tbuckley/cabot-search huggingface dataset:
Evaluation and Prognostic Significance of Circulating Tumor Cells in Patients With Non–Small-Cell Lung Cancer
Authors: Matthew G. Krebs, Robert Sloane, Lynsey Priest, Lee Lancashire, Jian-Mei Hou, Alastair Greystoke, Tim H. Ward, Roberta Ferraldeschi, Andrew Hughes, Glen Clack, Malcolm Ranson, Caroline Dive, Fiona H. Blackhall
Journal: Journal of Clinical Oncology (2011)

Lung cancer is the leading cause of cancer-related death worldwide. Non-small-cell lung cancer (NSCLC) lacks validated biomarkers to predict treatment response. This study investigated whether circulating tumor cells (CTCs) are detectable in patients with NSCLC and what their ability might be to provide prognostic information and/or early indication of patient response to conventional therapy.In this single-center prospective study, blood samples for CTC analysis were obtained from 101 patients with previously untreated, stage III or IV NSCLC both before and after administration of one cycle of standard chemotherapy. CTCs were measured using a semiautomated, epithelial cell adhesion molecule-based immunomagnetic technique.The number of CTCs in 7.5 mL of blood was higher in patients with stage IV NSCLC (n = 60; range, 0 to 146) compared with patients with stage IIIB (n = 27; range, 0 to 3) or IIIA disease (n = 14; no CTCs detected). In univariate analysis, progression-free survival was 6.8 v 2.4 months with P < .001, and overall survival (OS) was 8.1 v 4.3 months with P < .001 for patients with fewer than five CTCs compared with five or more CTCs before chemotherapy, respectively. In multivariate analysis, CTC number was the strongest predictor of OS (hazard ratio [HR], 7.92; 95% CI, 2.85 to 22.01; P < .001), and the point estimate of the HR was increased with incorporation of a second CTC sample that was taken after one cycle of chemotherapy (HR, 15.65; 95% CI, 3.63 to 67.53; P < .001).CTCs are detectable in patients with stage IV NSCLC and are a novel prognostic factor for this disease. Further validation is warranted before routine clinical application.
Receptor Revision of Immunoglobulin Heavy Chain Variable Region Genes in Normal Human B Lymphocytes
Authors: Patrick C. Wilson, Kenneth Wilson, Yong-Jun Liu, Jacques Banchereau, Virginia Pascual, J. Donald Capra
Journal: The Journal of Experimental Medicine (2000)

Contrary to the general precepts of the clonal selection theory, several recent studies have provided evidence for the secondary rearrangement of immunoglobulin (Ig) genes in peripheral lymphoid tissues. These analyses typically used transgenic mouse models and have only detected secondary recombination of Ig light chain genes. Although Ig heavy chain variable region (VH) genes encode a substantial element of antibody combining site specificity, there is scant evidence for VH gene rearrangement in the periphery, leaving the physiological importance of peripheral recombination questionable. The extensive somatic mutations and clonality of the IgD+Strictly-IgM−CD38+ human tonsillar B cell subpopulation have now allowed detection of the first clear examples of receptor revision of human VH genes. The revised VDJ genes contain “hybrid” VH gene segments consisting of portions from two separate germline VH genes, a phenomenon previously only detected due to the pressures of a transgenic system.
Conductance catheter measurements of left ventricular volume in the intact dog: parallel conductance is independent of left ventricular size
Authors: R. S Szwarc, L. L Mickleborough, S.-I. Mizuno, G. J Wilson, P. Liu, S. Mohamed
Journal: Cardiovascular Research (1994)

