolism at primary tumor sites in comparison to healthy mucosa suggesting a prometastatic role of TXB2 and supporting the hypothesis of the occurrence of an imbalance between TXB2 and 6ketoPGF1 alpha production in favouring metastatic spread.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Carcinoma, Squamous Cell; Dinoprostone; Epoprostenol; Humans; Laryngeal Neoplasms; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Radioimmunoassay; Thromboxane A2

Prostaglandin (PG) E2, 6ketoPGF1 alpha and Thromboxane B2 (TxB2) production by the tumor, peritumor and control tissue were investigated in specimens from patients (n = 11) with squamous cell carcinoma of the larynx, in relation to the extension and infiltration of the neoplasm and to the presence of inflammation, fibrosis and necrosis. In all specimens detectable amounts of 6ketoPGF1+ and TxB2 were found, but the predominant metabolite was PGE2. No differences in the levels of TxB2 and 6ketoPGF1 alpha were observed, but the only patient with lymphnodal involvement showed the lowest levels of 6ketoPGF1 alpha both in tumor and peritumor tissue. Higher amounts (p less than 0.05) of PGE2 were synthesized by peritumor tissues in comparison to control mucosa and tumor tissue independently of the occurrence of reactive infiltration. PGs synthesis did not correlate with inflammation, fibrosis, necrosis or staging of the neoplasm. However the two cases in stage T4 showed PGE2 generation at the highest levels both in neoplastic and perineoplastic tissue. These findings indicate that in squamous cell carcinoma of the larynx an increased production of PGE2 occurs, stemming not only from inflammatory cells but at least in part from neoplastic cells. This suggests that the study of arachidonic acid metabolism may contribute to characterization of the primary cancer and lead to better understanding of the mechanisms of tumor growth and diffusion.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Aged, 80 and over; Arachidonic Acids; Carcinoma, Squamous Cell; Dinoprostone; Female; Fibrosis; Humans; Laryngeal Neoplasms; Laryngitis; Larynx; Male; Middle Aged; Necrosis; Prostaglandins; Thromboxane B2

Circulating prostaglandins, including thromboxane A2 and prostacyclin, have been implicated as possible facilitative agents in the growth and dissemination of squamous cell carcinomas of the head and neck. The purpose of this study was to evaluate the relationship of plasma concentrations of these compounds to tumor stage and the effect of surgical resection on plasma prostaglandin levels. Blood samples were obtained from 40 patients with head and neck cancer. Ten treated patients were clinically disease-free (NED), and 30 patients with active disease were previously untreated at the time of this study. Plasma concentrations of thromboxane A2 and prostacyclin were measured by radioimmunoassay of their stable metabolites thromboxane B2 (TxB) and prostaglandin 6-keto-F1 (PGI). Platelet aggregation was performed with normal donor platelets (PRP) and normal control or patient plasma (PPP). TxB and TxB/PGI ratios were increased in T1N0M0 patients, compared with NED and with T4N0M0 primary lesions versus all other groups. With lymphatic and hematogenous metastases, TxB and TxB/PGI ratios fell to NED levels. ADP-induced platelet aggregation was significantly increased in head and neck cancer patients, compared with normal controls, and with T4N0M0 lesions, compared with NED. There were no significant differences in PGI levels. TxB, PGI, TxB/PGI, and platelet aggregometry did not change significantly with curative surgery. TxB and TxB/PGI interactions are involved in head and neck cancer. Changes in TxB and TxB/PGI may be related to increased platelet aggregation.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Epoprostenol; Female; Head and Neck Neoplasms; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Platelet Aggregation; Thromboxane A2; Thromboxane B2

In 56 patients with histologically verified maxillo-facial cancer the plasma 6-oxo-PGF1-alpha was determined prior surgery using a specific RIA and the double antibody technique. Furthermore, the half-life of synthetic PGI2 has been assessed via the disappearance curve of biological activity on platelet aggregation inhibition. Part of the patients has been monitored by the same test different time intervals after radical surgery. Normal values of 6-oxo-PGF1-alpha amount below 1 pg/ml. - normal half-life of PGI2 in plasma in-vitro about 10 minutes. Prior surgery a significantly increased 6-oxo-PGF1-alpha can be seen, whereas the PGI2 half-life is unaffected. In patients without local or general recurrence normal 6-oxo-PGF1-alpha levels are monitored. No change occurred in the half-life of PGI2. These findings underline the additive value of 6-oxo-PGF1-alpha as a tumor marker. The data do not support the view presented earlier, that a change in plasmatic PGI2 half-life might favour the onset and the extent of recurrence at least in patients suffering on maxillo-facial cancer.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Epoprostenol; Female; Half-Life; Humans; Male; Maxillary Neoplasms; Middle Aged; Mouth Neoplasms; Reference Values

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Bone Resorption; Carcinoma, Squamous Cell; Dinoprost; Dinoprostone; Humans; In Vitro Techniques; Interleukin-1; Mice; Odontogenic Cysts; Prostaglandins; Prostaglandins E; Prostaglandins F; Sarcoma, Ewing

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