tbuckley/cabot-search huggingface dataset:
Abstract 4999: Genome-wide methylation array of human prostate tissues using illumina infunium 450K bead chip reveals distinct DNA methylation signatures with potential as clinical predictors
Authors: Bernard Kwabi-Addo, Songping Wang, Norman H. Lee, Michael Ittmann, Funda Suer, Joseph Devaney
Journal: Cancer Research (2012)

Abstract Prostate cancer (PCa) harbors a myriad of aberrant genomic and epigenetic alterations. Epigenetic inactivation of genes in PCa is largely based on transcriptional silencing by aberrant CpG methylation of CpG rich promoter regions. Candidate gene-based studies have identified a handful of aberrant CpG DNA methylation events in PCa. To better understand the role of aberrant epigenetic alterations and identify biological pathways likely to be affected by methylation mediated alterations in gene expression in PCa, we have examined the methylation status of 450,000 (450K) cytosine microarray (illumina). The 450K microarray includes CpG islands/shores/shelves/open sea, non-coding RNA and sites surrounding the transcription start sites for coding genes, but also for the corresponding gene bodies and the 3′-UTR. We demonstrate that the 450k DNA methylation array can significantly detect CpG methylation changes in radical prostatectomy prostate tissue samples. Cluster analysis revealed distinct DNA methylation profiles for prostate cancer tissues in comparison with non-malignant tissues. A total of 225 CpG loci (p &amp;gt; 0.00049) showed differential methylation in the cancer tissues in comparison with non-malignant tissues. Each of the 225 CpG locus was validated in silico using an independent, publicly available methylome dataset from the Cancer Genome Atlas. The majority of these loci were informative particularly in the prostate cancer. Overall, cluster analysis showed gene set enriched in pathways including transcriptional modifications, apoptosis/autophagy, chromatin assembly, growth factor signaling, cell cycle regulation and oxidative-redox reaction. This study shows that CpG locus methylation arrays could reveal important biological differences in the epigenome between prostate cancer and non-malignant tissues and provide potential markers for disease detection and/or progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4999. doi:1538-7445.AM2012-4999
Response to “Comment on ‘Optimal Exposure Biomarkers for Nonpersistent Chemicals in Environmental Epidemiology’”
Authors: Antonia M. Calafat, Matthew P. Longnecker, Holger M. Koch, Shanna H. Swan, Russ Hauser, Lynn R. Goldman, Bruce P. Lanphear, Ruthann A. Rudel, Stephanie M. Engel, Susan L. Teitelbaum, Robin M. Whyatt, Mary S. Wolff
Journal: Environmental Health Perspectives (2016)
Abstract 3249: Intersectin 1 is required for neuroblastoma tumorigenesis
Authors: Angela Russo, John P. O'Bryan
Journal: Cancer Research (2012)

Abstract Neuroblastoma (NB) is a malignant tumor deriving from the neural crest and is responsible for 13% of cancer-related deaths in children. Phosphoinositide 3-kinases (PI3Ks) play a central role in NB tumorigenesis. PI3Ks activate AKT, which regulates survival and stabilizes the MYCN oncogene. Both MYCN and AKT are markers for poor prognosis in NBs. Inhibiting PI3Ks with pan-inhibitors blocks malignant progression in vivo; however, these inhibitors have high toxicity that limits their use in NB treatment. Though there are three classes of PI3Ks, only Class I isoforms have been implicated in NB tumorigenesis. We have previously found that the scaffold protein intersectin 1 (ITSN1) interacts with PI3KC2α and regulates its activation as well as AKT activation in neuronal cell lines. In addition, ITSN1 overexpression is transforming in rodent fibroblasts. Thus, we examined the role of the ITSN1-PI3KC2α pathway in human NB tumorigenesis. ITSN1 and PI3KC2α are highly expressed in primary human neuroblastoma tumors of varying stage and MYCN amplification status. In addition, both ITSN1 and PI3KC2α are expressed in NB tumor cell lines derived from high grade NB tumors. Silencing ITSN1 dramatically inhibited the anchorage-independent growth of NB tumor cells in vitro and tumor formation in xenograft assays in vivo independent of MYCN status. Conversely, heterologous overexpression of ITSN1 increased the formation of soft agar colonies. These results suggest that ITSN1 functions as an oncogene in NB cells. Furthermore, PI3KC2α overexpression restores anchorage-independent growth of ITSN1-depleted NB cells demonstrating that PI3KC2α mediates ITSN1's tumorigenic properties. This study reveals a new pathway, i.e., ITSN1-PI3KC2α, involved in regulating the pathogenesis of NBs and suggests that this pathway may represent a new target for therapeutic intervention in the treatment of NB patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3249. doi:1538-7445.AM2012-3249
<i>Notes from the Field</i>: Acute Mercury Poisoning After Home Gold and Silver Smelting — Iowa, 2014
Authors: Samir Koirala, Kathy Leinenkugel
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