Journal Article Conductance catheter measurements of left ventricular volume in the intact dog: parallel conductance is independent of left ventricular size Get access Richard S Szwarc, Richard S Szwarc University of Toronto, Toronto, Canada: R S Szwarc, L L Mickleborough, S-I Mizuno, G J Wilson, P Liu, S Mohamed. Correspondence to Dr Szwarc, at Ciba-Geigy, Division CV Biology, K-125 9.12, Basel CH-4002, Switzerland. Search for other works by this author on: Oxford Academic PubMed Google Scholar Lynda L Mickleborough, Lynda L Mickleborough University of Toronto, Toronto, Canada: R S Szwarc, L L Mickleborough, S-I Mizuno, G J Wilson, P Liu, S Mohamed. Search for other works by this author on: Oxford Academic PubMed Google Scholar Shun-Ichi Mizuno, Shun-Ichi Mizuno University of Toronto, Toronto, Canada: R S Szwarc, L L Mickleborough, S-I Mizuno, G J Wilson, P Liu, S Mohamed. Search for other works by this author on: Oxford Academic PubMed Google Scholar Gregory J Wilson, Gregory J Wilson University of Toronto, Toronto, Canada: R S Szwarc, L L Mickleborough, S-I Mizuno, G J Wilson, P Liu, S Mohamed. Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter Liu, Peter Liu University of Toronto, Toronto, Canada: R S Szwarc, L L Mickleborough, S-I Mizuno, G J Wilson, P Liu, S Mohamed. Search for other works by this author on: Oxford Academic PubMed Google Scholar Shanas Mohamed Shanas Mohamed University of Toronto, Toronto, Canada: R S Szwarc, L L Mickleborough, S-I Mizuno, G J Wilson, P Liu, S Mohamed. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 2, February 1994, Pages 252–258, https://doi.org/10.1093/cvr/28.2.252 Published: 01 February 1994 Article history Received: 04 August 1993 Accepted: 11 October 1993 Published: 01 February 1994
Impaired reflex control of intestinal gas transit in patients with abdominal bloating
Authors: M C Passos
Journal: Gut (2005)

<b>Background:</b> Patients with abdominal bloating and distension exhibit impaired transit of intestinal gas which may lead to excessive gas retention and symptoms. Furthermore, we have previously shown that intestinal gas transit is normally accelerated by rectal distension. We hypothesise that in patients with functional bloating this modulatory mechanism fails and impairs gas transit. <b>Methods:</b> In 12 healthy subjects and eight patients with abdominal bloating we compared, by paired studies, the effect of rectal versus sham distension on intestinal gas transit. Gas was infused into the jejunum (12 ml/min) for three hours with simultaneous perfusion of lipids into the duodenum (Intralipid 1 kcal/min) while measuring evacuation of gas per rectum. <b>Results:</b> In healthy subjects, duodenal lipid infusion produced gas retention (409 (68) ml) which was prevented by rectal distension (90 (90) ml; p&lt;0.05 <i>v</i> sham distension). In contrast, rectal distension in patients with abdominal bloating failed to reduce lipid induced gas retention (771 (217) ml retention during rectal distension <i>v</i> 730 (183) ml during sham distension; NS; p&lt;0.05 <i>v</i> healthy controls for both). <b>Conclusion:</b> Failure of distension related reflexes impairs intestinal gas propulsion and clearance in patients with abdominal bloating.
Use of a Case Definition Approach to Identify Cancer-Related Fatigue in Women Undergoing Adjuvant Therapy for Breast Cancer
Authors: Michael A. Andrykowski, John E. Schmidt, John M. Salsman, Abbie O. Beacham, Paul B. Jacobsen
Journal: Journal of Clinical Oncology (2005)

Purpose Use a proposed case-definition approach to identify the prevalence of cancer-related fatigue (CRF), demographic, clinical and psychosocial predictors of subsequent CRF, and psychosocial factors associated with concurrent CRF. Patients and Methods Women (n = 288) undergoing adjuvant therapy for early-stage breast cancer were recruited from two outpatient clinics. Women completed a baseline assessment before adjuvant therapy and a post-treatment assessment at the conclusion of an initial course of adjuvant chemotherapy or radiotherapy. At both assessments, women completed a clinical interview and measures of fatigue, distress, coping, and quality of life (QOL). The clinical interview consisted of modules from the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) and a diagnostic interview to identify cases of CRF. Results CRF prevalence at the baseline and post-treatment assessments was 10% and 26%, respectively. Multivariate analyses identified factors prospectively associated with greater risk for CRF at the post-treatment assessment, including receipt of adjuvant chemotherapy and a tendency to catastrophize in response to fatigue. Patients with and without CRF differed on a host of concurrent measures of fatigue, depression, functioning, and QOL with mean effect sizes in the range of 1.0 standard deviation. Conclusion CRF is a clinical syndrome experienced before and during adjuvant therapy for breast cancer. Results suggest CRF has a multifactorial etiology and support use of the proposed case definition approach to defining CRF. Future research is necessary to determine the scientific value of these criteria for understanding the etiology and management of fatigue in the oncology setting.
Effect of allopurinol, sulphasalazine, and vitamin C on aspirin induced gastroduodenal injury in human volunteers.
Authors: M E McAlindon, A F Muller, B Filipowicz, C J Hawkey
Journal: Gut (1996)

