dinoprost and Carcinoma

The objective of this study, in addition to confirming that therapy with 131I causes oxidative stress, was to evaluate the effect of supplementation with vitamins C and E and selenium on this phenomenon by measuring plasma 8-epi-PGF2a, a marker of lipid peroxidation.. Forty patients with thyroid cancer submitted to thyroidectomy, who received 3.7 GBq 131I after levothyroxine withdrawal, were selected; 20 patients did not receive (control group) and 20 patients received (intervention group) daily supplementation consisting of 2000 mg vitamin C, 1000 mg vitamin E and 400 µg selenium for 21 days before 131I. Plasma 8-epi-PGF2a was measured immediately before and 2 and 7 days after 131I.. A significant increase in plasma 8-epi-PGF2a after 131I was observed in the two groups. The concentrations of 8-epi-PGF2α were significantly higher in the control group before and 2 and 7 days after 131I. The percentage of patients with elevated 8-epi-PGF2α was also significantly higher in the control group before and after 131I. Furthermore, the increase (percent) in 8-epi-PGF2α was significantly greater in the control group (average of 112.3% versus 56.3%). Only two patients (10%) reported side effects during supplementation.. Ablation with 131I causes oxidative stress which can be minimized by the use of antioxidants.

Topics: Adult; Analysis of Variance; Antioxidants; Ascorbic Acid; Carcinoma; Dietary Supplements; Dinoprost; Female; Humans; Iodine Radioisotopes; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Prospective Studies; Reproducibility of Results; Selenium; Thyroid Neoplasms; Thyroidectomy; Thyroxine; Time Factors; Treatment Outcome; Vitamin E; Young Adult

Increased expression of cyclooxygenase-2 (COX-2) and subsequent prostaglandin production is an important event in several human malignancies, including colorectal cancer. COX-2 mediated prostanoid synthesis has been shown to play a key role in tumor progression with prostaglandin E(2) (PGE(2)) being shown to promote tumor growth, invasion and angiogenesis. The role of the other prostaglandins produced by COX-2 in tumors remains poorly understood. We have shown that colorectal tumor cells produce prostaglandin F(2alpha) (PGF(2alpha)) and provide evidence that PGF(2alpha) may play an important role in colorectal tumorigenesis. Our data show that PGF(2alpha) is secreted by both colorectal adenoma and carcinoma-derived cell lines at levels in excess of those detected for PGE(2). These cell lines were also found to express the PGF(2alpha) receptor (FP) indicating potential autocrine effects of PGF(2alpha). This finding is further supported by an in vivo immunohistochemical study of FP expression in resected colon tissue. These data show epithelial expression of FP in normal colorectal mucosa and also in colorectal adenomas and carcinomas. We compared the relative abilities of PGF(2alpha) and PGE(2) to induce cell motility in vitro in colorectal tumor cell lines and show the first evidence of prostaglandin-induced cell motility in colorectal adenoma cell lines. PGF(2alpha) induced cell motility with equivalent potency to PGE(2) in all the cell lines tested and was also shown to increase the invasion of carcinoma-derived cells into reconstituted basement membrane. These data show that PGF(2alpha) may play an important role in the malignant progression of colorectal tumors.

Topics: Adenoma; Carcinoma; Cell Line, Tumor; Cell Movement; Colorectal Neoplasms; Dinoprost; Dinoprostone; Disease Progression; Humans; Immunohistochemistry; Neoplasm Invasiveness

Malignant ascites is a major source of morbidity and mortality in ovarian cancer patients. It functions as a permissive reactive tumor-host microenvironment and provides sustenance for the floating tumor cells through a plethora of survival/metastasis-associated molecules. Using a syngeneic, immunocompetent model of peritoneal ovarian carcinomatosis in SP(-/-) mice, we investigated the molecular mechanisms implicated in the interplay between host secreted protein acidic and rich in cysteine (SPARC) and ascitic fluid prosurvival/prometastasis factors that result in the significantly augmented levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP). Ascitic fluid-enhanced ID8 invasiveness was mediated through VEGF via a positive feedback loop with MMP-2 and MMP-9 and through activation of alpha(v) and beta(1) integrins. Host SPARC down-regulated the VEGF-MMP axis at the transcriptional and posttranscriptional levels. In vitro, SPARC attenuated the basal as well as VEGF-induced integrin activation in tumor cells. SPARC inhibited the VEGF- and integrin-mediated ID8 proliferation in vitro and significantly suppressed their tumorigenicity in vivo. Relative to SP(+/+), SP(-/-) ascitic fluid contained significantly higher levels of bioactive lipids and exerted stronger chemotactic, proinvasive, and mitogenic effects on ID8 cells in vitro. SP(-/-) ascites also contained high levels of interleukin-6, macrophage chemoattractant protein-1, and 8-isoprostane (prostaglandin F(2)alpha) that were positively correlated with extensive infiltration of SP(-/-) ovarian tumors and ascites with macrophages. In summary, our findings strongly suggest that host SPARC normalizes the microenvironment of ovarian cancer malignant ascites through down-regulation of the VEGF-integrin-MMP axis, decreases the levels and activity of bioactive lipids, and ameliorates downstream inflammation.

Topics: Animals; Ascitic Fluid; Carcinoma; Cell Adhesion; Cell Proliferation; Cell Survival; Chemokine CCL2; Dinoprost; Female; Inflammation; Integrins; Interleukin-6; Metalloendopeptidases; Mice; Mice, Mutant Strains; Osteonectin; Ovarian Neoplasms; Peritoneal Neoplasms; Tissue Inhibitor of Metalloproteinases; Vascular Endothelial Growth Factor A

The effects of prostaglandins (PGs) on the growth of human gastric carcinoma cell line KATO III were investigated. PGE2 as well as PGF2 alpha significantly and dose-dependently inhibited the growth of this gastric carcinoma cell line (PGE2 greater than PGF2 alpha). This inhibition of cell growth by the PGs was associated with the increase in cyclic AMP production (PGE2 greater than PGF2 alpha), whereas inositol-phospholipid turnover was not affected by either PGE2 or PGF2 alpha as assessed by the formation of 3H-inositol phosphates. Furthermore, the proliferation of these gastric carcinoma cells was also suppressed by the administration of forskolin as well as of dibutyryl cyclic AMP. These results suggest that PGE2 and PGF2 alpha inhibit the growth of cultured human gastric carcinoma cells KATO III via stimulation of cyclic AMP production.

Topics: Bucladesine; Carcinoma; Cell Division; Colforsin; Cyclic AMP; Depression, Chemical; Dinoprost; Dinoprostone; Humans; Inositol Phosphates; Stomach Neoplasms; Tumor Cells, Cultured