In March 2014, a man, aged 59 years, who lived alone and had been using different smelting techniques viewed on the Internet to recover gold and silver from computer components, was evaluated at a local emergency department for shortness of breath, tremors, anorexia, and generalized weakness. During the smelting processes, he had used hydrogen peroxide, nitric acid, muriatic acid, and sulfuric acid purchased from local stores or Internet retailers. For protection, he wore a military gas mask of unknown type. The mask was used with filter cartridges, but their effectiveness against chemical fumes was not known.
OC-015 Prognostic indicators for short and long-term outcomes of colorectal endoscopic mucosal resection (EMR): a multi-centre (CERT-n) study
Authors: J Geraghty, K Bodger, S Alam, W Jafar, M Gillon, C Babbs, J Ramesh, R Willert, S Lal, S Sarkar
Journal: Gut (2012)

<h3>Introduction</h3> EMR is an established treatment for large colorectal polyps, yet the data regarding efficacy and outcome are principally limited to single centre experience. We present a multicentre study to determine prognostic factors of short-term (3 month) and long-term (1 year) outcomes following an index (intention to treat (ITT)) EMR for large sessile colorectal polyps. <h3>Methods</h3> Endoscopy databases &amp; hospital coding records identified patients that had an ITT EMR for colonic polyps 2 cm or greater between 2005 and 2010 in five North-West teaching hospitals. Patients were audited longitudinally for 1 year. Multivariate analysis (Logistic Regression Model) determined significant prognostic factors (OR [95% CI]; p&lt;0.05 as significant). <h3>Results</h3> Demographics: 313 patients (mean [SD] age 69.7[10.4] years, 65.5% male, 86% ASA grade 1–2) underwent EMR for mean polyp size of 33.5 [11.5] mm. Morphologically; 63.8% were flat lesions and 21.7% were located in the right colon. Procedure: 26% were performed by inexperienced endoscopists (Outcomes: Cancer diagnosis was in 9.5% (6.3% invasive &amp; 3.2% intra-mucosal). Complications; Perforation rate 0.5%, bleeding rate 0.5% &amp; all cause 30-day mortality 0.6 %, with no procedure related mortality. Recurrence rate was 26% &amp; treated endoscopically in 64.6%, &amp; surgically in 8.5%. Overall, surgery was required in 7.3%, of which 8.7% were emergencies (to treat perforation) and 56% was for cancer. ITT short-term success rate was 68% and 1-year success rate was 82.4%, with an adjusted rate of 87.2%. Prognostic Factors: Predictors of recurrence were cancer histology (OR 9 [95% CI 4 to 22]=&lt;0.05), piecemeal resection (OR 4 [95% CI 1.5 to 11] p&lt;0.005) and EMR session &gt;1 (OR 22 [95% CI 10 to 50] p&lt;0.005). Poor prognostic indicators for long-term success were cancer (OR 11 [95% CI 4.5 to 28] p&lt;0.005) and EMR session &gt;1 (OR 3.6 [95% CI 1.5 to 8.4] p=0.003). While endoscopist inexperience, increasing polyp size, no adjuvant APC were poor prognostic factors univariately, on multivariate analysis they were insignificant. Gender, age, ASA, Training, site, morphology and complications were not significant factors. <h3>Conclusion</h3> While recurrence rates in EMR for large colonic lesions were high (&gt;1/4), long-term outcomes were good (cure rate 87.2%) with complications similar to previous series. Most important poor prognostic factors were cancer histology and requirement of more than 1 session. <h3>Competing interests</h3> J Geraghty grant/research support from: Cook Medical, K Bodger: None declared, S Alam: None declared, W Jafar: None declared, M Gillon: None declared, C Babbs: None declared, J Ramesh: None declared, R Willert: None declared, S Lal: None declared, S Sarkar: None declared.
Genetic Factors in Self-reported Snoring and Excessive Daytime Sleepiness
Authors: DORIT CARMELLI, DONALD L. BLIWISE, GARY E. SWAN, TERRY REED
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Subjects in this study included 1,560 intact male–male twin pairs (818 monozygotic [MZ], 742 dizygotic [DZ]) of mean age ( ± SD) 74.2 ± 2.8 yr. The Epworth Sleepiness Scale (ESS) was used to assess daytime sleepiness and standardized questionnaires assessed snoring. Multivariate genetic model fitting was used to estimate the contribution of genetic and nongenetic (environmental) influences to the variation and covariation of obesity with snoring and daytime sleepiness. In this sample, 26% were habitual snorers, 18% reported excessive daytime sleepiness (ESS ⩾ 11), and 29% were obese (body mass index [BMI] ⩾ 28). By using structural equation modeling, we estimated that genetic factors accounted for 64% of the variance in obesity, 40% of the variance in daytime sleepiness, and 23% of the variability in self-reports of snoring. We found a significant genetic correlation between obesity and snoring and between obesity and excessive daytime sleepiness (EDS), although for the most part the genetic variance in snoring and sleepiness was nonoverlapping with the genetic variance for obesity. We conclude from these data that self-reported symptoms of snoring and daytime sleepiness in older men have a genetic basis that is largely independent of genes associated with obesity.
Bone Marrow Transplantation for Sickle Cell Disease
Authors: Mark C. Walters, Melinda Patience, Wendy Leisenring, James R. Eckman, J. Paul Scott, William C. Mentzer, Sally C. Davies, Kwaku Ohene-Frempong, Françoise Bernaudin, Dana C. Matthews, Rainer Storb, Keith M. Sullivan
Journal: New England Journal of Medicine (1996)

