Expression of the BAD pathway is a marker of triple-negative status and poor outcome.

Triple-negative breast cancer (TNBC) has few therapeutic targets, making nonspecific chemotherapy the main treatment. Therapies enhancing cancer cell sensitivity to cytotoxic agents could significantly improve patient outcomes. A BCL2-associated agonist of cell death (BAD) pathway gene expression signature (BPGES) was derived using principal component analysis (PCA) and evaluated for associations with the TNBC phenotype and clinical outcomes. Immunohistochemistry was used to determine the relative expression levels of phospho-BAD isoforms in tumour samples. Cell survival assays evaluated the effects of BAD pathway inhibition on chemo-sensitivity. BPGES score was associated with TNBC status and overall survival (OS) in breast cancer samples of the Moffitt Total Cancer Care dataset and The Cancer Genome Atlas (TCGA). TNBC tumours were enriched for the expression of phospho-BAD isoforms. Further, the BPGES was associated with TNBC status in breast cancer cell lines of the Cancer Cell Line Encyclopedia (CCLE). Targeted inhibition of kinases known to phosphorylate BAD protein resulted in increased sensitivity to platinum agents in TNBC cell lines compared to non-TNBC cell lines. The BAD pathway is associated with triple-negative status and OS. TNBC tumours were enriched for the expression of phosphorylated BAD protein compared to non-TNBC tumours. These findings suggest that the BAD pathway it is an important determinant of TNBC clinical outcomes.

Chorionic villus sampling and the risk of adverse outcome in patients undergoing multifetal pregnancy reduction.

OBJECTIVE: The objective of the study was to determine whether patients undergoing chorionic villus sampling (CVS) prior to MPR are at increased risk for adverse outcome compared to those who did not. STUDY DESIGN: We retrospectively identified multifetal pregnancy reduction (MPR) patients from an established database. Maternal demographic data were collected. Outcomes including complete pregnancy loss prior to 24 weeks' gestation, gestational age at delivery, and birthweight were analyzed. RESULTS: There was no significant difference in pregnancy loss between the 2 groups (CVS [4%] vs no CVS [7%], P = .098). When stratified by finishing number, there was a significantly lower loss rate in the singleton CVS group (2% vs 9%, P = .025) and no significant difference in reduced twins. There was no significant difference in the average gestational age of delivery or birthweight. CONCLUSION: CVS prior to MPR does not increase the risk of pregnancy loss. Our data suggest that CVS prior to singleton reduction may decrease the risk of adverse outcome.

Inflammatory response after influenza vaccination in men with and without carotid artery disease.

OBJECTIVE: Inflammatory markers are associated with vascular disease; however, variation in the acute phase response (APR) has not been evaluated. We evaluated whether the APR magnitude in men with severe carotid artery disease (CAAD) (>80% stenosis) differed from that of men without stenosis (<15% stenosis). METHODS AND RESULTS: White males with (n=43) and without (n=61) severe CAAD receiving clinical influenza vaccinations were recruited. Their baseline and 24-hour after -vaccination blood samples were assayed for C-reactive protein (CRP), IL-6, and serum amyloid-a (SAA). In vivo APR to vaccination was measurable and varied among subjects. Adjusted for age, smoking, oral hypoglycemics, aspirin, and stain use, the relative 24-hour changes in levels of ln(CRP), ln(IL-6), and ln(SAA) were higher in men with CAAD than in men without, but only the SAA response was significant (P=0.02); the relative SAA response was 1.6 (95% confidence interval, 1.1 to 2.5) times higher in men with than without CAAD. The APR for all markers appeared to be independent of baseline levels. CONCLUSIONS: Influenza vaccination results in a mild, but measurable, APR in men with and without CAAD. SAA APR variability may be a predictor of severe vascular disease that is independent of basal SAA level.

Profile of bevacizumab in the treatment of platinum-resistant ovarian cancer: current perspectives.

Patients with platinum-resistant ovarian cancer have progression of disease within 6 months of completing platinum-based chemotherapy. While several chemotherapeutic options exist for the treatment of platinum-resistant ovarian cancer, the overall response to any of these therapies is ~10%, with a median progression-free survival of 3-4 months and a median overall survival of 9-12 months. Bevacizumab (Avastin), a humanized, monoclonal antivascular endothelial growth factor antibody, has demonstrated antitumor activity in the platinum-resistant setting and was recently approved by US Food and Drug Administration for combination therapy with weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan. This review summarizes key clinical trials investigating bevacizumab for recurrent, platinum-resistant ovarian cancer and provides an overview of efficacy, safety, and quality of life data relevant in this setting. While bevacizumab is currently the most studied and clinically available antiangiogenic therapy, we summarize recent studies highlighting novel alternatives, including vascular endothelial growth factor-trap, tyrosine kinase inhibitors, and angiopoietin inhibitor trebananib, and discuss their application for the treatment of platinum-resistant ovarian cancer.

Primary peritoneal carcinoma presenting as a Sister Mary Joseph's nodule: A case report and review of the literature.

Sister Mary Joseph's nodule is sometimes the first sign of an internal malignancy, including gastrointestinal, gynecological, or malignancy of unknown primary. It is rarely the sole presentation of a primary peritoneal cancer. In this report, we present the case of a 70-year-old female with umbilical drainage and a computed tomography scan consistent with solitary umbilical nodule. Excision of the nodule revealed adenocarcinoma of likely müllerian origin. Surgical staging did not show any evidence of malignancy with the exception of pelvic washings. She was considered to have primary peritoneal adenocarcinoma and was treated with adjuvant chemotherapy.

The Chinese herb polyphyllin D sensitizes ovarian cancer cells to cisplatin-induced growth arrest.

PURPOSE: We evaluated the effects of polyphyllin D (PD), a natural compound with anti-neoplastic activity and a major component of the Chinese herb Paris polyphylla, on ovarian cancer (OVCA) cell line proliferation and platinum sensitivity. METHODS: A panel of 20 OVCA cell lines was subjected to PD treatment, MTS proliferation assays, and determination of IC50. Pre-treatment, baseline genome-wide Affymetrix expression analysis was performed on each cell line, and Pearson's correlation was performed to identify genes associated with OVCA PD sensitivity. Twelve cell lines were treated with PD with and without cisplatin, and the effects of PD on cisplatin IC50 were quantified. Genes associated with OVCA PD sensitivity were evaluated for associations with survival in a publically available clinico-genomic dataset of 218 patients with OVCA. RESULTS: Our results showed that PD exhibited anti-proliferative effects against all OVCA cell lines tested, with IC50 values ranging from 0.2 to 1.4 µm. Furthermore, in all cell lines, PD treatment significantly decreased cisplatin IC50 (mean IC50 reduction of 2.1 µm; P < 0.02). Pearson's correlation test identified 25 probe sets, representing 18 unique genes to be associated with PD sensitivity (FDR = 0). We found that one of these genes was associated with overall survival in women with OVCA: CLDN4 (P = 0.014). CONCLUSION: Our findings highlight the value of PD as a natural product with anti-cancer properties, which may also enhance the activity of existing therapeutic agents.