BACKGROUND--The mechanisms of aspirin induced gastroduodenal injury are not fully understood. Aspirin induces the release of reactive oxygen metabolites in animal models, which may contribute to mucosal injury. AIMS--To investigate the effects of aspirin administered with placebo or antioxidants on gastric mucosal reactive oxygen metabolite release and gastroduodenal injury in human volunteers. SUBJECTS--Fourteen healthy volunteers participated in the study (seven male; mean age 27 years, range 20-40). METHODS--In a double blind, randomised, crossover study, volunteers received aspirin 900 mg twice daily and either placebo, allopurinol 100 mg twice daily, sulphasalazine 1 g twice daily or vitamin C 1 g twice daily for three days. Injury was assessed endoscopically and by quantifying mucosal reactive oxygen metabolite release by measuring chemiluminescence before and after each treatment. The effect on prostanoids was determined by measuring ex vivo antral prostaglandin E2 (PGE2) synthesis and serum thromboxane B2 (TXB2). RESULTS--No drug reduced any parameter of gastric injury but vitamin C reduced duodenal injury assessed by Lanza score (p &lt; 0.005). Chemiluminescence increased after aspirin both with placebo (p &lt; 0.05) and vitamin C (p &lt; 0.05). Post-treatment chemiluminescence was lower in subjects taking allopurinol (p &lt; 0.05) or sulphasalazine (p &lt; 0.005) than in those taking placebo with aspirin. CONCLUSIONS--In this study, aspirin induced gastric injury was associated with reactive oxygen metabolite release. This was reduced by sulphasalazine and allopurinol, although macroscopic injury was not affected. Vitamin C, however, was shown to have a previously unrecognised protective effect against aspirin induced duodenal injury.
Elderly Patients With Acute Coronary Syndromes Managed Without Revascularization
Authors: Matthew T. Roe, Shaun G. Goodman, E. Magnus Ohman, Susanna R. Stevens, Judith S. Hochman, Shmuel Gottlieb, Felipe Martinez, Anthony J. Dalby, William E. Boden, Harvey D. White, Dorairaj Prabhakaran, Kenneth J. Winters, Philip E. Aylward, Jean-Pierre Bassand, Darren K. McGuire, Diego Ardissino, Keith A. A. Fox, Paul W. Armstrong
Journal: Circulation (2013)

Background— Dual antiplatelet therapy in older versus younger patients with acute coronary syndromes is understudied. Low-dose prasugrel (5 mg/d) is recommended for younger, lower-body-weight patients and elderly patients with acute coronary syndromes to mitigate the bleeding risk of standard-dose prasugrel (10 mg/d). Methods and Results— A total of 9326 medically managed patients with acute coronary syndromes from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial (&lt;75 years of age, n=7243; ≥75 years of age, n=2083) were randomized to prasugrel (10 mg/d; 5 mg/d for those ≥75 or &lt;75 years of age and &lt;60 kg in weight) or clopidogrel (75 mg/d) plus aspirin for ≤30 months. A total of 515 participants ≥75 years of age (25% of total elderly population) had serial platelet reactivity unit measurements in a platelet-function substudy. Cumulative risks of the primary end point (cardiovascular death/myocardial infarction/stroke) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding increased progressively with age and were ≥2-fold higher in older participants. Among those ≥75 years of age, TIMI major bleeding (4.1% versus 3.4%; hazard ratio, 1.09; 95% confidence interval, 0.57–2.08) and the primary end point rates were similar with reduced-dose prasugrel and clopidogrel. Despite a correlation between lower 30-day on-treatment platelet reactivity unit values and lower weight only in the prasugrel group, there was a nonsignificant treatment-by-weight interaction for platelet reactivity unit values among participants ≥75 years of age in the platelet-function substudy ( P =0.06). No differences in weight were seen in all participants ≥75 years of age with versus without TIMI major/minor bleeding in both treatment groups. Conclusions— Older age is associated with substantially increased long-term cardiovascular risk and bleeding among patients with medically managed acute coronary syndromes, with no differences in ischemic or bleeding outcomes with reduced-dose prasugrel compared with clopidogrel in elderly patients. No significant interactions among weight, pharmacodynamic response, and bleeding risk were observed between reduced-dose prasugrel and clopidogrel in elderly patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov/ct2/home . Unique identifier: NCT0069999.
Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade gliomas—a Pediatric Brain Tumor Consortium study
Authors: Sridharan Gururangan, Jason Fangusaro, Tina Young Poussaint, Roger E. McLendon, Arzu Onar-Thomas, Shengjie Wu, Roger J. Packer, Anu Banerjee, Richard J. Gilbertson, Frederic Fahey, Sridhar Vajapeyam, Regina Jakacki, Amar Gajjar, Stewart Goldman, Ian F. Pollack, Henry S. Friedman, James M. Boyett, Maryam Fouladi, Larry E. Kun
Journal: Neuro-Oncology (2013)