We investigated the risks and benefits of allogeneic bone marrow transplantation in children with complications of sickle cell disease.Twenty-two children less than 16 years of age who had symptomatic sickle cell disease received marrow allografts from HLA-identical siblings between September 1991 and April 1995. The indications for transplantation included a history of stroke (n = 12), recurrent acute chest syndrome (n = 5), and recurrent painful crises (n = 5). Patients were prepared for transplantation with busulfan, cyclophosphamide, and antithymocyte globulin.Twenty of the 22 patients survived, with a median follow-up of 23.9 months (range, 10.1 to 51.0), and 16 patients had stable engraftment of donor hematopoietic cells. In three patients the graft was rejected and sickle cell disease recurred; in a fourth patient graft rejection was accompanied by marrow aplasia. In 1 of the 16 patients with engraftment, there was stable mixed chimerism. Two patients died of central nervous system hemorrhage or graft-versus-host disease. Kaplan-Meier estimates of survival and event-free survival at four years were 91 percent and 73 percent, respectively. Among patients with a history of acute chest syndrome, lung function stabilized; among patients with prior central nervous system vasculopathy who had engraftment, stabilization of cerebrovascular disease was documented by magnetic resonance imaging.Allogeneic stem-cell transplantation can be curative in young patients with symptomatic sickle cell disease.
Which Nodular Goiters Should Be Removed?
Authors: Martin Perlmutter, Stanley L. Slater
Journal: New England Journal of Medicine (1956)

WHEN the clinician discovers a nontoxic nodular goiter, he is often confronted with the decision whether it is necessary to remove the thyroid nodule. One group of authors cites a high incidence of thyroid cancer in nodular goiter and advises immediate surgical removal.1 2 3 Contrariwise, another group states that thyroid cancer is quite rare, even in nodular goiter, and advises either medical or no therapy in the majority of such patients.4 5 6 Much of the controversy over the management of nontoxic nodular goiter stems from this conflict concerning the incidence of thyroid cancer.It is the purpose of this report to review . . .
Abstract P4-09-11: Variables of Worse Outcome in Premenopausal ≥35 Years old Patients (pts)
Authors: CS Vallejos, HL Gómez, JM Cotrina, MJ Marcelo, FF Doimi, SP Neciosup, JF Suazo, JA Pinto, RG Velarde, CE. Vigil
Journal: Cancer Research (2010)

