6-ketoprostaglandin-f1-alpha and Breast-Neoplasms

Several studies have shown an overexpression of cyclooxygenase-2 (COX-2) and elevated levels of prostacyclin (PGI(2)) and thromboxane (TXA(2)) in colon cancer. In this report, we determined the distribution of inducible form of nitric oxide synthase (iNOS), PGI(2), and TXA(2) in cancerous and adjoining areas of specimens from human colon and breast cancer obtained during surgery. Additionally, we investigated differences in expression and histological localization of COX-2 in colon and breast cancer.. Specimens were obtained during surgery, one centrally located, the second from an adjacent, cancer-free area. Activity of iNOS was determined, using the conversion of L-[(14)C]arginine to L-[(14)C]citrulline. PGI(2) and TXA(2) were measured as their stable metabolites, using enzyme immunoassay. A standard immunoperoxidase method was used for immunohistochemical expression of COX-2.. Significant differences in iNOS, PGI(2), and TXA(2) expressions between colon and breast cancer were noted, with an enhanced expression of COX-2 in colon cancer, including the cancerous, adjoining, and stromatous fields.. Increased expression of iNOS and production of prostanoids in colon cancer parallels the increase in COX-2, confirming the importance of this enzyme in colon cancer. The overexpression of COX-2, prostanoids, and nitric oxide in areas adjoining the tumor indicates increased metastatic potential for neoplastic cells in this area. Inflammatory changes in the tissue adjoining the cancer may play a role. COX-2 may result in the formation of new blood vessels and the spread of cancer.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Colonic Neoplasms; Cyclooxygenase 2; Female; Humans; Isoenzymes; Male; Membrane Proteins; Middle Aged; Neovascularization, Pathologic; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Thromboxane B2

In this prospective follow-up study the prognostic value of the tumor prostacyclin/thromboxane ratio in human breast carcinoma was investigated. The stable degradation products of prostacyclin and thromboxane (6-keto-PGF1 alpha and TXB2, respectively), were measured by radio-immunoassay in homogenized primary tumours from 29 patients with primary non-metastatic breast cancer. The median follow-up was 43 months (range 24-58 months). Patients with recurrent disease or patients who died of breast cancer had a significantly higher 6-keto-PGF1 alpha/TXB2 ratio than the disease-free survivors (p = 0.018 and p = 0.047, respectively). There was no significant difference in the 6-keto-PGF1 alpha and TXB2 levels. These data indicate that the prostacyclin/thromboxane balance in the tumour might be a prognostic factor in breast cancer. Prostanoid may contribute to metastasis in breast cancer, but the problem is complex because the different prostaglandins have numerous actions that may produce both undesirable and desirable effects.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Epoprostenol; Humans; Middle Aged; Prognosis; Prospective Studies; Radioimmunoassay; Thromboxanes

Platelets may promote the development of metastasis, and tumor cells that aggregate platelets are believed to be more malignant. We studied three different human mammary carcinoma cell lines, which had different interactions with human platelet-rich plasma (PRP). The MCF-7 and the T47-D cell lines induced an adenosine diphosphate (ADP)-mediated platelet aggregation. The third cell line, MDA-MB 231 did not induce any platelet aggregation. On the contrary, this cell line inhibited ADP- and arachidonic acid-induced platelet aggregation. This inhibiting activity is mainly adenosine-mediated. The mechanism by which platelets may contribute to the dissemination of cancer could be related to platelet growth factors. MCF-7 and T47-D cell lines induced a release of platelet-derived growth factor (PDGF). On the contrary, the MDA-MB 231 cell line did not induce any platelet release. The role of these platelet growth factors in tumor cell growth is discussed.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine Diphosphate; Alprostadil; Apyrase; Arachidonic Acid; Arachidonic Acids; Blood Platelets; Breast Neoplasms; Carcinoma; Cell Line; Creatine Kinase; Humans; Neoplasm Metastasis; Platelet Aggregation; Thromboxane B2

