dinoprost and Prostatic-Neoplasms

Previous studies have demonstrated that urinary 8-iso-prostaglandin F (PGF)2alpha serves as a powerful biomarker of lipid peroxidation in diseases in which oxidative stress plays an important role in its pathophysiology. The goal of this study was to measure the urinary isoprostane levels in patients with prostate cancer treated with radiotherapy (RT) in an effort to determine whether isoprostane levels are elevated compared with in historical controls, whether the levels increase after RT, and whether such an increase would correlate positively with the degree of GU symptoms during treatment.. Urine samples were obtained before and during RT from patients enrolled on a recently reported Phase III trial examining the therapeutic efficacy of ibuprofen in decreasing the acute urinary symptoms of RT. Radioimmunoassays were performed on urine samples for 8-iso-PGF2alpha or 15-keto-dihydro-PGF2alpha.. Fifteen patients provided samples both before and during RT. The levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF2alpha in the urine samples obtained before prostate RT (0.27 and 0.41 nmol/mmol creatinine) did not differ appreciably from the values observed in a normal cohort (0.27 and 0.46 nmol/mmol creatinine) and did not change after RT (0.23 and 0.37 nmol/mmol creatinine).. We were unable to detect an increase in either 8-iso-PGF2alpha or 15-keto-dihydro-PGF2alpha in the urine of patients with prostate cancer compared with in historical normal controls. We were also unable to measure an increase in either of the eicosanoids during RT to the prostate gland.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Biomarkers, Tumor; Creatinine; Dinoprost; Humans; Ibuprofen; Isoprostanes; Male; Oxidative Stress; Prostatic Neoplasms; Radiation Injuries

Urinary 8-isoprostane is an established biomarker for lipid peroxidation. However, the association between its pre-diagnostic levels and cancer incidence has rarely been evaluated.. 8793 older adults from the German ESTHER cohort were followed up for cancer incidence by cancer registry data. A directed acyclic graph was utilized to identify potential confounders. Multivariate Cox regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI).. During 14-year follow-up, 1540 incident cancer cases, including 207 lung, 196 colorectal, 218 breast and 245 prostate cancer cases were detected. 8-isoprostane concentrations were positively associated with lung cancer, but not with cancer at the other sites. The HR (95% CI) for the association with lung cancer was 1.61 (1.10, 2.34) for comparison of the top with bottom tertile in total population. The association of 8-isoprostane levels with lung cancer persisted after the adjustment for smoking and other potential confounders and was multiplicative to the effect of smoking. However, 8-isoprostane levels did not improve lung cancer prediction when added to a model containing age, sex and smoking. A protective association of increasing 8-isoprostane levels was observed for prostate cancer incidence but this association was only statistically significant among current smokers.. Our findings suggest that lipid peroxidation is involved in the development of lung cancer. However, high oxidative stress may be a protective factor for prostate cancer, especially among current smokers.

Topics: Aged; Biomarkers; Breast Neoplasms; Colorectal Neoplasms; Dinoprost; Female; Follow-Up Studies; Germany; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Prognosis; Prospective Studies; Prostatic Neoplasms

Prostate cancer is the most common non-cutaneous cancer and the second leading cause of cancer-related mortality among men in the USA. Growing evidence suggests that oxidative stress is involved in the development and progression of prostate cancer. In this study, the association between antioxidants from diet and supplements and biomarkers of oxidative stress in blood (n 278), urine (n 298) and prostate tissue (n 55) were determined among men from the North Carolina-Louisiana Prostate Cancer Project. The association between antioxidant intake and oxidative stress biomarkers in blood and urine was determined using linear regression, adjusting for age, race, prostate cancer aggressiveness and smoking status. Greater antioxidant intake was found to be associated with lower urinary 8-isoprostane concentrations, with a 10% increase in antioxidant intake corresponding to an unadjusted 1·1% decrease in urinary 8-isoprostane levels (95% CI -1·7, -0·3%; P value<0·01) and an adjusted 0·6% decrease (95% CI -1·4, 0·2%; P value=0·16). In benign prostate tissue, thioredoxin 1 was inversely associated with antioxidant intake (P=0·02). No significant associations were found for other blood or urinary biomarkers or for malignant prostate tissue. These results indicate that antioxidant intake may be associated with less oxidative stress among men diagnosed with prostate cancer.

