Isoprostane levels in the urine of patients with prostate cancer receiving radiotherapy are not elevated

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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). CONCLUSION: 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.     

The role of hemoglobin concentration in clinically localized prostate cancer treated with radical radiotherapy +/- neoadjuvant androgen deprivation

PURPOSE: Serum hemoglobin level (Hb) is a significant determinant of treatment outcome after radical radiotherapy (RT) for several cancer types, but its importance in prostate cancer is not well established. METHODS AND MATERIALS: Two treatment-specific cohorts of men with localized prostate cancer (T1-4, Nx/N0, M0) were analyzed. Seven hundred six men who received radical RT at Princess Margaret Hospital between 1987 and 2000 comprise the RT-alone cohort, of whom 536 had a pre-RT Hb. Six hundred fifty-eight men received 3-6 months' neoadjuvant androgen deprivation (NAD) and radical RT at Royal Marsden Hospital between 1989 and 2000 and comprise the NAD + RT cohort, of whom 475 had a pre-NAD Hb and 513 a pre-RT Hb. Time to biochemical failure (TTBF) was the primary end point. Univariate and multivariate analyses using the Cox proportional hazards regression model were used for each data set independently to study the prognostic role of pre-RT Hb, pre-NAD Hb, nadir Hb (lowest Hb during RT), Hb decrement (pre-NAD Hb - pre-RT Hb), Gleason score, presenting PSA, and T stage. RESULTS: On univariate analysis, no significant association was seen between TTBF and any of the Hb variables for either data set. On multivariate analysis, TTBF was associated with presenting PSA (p < 0.001), Gleason score (p < 0.01), and (for the NAD + RT data set) T stage (p < 0.001), but not pre-NAD Hb (p = 0.24) or pre-RT Hb (p > 0.3). CONCLUSION: Hemoglobin level is not an important determinant of RT outcome in localized prostate cancer.     

The effect on the fetus of medications used to treat pregnant inflammatory bowel-disease patients

OBJECTIVES: We reviewed data to investigate the effect of 5-ASA drugs, metronidazole, ciprofloxacin, prednisone, 6-mercaptopurine, azathioprine, and cyclosporine on pregnancy outcomes in patients with inflammatory bowel disease (IBD). METHODS: One hundred and thirteen female patients with a total of 207 documented conceptions were studied. Treatment information included: smoking history (patient and spouse), dates of conception and termination, and outcome of pregnancy (spontaneous abortion, therapeutic abortion, maternal or fetal illness resulting in abortion, premature birth, healthy full-term birth, multiple births, ectopic pregnancy, congenital defects), weight of baby, type of delivery (cesarian section, vaginal), medication history during each trimester (mean dose, maximum dose, frequency). We analyzed the effect on pregnancy outcome of medication use during the first trimester or at any time during the pregnancy. RESULTS: Thirty-nine patients (34.5%) had ulcerative colitis (UC), 73 (64.5%) had crohn's disease (CD), and 1 patient (1%) had indeterminate colitis. For 100 of the 207 conceptions, the patients were on 5-ASA drugs at some time during the pregnancy, 49 on prednisone, 101 on an immunomodulator (6-MP/azathioprine), 27 on metronidazole, 18 on ciprofloxacin, and 2 on cyclosporine. In 85 (31%) of the conceptions, patients were on none of these medications. No significant differences were found among the groups in each pregnancy with respect to outcome (p values 0.091 to 0.9). In multivariate analyses controlling for age of mother, there was no evidence that 5-ASA type drugs or any type of drug influenced pregnancy outcome. CONCLUSIONS: In 113 female patients with 207 conceptions none of the drugs used to treat IBD is associated with poor pregnancy outcomes.     

Atherogenic effect of interleukin-2 and antiatherogenic effect of interleukin-2 antibody in apo-E-deficient mice

Growing evidence suggests that atherosclerosis is an immune-mediated inflammatory process and that cytokines participate as mediators in this process. Of the cytokines, interleukins, which are released from both immune and nonimmune cells of vascular wall, are found to have multiple effects. Interleukin-2 (IL-2), a cytokine produced by activated T-lymphocytes, has been found to further activate the T cells and may potentially enhance atherogenesis. Apo-E-deficient mice fed with atherogenic diet were injected intraperitoneally twice a week with placebo, IL-2, or anti-IL-2 antibody for a period of 6 weeks. Group 1 (n = 6) was injected with bovine serum albumin (BSA) in phosphate-buffered saline (PBS) and served as controls. Group 2 (n=6) was injected with 2 x 10(4) units of recombinant murine IL-2 (rmIL-2) per dose reconstituted with BSA in PBS. Group 3 (n=6) was injected with 5 microg of anti-IL-2 per dose reconstituted with BSA in PBS. Aortic sections were analyzed and atherosclerotic burden was quantified. Compared to controls, injection of IL-2 increased measures of atherosclerosis such as the average lesion score (10.7 +/-0.5 vs 9.3 +/-1.1, p=0.04) and the lesion size as a fraction of aortic area (0.51 +/-0.03 vs 0.41 +/-0.05, p=0.01). Injection of anti-IL-2 had a profound antiatherogenic effect. It significantly reduced the average number of lesions per cross section (2.6 +/-0.6 vs 4.3 +/-0.6, p=0.03), the average lesion score (4.6 +/-1.9 vs 9.3 +/-1.1, p=0.02), the lesion area/circumference (0.35 +/-0.08 vs 0.62 +/-0.10, p=0.007), and the lesion size/aortic area (0.23 +/-0.07 vs 0.41 +/-0.05, p=0.03). These results indicate that IL-2 is an atherogenic cytokine in apo-E-deficient mice and anti-IL-2 is protective against atherosclerosis. This may have important clinical implications in modifying the atherosclerotic process.