duloxetine induced pseudolymphoma with features of lymphocytic infiltration of jessner kanof

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mRNA/microRNA gene expression profile in microsatellite unstable colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer develops through two main genetic instability pathways characterized by distinct pathologic features and clinical outcome.</p> <p>Results</p> <p>We investigated colon cancer samples (23 characterized by microsatellite stability, MSS, and 16 by high microsatellite instability, MSI-H) for genome-wide expression of microRNA (miRNA) and mRNA. Based on combined miRNA and mRNA gene expression, a molecular signature consisting of twenty seven differentially expressed genes, inclusive of 8 miRNAs, could correctly distinguish MSI-H versus MSS colon cancer samples. Among the differentially expressed miRNAs, various members of the oncogenic miR-17-92 family were significantly up-regulated in MSS cancers. The majority of protein coding genes were also up-regulated in MSS cancers. Their functional classification revealed that they were most frequently associated with cell cycle, DNA replication, recombination, repair, gastrointestinal disease and immune response.</p> <p>Conclusion</p> <p>This is the first report that indicates the existence of differences in miRNA expression between MSS versus MSI-H colorectal cancers. In addition, the work suggests that the combination of mRNA/miRNA expression signatures may represent a general approach for improving bio-molecular classification of human cancer.</p

Groundwater of Rome

This paper describes the contents of the new Hydrogeological Map of the City of Rome (1:50,000 scale). The map extends to the entire municipality (1285 km2) and is based on both the most recent scientific studies on the groundwater field and new survey activities carried out in order to fill the data gaps in several areas of the examined territory. The map is the result of a combination of different urban groundwater expertise and Geographic Information System (GIS)-based mapping performed using the most recent available data and has been produced with the intention of furnishing the City of Rome with the most recent and updated information regarding groundwater

Prognostic value of morphology and hormone receptor status in breast cancer - a population based study

We analysed the 5-year relative survival among 4473 breast cancer cases diagnosed in 1990-1992 from cancer registries in Estonia, France, Italy, Spain, the Netherlands and the UK. Among eight categories based on ICD-O codes (infiltrating ductal carcinoma, lobular plus mixed carcinoma, comedocarcinoma, 'special types', medullary carcinoma, not otherwise specified (NOS) carcinoma, other carcinoma and cancer without microscopic confirmation), the 5-year relative survival ranged from 66% (95% CI 61-71) for NOS carcinoma to 95% (95% CI 90-100) for special types (tubular, apocrine, cribriform, papillary, mucinous and signet ring cell); 27% (95% CI 18-36) for cases without microscopic confirmation. Differences in 5-year relative survival by tumor morphology and hormone receptor status were modelled using a multiple regression approach based on generalised linear models. Morphology and hormone receptor status were confirmed as significant survival predictors in this population-based study, even after adjusting for age and stage at diagnosis

Strand-specific miR-28-5p and miR-28-3p have distinct effects in colorectal cancer cells

The authors thank Sue Moreau from the Department of Scientific Publications at The University of Texas MD Anderson Cancer Center for English language editing of the manuscript. Author contributions: Study concept and design: M.I.A., P.A.Z, G.A.C. Acquisition of data: M.I.A., L.Z., X.Z. Drafting of the manuscript: M.I.A., M.N., R.S., M.F., R.M.R., P.A.Z, G.A.C. Analysis and interpretation of data: M.I.A., M.N., R.S., R.M., P.A.Z, G.A.C. Critical revision of the manuscript for important intellectual content: M.I.A., M.N., R.S., M.F., R.M.R., P.A.Z, G.A.C. Statistical analysis: M.I.A., C.I., L.X. Obtained funding: G.A.C. Administrative, technical, or material support: R.G., I.V., F.F., M.F., G.L. Study supervision: G.A.C. Drs Nicoloso and Spizzo are currently at the Division of Experimental Oncology, CRO, National Cancer Institute, Aviano, ItalyBackground & Aims MicroRNAs (miRNAs) can promote or inhibit tumor growth and are therefore being developed as targets for cancer therapies. They are diverse not only in the messenger RNAs (mRNA) they target, but in their production; the same hairpin RNA structure can generate mature products from each strand, termed 5p and 3p, that can bind different mRNAs. We analyzed the expression, functions, and mechanisms of miR-28-5p and miR-28-3p in colorectal cancer (CRC) cells. Methods We measured levels of miR-28-5p and miR-28-3p expression in 108 CRC and 49 normal colorectal samples (47 paired) by reverse transcription, quantitative real-time polymerase chain reaction. The roles of miR-28 in CRC development were studied using cultured HCT116, RKO, and SW480 cells and tumor xenograft analyses in immunodeficient mice; their mRNA targets were also investigated. Results miR-28-5p and miR-28-3p were down-regulated in CRC samples compared with normal colon samples. Overexpression of miRNAs in CRC cells had different effects and the miRNAs interacted with different mRNAs: miR-28-5p altered expression of CCND1 and HOXB3, whereas miR-28-3p bound NM23-H1. Overexpression of miR-28-5p reduced CRC cell proliferation, migration, and invasion in vitro, whereas miR-28-3p increased CRC cell migration and invasion in vitro. CRC cells overexpressing miR-28 developed tumors more slowly in mice compared with control cells, but miR-28 promoted tumor metastasis in mice. Conclusion miR-28-5p and miR-28-3p are transcribed from the same RNA hairpin and are down-regulated in CRC cells. Overexpression of each has different effects on CRC cell proliferation and migration. Such information has a direct application for the design of miRNA gene therapy trials.M.I.A. is supported by a PhD fellowship (SFRH/BD/47031/2008) from Fundação para a Ciência e Tecnologia, Portugal. G.A.C. is supported as a fellow by The University of Texas MD Anderson Cancer Center Research Trust, The University of Texas System Regents Research Scholar, and the Chronic Lymphocytic Leukemia Global Research Foundation. Work in Dr Calin’s laboratory is supported in part by grants from the National Institutes of Health (CA135444), the US Department of Defense, the Pancreatic Cancer Action Network (2009 Seena Magowitz AACR Pilot Grant), and the US-European Alliance for the Therapy of Chronic Lymphoid Leukemia. STR DNA fingerprinting was done by the Cancer Center Support grant funded Characterized Cell Line core, NCI # CA16672

