Mammaglobin B (SCGB2A1) is a novel tumour antigen highly differentially expressed in all major histological types of ovarian cancer: implications for ovarian cancer immunotherapy.

Background: We studied the genetic fingerprints of ovarian cancer and validated the potential of Mammaglobin b (SCGB2A1), one of the top differentially expressed genes found in our analysis, as a novel ovarian tumour rejection antigen.

Methods: We profiled 70 ovarian carcinomas including 24 serous (OSPC), 15 clear-cell (CC), 24 endometrioid (EAC) and 7 poorly differentiated tumours, and 14 normal human ovarian surface epithelial (HOSE) control cell lines using the Human HG-U133 Plus 2.0 chip (Affymetrix).

Toward standard HER2 testing of endometrial serous carcinoma: 4-year experience at a large academic center and recommendations for clinical practice.

HER2 overexpression and/or amplification have been reported in endometrial serous carcinoma, suggesting that HER2 may be a promising therapeutic target. However, there is considerable variation in the reported rates of HER2 overexpression and amplification, likely--at least in part--resulting from variability in the testing methods, interpretation, and scoring criteria used. Unlike in breast and gastric cancer, currently there are no established guidelines for HER2 testing in endometrial carcinoma.

Claudins overexpression in ovarian cancer: potential targets for Clostridium Perfringens Enterotoxin (CPE) based diagnosis and therapy.

Claudins are a family of tight junction proteins regulating paracellular permeability and cell polarity with different patterns of expression in benign and malignant human tissues. There are approximately 27 members of the claudin family identified to date with varying cell and tissue-specific expression. Claudins-3, -4 and -7 represent the most highly differentially expressed claudins in ovarian cancer.

Glycated hemoglobin is not an accurate indicator of glycemia in rainbow trout.

Glycation occurs when glucose reacts non-enzymatically with proteins. This reaction depends upon time, ambient glucose concentration, and the molecular conformation of reactive amino acids. Little is known about protein glycation in fishes and the main objective of this study was to measure glycated hemoglobin (GHb) in rainbow trout, a glucose-intolerant species, under normoglycemic and hyperglycemic conditions.

Tubulin-β-III overexpression by uterine serous carcinomas is a marker for poor overall survival after platinum/taxane chemotherapy and sensitivity to epothilones.

Background: Uterine serous carcinoma (USC) is a subtype of endometrial cancer associated with chemoresistance and poor outcome. Overexpression of tubulin-β-III and p-glycoprotein has been linked to paclitaxel resistance in many cancers but has been undercharacterized among USCs. Epothilones have demonstrated activity in certain paclitaxel-resistant malignancies.

Class III β-tubulin overexpression in ovarian clear cell and serous carcinoma as a maker for poor overall survival after platinum/taxane chemotherapy and sensitivity to patupilone.

Objective: Clear cell carcinoma of the ovary is a distinct subtype of epithelial cancer associated with chemoresistance and poor outcome compared with serous papillary carcinomas. Resistance to paclitaxel has been linked to serous papillary overexpression of class III β-tubulin in several human cancers but inadequately characterized among clear cell carcinoma of the ovary. Chemoresistance has also been variably linked to the drug efflux pump p-glycoprotein.

HER2 expression beyond breast cancer: therapeutic implications for gynecologic malignancies.

HER2 or ErbB2 is a member of the epidermal growth factor family and is overexpressed in subsets of breast, ovarian, gastric, colorectal, pancreatic, and endometrial cancers. HER2 regulates signaling through several pathways (Ras/Raf/mitogen-activated protein kinase and phosphatidylinositol-3 kinase/protein kinase B/mammalian target of rapamycin pathways) associated with cell survival and proliferation. HER2-overexpressed and/or gene-amplified tumors are generally regarded as biologically aggressive neoplasms.

Landscape of somatic single-nucleotide and copy-number mutations in uterine serous carcinoma.

Uterine serous carcinoma (USC) is a biologically aggressive subtype of endometrial cancer. We analyzed the mutational landscape of USC by whole-exome sequencing of 57 cancers, most of which were matched to normal DNA from the same patients. The distribution of the number of protein-altering somatic mutations revealed that 52 USC tumors had fewer than 100 (median 36), whereas 5 had more than 3,000 somatic mutations.

Early stage uterine serous carcinoma: management updates and genomic advances.

Objective: Even in cases of early stage disease, uterine serous carcinoma (USC) is associated with high recurrence rates and a disproportionate number of cancer-related deaths. Prospective data to guide therapy for women with this disease are limited. This article reviews the currently available literature regarding optimal management of women with early stage USC.

Class III b-tubulin overexpression in gynecologic tumors: implications for the choice of microtubule targeted agents?