Topics: Adult; Aged; Antioxidants; Biomarkers; Diet; Dietary Supplements; Dinoprost; Feeding Behavior; Humans; Louisiana; Male; Middle Aged; North Carolina; Oxidative Stress; Prostate; Prostatic Neoplasms; Thioredoxins

Aldo-keto reductase 1C3(AKR1C3) is an enzyme involved in prostaglandins metabolism. Studies suggest that AKR1C3 has a pivotal role in the radioresistance of esophageal cancer and non-small-cell lung cancer, yet the role of AKR1C3 in prostate cancer cells radiation resistance has not yet been clarified. In our study, we established a stable overexpressing AKR1C3 cell line (AKR1C3-over) derived from the prostate cell line DU145 and its control cell line (Control). We conducted colony formation assay to determine the role of AKR1C3 in radioresistance and we used its chemical inhibitor to detect whether it can restored the sensitivity of the acquired tumor cells. Flow cytometry assay was carried out to detect IR-induced ROS accumulation. Elisa was adopted to dedect the concentration of PGF2α in the suspension of the cells after 6GY radiation. Western blotting was used to dedect the MAPK and PPAR γ. The results demonstrated that overexpression of AKR1C3 in prostate cancer can result in radioresistance and suppression of AKR1C3 via its chemical inhibitor indocin restored the sensitivity of the acquired tumor cells. According to the flow cytometry assay, ROS was decreased by 80% in DU145-over cells. Also overexpression of AKR1C3 could result in the accumulation of prostaglandin F2α (PGF2α), which can not only promote prostate cancer cell 's proliferation but also could enhance prostate cancer cells resistance to radiation and activated the MAPK pathway and inhibited the expression of PPARγ. In conclusion, we found that overexpression of AKR1C3 significantly enhanced human prostate cancer cells resistance to radiation through activation of MAPK pathway.

Topics: Aldo-Keto Reductase Family 1 Member C3; Cell Line, Tumor; Cell Proliferation; Dinoprost; Drug Resistance, Neoplasm; Humans; Indomethacin; Male; Prostatic Neoplasms; Radiation Tolerance; Transfection

To estimate the oxidative stress in patients with prostate cancer and in a control group, we used the biomarker of lipid peroxidation-isoprostanes (8-isoPGF(2)) and the level of selected antioxidants (glucose and uric acid [UA]). The level of urinary isoprostanes was determined in patients and controls using an immunoassay kit according to the manufacturer's instruction. The levels of UA and glucose were also determined in serum by the use of UA Assay Kit and Glucose Assay Kit. We observed a statistically increased the level of isoprostanes in urine of patients with prostate cancer in compared with a control group. The concentration of tested antioxidants in blood from patients with prostate cancer was also higher than in healthy subjects. Moreover, our experiments indicate that the correlation between the increased amount of UA and the lipid peroxidation exists in prostate cancer patients (in all tested groups). Prostate cancer risk by urinary isoprostanes level was analyzed, and a positive association was found (relative risk for highest vs. lowest quartile of urinary isoprostanes = 1.6; 95 % confidence interval 1.2-2.4; p for trend = 0.03). We suggest that reactive oxygen species induce peroxidation of unsaturated fatty acid in patients with prostate cancer, and the level of isoprostanes may be used as a non-invasive marker for determination of oxidative stress. We also propose that UA may enhance the oxidative stress in patients with prostate cancer.

