tbuckley/cabot-search huggingface dataset:
Abstract 5106: Development of plasma biomarkers for pancreatic cancer diagnosis
Authors: Sheng Pan, Ru Chen, David A. Crispin, Damon May, Martin McIntosh, Hoda Anton-Culver, Brian Cao, Tyler K. Stevens, Mary P. Bronner, Teresa A. Brentnall
Journal: Cancer Research (2011)

Abstract Pancreatic cancer is the fourth leading cause of cancer deaths in the United States. It has the worst five year survival rate (1 to 4%) among all the cancers. This cancer is deadly because the diagnosis occurs at a late stage when the disease is inoperable and because there is a lack of effective therapy. The current pancreatic cancer biomarker CA19-9 does not provide the high sensitivity and specificity required to screen an asymptomatic population for diagnosis. Therefore, biomarkers that can improve current pancreatic cancer diagnosis would have great value to improve the patient management and survival rate of this deadly disease. In this study, we perform a large scale quantitative proteomics profiling to identify differential plasma proteins that are associated with pancreatic cancer. The proteome of plasma samples from patients with pancreatic ductal adenocarcinoma were quantitatively compared with that of non-pancreatic disease controls and patients of chronic pancreatitis, a pancreas disease that shares many molecular features with pancreatic cancer. To tackle the challenge presented by the enormous complexity and heterogeneity of plasma proteome, we applied an integrated proteomics strategy, including immunodepletion, multi-dimensional fractionations at both protein and peptide level, to enhance the detection of low abundance proteins, especially those derived from tumor cells. With stringent criteria, 1340 proteins were identified in plasma across 8-order of magnitude in protein concentration. A group of differential proteins that are associated with pancreatic cancer was identified, and their relationship with the previous studies in pancreatic tissue and pancreatic juice was investigated. A pilot study was performed to confirm a subgroup of differential proteins with ELISA using independent cohort of blood samples from well-diagnosed patients of pancreatic cancer, pancreatitis and non-pancreatic disease control. The performance of the selected protein candidates were benchmarked against CA19-9. Among the nine protein candidates tested, two demonstrated better specificity and sensitivity than CA19-9 in distinguishing pancreatic cancer from the controls; and one protein candidate was verified as a biomarker candidate for chronic pancreatitis. The protein candidates identified in this study provide a biomarker candidate pool for future development of blood-based assays for pancreatic cancer diagnosis. The discovery and technical strategy presented by this study may be pertinent to biomarker development for other cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5106. doi:10.1158/1538-7445.AM2011-5106
Prevention of Surgical-Wound Infections
Authors: Finn Gottrup
Journal: New England Journal of Medicine (2000)

Wound infections are common, serious, and expensive complications after surgery. About 5 percent of all patients who have undergone surgery and as many as 10 to 20 percent of patients who have undergone colorectal surgery have postoperative wound infections. Historically, surgical wounds have been classified as clean, clean–contaminated, contaminated, or infected.1 However, this classification has not proved useful in predicting the occurrence of wound infection,2 which is the key to effective prevention. Scoring systems such as that developed by the Centers for Disease Control and Prevention for the Study on the Efficacy of Nosocomial Infection Control and the National Nosocomial . . .
OPTIMIZACIÓN DE LA DOSIS DE PROPOFOL EN INFUSIÓN CONTINUA PARA LA SEDACIÓN PROFUNDA EN COLONOSCOPIA
Authors: EJ De la Morena, E Pérez-Arellano, L Achecar Justo, ML Leal
Journal: Endoscopy (2011)

Introducción: La dosis óptima de propofol para la infusión continua con bombas convencionales no está plenamente establecida para la sedación profunda en colonoscopias.
1004 RADIOFREQUENCY ABLATION VERSUS SURGICAL RESECTION FOR THE TREATMENT OF EARLY STAGE HEPATOCELLULAR CARCINOMA (HCC) - A LARGE MULTICENTRE STUDY
Authors: I. Gory, M. Fink, S. Bell, P. Gow, A. Nicoll, V. Knight, A. Dev, A. Rode, M. Kitson, M. Bailey, W. Kemp, S.K. Roberts
Journal: Journal of Hepatology (2012)
Abstract 3462: A DNA methyltransferase inhibitor and all-trans retinoic acid reduce oral cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide
Authors: Xiaohan Tang, Martin Albert, Theresa Scognamiglio, Lorraine Gudas
Journal: Cancer Research (2010)