The tubulins are significant players in maintaining microtubule dynamics and have important signaling and apoptotic functions. Alterations in microtubules as a result of changes in tubulin isotype content or polymerization affect the sensitivity of cell lines to tubulin-binding agents (e.g.

Trop-2 protein overexpression is an independent marker for predicting disease recurrence in endometrioid endometrial carcinoma.

Background: Endometrial cancer is the most common gynecologic malignancy in developed countries. Trop-2 is a glycoprotein involved in cellular signal transduction and is differentially overexpressed relative to normal tissue in a variety of human adenocarcinomas, including endometrioid endometrial carcinomas (EEC). Trop-2 overexpression has been proposed as a marker for biologically aggressive tumor phenotypes.

Updates in therapy for uterine serous carcinoma.

Purpose Of Review: Uterine serous carcinoma (USC) is a highly aggressive variant of endometrial cancer with distinct molecular pathogenesis. This review summarizes the rationale behind current clinical approaches, as well as advances made in 2012 toward the elucidation of underlying pathway aberrations and development of targeted therapies that exploit these unique characteristics.

Recent Findings: Within the last year, exome-wide analyses have highlighted key mutations to guide rational drug design.

Prognostic significance of vascular endothelial growth factor serum determination in women with ovarian cancer.

Introduction. We performed a review of the literature to elucidate the potential prognostic significance of serum vascular endothelial growth factor (sVEGF) levels in ovarian cancer. Methods.

Validation of reference genes for normalizing gene expression in real-time quantitative reverse transcription PCR in human thyroid cells in primary culture treated with progesterone and estradiol.

The use of appropriately chosen reference genes for normalizing gene expression in real-time quantitative reverse transcription polymerase chain reaction is an important step in the analysis of gene expression, compensating for several technical factors. As female sex hormones have been shown to influence growth and differentiation of thyroid follicular cells, the establishment of normalizer genes in human thyroid cells in primary culture, treated with progesterone, and estradiol, is important to evaluate their effect on gene expression in these cells, so candidate reference genes were studied. β-Actin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), β2-microglobulin (B2M), and TATA box binding protein (TBP) were evaluated in thyroid cells treated with estradiol, progesterone, and their inhibitors.

Neoadjuvant chemotherapy (NACT) is an effective way of managing elderly women with advanced stage ovarian cancer (FIGO Stage IIIC and IV).

Background: To compare outcomes in women ≥ age 70 who receive neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer (EOC) followed by cytoreductive surgery with those undergoing upfront cytoreductive surgery followed by the same chemotherapy.

Methods: A retrospective cohort study was performed for women ≥ age 70 with Stage IIIC or Stage IV EOC from 1996 to 2009.

Results: Sixty-two patients who underwent upfront cytoreductive surgery and 42 patients who received NACT were eligible for analysis.

Downregulation of membrane complement inhibitors CD55 and CD59 by siRNA sensitises uterine serous carcinoma overexpressing Her2/neu to complement and antibody-dependent cell cytotoxicity in vitro: implications for trastuzumab-based immunotherapy.

Background: We evaluated the expression of CD46, CD55 and CD59 membrane-bound complement-regulatory proteins (mCRPs) in primary uterine serous carcinoma (USC) and the ability of small interfering RNA (siRNA) against these mCRPs to sensitise USC to complement-dependent cytotoxicity (CDC) and antibody (trastuzumab)-dependent cellular cytotoxicity (ADCC) in vitro.

Methods: Membrane-bound complement-regulatory proteins expression was evaluated using real-time PCR (RT-PCR) and flow cytometry, whereas Her2/neu expression and c-erbB2 gene amplification were assessed using immunohistochemistry, flow cytometry and fluorescent in-situ hybridisation. The biological effect of siRNA-mediated knockdown of mCRPs on HER2/neu-overexpressing USC cell lines was evaluated in CDC and ADCC 4-h chromium-release assays.

HER2/neu as a potential target for immunotherapy in gynecologic carcinosarcomas.

Carcinosarcomas of the female genital tract are rare tumors with an aggressive clinical behavior. Trastuzumab, a humanized monoclonal antibody, acts by binding to HER2/neu extracellular domain and exhibits therapeutic efficacy in HER2/neu-overexpressing cancers. Two uterine carcinosarcomas (UMMT-ARK-1, UMMT-ARK-2) and 2 ovarian carcinosarcomas (OMMT-ARK-1, OMMT-ARK-2) were established as primary tumor cell lines in vitro and evaluated for HER2/neu expression by immunohistochemistry, fluorescent in situ hybridization analysis, quantitative real-time polymerase chain reaction, and for membrane-bound complement regulatory proteins CD46, CD55, and CD59 by flow cytometry.

