Purpose: To evaluate serum C-reactive protein (CRP) as prognostic variable in patients with epithelial ovarian cancer (EOC). Experimental Design: In a multicenter study, preoperative serum CRP was evaluated in 623 patients with EOC. Results were correlated with clinical data. Results: Mean (SD) preoperative serum CRP was 3.6 (4.8) mg/dL. Serum CRP was significantly associated with International Federation of Gynecologists and Obstetricians stage (P < 0.001) and postoperative residual tumor mass (P < 0.001) but not with histologic grade (P = 0.1) and type (P = 0.7), patients'age (Pearson's correlation coefficient = 0.05; P = 0.2), and serum CA125 (Pearson's correlation coefficient = 0.02; P = 0.6). Patients with platinum-resistant EOC had significantly higher CRP serum levels compared with patients with platinum-sensitive EOC [6.0 (6.6) mg/dL versus 2.8 (3.8) mg/dL; P < 0.001]. Higher International Federation of Gynecologists and Obstetricians stage (P < 0.001), presence of postoperative residual tumor mass (P < 0.001), tumor grade (P = 0.001), serum CA 125 (P = 0.03), and serum CRP (P = 0.001) were independently associated with overall survival. Patients with serum CRP V1 mg/dL versus >1mg/dL had an overall 5-year survival of 82% versus 58.5% (P < 0.001).Conclusion: Serum CRP can be seen as a novel, widely available independent prognostic variable of ovarian cancer.

Topical imiquimod is an efficacious and feasible treatment for patients with CIN 2-3.

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After completing this course, the reader will be able to:1. Describe the role of fibrinogen in coagulation and the inflammatory response and explain its importance in tumor proliferation, migration, and escape from immune regulation.2. Evaluate fibrinogen as a prognostic blood marker for survival and disease-free survival in patients with ovarian cancer.3. Incorporate fibrinogen testing as a relatively inexpensive, reliable, and available technique in the prognostic evaluation of ovarian cancer patients.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTIntroduction. To evaluate pretherapeutic plasma fibrinogen levels as a prognostic parameter in patients with epithelial ovarian cancer (EOC). Materials and Methods. In the present multicenter study, pretherapeutic plasma fibrinogen levels were

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The purpose of this study was to evaluate the influence of endothelial nitric oxide synthase (eNOS) deficiency on fetal growth, perinatal survival, and limb development in a mouse model with a targeted mutagenesis of the Nos3 gene. Wild-type (Nos3+/+) and eNOS-deficient fetuses (Nos3-/-) were evaluated on Gestational Day (E)15 and E17, and newborn pups were observed on Day 1 of life (D1). The average term duration of pregnancy was 19 days. For the evaluation of postnatal development, a breeding scheme consisting of Nos3+/- x Nos3+/- and Nos3-/- x Nos3-/- mice was established, and offspring were observed for 3 wk. Southern blotting was used for genotyping. No significant differences in fetal weight, crown-rump lengths (CRL), and placental weight were seen between Nos3+/+ and Nos3-/- fetuses on E15. By E17, Nos3-/- fetuses showed significantly reduced fetal weights, CRL, and placental weights. This difference in body weight was also seen throughout the whole postnatal period. In pregnancies of Nos3-/- females, the average number of pups alive on D1 was significantly decreased compared to either E15 or E17. Placental histology revealed no abnormalities. On E15, E17, and D1, Nos3(-/-) fetuses demonstrated focal acute hemorrhages in the distal limbs in 0%, 2.6%, and 5.7%, respectively, of all mutant mice studied on the respective days. Bone measurements showed significantly shorter bones in the peripheral digits of hindpaws of Nos3-/- newborns. We conclude mice deficient for eNOS show characteristically abnormal prenatal and postnatal development including fetal growth restriction, reduced survival, and an increased rate of limb abnormalities. The development of this characteristic phenotype of eNOS-deficient mice dates back to the prenatal development during the late third trimester of pregnancy.

Purpose: We aimed to determine the clinical role of the p53 family members p53 and p73 in the responsiveness to platinum-based chemotherapy and survival in ovarian cancer, considering their cross-talk and the p53 polymorphism at codon 72. Experimental Design: A detailed analysis of p53 and p73 in a series of122 ovarian cancers was done.We used a functional yeast-based assay to determine the p53 mutational status. Red yeast colonies, indicating mutant p53, were subsequently sequenced to determine the specific p53 alteration. p53 mutations were divided into two groups according to their previous characterization in the literature: those that efficiently inhibit transcriptionally activeTAp73 function and those that do not. A p53 polymorphism at codon 72 was determined in corresponding normal tissue or blood of ovarian cancer patients. Isoform-specific p73 expression analysis using real-time reverse transcription-PCR has previously been done in the majority of ovarian cancers included in this study. In a retrospective chart review, responsiveness to chemotherapy was assessed, and survival data with long follow-up times were collected. Results: Eighty of 122 (65.6%) of ovarian cancers harbored p53 mutations. p53 mutational status was an important determinant of responsiveness to platinum-based chemotherapy in all patients with a residual tumor of <2 cm in diameter after initial surgery (wild-type versus mutant, P = 0.029). In addition, p53 mutational status was a strong prognosticator for recurrence-free and overall survival (P < 0.0001and P = 0.003, respectively) in univariate analyses. High expression levels of dominant-negative p73 isoforms (DNp73 and DNVp73) significantly correlated with chemotherapeutic failure (P = 0.048) and with worse recurrence-free and overall survival in patients with p53 mutant cancers (P = 0.048 and P = 0.005, respectively). Eight p53 mutations, present in 19 cases, were found that efficiently inhibit TAp73 (i.e., 175H, 220C, 245S, 245D, 248W, 248Q, 266E, and 273H). Patients with p53 mutations that efficiently inhibit TAp73 function had a significantly shorter overall survival than patients with p53 mutations of unknown effect on TAp73 (P = 0.044). The p53 polymorphism at codon 72 had no influence on responsiveness to chemotherapy or survival. Conclusion: We provide the first clinical evidence that dominant-negative p73 isoforms contribute to drug resistance in vivo, underscoring the importance of a p53-p73 cross-talk. NH 2 -terminally truncated p73 isoforms were of significant clinical effect by providing an additional unfavorable factor for response to platinum-based chemotherapy and survival in p53 mutant ovarian cancers.