Abstract The transcriptional silencing of some cell cycle inhibitors and tumor suppressors, such as p16 and RARβ2, by DNA hypermethylation at CpG islands is commonly found in human oral squamous carcinoma cells. We examined the effects of the DNA methyltransferase (Dnmt) inhibitor 5-Aza-2′-deoxycytidine (5-Aza, 0.25 mg/kg body weight), all-trans retinoic acid (RA, given at 100 μg/kg body weight and 1 mg/kg body weight, respectively), and the combination of 5-Aza and the low dose RA on murine oral cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in a mouse model. All the drug treatments were performed for 15 weeks after a 10-week 4-NQO treatment. Mice in all drug treatment groups showed decreases in the average numbers of neoplastic tongue lesions. The combination of 5-Aza and RA effectively attenuated tongue lesion severity. While all drug treatments limited the increase in the percentage of PCNA positive cells and the decrease in the percentage of p16 positive cells caused by the 4-NQO treatment in mouse tongue epithelial regions without visible lesions and in the neoplastic tongue lesions, the combination of 5-Aza and RA was the most effective. Collectively, our results show that the combination of a DNA demethylating drug and RA has potential as a strategy to reduce oral cavity cancer in this 4-NQO model. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3462.
Evolution of evidence-based medicine to detect evidence mutations
Authors: Brian S Alper, Zbys Fedorowicz, Sheri A Strite, Michael E Stuart, Allen F Shaughnessy
Journal: Journal of the Royal Society of Medicine (2015)

Frustrating to some and exhilarating to others, medical knowledge is in continual evolution. Medicine’s evidence base evolves in many ways, sometimes in ways that can be compared to random mutations (such as adverse effects of a drug leading to investigation of its use where the effect could be beneficial) and other times through selection pressure that allows substandard evidence to flourish in ecological niches (such as a research community accepting existing reports as an established and unquestioned foundation). We describe several ways in which pathways resembling aberrant evolutionary changes distort our evidence base (how has our evidence evolved?), and discuss areas where evidence-based medicine (EBM) processes can adapt (how does EBM need to evolve?).
PTU-175 Differences In Intestinal Metaplasia In Barrett’s Oesophagus Patients From An Ethnically Diverse South London Population
Authors: R Hewett, V Chhaya, D Chan, A Poullis, J-Y Kang
Journal: Gut (2014)

<h3>Introduction</h3> Barrett’s oesophagus (BO) is where any portion of the normal distal squamous epithelial lining has been replaced by metaplastic columnar epithelium and is a risk factor for oesophageal adenocarcinoma. The recent BSG guidelines for the endoscopic surveillance of BO have stratified the risk according to the length of the BO segment and the presence or absence of intestinal metaplasia (IM). We aimed to identify risk factors and ethnic differences for the presence of IM. <h3>Methods</h3> We performed a retrospective database analysis in our unit which serves a large ethnically diverse southwest London population. Gastroscopy records between 2009 and 2012 were retrieved and patients with an endoscopic diagnosis of BO were identified. Multiple procedure reports for individual patients were removed from the analysis. Demographic information included age, sex and length of the BO segment. Patients from the Indian sub-continent were also identified, as previously described<sup>.1</sup> The presence of IM was retrieved from the hospital pathology database and was the primary outcome measured. We performed a multivariate logistic regression analysis to determine the odds of having IM by ethnic origin and other demographics. <h3>Results</h3> 463 patients with an endoscopic diagnosis of Barrett’s oesophagus were identified. Median age of diagnosis was 67.2 years (IQR: 56.7–76.6 years). Men were more likely to have an endoscopic diagnosis of BO than females (71.3% vs. 29.7%, p = 0.01). 9.7% of the cohort were from the Indian sub-continent. There was an increased odds of IM amongst men although this was not statistically significant (OR 1.44, 95% CI: 0.94–2.21, p = 0.09). Lesion length greater than 3cm compared with less than 3cm was associated with a greater odds of IM (2.37, 95% CI: 1.61–3.51, p= &lt;0.001). Patients from the Indian sub-continent were 70% less likely to have IM compared to other ethnicities (OR 0.32, 95% CI: 0.16–0.61, p = 0.001). <h3>Conclusion</h3> This data supports the previous findings that the BO lesion length of greater than 3 cm is associated with the presence of IM. Furthermore, the odds of having IM are significantly reduced in patients from the Indian sub-continent. Ethnicity should thus be taken into account in the future risk stratification of BO patients and requires further study. <h3>Reference</h3> Kang <i>et al</i>. Diverticular disease of the colon: ethnic differences in frequency. <i>Aliment. Pharmacol. Ther. </i>2004: 19: 765-769 <h3>Disclosure of Interest</h3> None Declared.
AI-21 * HIF-1A TARGETING IN AN ORTHOTOPIC XENOGRAFT MODEL THAT RECAPITULATES THE HYPOXIC MICROENVIRONMENT OF GLIOBLASTOMA
Authors: F. Nigim, J. Cavanaugh, A. P. Patel, W. T. Curry, E. M. Kasper, A. S. Chi, R. L. Martuza, S. D. Rabkin, H. Wakimoto
Journal: Neuro-Oncology (2014)