A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in children with recurrent low-grade glioma to measure sustained response and/or stable disease lasting ≥6 months and progression-free survival. Thirty-five evaluable patients received 2 doses (10 mg/kg each) of single-agent BVZ intravenously 2 weeks apart and then BVZ + CPT-11 every 2 weeks until progressive disease, unacceptable toxicity, or a maximum of 2 years of therapy. Correlative studies included neuroimaging and expression of tumor angiogenic markers (vascular endothelial growth factor [VEGF], VEGF receptor 2, hypoxia-inducible factor 2α, and carbonic anhydrase 9). Thirty-five evaluable patients (median age 8.4 y [range, 0.6–17.6]) received a median of 12 courses of BVZ + CPT-11 (range, 2–26). Twenty-nine of 35 patients (83%) received treatment for at least 6 months. Eight patients progressed on treatment at a median time of 5.4 months (range, 1–17.8). Six patients (17.7%) still in follow-up have had stable disease without receiving additional treatment for a median of 40.1 months (range, 30.6–49.3) from initiating therapy. The 6-month and 2-year progression-free survivals were 85.4% (SE ± 5.96%) and 47.8% (SE ± 9.27%), respectively. The commonest toxicities related to BVZ included grades 1–2 hypertension in 24, grades 1–2 fatigue in 23, grades 1–2 epistaxis in 18, and grades 1–4 proteinuria in 15. The median volume of enhancement decreased significantly between baseline and day 15 (P < .0001) and over the duration of treatment (P < .037). The combination of BVZ + CPT-11 appears to produce sustained disease control in some children with recurrent low-grade gliomas.
Prevalence of Refractive Errors and Associated Risk Factors in Subjects with Type 2 Diabetes Mellitus
Authors: Padmaja Kumari Rani, Rajiv Raman, Sudhir R. Rachapalli, Vaitheeswaran Kulothungan, Govindasamy Kumaramanickavel, Tarun Sharma
Journal: Ophthalmology (2010)
Inhibition of acid and gastric carcinoids.
Authors: J B Elder
Journal: Gut (1985)

Leading articleInhibition of acid and gastric carcinoids Control of gastric acid secretion has long been one of the principal aims of medical and surgical approach to the management of peptic ulcer disease.Prolonged maintenance treatment with more and more powerful drugs now appears to be on the horizon.Extensive testing of loxtidine, a very potent histamine H2 antagonist which differs from cimetidine and ranitidine in that it offers non-
<i>LRRC3B</i>, Encoding a Leucine-Rich Repeat-Containing Protein, Is a Putative Tumor Suppressor Gene in Gastric Cancer
Authors: Mirang Kim, Jeong-Hwan Kim, Hay-Ran Jang, Hwan-Mook Kim, Chang-Woo Lee, Seung-Moo Noh, Kyu-Sang Song, June-Sik Cho, Hyun-Yong Jeong, Yoonsoo Hahn, Young-Il Yeom, Hyang-Sook Yoo, Yong Sung Kim
Journal: Cancer Research (2008)

