Carboplatin-induced gene expression changes in vitro are prognostic of survival in epithelial ovarian cancer

<p>Abstract</p> <p>Background</p> <p>We performed a time-course microarray experiment to define the transcriptional response to carboplatin <it>in vitro</it>, and to correlate this with clinical outcome in epithelial ovarian cancer (EOC). RNA was isolated from carboplatin and control-treated 36M2 ovarian cancer cells at several time points, followed by oligonucleotide microarray hybridization. Carboplatin induced changes in gene expression were assessed at the single gene as well as at the pathway level. Clinical validation was performed in publicly available microarray datasets using disease free and overall survival endpoints.</p> <p>Results</p> <p>Time-course and pathway analyses identified 317 genes and 40 pathways (designated time-course and pathway signatures) deregulated following carboplatin exposure. Both types of signatures were validated in two separate platinum-treated ovarian and NSCLC cell lines using published microarray data. Expression of time-course and pathway signature genes distinguished between patients with unfavorable and favorable survival in two independent ovarian cancer datasets. Among the pathways most highly induced by carboplatin <it>in vitro</it>, the NRF2, NF-kB, and cytokine and inflammatory response pathways were also found to be upregulated prior to chemotherapy exposure in poor prognosis tumors.</p> <p>Conclusion</p> <p>Dynamic assessment of gene expression following carboplatin exposure <it>in vitro </it>can identify both genes and pathways that are correlated with clinical outcome. The functional relevance of this observation for better understanding the mechanisms of drug resistance in EOC will require further evaluation.</p

Integrated Analysis of Multiple Microarray Datasets Identifies a Reproducible Survival Predictor in Ovarian Cancer

BACKGROUND: Public data integration may help overcome challenges in clinical implementation of microarray profiles. We integrated several ovarian cancer datasets to identify a reproducible predictor of survival. METHODOLOGY/PRINCIPAL FINDINGS: Four microarray datasets from different institutions comprising 265 advanced stage tumors were uniformly reprocessed into a single training dataset, also adjusting for inter-laboratory variation ("batch-effect"). Supervised principal component survival analysis was employed to identify prognostic models. Models were independently validated in a 61-patient cohort using a custom array genechip and a publicly available 229-array dataset. Molecular correspondence of high- and low-risk outcome groups between training and validation datasets was demonstrated using Subclass Mapping. Previously established molecular phenotypes in the 2(nd) validation set were correlated with high and low-risk outcome groups. Functional representational and pathway analysis was used to explore gene networks associated with high and low risk phenotypes. A 19-gene model showed optimal performance in the training set (median OS 31 and 78 months, p < 0.01), 1(st) validation set (median OS 32 months versus not-yet-reached, p = 0.026) and 2(nd) validation set (median OS 43 versus 61 months, p = 0.013) maintaining independent prognostic power in multivariate analysis. There was strong molecular correspondence of the respective high- and low-risk tumors between training and 1(st) validation set. Low and high-risk tumors were enriched for favorable and unfavorable molecular subtypes and pathways, previously defined in the public 2(nd) validation set. CONCLUSIONS/SIGNIFICANCE: Integration of previously generated cancer microarray datasets may lead to robust and widely applicable survival predictors. These predictors are not simply a compilation of prognostic genes but appear to track true molecular phenotypes of good- and poor-outcome

Development of egg packets and silica from rice husk

555-559The extraction of nano-size silica and development of hard packets for egg storage from rice husk (RH) using chemical method has been carried out. The obtained silica and egg packets have been characterized using Infra red spectrometer (FT-IR), X-ray diffraction (XRD), Scanning electron microcopy (SEM) and Shore D. The result reveals the formation of nano size silica with size 50-60 nm with surface area of 542 m2 g/L. The physical hardness of egg packets is found 52 D, suitable for egg storage. The efficacy of developed packets on fresh market egg quality during storage at ambient temperature is investigated in terms of weight loss, pH and albumen quality. The developed packets show 35% lesser weight loss and pH 0.3 during 4 weeks of storage time

Evaluation of Phytochemical Parameters, Antibacterial and Antihelminthic Activity of Leaves and Bark Extracts of Plant Bombax Ceiba

Bombax ceiba, commonly known as the red silk-cotton tree, is a large, briefly deciduous tree occurring in warm monsoon forests in southern Asia. Various phytochemical constituents present in different plant parts has been already reported earlier to possess many biological activities, here in this work extraction was performed by mixture of solvent (distilled water: ethanol) as well as the individual solvents (water) and (ethanol). The phytochemical screening of the leaves and barks was found to exhibit the presence of carbohydrates, glycoside, saponin, phytosterol phenol, tannins, flavonoid, proteins and diterpenes and negative result for alkaloids in all the solvent extracts. The ethanolic extract of leaves was subjected to antihelmenthic activity and the result was found to be moderat

Herbal and traditional medicines pharmacovigilance for holistic treatment

13-21Compared to allopathic medicines or chemically synthesized drugs, there is a growing use of natural compounds and supplements in herbal medicine to treat various diseases as they are safe and devoid of side effects. Though, this is not completely true as many cases of the detrimental impact of herbal or traditional medicine have been reported. Herbal medicines contain unpurified plant portions or extracts which may have these side effects. How effective are the drug molecules derived from natural products, or how destructive are the undesirable compounds that must be investigated? Natural extracts are mixtures of various components, and there is uncertainty about the mechanism of action of certain herbal medicines. There may be a lot of factors involved like placebo effects, and other molecules without which medicine may not work in isolation. In this study, we have reviewed the effects of herbal medicines, possible causes for their benefits like epigenetic changes, adverse drug reactions, and the provision to control these issues. We have also explored the measures being taken at the national and international levels. There have been efforts to minimize the issues related to side effects based on reporting from the population using remedies monitored by pharmacovigilance