Topics: Aged; Biomarkers, Tumor; Blood Glucose; Case-Control Studies; Dinoprost; Humans; Lipid Peroxidation; Male; Middle Aged; Neoplasm Grading; Organ Size; Oxidative Stress; Prostate; Prostatic Neoplasms; Risk; Uric Acid

Members of the aldo-keto reductase (AKR) superfamily have been implicated in prostaglandin (PG) metabolism and prostate cancer. AKR1C3 possesses 11-ketoprostaglandin reductase activity and is capable of converting PGD2 to 9alpha, 11beta-PGF2alpha, whereas AKR1C2-mediated PG metabolism remains unclear. The accumulation of PGF2alpha may generate proliferative signals to promote prostate cell growth. Levels of AKR1C2 and AKR1C3 expression are elevated in localized and advanced prostate cancer. To study the significance of AKR1C2- and AKR1C3-mediated PGD2 conversion in human prostate cell proliferation, we stably transfected androgen insensitive human prostate cancer PC-3 cells with AKR1C2 or AKR1C3 cDNA. PC-3 cells overexpressing AKR1C2 and AKR1C3 had elevated cell proliferation in response to PGD2 stimulation as compared to mock transfectants. Overexpression of AKR1C2 or AKR1C3 did not alter levels of PGF receptor (FP) expression. Inclusion of an FP antagonist (AL8810) significantly suppressed PGD2-stimulated PC-3 cell proliferation in these stable transfectants. In addition, PGD2 significantly elevated levels of total Akt protein expression and Akt Ser473 phosphorylation in AKR1C2 and AKR1C3 stable transfectants; and inclusion of a phosphatidylinositol 3-kinase (PI3K) chemical inhibitor (LY294002) attenuated PGD2-stimulated cell proliferation in these transfectants. Our results suggested that both AKR1C2 and AKR1C3 mediate similar PGD2 conversion toward the accumulation of proliferative signals through FP and PI3K/Akt signaling pathways to promote prostate cell proliferation.

Topics: 3-Hydroxysteroid Dehydrogenases; Aldo-Keto Reductase Family 1 Member C3; Cell Line, Tumor; Cell Proliferation; Chromones; Dinoprost; Humans; Hydroxyprostaglandin Dehydrogenases; Hydroxysteroid Dehydrogenases; Male; Morpholines; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Prostaglandin D2; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; Receptors, Prostaglandin; Signal Transduction; Transfection

The PC-3 Low Invasive cells and the PC-3 High Invasive cells were used to investigate the correlation of the COX-2 expression and its arachidonic acid metabolites, prostaglandins, with their invasiveness through Matrigel using a Boyden chamber assay. The COX-2 expression in PC-3 High Invasive cells was approximately 3-fold higher than in PC-3 Low Invasive cells while the COX-1 expression was similar in both cell sublines. When incubated with arachidonic acid, PGE2 was the major prostaglandin produced by these cells. PC-3 High Invasive cells produced PGE2 approximately 2.5-fold higher than PC-3 Low Invasive cells. PGD2 was the second most abundant prostaglandin produced by these cells. Both indomethacin (a nonspecific COX inhibitor) and NS-398 (a specific COX-2 inhibitor) inhibited the production of prostaglandins and the cell invasion. PGE2 alone did not induce the cell invasion of PC-3 Low Invasive cells. However, PGE2 reversed the inhibition of cell invasion by NS-398 and enhanced the cell invasion of the PC-3 High Invasive cells. In contrast, PGD2 slightly inhibited the cell invasion. These results suggest that in the PC-3 Low Invasive cells, COX-2-derived PGE2 may not be sufficient to induce cell invasion while in the PC-3 High Invasive cells, PGE2 may be sufficient to act as an enhancer for the cell invasion. Further, PGD2 may represent a weak inhibitor and counteracts the effect of PGE2 in the cell invasion.