Abstract Background: Breast cancer (BC) has a worse prognosis in young than in older women; there is a lack of a standard definition of ages included in definition of young women; however ≥35 years old (yo) is frequently used. We analyzed pts according to their age at diagnosis and menopausal status (premenopausal ≥35 yo, premenopausal &amp;gt;35 yo and postmenopausal). Methods: We reviewed 1024 cases with operable stage I-III BC from INEN, Lima-Perú (2000 - 2002). We used Kaplan-Meier estimates for comparing disease free survival (DFS) and overall survival (OS) by age at diagnosis and menopausal status according to clinicopathologic characteristics and IHC phenotype: [ER+ and/or PR+, HER2-], [ER-, PR-, HER2-] and [HER2+ (regardless ER/PR status)]. Results: 84 pts were premenopausal ≥35yo (8.2%), 425 premenopausal &amp;gt;35yo (41.5%) and 515 postmenopausal (50.3%). We found significant association between groups and RP (P&amp;lt;0.001) and RE (P=0.042) status; tumor size (P=0.002); nodal involvement (P=0.014); extracapsular extension (P=0.04); pathological stage (P=0.028) and phenotype (P=0.007). With a median of follow-up of 7.6 years, the DFS and OS to 6 years show differences in the group of ≥35 yo pts compared to premenopausal &amp;gt; 35 yo and postmenopausal pts (DFS: 58.4, 79.4 and 78.7%, P&amp;lt;0.001; OS: 64.7, 84.3 and 80.5% respectively, P&amp;lt;0.001). We found significant differences in DFS and OS between groups stratified by phenotype. differences were greater in [ER+ and/or PR+, HER2-] pts. OS y phenotype In this subset, we found significant association between ER status with premenopausal ≥35yo, &amp;gt;35yo and postmenopausal pts (ER-=20.6 v 3.5 v 1.9%; P&amp;lt;0.001). Conclusion: Premenopausal pts with ≥35 yo has a worse prognosis than older premenopausal and postmenopausal pts; phenotypes [ER+ and/or PR+, HER2-] and [HER2+] present higher recurrence risks in premenopausal ≥35yo pts. In [ER+ and/or PR+, HER2-] ≥35yo pts, negative RE is an indicator of worse prognosis. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-11.
Case 19-2006
Authors: J. Patrick Whelan, Artur Zembowicz
Journal: New England Journal of Medicine (2006)

A 22-month-old boy was seen in the pediatric rheumatology clinic because of subcutaneous nodules on the legs, right hand, and neck that had been increasing in size and number during the preceding six weeks. The child was otherwise well. The lesions were firm, nontender, slightly mobile, and nonpigmented. A diagnostic procedure was performed.
Abstract A20: Protein kinase C beta II is crucial for Ewing sarcoma cell survival
Authors: Dider Surdez, Magdalena Benetkiewicz, Virginie Perrin, Olivier Delattre, Franck Tirode
Journal: Cancer Research (2009)

Abstract Ewing sarcoma, the second most frequent bone tumor of young adults, is most frequently characterized by a specific translocation t(11;22) leading to the formation of the aberrant transcription factor EWS-FLI1. By analyzing transcriptional profiles of Ewing tumors with other pediatric tumors, we identified genes that were highly and very specifically over-expressed in Ewing sarcomas, as compared to the others. Beside already identified EWS-FLI1 targets like NKX2-2 or NR0B1, we focused our attention on a novel potential EWS-FLI1 target gene: the protein kinase C beta (PRKCB). Firstly, we confirmed at the protein level, that PRKCB is highly expressed in different Ewing cell lines. Secondly, EWS-FLI1 shRNA inhibition experiments in different Ewing cell lines demonstrated that the PRKCB over-expression is dependent on the expression of the fusion protein. Thirdly, using luciferase reporter experiments together with chromatin immunoprecipitation, we could show that EWS-FLI1 can bind directly to the PRKCB promoter and regulate its activity, demonstrating that PRKCB is a new direct target of EWS-FLI1. Finally, we investigated the role of the two different PRKCB isoforms in Ewing cells by inhibiting either both or the second one only by knock-down experiments. Both strategies led to a dramatic decrease of cell proliferation together with a massive cell death, indicating that at least PRKCB isoform 2, which seems to be the most expressed isoform in Ewing cells, is crucial for Ewing cell survival. We obtained the same results while using specific inhibitor compounds of PRKCB. Altogether, these results show that protein kinase C beta is highly expressed in Ewing tumors and that its inhibition could be of major interest for developing new therapeutic strategies. Citation Information: Cancer Res 2009;69(23 Suppl):A20.
1072 ACOUSTIC RADIATION FORCE IMPULSE (ARFI) ELASTOGRAPHY FOR THE ASSESSMENT OF LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS B AND C - AN INTERNATIONAL STUDY
Authors: I. Sporea, S. Bota, R. Sirli, H. Tanaka, H. Iijima, R. Badea, M. Lupsor, C. Fierbinteanu-Braticevici, A. Petrisor, H. Saito, H. Ebinuma, M. Friedrich-Rust, C. Sarrazin, H. Takahashi, N. Ono, F. Piscaglia, A. Borghi, M. D'Onofrio, A. Gallotti, M. Peck-Radosavljevic, A. Ferlitsch, A. Popescu, M. Danila
Journal: Journal of Hepatology (2012)
Treatment of a refractory biliary stricture after living donor liver transplantation, with a short fully covered metal stent with a long string
Authors: G. Curcio, M. Traina, R. Miraglia, I. Tarantino, L. Barresi, A. Granata
Journal: Endoscopy (2012)