N-BLR, a primate-specific non-coding transcript leads to colorectal cancer invasion and migration

Background: non-coding RNAs have been drawing increasing attention in recent years as functional data suggest that they play important roles in key cellular processes. N-BLR is a primate-specific long non-coding RNA that modulates the epithelial-to-mesenchymal transition, facilitates cell migration, and increases colorectal cancer invasion. Results: we performed multivariate analyses of data from two independent cohorts of colorectal cancer patients and show that the abundance of N-BLR is associated with tumor stage, invasion potential, and overall patient survival. Through in vitro and in vivo experiments we found that N-BLR facilitates migration primarily via crosstalk with E-cadherin and ZEB1. We showed that this crosstalk is mediated by a pyknon, a short ~20 nucleotide-long DNA motif contained in the N-BLR transcript and is targeted by members of the miR-200 family. In light of these findings, we used a microarray to investigate the expression patterns of other pyknon-containing genomic loci. We found multiple such loci that are differentially transcribed between healthy and diseased tissues in colorectal cancer and chronic lymphocytic leukemia. Moreover, we identified several new loci whose expression correlates with the colorectal cancer patients' overall survival. Conclusions: the primate-specific N-BLR is a novel molecular contributor to the complex mechanisms that underlie metastasis in colorectal cancer and a potential novel biomarker for this disease. The presence of a functional pyknon within N-BLR and the related finding that many more pyknon-containing genomic loci in the human genome exhibit tissue-specific and disease-specific expression suggests the possibility of an alternative class of biomarkers and therapeutic targets that are primate-specific

Comparison of risk patterns in carcinoma and melanoma of the skin in men: a multi-centre case–case–control study

We directly compared risk factors between 214 histologically confirmed melanomas (CMM), 215 basal-cell carcinomas (BCC) and 139 squamous-cell carcinomas (SCC) in a multiple case–case–control study with 349 controls from patients without dermatological disease admitted to the same hospitals. Subjects with fair hair had a significant risk increase for all types of tumours at a comparable level (ORadj for blonde hair: CMM 2.3; SCC 2.4; BCC 2.3). The effect of pale eyes was significant and similar for CMM and BCC (ORadj 2.6). Intermittent sun exposure measured in hours spent at beach during holidays was significant for both CMM (ORadj 2.6 for more than 7000 lifelong hours) and BCC (ORadj 2.1 for more than 7000 lifelong hours), while SCC exhibited a significant risk increase for chronic exposure to sunlight measured in hours of outdoor work (ORadj 2.2 for more than 6000 lifelong hours). In the case–case comparison using a multinomial logistic regression model, we found a statistically significant risk difference for pale eyes, and number of naevi in the CMM group, compared to other skin cancers. For intermittent sun exposure, there was a significant risk difference of BCC when compared to the risk of SCC. Factors influencing risk of SCC are different, with chronic exposure to sun playing a major role in causing this type of carcinoma

Occupation and skin cancer: the results of the HELIOS-I multicenter case-control study

<p>Abstract</p> <p>Background</p> <p>Non-melanoma skin cancer (NMSC) is the most frequent tumour among Caucasian populations worldwide. Among the risk factors associated with this tumour, there are host-related factors and several environmental agents. A greater likelihood of high exposure to physical agents (with the exception of solar radiation) and chemical agents depends on the work setting. Our objective is to evaluate the role of occupational exposures in NMSC, with special emphasis on risk factors other than solar radiation and skin type.</p> <p>Methods</p> <p>We analysed 1585 cases (1333 basal cell carcinoma (BCC) and 183 squamous cell carcinoma (SCC)) and 1507 controls drawn from the Helios-I multicenter study. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression mixed models.</p> <p>Results</p> <p>For NMSC as a whole (both <it>histological types</it>), miners and quarrymen, secondary education teachers, and masons registered excess risk, regardless of exposure to solar radiation and skin type (OR 7.04, 95% CI 2.44–20.31; OR 1.75, 95% CI 1.05–2.89 and OR 1.54, 95% CI 1.04–2.27, respectively). Frequency of BCC proved higher among railway engine drivers and firemen (OR 4.55; 95% CI 0.96–21.57), specialised farmers (OR 1.65; 95% CI 1.05–2.59) and salesmen (OR 3.02; 95% CI 1.05–2.86), in addition to miners and quarrymen and secondary education teachers (OR 7.96; 95% CI 2.72–23.23 and OR 1.76; 95% CI 1.05–2.94 respectively). The occupations that registered a higher risk of <it>SCC (though not of BCC</it>) were those involving direct contact with livestock, construction workers not elsewhere classified (OR 2.95, 95% CI 1.12–7.74), stationary engine and related equipment operators not elsewhere classified (OR 5.31, 95% CI 1.13–21.04) and masons (OR 2.55, 95% CI 1.36–4.78).</p> <p>Conclusion</p> <p>Exposure to hazardous air pollutants, arsenic, ionizing radiations and burns may explain a good part of the associations observed in this study. The Helios study affords an excellent opportunity for further in-depth study of physical and chemical agents and NMSC based on matrices of occupational exposure.</p