INTRODUCTION: Tissue hypoxia and necrosis represent a pathological hallmark of glioblastoma. Hypoxia inducible factor 1a (HIF-1a) plays crucial roles in the malignant phenotypes of glioblastoma, and may offer a therapeutic target. However, developing HIF-1a targeted agents has been hampered by the lack of a preclinical model that recapitulates the disease relevant hypoxic microenvironment. MATERIALS AND METHODS: MGG123 neurosphere culture was established from a surgical specimen of a recurrent glioblastoma. Tumorigenicity of MGG123 cells was assessed by orthotopic xenografting in SCID-mice. The original tumor and xenografts were characterized by H&E staining and immunohistochemistry for HIF-1a, MIB-1, CD34, nestin and CD44. Hypoxic foci within xenografts were detected by pimonidazole immunofluorescence. In vitro, HIF-1a expression was evaluated by Western blot under normoxia and hypoxia after treatment with Digoxin and Ouabain, shown to inhibit HIF-1a synthesis. In vivo, mice bearing intracerebral MGG123 tumors were treated with intraperitoneal injections of digoxin, and its effects on HIF-1a expression, CD34+ vasculature, and overall survival were examined. RESULTS: MGG123 cells generated aggressive orthotopic xenografts that contain foci of pseudopalisading necrosis. The patient and xenografted tumors showed histopathological similarities as they both have high MIB-1 indices and are diffusely positive for CD44 and nestin. HIF-1a immunopositivity was specifically found in peudopalisading cells surrounding necrosis in both tumors. Within the xenografts, hypoxic areas were never found within 50mm proximity to CD34+ blood vessels. Hypoxia enhanced HIF-1a expression in cultured MGG123, and this was abrogated by treatment with Digoxin or Ouabain. In vivo, digoxin decreased HIF-1a expression and CD34+ vasculature within orthotopic MGG123 tumors, and extended overall survival of brain tumor-bearing mice. CONCLUSION: We established a preclinical glioblastoma model that uniquely mirrors the hypoxic microenvironment of human glioblastoma, and is suitable for developing HIF-1a targeted agents. Digoxin down-regulated HIF-1a and angiogenesis and increased overall survival in this clinically relevant glioblastoma model.
Suture material in the common bile duct causing recurrent post-cholecystectomy pain
Authors: K. Das, K. Basu, S. Ray, S. Chatterjee
Journal: Endoscopy (2010)