Outcomes of early, late, and no admission to the intensive care unit for patients hospitalized with community-acquired pneumonia.

Objectives: The objective was to compare outcomes associated with early, late, and no admission to the intensive care unit (ICU) for patients hospitalized with community-acquired pneumonia (CAP).

Methods: This was a post hoc analysis of the original data from the Emergency Department Community-Acquired Pneumonia (EDCAP) and Pneumocom-1 prospective multicenter cohort studies of adult patients hospitalized with CAP. Propensity score-adjusted analysis was used to compare 28-day mortality and hospital length of stay (LOS) for 199, 144, and 2,215 patients with early (i.

EGFR/HER-targeted therapeutics in ovarian cancer.

Despite decades of research and evolving treatment modalities, survival among patients with epithelial ovarian cancer has improved only incrementally. During this same period, the development of biologically targeted therapeutics has improved survival for patients with diverse malignancies. Many of these new drugs target the human epidermal growth factor receptor (EGFR/HER/ErbB) family of tyrosine kinases, which play a major role in the etiology and progression of many carcinomas, including epithelial ovarian cancer.

Differential in vitro sensitivity to patupilone versus paclitaxel in uterine and ovarian carcinosarcoma cell lines is linked to tubulin-beta-III expression.

Objective: To compare the in vitro sensitivity/resistance to patupilone versus paclitaxel in uterine and ovarian carcinosarcomas (CS).

Methods: Five primary carcinosarcoma cell lines, two from uterine and three of ovarian origin, were evaluated for growth rate and tested for their in vitro sensitivity/resistance to patupilone versus paclitaxel by MTS assays. To identify potential mechanisms underlying the differential sensitivity/resistance to patupilone, expression levels of β-tubulin III (TUBB3) were determined with quantitative-real-time-polymerase-chain-reaction (q-RT-PCR) in primary uterine and ovarian CS cell lines and in 26 uterine and 9 ovarian CS fresh-frozen-tissues.

Claudin-6: a novel receptor for CPE-mediated cytotoxicity in ovarian cancer.

Claudins are integral tight junction proteins that are responsible for maintaining the integrity of epithelial cell architecture and cell polarity. Claudin-3 and -4 are overexpressed in several cancers and have been shown to act as receptors for the Clostridium perfringens enterotoxin (CPE), a toxin that causes rapid cell lysis. CPE has demonstrated effectiveness in treating several different cancers in mouse models, provided that these cancers express claudin-3 or claudin-4.

Serum sodium abnormalities during nonexertional heatstroke: incidence and prognostic values.

Background: Although heatstroke is often associated with dehydration, the clinical significance of serum sodium abnormalities in patients with heat-related illness during heat wave has been poorly documented.

Method: We evaluated 1263 patients (age, 82±15 years; body temperature, 40.1°C+1.

Development of targeted therapy in uterine serous carcinoma, a biologically aggressive variant of endometrial cancer.

Endometrial cancer (EC) is the most common female genital malignancy in the USA. Most carcinomas arising from the uterus are estrogen dependent and are associated with obesity and hypertension. They are designated type I ECs and typically, due to their early diagnosis secondary to postmenopausal bleeding, have a good prognosis.

A KRAS variant is a biomarker of poor outcome, platinum chemotherapy resistance and a potential target for therapy in ovarian cancer.

Germline variants in the 3' untranslated region (3'UTR) of cancer genes disrupting microRNA (miRNA) regulation have recently been associated with cancer risk. A variant in the 3'UTR of the KRAS oncogene, referred to as the KRAS variant, is associated with both cancer risk and altered tumor biology. Here, we test the hypothesis that the KRAS variant can act as a biomarker of outcome in epithelial ovarian cancer (EOC), and investigate the cause of altered outcome in KRAS variant-positive EOC patients.

Uterine and ovarian carcinosarcomas overexpressing Trop-2 are sensitive to hRS7, a humanized anti-Trop-2 antibody.

Background: We evaluated the expression of human trophoblastic cell-surface marker (Trop-2) and the potential of hRS7 - a humanized monoclonal anti-Trop-2 antibody - as a therapeutic strategy against treatment-refractory human uterine (UMMT) and ovarian (OMMT) carcinosarcoma cell lines.

Materials And Methods: Trop-2 expression was evaluated by immunohistochemistry (IHC) in paraffin-embedded tumor tissues, by real-time polymerase-chain-reaction (RT-PCR) and flow-cytometry in cell lines. Sensitivity to hRS7 antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested using 5-hour chromium-release assays against UMMT and OMMT cells.