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To identify a biomarker of ovarian cancer response to chemotherapy. PATIENTS AND METHODS Study: participants had epithelial ovarian cancer treated with surgery followed by platinum-based chemotherapy. DNA and RNA were isolated from frozen tumors and normal DNA was isolated from matched peripheral blood. A whole-genome loss of heterozygosity (LOH) analysis was performed using a high-density oligonucleotide array. Candidate genomic areas that predicted enhanced response to chemotherapy were identified with Cox proportional hazards methods. Gene expression analyses were performed through microarray experiments. Candidate genes were tested for independent effects on survival using Cox proportional hazards models, Kaplan-Meier survival curves, and the log-rank test.', 'Using a whole-genome approach to study the molecular determinants of ovarian cancer response to platinum-based chemotherapy, we identified LOH of a 13q region to predict prolonged progression-free survival (PFS; hazard ratio, 0.23; P = .006). ERCC5 was identified as a candidate gene in this region because of its known function in the nucleotide excision repair pathway, the unique DNA repair pathway that removes platinum-DNA adducts. We found LOH of the ERCC5 gene locus and downregulation of ERCC5 gene expression to predict prolonged PFS. Integration of genomic and gene expression data shows a correlation between 13q LOH and ERCC5 gene downregulation.
Is eRCC5 a novel biomarker of ovarian cancer prognosis?

Wnt proteins are important for developmental processes and certain diseases. WNT5A is a non-canonical Wnt protein that previously has been shown to play a role in the progression of malignant melanoma. High expression of WNT5A in melanoma tumors correlates to formation of distant metastasis and poor prognosis. This has partly been described by the findings that WNT5A expression in melanoma cell lines increases migration and invasion.', 'Malignant melanoma cell lines were treated with rWNT5A or WNT5A siRNA, and mRNA versus protein levels of soluble mediators were measured using RT-PCR, cytokine bead array and ELISA. The induced signaling pathways were analyzed using inhibitors, Rho-GTPase pull down assays and western blot. Ultracentrifugation and electron microscopy was used to analyze microvesicles. Gene expression microarray data obtained from primary malignant melanomas was used to verify our data.', 'We show that WNT5A signaling induces a Ca2+-dependent release of exosomes containing the immunomodulatory and pro-angiogenic proteins IL-6, VEGF and MMP2 in melanoma cells. The process was independent of the transcriptional machinery and depletion of WNT5A reduced the levels of the exosome-derived proteins. The WNT5A induced exosomal secretion was neither affected by Tetanus toxin nor Brefeldin A, but was blocked by the calcium chelator Bapta, inhibited by a dominant negative version of the small Rho-GTPase Cdc42 and was accompanied by cytoskeletal reorganization. Co-cultures of melanoma/endothelial cells showed that depletion of WNT5A in melanoma cells decreased endothelial cell branching, while stimulation of endothelial cells with isolated rWNT5A-induced melanoma exosomes increased endothelial cell branching in vitro. Finally, gene expression data analysis of primary malignant melanomas revealed a correlation between WNT5A expression and the angiogenesis marker ESAM.
Does wNT5A induce release of exosomes containing pro-angiogenic and immunosuppressive factors from malignant melanoma cells?

Kochia scoparia (Chenopodiaceae) has been reported to have anti-nociceptive, anti-inflammatory, anti-allergic, and anti-pruritic actions. This study investigated the anti-inflammatory effects of externally applied Kochia scoparia water extract (KSW) in 2,4-dinitrochlorobenzene (DNCB)-induced contact dermatitis mouse model.', 'To develop atopic dermatitis-like skin lesions, 100L of 1% DNCB in acetone/olive oil (4:1) had been applied for three days on shaved dorsal skin. 1% KSW was topically applied to DNCB-induced mice. After KSW treatment, histological analysis was measured by hematoxylin eosin staining. The cytokine and pro-inflammatory expressions were examined using reverse transcription polymerase chain reaction and western blotting analysis.', 'Histological studies showed that hyperplasia of the epidermis and dermis in the KSW treated group was markedly decreased as compared with the DNCB group. The expression levels of pro-inflammatory cytokine such as IL-1, and TNF- mRNA were significantly reduced by topical application of KSW, whereas these cytokines were increased in DNCB-induced dorsal skin. In addition, NF-B expression was inhibited by KSW treatment in DNCB-induced mice. Similarly, KSW treatment significantly suppressed the expression of several MAP kinases, including ERK1/2, p38, and JNK compared to their expression in DNCB-induced mice.
Does topical application of Kochia scoparia inhibit the development of contact dermatitis in mice?