A 55-year-old woman presented with recurrent biliary colic for the past 10 months. She had undergone an open cholecystectomy with common bile duct (CBD) exploration 14 months prior to presentation. Transabdominal ultrasound revealed a dilated CBD (11 mm), with echogenic material in lower third of the duct. Her complete blood counts and liver function tests were normal. An endoscopic retrograde cholangiography (ERC) also showed a dilated CBD but no filling defects ([Fig. 1 a]).
AB0050 Association of il12b gene polymorphisms with ankylosing spondylitis
Authors: M. Ivanova, I. Manolova, L. Miteva, N. Stoilov, R. Stoilov, R. Rashkov, S. Stanilova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> IL12B encodes the IL-12p40 subunit of both the IL-12 and IL-23 cytokines, which play critical and unique roles in bridging the innate and adaptive immune systems. Whereas IL-12 induces development of Th1 cells, which produce IFN-gamma, IL-23 is involved in Th-17 cells that appear to play a role in the pathogenesis of ankylosing spondylitis (AS). Although the precise etiology of AS is unclear, high prevalence of HLA-B27 predisposition and predominantly involved pro-inflammatory cytokines suggest a substantial association with an immunogenetic basis and support the hypothesis that IL12B gene polymorphisms could affect the development of AS. <h3>Objectives</h3> In this regard, the aimof this study was to determine whether genetic polymorphisms of the IL-12B gene are associated with AS in Bulgarian populationby genotyping for A/C SNP in the 3′-UTR of the <i>IL-12B</i> (rs3212227) and <i>IL12Bpro</i> (rs17860508)<i>, a</i> complex polymorphism in promoter region of the <i>IL12B,</i> resulting from 4 bp microinsertion combined with AA/GC transition. <h3>Methods</h3> A total of 58 patients with AS and 132 matched healthy individuals were enrolled it the study. Genotyping for the rs3212227was performed by restriction fragment length polymorphisms-PCR assay and for the rs17860508 by allele specific-PCR. <h3>Results</h3> There were no significant differences in the genotype and allele frequencies of rs3212227 and rs17860508 polymorphism of the I<i>L12B</i> between AS patients and controls. However, in logistic regression analysis the presence of 3′-UTR allele C in the genotype (CT + CC vs. TT) and <i>IL12Bpro allele 2</i> in the genotype (1.2+2.2 vs. 1.1) were associated with an increasing risk of developing AS (OR=1.454 and OR-2.04, respectively). Also, AS patients carrying 3′-UTR CC genotype had earlier age at diseases onset (20.6±5.97 years) than those carrying allele A in the genotype (AA+AC; 27.8±7.93 years; p=0.054). In addition, the presence of <i>IL12Bpro allele 2</i> in the genotype (1.2+2.2 vs. 1.1) is associated with increased risk of peripheral joints involvement (OR=2.625) and the carriage of IL12Bpro genotype 2.2 is associated with 2-fold increased risk of having higher functional disability (BASFI&gt;4; OR=2.286). <h3>Conclusions</h3> In conclusion, our data support the hypothesis that genetic variations in <i>IL12B</i> gene affecting inducible production of IL-12p40, may contribute to development of AS in the Bulgarian population. <h3>Disclosure of Interest</h3> None Declared
Abstract 1170: MicroRNA gene polymorphisms in cancer susceptibility loci 5p12, 8q24 and 11q13
Authors: Hye Kyung Kim, Stephen J. Chanock, Jun Fang, Irene Collins, Laufey Amundadottir
Journal: Cancer Research (2011)

Abstract Using Genome Wide Association Studies (GWAS), we and others have previously identified and replicated genetic variations in chromosome 5p12, 8q24 and 11q13. Interestingly, the majority of risk-associated variations map to non-coding regions of the genome and thus, the molecular mechanism of single nucleotide polymorphisms (SNPs) underlying increased cancer risk remains unknown. To assess whether these SNPs could affect the biogenesis and function of non-coding RNA species, such as microRNAs (miRNA), here we assessed miRNA gene polymorphisms in these cancer susceptibility loci. We catalogued two miRNA genes in 5p12, sixteen miRNA genes in 8q24, and seven miRNA genes in 11q13. We re-sequenced the pri- and pre-miRNA genomic sequences in these loci using HapMap DNA samples. As a result, in 8q24 miRNA genes, we identified three new SNPs and confirmed two previously reported SNPs. In 11q13, we identified four genetic variations within different miRNA genes. However, linkage disequilibrium plot analysis of both loci didn't show any statistically significant association of any of these SNPs with their corresponding GWAS signals. Thus, we consider it unlikely that miRNA in these regions are direct downstream effectors of cancer-associated genetic variations. Nevertheless, because these risk loci are prone to genomic instability, we assessed whether the SNPs could affect miRNA gene expression since indirect associations with increased cancer susceptibility can't be excluded. To address this question, we cloned pre-miRNA genes from these loci, with or without genetic variations, into miRNA expression vectors and determined their relative expression in transfected 293T cells. We tested for an 8q24-encoded miRNA (miR-1206) or an 11q13 encoded-miRNA (miR-612) expression using miRNA TaqMan assays, and we found that the G allele polymorphism (rs2114358) in miR-1206 significantly downregulated miRNA expression levels compared to the reference A allele. On the other hand, an rs550894 (C/A) in miR-612 significantly upregulated miRNA expression levels compared to that of the reference C allele. These data indicate that the miRNA SNPs in these loci have indeed functional consequences that lead to dysregulation of miRNA biogenesis. Whether such changes in miRNA expression could also result in increased cancer risk needs to be assessed in future studies by identifying the downstream target genes of these miRNAs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1170. doi:10.1158/1538-7445.AM2011-1170
Case 7-2002
Authors: Arthur E Broadus, Kristina M Braaten
Journal: New England Journal of Medicine (2002)

