The effect of cyclooxygenase-2 expression on tumor vascularity in advanced stage ovarian serous carcinoma

BACKGROUND: Cyclooxygenase-2 (COX-2) seems to be involved at various steps in the processes of malignant transformation and tumor progression. Investigations have shown that COX-2 overexpression is associated with increased proliferation, reduced apoptosis, and angiogenesis. METHODS: Specimens from 125 patients with high-grade, advanced-stage (Stage III-IV) serous ovarian carcinoma were evaluated by immunohistochemistry for COX-2, p53, bcl-2, epidermal growth factor receptor (EGFR), and Her-2/neu expression and for CD34-stained microvessel density (MVD). Statistical analysis was performed to investigate the correlations between COX-2 expression and 1) clinicopathologic characteristics, 2) tumor MVD, and 3) expression of other molecular markers. The effect of COX-2 expression on survival was determined using survival analysis. RESULTS: Increased COX-2 expression was significantly correlated with tumor MVD (Spearman rank correlation test: r = 0.41; P < 0.001). There was no association observed between COX-2 expression and expression levels of EGFR, Her-2/neu, bcl-2, or p53. Patients who had tumors that showed high COX-2 expression had a worse prognosis compared with patients who had tumors with low expression (death hazard ratio, 2.0; 95% confidence interval, 1.2-3.5; P < 0.001). A multivariate analysis revealed that COX-2 expression was the strongest predictor of survival among the different prognostic factors analyzed. CONCLUSIONS: The current study demonstrated that COX-2 expression was correlated significantly with survival in patients with high-grade, high-stage serous ovarian carcinoma. Expression of COX-2 also was correlated with tumor angiogenesis but not with EGFR, Her-2/neu, or p53 expression. In addition to their prognostic significance, a better understanding of the biology of these molecular changes may help identify new targets for therapy in patients with ovarian carcinoma.     

Leydig cell tumor. Two new cases

The Leydig's cell tumours are the most common of all non germ cell tumour of the testis, that clinical findings is different by age of presented. We report two new cases of Leydig cell tumour diagnosed in our centre having different presentation form, in old adults with feminizing features and occult tumour, and as a testicular nodule pain, respectively. The analytical, clinical, diagnostic aspects and therapeutic of the uncommon disease are discussed.     

Squamous cell carcinoma of the prostate: a further case

We report one rare case of squamous cells prostate tumor. This histological pattern accounts for the 0.5-1% of all prostatic malignancies with certain clinical and evolutive aspects that are from those of prostate adenocarcinoma. Review of the literature seems to have a very poor prognosis such that occurred in our patient who died after 2 month of diagnosis with a poor response to the habitual treatment, perhaps due to this different cell of origin.     

The impact of c-kit and ki-67 expression on patients prognosis in advanced ovarian serous carcinoma.

The transmembrane-tyrosine-kinase receptor, c-kit, is involved in cell differentiation and has been found to be expressed in normal human cell types and solid tumors. This study was designed to investigate the effects of c-kit expression on: 1) tumor proliferation and apoptosis, and 2) survival in patients with high-grade advanced stage ovarian serous carcinoma (OSC). We identified 118 patients with high-grade advanced stage OSC from our files. Clinical data, including demographics and overall survival, were collected. Immunohistochemical panel consisting of c-kit, ki-67, p53, and bcl-2 was performed. C-kit was categorized as positive if any cytoplasmic or membranous staining pattern was identified. Correlation between c-kit expression and the other markers was performed. Survival analysis was performed using COX proportional hazards regression and Kaplan-Meier test. Of 118 cases, 25 (21.2%) expressed c-kit. Of 93 c-kit-negative tumors, 87.1% had a high proliferation index. High p53 and bcl-2 expression was identified in 96 (81.4%) and 59 (50%) cases respectively. No significant statistical correlation was identified between c-kit and apoptosis markers. Tumors lacking c-kit expression showed a trend toward having high proliferation index, but this did not achieve statistical significance (p = 0.07). Of the seven variables included in the multivariate survival analysis, only c-kit (odds ratio, 2.12; 95% confidence interval, 08-4.17; p = 0.02) and ki-67 (odds ratio, 1.9; 95% confidence interval, 1.1-3.1; p = 0.03) showed an independent statistically significant impact on survival. High-grade advanced stage OSC lacking c-kit expression correlates with poor outcome. Interestingly, cases lacking c-kit expression also showed a trend to have high proliferation index.     

