A protein network-guided screen for cell cycle regulators in Drosophila

Background: Large-scale RNAi-based screens are playing a critical role in defining sets of genes that regulate specific cellular processes. Numerous screens have been completed and in some cases more than one screen has examined the same cellular process, enabling a direct comparison of the genes identified in separate screens. Surprisingly, the overlap observed between the results of similar screens is low, suggesting that RNAi screens have relatively high levels of false positives, false negatives, or both

Nuclear and Cytoplasmic Accumulation of Ep-ICD Is Frequently Detected in Human Epithelial Cancers

BACKGROUND: We previously demonstrated that nuclear and cytoplasmic accumulation of the intracellular domain (Ep-ICD) of epithelial cell adhesion molecule (EpCAM) accompanied by a reciprocal reduction of its extracellular domain (EpEx), occurs in aggressive thyroid cancers. This study was designed to determine whether similar accumulation of Ep-ICD is a common event in other epithelial cancers. METHODOLOGY AND RESULTS: Ten epithelial cancers were immunohistochemically analyzed using Ep-ICD and EpEx domain-specific antibodies. The subcellular localization of EpEx and Ep-ICD in the human colon adenocarcinoma cell line CX-1 was observed using immunofluorescence. Nuclear and cytoplasmic Ep-ICD expression was increased in cancers of the breast (31 of 38 tissues, 82%), prostate (40 of 49 tissues, 82%), head and neck (37 of 57 tissues, 65%) and esophagus (17 of 46 tissues, 37%) compared to their corresponding normal tissues that showed membrane localization of the protein. Importantly, Ep-ICD was not detected in the nuclei of epithelial cells in most normal tissues. High nuclear and cytoplasmic Ep-ICD accumulation also occurred in the other six epithelial cancer types analyzed - lung, colon, liver, bladder, pancreatic, and ovarian. A concomitant reduction in membrane EpEx expression was observed in a subset of all cancer types. Receiver operating characteristic curve analysis revealed nuclear Ep-ICD distinguished breast cancers with 82% sensitivity and 100% specificity and prostate cancers with 82% sensitivity and 78% specificity. Similar findings were observed for cytoplasmic accumulation of Ep-ICD in these cancers. We provide clinical evidence of increased nuclear and cytoplasmic Ep-ICD accumulation and a reduction in membranous EpEx in these cancers. CONCLUSIONS: Increased nuclear and cytoplasmic Ep-ICD was observed in all epithelial cancers analyzed and distinguished them from normal tissues with high-sensitivity, specificity, and AUC. Development of a robust high throughput assay for Ep-ICD will facilitate the determination of its diagnostic, prognostic and therapeutic relevance in epithelial cancers

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

The thymus is a central lymphoid organ with crucial role in generating T cells and maintaining homeostasis of the immune system. More than 30 peptides, initially referred to as “thymic hormones,” are produced by this gland. Although the majority of them have not been proven to be thymus-speciWc, thymic peptides comprise an eVective group of regulators, mediating important immune functions. Thymosin fraction Wve (TFV) was the Wrst thymic extract shown to stimulate lymphocyte proliferation and diVerentiation. Subsequent fractionation of TFV led to the isolation and characterization of a series of immunoactive peptides/polypeptides, members of the thymosin family. Extensive research on prothymosin (proT) and thymosin 1 (T1) showed that they are of clinical signiWcance and potential medical use. They may serve as molecular markers for cancer prognosis and/or as therapeutic agents for treating immunodeWciencies, autoimmune diseases and malignancies. Although the molecular mechanisms underlying their eVect are yet not fully elucidated proT and T1 could be considered as candidates for cancer immunotherapy. In this review, we will focus in principle on the eventual clinical utility of proT, both as a tumor biomarker and in triggering anticancer immune responses. Considering the experience acquired via the use of T1 to treat cancer patients, we will also discuss potential approaches for the future introduction of proT into the clinical setting

Proteomics of Thyroid Carcinoma: Detection of Potential Biomarkers of Aggressive and Non-aggressive Subtypes

In search of thyroid carcinoma biomarkers, proteins secreted by thyroid cancer cell lines, papillary-derived TPC-1 and anaplastic-derived CAL62, were analyzed using liquid chromatography-tandem mass spectrometry. Of forty six high-confidence identifications, six proteins were considered for verification in thyroid cancer patients’ tissues and blood. The localization of two proteins, nucleolin and prothymosin-alpha (PTMA), was confirmed in TPC-1 and CAL62 by confocal microscopy and immunohistochemically in xenografts of TPC-1 cells and human thyroid carcinomas. Increased nuclear and cytoplasmic expression of PTMA was observed in anaplastic carcinomas compared to normal thyroid tissues, papillary and poorly differentiated carcinomas. Importantly, six proteins were detected in thyroid cancer patients’ sera, warranting future analysis to confirm their potential as blood-based thyroid cancer markers. Herein we demonstrate the ability of secretome analysis of thyroid cancer cell lines to identify proteins that may be studied for application in management of thyroid carcinomas upon future validation.MAS

Contemporary outcomes and risk factors of acute graft-versus-host disease after liver transplant.

Introduction: Acute graft-versus-host-disease (GVHD) is a rare complication of orthotopic liver transplant (LT) that has an estimated incidence of 0.1%-2% per year. This complication of OLT carries a high mortality and affects the skin, gastrointestinal tract, and bone marrow. GVHD usually presents within 6 weeks after LT. There is limited data on GVHD after LT, and prior reported risk factors include: older age of recipient, HLA A and B matching, \u3e 20-year donor to recipient age difference, and alcoholic liver disease. We aimed to study outcomes of recent cases of acute GVHD after LT and explore potential risk factors due to the dearth of literature in this area. Methods: This is a retrospective, single center, review of patients who underwent LT between 2014-2016 and diagnosed with acute GVHD. GVHD was diagnosed both on clinical characteristics (fever, rash, diarrhea) as well as skin biopsy. Chimerism was tested on the skin biopsies. Descriptive statistics were utilized to analyze the outcomes and risk factors. Results: Seven patients were diagnosed with acute GVHD after LT during this time period. The mean time from transplant to diagnosis of GVHD was 42 days and all had a rash. The etiology of cirrhosis was 71% NASH, 14% Hepatitis C, and 14% alcoholic cirrhosis. An age gap of \u3e20 years was identified in 86% of our patients. All patient had positive chimerism in the skin. HLA matching was compared between the donor and recipient; specifically A, B, C, DR, DQA1 and DQB1. Zero shared class 1 alleles were noted in 43% of patients and 25% of those did not share a class 2 allele. Of the class II alleles, 86% had one or more common alleles with the donor. Topical steroids were used in 14% of cases. IV solumedrol was used in 86% of patients. Etanercept was used on 57% of the patients and 50% of those were were also treated with photophoresis. Death occurred in 43%. Conclusion: In our study, risk factors for acute GVHD patients included a greater than 20 year age difference and HLA crossmatch. The majority of our patients shared at least one class 1 allele with their donor, however, we have a significant amount of class 2 allele crossmatch. The number of shared alleles did not appear to correlate with risk of developing GVHD after LT or intensity of treatment required. With early recognition and more aggressive treatment options, our data suggests that mortality for acute GVHD after LT may be improving over time. This needs to be confirmed with larger studies

Spread of Carbapenem and Colistin-Resistant Klebsiella pneumoniae ST512 Clinical Isolates in Israel: A Cause for Vigilance

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