Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Autoimmune gastrointestinal complications in patients with Systemic Lupus Erythematosus: case series and literature review

The association of systemic lupus erythematosus (SLE) with gastrointestinal autoimmune diseases is rare, but has been described in the literature, mostly as case reports. However, some of these diseases may be very severe, thus a correct and early diagnosis with appropriate management are fundamental. We have analysed our data from the SLE patient cohort at University College Hospital London, established in 1978, identifying those patients with an associated autoimmune gastrointestinal disease. We have also undertaken a review of the literature describing the major autoimmune gastrointestinal pathologies which may be coincident with SLE, focusing on the incidence, clinical and laboratory (particularly antibody) findings, common aetiopathogenesis and complications

Therapeutic opportunities within the DNA damage response

The DNA damage response (DDR) is essential for maintaining the genomic integrity of the cell, and its disruption is one of the hallmarks of cancer. Classically, defects in the DDR have been exploited therapeutically in the treatment of cancer with radiation therapies or genotoxic chemotherapies. More recently, protein components of the DDR systems have been identified as promising avenues for targeted cancer therapeutics. Here, we present an in-depth analysis of the function, role in cancer and therapeutic potential of 450 expert-curated human DDR genes. We discuss the DDR drugs that have been approved by the US Food and Drug Administration (FDA) or that are under clinical investigation. We examine large-scale genomic and expression data for 15 cancers to identify deregulated components of the DDR, and we apply systematic computational analysis to identify DDR proteins that are amenable to modulation by small molecules, highlighting potential novel therapeutic targets

The landscape of somatic copy-number alteration across human cancers

available in PMC 2010 August 18.A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-κΒ pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types.National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, P50CA90578)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, R01CA109038))National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, R01CA109467)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, P01CA085859)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, P01CA 098101)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, K08CA122833

Identification of prognostic phenotypes of esophageal adenocarcinoma in two independent cohorts.

BACKGROUND & AIMS: Most patients with esophageal adenocarcinoma (EAC) present de novo. Although this may be due to inadequate screening strategies, the precise reason for this observation is not clear.. We compared survival of patients with prevalent EAC with and without synchronous BE/intestinal metaplasia of the esophagus (IM) at the time of EAC diagnosis. METHODS: Clinical data were studied using Cox Proportional Hazards regression to evaluate the effect of synchronous BE/IM on EAC survival independent of age, sex, TNM stage and tumor location. Two cohorts from the Mayo Clinic and a U.K. multicenter prospective cohort were included. RESULTS: The Mayo cohort had 411 EAC patients with 49.3% with BE/IM demonstrating a survival benefit as compared to those without (hazard ratio (HR), 0.44; 95% CI: 0.34 - 0.57, P<0.001). In a multivariable analysis BE/IM was associated with better survival independent of age, sex, stage and tumor location and length (adjusted HR: 0.66, 95% CI: 0.5-0.88, P=0.005). The UK cohort contained 1417 patients, 45% with BE/IM demonstrating a survival benefit as compared with non-BE/IM patients (HR 0.59, 95% CI: 0.5-0.69, P<0.001) with continued significance in multivariable analysis that included age, sex, stage, and tumor location (adjusted HR 0.77, 95% CI: 0.64-0.93, P=0.006). CONCLUSION: Two types of esophageal adenocarcinoma can be characterized based on the presence or absence of Barrett's epithelium. These findings have implications for understanding the etiology of EAC and determining prognosis as well as for development of optimal clinical strategies to identify patients at risk

Prevalence of Hepatitis B surface antigen (HBsAg) among visitors of Shashemene General Hospital voluntary counseling and testing center

<p>Abstract</p> <p>Background</p> <p>Hepatitis B virus (HBV) infection is significant health problem, as it can lead to chronic hepatitis, liver cirrhosis, and hepatic carcinoma. Due to shared routes of transmission, HBV and human immunodeficiency virus (HIV) co-infection is common and is an emerging concern in the clinical management of patients because of increased mortality, accelerated hepatic disease progression, and the frequent hepatotoxicity caused by anti-retroviral therapy. The aim of this study was to determine the prevalence of Hepatitis B surface antigen (HBsAg) and its risk factors, among individuals visiting Shashemene General Hospital VCT center.</p> <p>Findings</p> <p>Institution based cross-sectional study was performed from November 3, 2008 to December 29, 2008 and 384 voluntary counseling and testing (VCT) clients were investigated. Data on socio demographic and HBV risk factors was collected using structured questionnaires. Blood samples were collected and screened for hepatitis B surface antigen (HBsAg) and HIV by commercially available rapid test kits. The prevalence of HBsAg in this study group was 5.7%. Fourteen percent of HIV positive subjects (8/57) and 4.3% (14/327) of HIV negative subjects were positive for HBsAg. Significantly high prevalence of HBsAg was observed among individuals who had history of invasive procedures, like tooth extraction, abortion and ear piercing; history of hospital admission, history of unsafe inject and HIV positives.</p> <p>Conclusions</p> <p>Although HBsAg prevalence is much higher among subjects who are HIV positive (14.0% versus 4.3%), the prevalence of HBsAg in HIV negative subjects is high enough to warrant a recommendation to screen all clients at VCT centers irrespective of HIV status.</p

The Role of Quantitative Pharmacology in an Academic Translational Research Environment

Translational research is generally described as the application of basic science discoveries to the treatment or prevention of disease or injury. Its value is usually determined based on the likelihood that exploratory or developmental research can yield effective therapies. While the pharmaceutical industry has evolved into a highly specialized sector engaged in translational research, the academic medical research community has similarly embraced this paradigm largely through the motivation of the National Institute of Health (NIH) via its Roadmap initiative. The Clinical and Translational Science Award (CTSA) has created opportunities for institutions which can provide the multidisciplinary environment required to engage such research. A key component of the CTSA and an element of both the NIH Roadmap and the FDA Critical Path is the bridging of bench and bedside science via quantitative pharmacologic relationships. The infrastructure of the University of Pennsylvania/Children’s Hospital of Philadelphia CTSA is highlighted relative to both research and educational objectives reliant upon quantitative pharmacology. A case study, NIH-sponsored research program exploring NK1r antagonism for the treatment NeuroAIDS is used to illustrate the application of quantitative pharmacology in a translational research paradigm