Presentation of CaseA 47-year-old woman was admitted to the hospital because of recurrent hypercalcemia.The patient had been admitted 14 years earlier because of hyperparathyroidism, with an increased level of calcium (12.3 mg per deciliter [3.1 mmol per liter]), markedly increased levels of alkaline phosphatase and parathyroid hormone (293 pg per milliliter; normal range, 10 to 60), and a low phosphorus level (1.8 mg per deciliter [0.58 mmol per liter]). Physical examination revealed a nodule in the left lower pole of the thyroid gland.The patient worked as a machinist. At 20 years of age she had had urolithiasis . . .
PMO-227 Infliximab induction therapy alone for ulcerative colitis does not result in long term remission
Authors: A J Brooks, K Robinson, A Wright, M E McAlindon, A Lobo
Journal: Gut (2012)

<h3>Introduction</h3> Infliximab (IFX) has demonstrated efficacy in moderate to severe ulcerative colitis (UC) with a reduction in short-term colectomy rates.<sup>1</sup> In the UK, the National Institute for Health and Clinical Excellence (NICE) guidance relates to an induction course of three-doses for severely active ulcerative colitis.<sup>2</sup> The aim of this study was to determine outcomes following IFX induction, including colectomy rate, use of corticosteroids (CS) or repeat IFX induction. <h3>Methods</h3> Patients with UC at a single large teaching centre received IFX induction for UC requiring hospitalisation or when urgent consideration of surgery was given for resistant or rapidly relapsing disease were retrospectively reviewed (2008–2011). All patients had a Simple Colitis Activity Index (SCAI) at 0, 2, 6 weeks. <h3>Results</h3> Twenty-seven patients were studied, median age 38 (range 23–64), with 17 (63%) refractory to oral or intravenous CS (13 and 4 respectively). All received CS in the year preceding IFX; median 1course (range 1–4). 23 (85%) were on immunosuppression (IS) (16 thiopurines, 7 methotrexate), 3 intolerant or non-responsive and 1 naïve to IS. Twenty (74%) received induction IFX alone. Median SCAI was 8 (range 4–13), 4 (range 0–9), 2 (range 0–10) at 0, 2 and 7 weeks respectively. Nine (45%) had a good clinical response, 6 (30%) had a partial response, and 5 (25%) had no response; median SCAI at end of induction 0, 4 and 7 respectively. Colectomy rate at 1 year post IFX induction by response was 2/9 (22%) with a good response, 3/6 (50%) with a partial response, 5/5 (100%) for no response, with partial or no response significantly more likely to result in colectomy compared a good response (p=0.02). Overall, the colectomy rate for induction IFX at 1 year was 0.50 (10/20; 0.30 in 1st 3 months, 0.20 in months 4–12). Seven (35%) required CS at a median of 3 months (range 0–5) and 25% (5/20) a 2<sup>nd</sup> induction course of IFX at a median of 4.5 months (range 2–25) post IFX induction. Of these 5, 2 (33%) had a colectomy, 1 is receiving maintenance IFX, 1 had 3<sup>rd</sup> induction with IFX, 1 had an infusion reaction and commenced adalimumab. Following initial IFX induction, a further 26% (7/27) received maintenance IFX infusions, median 3 (range 1–6). Of these, 1 receives maintenance IFX, 3 stopped due to lack of funding and are in remission, and 3 (43%) lost response-requiring colectomy. <h3>Conclusion</h3> Response to induction IFX determined by SCAI is useful in predicting colectomy in challenging UC patients with resistant or rapidly relapsing UC despite IS. Further induction or maintenance IFX is unlikely to result in remission with partial response on SCAI post induction IFX alone and in this group may be considered as a bridge to surgery. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Rutgeerts P</b>, <i>et al.</i><i>N Engl J Med</i> 2005;<b>353</b>:2462–76. 2. <i>NICE Guidance 163</i>, 2008.
Treatment of Nevus of Ota with the Q-Switched Ruby Laser
Authors: Shinichi Watanabe, Hisashi Takahashi
Journal: New England Journal of Medicine (1994)

Nevus of Ota is a benign bluish or gray-brown lesion of the eye and the surrounding skin that has been reported to occur in about 1 in 200 people in Japan. Prior treatments have either been ineffective or caused scarring. The Q-switched ruby laser can produce very short high-energy pulses and can selectively target cells that contain pigment, such as dermal melanocytes.