To study the production and significance of prostacyclin (PGI2) and thromboxane A2 (TxA2) in breast cancer, tissue fragments of breast cancer (n=23) and mastopathy (n=10) were superfused in vitro and the release of 6-keto-PGF1 alpha (a metabolite of PG12) and TxB2 (a metabolite of TxA2) measured by radioimmunoassay. Breast cancer formed more 6-keto-PGF1 alpha (4.5 +/- 0.9 ng min-1 g-1 of tissue dry weight, mean +/- s.e.) and TxB2 (2.5 +/- 0.6 ng min-1 g-1) (P less than 0.01) than did mastopathic breast (1.4 +/- 0.5 and 0.4 +/- 0.1 ng min-1 g-1, respectively). These productions were similar in steroid receptor positive and negative tumours. Breast cancer metastasized in 15 patients during the follow-up time of 3.7 +/- 0.7 years, but the initial prostanoid productions in these patients were not different from those in nonmetastatic patients. Two patients died from metastases, but their initial mammary production of prostanoids was not profoundly different from those in the survivors. In 8 patients (4 with steroid receptor positive and 4 with negative tumour), the cancer tissue was superfused in the presence or absence of medroxyprogesterone acetate (100-5000 ng ml-1), which is commonly used for treatment of breast cancer. This hormone had no effect on mammary PGI2 and TxA2 production. We thus conclude that the PGI2 and TxA2 productions are increased in mammary cancer but that this may not be of primary significance for metastastic spread.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Antineoplastic Agents; Breast Diseases; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Epoprostenol; Female; Humans; In Vitro Techniques; Medroxyprogesterone; Medroxyprogesterone Acetate; Middle Aged; Receptors, Steroid; Thromboxane A2; Thromboxane B2; Thromboxanes

Peripheral plasma concentrations of 6-keto-PGF1 alpha and TXB2 were measured in patients with benign and malignant tumours of the breast, in patients with non-gynecological diseases, and in healthy female controls. The values were significantly higher in female patients with malignant tumours of the breast than in healthy controls (146 +/- 28 vs 13 +/- 2.5 pg/ml for 6-keto-PGF1 alpha p less than 0.01 and 78 +/- 17 vs 11 +/- 2 pg/ml for TXB2, p less than 0.01). Benign tumours of the breast were also associated with significantly raised plasma levels of 6-keto-PGF1 alpha and TXB2 compared to normal controls (52 +/- 5 vs 13 +/- 2.5 pg/ml for 6-keto-PGF1 alpha, p less than 0.01 and 26 +/- 5 vs 11 +/- 2 pg/ml for TXB2, p less than 0.05). The high levels of 6-keto-PGF1 alpha and TXB2 were not found to be correlated with clinical and histopathological data. The surgical removal of the primary tumour has apparently no effect on the plasma concentrations of 6-keto-PGF1 alpha and TXB2 over a follow-up period of 9 days after operation. The lack of alterations in the ratio of TXB2:6-keto-PGF1 alpha in the cancer patients and other subjects studied before and after surgery is indicative of the regulatory power of metabolic systems to preserve the homeostatic balance.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Breast Neoplasms; Female; Humans; Menopause; Middle Aged; Thromboxane B2; Thromboxanes

Topics: 6-Ketoprostaglandin F1 alpha; Breast Neoplasms; Dinoprostone; Female; Gas Chromatography-Mass Spectrometry; Humans; Lymphatic Metastasis; Neoplasm Metastasis; Prognosis; Prostaglandins; Prostaglandins E

Tissue prostaglandin (PG) content and production by human breast cancers were measured in 24 human mammary carcinoma specimens. The 5 compounds studied were PGE1, PGE2, PGF2 alpha, 6-keto-PGF1 alpha, and TXB2. The tissue content of all 5 compounds was higher in neoplastic tissue in comparison with the paired noncancerous breast tissue. However, microsomal PG synthetase activity in vitro in noncancerous and neoplastic breast tissue was comparable. Increased thromboxane formation was associated with three clinical variables--tumour size, axillary lymph node metastases and distant metastasis. A lesion negative for either oestrogen or progesterone receptor content tended to produce more TXB2 but lower PGE2 and 6-keto-PGF1 alpha. Results obtained in this pilot study may provide clues as to what direction future larger studies could take in the search for reliable prognostic indicators for breast cancer.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Alprostadil; Breast Neoplasms; Dinoprost; Dinoprostone; Humans; Lymphatic Metastasis; Microsomes; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Prostaglandins E; Prostaglandins F; Receptors, Estrogen; Receptors, Progesterone; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Aminoglutethimide; Breast Neoplasms; Dinoprost; Female; Humans; Menopause; Middle Aged; Prostaglandins F