Characterization of the Solubility and Solid-State Properties of Saccharin Salts of Fluoroquinolones

Saccharinates salts of the fluoroquinolone antibiotics norfloxacin, ciprofloxacin, ofloxacin, and enrofloxacin were obtained as pure crystalline anhydrous solids with sweet taste. The products were characterized by one- (¹³C) and two-dimensional (¹H–¹³C) dimensions solid state Nuclear Magnetic Resonance and infrared spectroscopy showing ionic interactions between the saccharine amide and the fluoroquinolone piperazine. Several intermolecular bindings were also identified. Thermal behavior and powder X-ray diffraction provided complementary evidences of salt formation. The series of products showed improved properties with respect to water solubility. A solubility model was developed. These salts would be a good way forward to developing more suitable formulations of these APIs. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3788–3801, 2009     

Effect of chronic ethanol consumption on activation of nitrosopyrrolidine to a mutagen by rat upper alimentary tract, lung, and hepatic tissue

Tissues derived from male Sprague-Dawley rats which had been pair-fed isocaloric ethanol or carbohydrate control diets for 4 weeks were used to determine the effect of chronic ethanol exposure on the activation of the smoking and diet-associated procarcinogen nitrosopyrrolidine (NPY). Microsomal preparations from lungs and liver and S9 fractions from alimentary tract mucosa were tested for their capacity to activate NPY to a mutagen by the Ames Salmonella assay. Chronic ethanol exposure resulted in an increased capacity to activate NPY by microsomes derived from liver, lungs, and esophagus but not from stomach. The three tissues in which enhanced activation of NPY was observed in the present study also have been noted in epidemiological studies to be target sites of alcohol abuse-associated increased cancer risk. The results presented here suggest that dietary ethanol's effect on carcinogen metabolism may be responsible, at least in part, for the increased cancer risk observed in chronic alcohol abusers.     

Expression of cyclooxygenase-2 in advanced stage ovarian serous carcinoma: correlation with tumor cell proliferation, apoptosis, angiogenesis, and survival

OBJECTIVE: Cyclo-oxygenase-2 seems to be involved at various steps in the processes of tumor progression. The objective of this study was to examine the relationship between cyclo-oxygenase-2 expression and tumor proliferation, apoptosis and angiogenesis in patients with advanced stage high-grade ovarian carcinoma. STUDY DESIGN: Specimens from 118 patients with high-grade and advanced stage (III, IV) serous ovarian carcinoma were evaluated by immunohistochemistry for cyclo-oxygenase-2, Ki-67, vascular endothelial growth factor, and bcl-2 expression. Tumor microvessel density was assessed with CD34 immunostaining. We investigated the relationships between cyclo-oxygenase-2 expression and clinicopathologic characteristics, tumor angiogenesis (tumor microvessel density and vascular endothelial growth factor expression), and tumor proliferation and apoptosis. The effect of cyclooxygenase-2 expression on patient survival was determined. RESULTS: There was a significant positive correlation between cyclo-oxygenase-2 expression in tumor cells and markers of tumor proliferation and angiogenesis. In univariate survival analysis, high cyclo-oxygenase-2 and high Ki-67 expression showed a significant impact of on patient survival (P < .001). In multivariate regression analysis, only Ki-67 expression retained its significance as an independent poor prognostic factor (death hazard ratio, 2.0; 95% CI, 1.2-3.3; P < .001). CONCLUSION: Expression of cyclo-oxygenase-2 correlates with tumor proliferation and tumor angiogenesis but not with apoptotic markers (bcl-2 expression) in high-grade, advanced-stage serous ovarian carcinoma.