In July 2007, a 56-year-old man with hepatitis B-related cirrhosis and hepatocarcinoma underwent living donor liver transplantation (LDLT), at our institute, using the right lobe graft. We carried out double duct-to-duct biliary anastomoses of the two graft bile ducts – one to the recipient's common hepatic duct and the other to the cystic duct.
Hereditary Alpha1-Antitrypsin Deficiency
Authors: Richard C. Talamo, John D. Allen, Morton G. Kahan, K. Frank Austen
Journal: New England Journal of Medicine (1968)

Serum specimens from 93 members of six families and three additional persons in the United States with serum alpha1-antitrypsin deficiency and familial emphysema were studied to define the genetics of this protein deficiency. The total antitryptic activity of serum, used as a measure of functional integrity of alpha1-antitrypsin, correlated highly with a radial gel immunoassay of its protein concentration. Studies of these two quantitative technics suggest an autosomal recessive mode of inheritance for the deficiency of alpha1-antitrypsin. Agarose electrophoresis was used to confirm these results and to recognize genetic variants. The patient material was highly selected from the clinical practice of pulmonary diseases, and a high correlation was found between homozygous deficiency of the alpha1-antitrypsin and chronic obstructive pulmonary disease. No remarkable rate of occurrence of pulmonary disease was noted among either genetic heterozygotes or family members with normal alpha1-antitrypsin function and concentration.
1071 SHORT AND LONG TERM OUTCOME OF KIDNEY TRANSPLANTED PATIENTS WITH CHRONIC VIRAL HEPATITIS B AND C
Authors: E. Ridruejo, G. Soler Pujol, C. Díaz, M. Dávalos Michel, S. Marciano, A. Martínez, A. Vilches, O.G. Mandó
Journal: Journal of Hepatology (2010)
P17.94 * GLIOMA GWAS HITS - MARKERS FOR RISK OR FOR PROGNOSIS?
Authors: C. Wibom, F. Spaeth, A. Dahlin, H. Langseth, E. Hovig, P. Rajaraman, U. Andersson, B. Melin
Journal: Neuro-Oncology (2014)

One obstacle to developing new treatments for glioma is the generally poor understanding of glioma aetiology. The only generally accepted environmental risk factor or glioma is ionizing radiation. Glioma aetiology has also been shown to contain a genetic component, in part through observations that individuals in families with a history of glioma have an elevated risk of developing glioma themselves. The genetic component in glioma aetiology has been further substantiated through genome wide association studies (GWAS). These studies have identified associations between a number of common genetic variants and an increased glioma risk. However, the studies have all been of case-control design (i.e. including cases at diagnosis), and as such they presumably suffer from a degree of survival bias. Survival bias risks being introduced in a study when rapidly fatal cases are not included. This is an inherent risk of case-control designs, which is particularly pronounced when studying a disease with very poor prognosis, such as glioma. Ultimately, survival bias may result in erroneous conclusions, as it is impossible to separate associations with prognosis from associations with risk of disease. To accurately confirm previously identified glioma risk variants, and ascertain whether they are associated with risk or with prolonged survival, we investigated these variants in a set of pre-diagnostic serum samples (594 cases and 591 matched controls). Analyses of population based, pre-diagnostic samples eliminates the risk of survival bias, and enables distinction between genetic variants associated with glioma risk (i.e. aetiology) and genetic variants associated with prognosis. The serum samples were acquired through The Janus Serum Bank, a Norwegian population based biobank reserved for cancer research. Variant detection was achieved by means of cycling temperature capillary electrophoresis. Our investigation confirmed the association with glioma risk for the investigated variants within five genomic regions; 8q24.21 (CCDC26), 9p21.3 (CDKN2B-AS1), 11q23.3 (PHLDB1), 17p13.1 (TP53), and 20q13.33 (RTEL1). This is indicative of these variants being truly associated with glioma risk, and thus may impact gliomagenesis. However, previously identified risk variants within the 5p15.33 (TERT) and 7p11.2 (EGFR) could not be positively confirmed by this study. The lack of positive confirmation raises the question whether EGFR and TERT genetic variants are linked with prolonged survival, rather than with glioma aetiology.