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.     

Antifungal saponins from Paris polyphylla Smith

Three steroidal saponins, including one new and two known compounds, were isolated from the rhizomes of Paris polyphylla Smith. One- and two-dimensional NMR, LC-MS, and interpretation of hydrolytic cleavage experiments led to the identification of the structure of the new saponin as ( 25R)-spirost-5-ene-3 beta,17 alpha-diol (pennogenin) 3- O-{ O- alpha- L-rhamnopyranosyl-(1-->2)- O-[ O- beta-xylopyranosyl-(1-->5)- alpha- L-arabinofuranosyl-(1-->4)]- beta- D-glucopyranoside}. The isolated saponins were evaluated for their antifungal activity against Cladosporium cladosporioides and Candida species and showed comparable activity to chemicals used in some commercial products.     

A comparison of model performance for six quantitative structure-activity relationship packages that predict acute toxicity to fish

Some regulatory programs rely on quantitative structure-activity relationship (QSAR) models to predict toxic effects to biota. Many currently existing QSAR models can predict the effects of a wide range of substances to biota, particularly aquatic biota. The difficulty for regulatory programs is in choosing the appropriate QSAR model or models for application in their new and existing substances programs. We evaluated model performance of six QSAR modeling packages: Ecological Structure Activity Relationship (ECOSAR), TOPKAT, a Probabilistic Neural Network (PNN), a Computational Neural Network (CNN), the QSAR components of the Assessment Tools for the Evaluation of Risk (ASTER) system, and the Optimized Approach Based on Structural Indices Set (OASIS) system. Using a testing data set of 130 substances that had not been included in the training data sets of the QSAR models under consideration, we compared model predictions for 96-h median lethal concentrations (LC50s) to fathead minnows to the corresponding measured toxicity values available in the AQUIRE database. The testing data set was heavily weighted with neutral organics of low molecular weight and functionality. Many of the testing data set substances also had a nonpolar narcosis mode of action and/or were chlorinated. A variety of statistical measures (correlation coefficient, slope and intercept from a linear regression analysis, mean absolute and squared difference between log prediction and log measured toxicity, and the percentage of predictions within factors of 2, 5, 10, 100, and 1,000 of measured toxicity values) indicated that the PNN model had the best model performance for the full testing data set of 130 substances. The rank order of the remainder of the models depended on the statistical measure employed. TOPKAT also had excellent model performance for substances within its optimum prediction space. Only 37% of the substances in the testing data set, however, fell within this optimum prediction space.     

Isolation and identification of a cis-C8-diol-ester of okadaic acid from Dinophysis acuta in New Zealand.

A cis-isomer of a C(8)-diol ester of okadaic acid (1) was isolated during large-scale purification of pectenotoxins (PTXs) from extracts of Dinophysis acuta collected from the west coast of South Island, New Zealand. The compound was identified by NMR spectroscopic and liquid chromatography-mass spectrometry (LC-MS) studies, and is the first reported cis-isomer of an okadaic acid C(8)-diol-ester identified in Dinophysis. The more abundant trans-C(8)-diol ester of okadaic acid (2) isolated from the same Dinophysis extract was rapidly hydrolyzed to okadaic acid in vitro by the supernatant from green-lipped mussel hepatopancreas.     

Influence of organizational functioning on client engagement in treatment

This study focused on the relationship between organizational functioning factors measured in a staff survey using the Texas Christian University (TCU) Organizational Readiness for Change assessment and client-level engagement measured by the TCU Client Evaluation of Self and Treatment in drug treatment programs. The sample consisted of 531 clinical and counseling staff and 3,475 clients from 163 substance abuse treatment programs located in nine states from three regional Addiction Technology Transfer Centers. Measures of client engagement in treatment (rapport, satisfaction, and participation) were shown to be higher in programs with more positive staff ratings of organizational functioning. In particular, these programs had fewer agency needs and more favorable ratings for their resources, staff attributes, and climate. These findings help establish the importance of addressing organizational factors as part of an overall strategy for improving treatment effectiveness.     

Social context as an explanation for race disparities in hypertension: findings from the Exploring Health Disparities in Integrated Communities (EHDIC) Study

Disparities in hypertension between African Americans and non-Hispanic whites have been well-documented, yet an explanation for this persistent disparity remains elusive. Since African Americans and non-Hispanic white Americans tend to live in very different social environments, it is not known whether race disparities in hypertension would persist if non-Hispanic whites and African Americans were exposed to similar social environments. We compared data from the Exploring Health Disparities in Integrated Communities-SWB (EHDIC-SWB) Study with the National Health and Nutrition Examination Survey (NHANES) 1999-2004 to determine if race disparities in hypertension in the USA were attenuated in EHDIC-SWB, which is based in a racially integrated community without race differences in income. Hypertension was defined as systolic blood pressure (BP) > or = 140 mmHg (millimeters of mercury) and/or diastolic BP > or = 90 mmHg or respondent's report of taking antihypertensive medications. Of the 1408 study participants, 835 (59.3%) were African American, 628 (44.6%) were men, and the mean age was 40.6 years. After adjustment for potential confounders, various analytic models from EHDIC-SWB and NHANES 1999-2004 data, we found the race odds ratio was between 29.0% and 34% smaller in the EHDIC-SWB sample. We conclude that social and environmental exposures explained a substantial proportion of the race difference in hypertension.