Topics: 6-Ketoprostaglandin F1 alpha; Adenocarcinoma; Arachidonic Acid; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Humans; Indomethacin; Isoenzymes; Male; Membrane Proteins; Neoplasm Invasiveness; Nitrobenzenes; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Prostatic Neoplasms; Sulfonamides; Tumor Cells, Cultured

Enhanced production of prostaglandins (PGs) by experimentally-induced and naturally occurring tumors and their effect on tumor growth and immunosurveillance have been noted. Directed toward further evaluation of the relationship between prostatic tumor growth and its milieu, i.e., microenvironment, we investigated the possible correlation between levels of PGs, tumor size, and metastatic potential. For this purpose, the levels of PGE2 and PGF2 alpha in plasma and tumor effusions of three tumor sublines of the Dunning R-3327 rat prostate adenocarcinoma were measured: R-3327H, well-differentiated, slow-growing, and poorly metastatic; R-3327G, poorly differentiated, fast-growing, and poorly metastatic; and R-3327 Mat LyLu, anaplastic, fast-growing, and highly metastatic. The level of PGF2 alpha was highly variable with no significant differences being noted between the tumor sublines. The mean values of PGF2 alpha were, however, higher, although not significantly so, in the smaller tumors within each of the sublines. The levels of PGE2 were significantly higher in Mat LyLu effusions than those from the nonmetastasizing R-3327G and H sublines. Evaluation and comparison of the relationship between tumor burden, i.e., size versus levels of PGE2 and PGF2 alpha showed no significant differences. A vasodilator and regulator of immunological responsiveness, PGE2, may function as a modulator of tumor metastases. In consonance with studies by others elevated levels of PGE2 may possibly serve as a prognostic marker for the high metastatic potential of neoplastic cells.

Topics: Adenocarcinoma; Androgens; Animals; Dinoprost; Dinoprostone; Immunologic Surveillance; Male; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms, Hormone-Dependent; Prostaglandins E; Prostaglandins F; Prostatic Neoplasms; Rats

Prostaglandin F2 alpha can be measured as a stable degradation product, 13,14-dihydro-15-keto-prostaglandin F2 alpha (DHK-PGF2 alpha). Pathological serum levels of this lipid compound have been observed in prostate hyperplasia and treated testicular cancer patients. In renal cancer patients elevated DHK-PGF2 alpha shows a trend to normalize 12 months following nephrectomy in stage T0N0M0. Bladder cancer patients have slightly increased DHK-PGF2 alpha that differ in relation to preinvasive bladder cancer. In contrast serum haptoglobin levels were significantly pathological in patients with kidney and bladder cancer, suggesting involved cancer metabolism. Patients with prostate and testis cancer are without distinct relation to the tumour stage. After specification of haptoglobin types no coincidence to urogenital tumours could be detected. Correlated aberration of PGF2 alpha and haptoglobin displayed different patterns depending on the type of urogenital tumour.

Topics: Adult; Aged; Dinoprost; Female; Haptoglobins; Humans; Kidney Neoplasms; Male; Middle Aged; Neoplasm Staging; Prostaglandins F; Prostatic Hyperplasia; Prostatic Neoplasms; Testicular Neoplasms; Urinary Bladder Neoplasms; Urogenital Neoplasms

13,14-Dihydro-15-keto-prostaglandin F2 alpha (13,14-DHK-PGF2 alpha) represents a stable product of degradation after pulmonary flow and it is shown to be reliably measured by radioimmunoassay. In patients with urogenital tumors, serum levels of 13,14-DHK-PGF2 alpha are distinctly elevated when compared to a control group. The rate of synthesis of this compound in urogenital tumors, however, appears to be different.

Topics: Adenocarcinoma; Dinoprost; Female; Humans; Kidney Neoplasms; Male; Neoplasms, Germ Cell and Embryonal; Prostaglandins F; Prostatic Hyperplasia; Prostatic Neoplasms; Radioimmunoassay; Testicular Neoplasms; Urinary Bladder Neoplasms; Urogenital Neoplasms