Abstract Leucine-rich repeat-containing 3B (LRRC3B) is an evolutionarily highly conserved leucine-rich repeat-containing protein, but its biological significance is unknown. Using restriction landmark genomic scanning and pyrosequencing, we found that the promoter region of LRRC3B was aberrantly methylated in gastric cancer. Gastric cancer cell lines displayed epigenetic silencing of LRRC3B, but treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine and/or the histone deacetylase inhibitor trichostatin A increased LRRC3B expression in gastric cancer cell lines. Real-time reverse transcription-PCR analysis of 96 paired primary gastric tumors and normal adjacent tissues showed that LRRC3B expression was reduced in 88.5% of gastric tumors compared with normal adjacent tissues. Pyrosequencing analysis of the promoter region revealed that LRRC3B was significantly hypermethylated in gastric tumors. Stable transfection of LRRC3B in SNU-601 cells, a gastric cancer cell line, inhibited anchorage-dependent and anchorage-independent colony formation, and LRRC3B expression suppressed tumorigenesis in nude mice. Microarray analysis of LRRC3B-expressing xenograft tumors showed induction of immune response–related genes and IFN signaling genes. H&amp;E-stained sections of LRRC3B-expressing xenograft tumors showed lymphocyte infiltration in the region. We suggest that LRRC3B is a putative tumor suppressor gene that is silenced in gastric cancers by epigenetic mechanisms and that LRRC3B silencing in cancer may play an important role in tumor escape from immune surveillance. [Cancer Res 2008;68(17):7147–55]
Naive CD8+ T cells differentiate into protective memory-like cells after IL-2–anti–IL-2 complex treatment in vivo
Authors: Daisuke Kamimura, Michael J. Bevan
Journal: The Journal of Experimental Medicine (2007)

An optimal CD8+ T cell response requires signals from the T cell receptor (TCR), co-stimulatory molecules, and cytokines. In most cases, the relative contribution of these signals to CD8+ T cell proliferation, accumulation, effector function, and differentiation to memory is unknown. Recent work (Boyman, O., M. Kovar, M.P. Rubinstein, C.D. Surh, and J. Sprent. 2006. Science. 311:1924–1927; Kamimura, D., Y. Sawa, M. Sato, E. Agung, T. Hirano, and M. Murakami. 2006. J. Immunol. 177:306–314) has shown that anti–interleukin (IL) 2 monoclonal antibodies that are neutralizing in vitro enhance the potency of IL-2 in vivo. We investigated the role of IL-2 signals in driving CD8+ T cell proliferation in the absence of TCR stimulation by foreign antigen. IL-2 signals induced rapid activation of signal transducer and activator of transcription 5 in all CD8+ T cells, both naive and memory phenotype, and promoted the differentiation of naive CD8+ T cells into effector cells. IL-2–anti–IL-2 complexes induced proliferation of naive CD8+ T cells in an environment with limited access to self–major histocompatibility complex (MHC) and when competition for self-MHC ligands was severe. After transfer into wild-type animals, IL-2–activated CD8+ T cells attained and maintained a central memory phenotype and protected against lethal bacterial infection. IL-2–anti–IL-2 complex–driven memory-like CD8+ T cells had incomplete cellular fitness compared with antigen-driven memory cells regarding homeostatic turnover and cytokine production. These results suggest that intense IL-2 signals, with limited contribution from the TCR, program the differentiation of protective memory-like CD8+ cells but are insufficient to guarantee overall cellular fitness.
Genome-Wide Pharmacogenetics of Antidepressant Response in the GENDEP Project
Authors: Rudolf Uher, Nader Perroud, Mandy Y.M. Ng, Joanna Hauser, Neven Henigsberg, Wolfgang Maier, Ole Mors, Anna Placentino, Marcella Rietschel, Daniel Souery, Tina Žagar, Piotr M. Czerski, Borut Jerman, Erik Roj Larsen, Thomas G. Schulze, Astrid Zobel, Sarah Cohen-Woods, Katrina Pirlo, Amy W. Butler, Pierandrea Muglia, Michael R. Barnes, Mark Lathrop<, Anne Farmer, Gerome Breen, Katherine J. Aitchison, Ian Craig, Cathryn M. Lewis, Peter McGuffin
Journal: American Journal of Psychiatry (2010)

Objective The purpose of this study was to identify genetic variants underlying the considerable individual differences in response to antidepressant treatment. The authors performed a genome-wide association analysis of improvement of depression severity with two antidepressant drugs. Method High-quality Illumina Human610-quad chip genotyping data were available for 706 unrelated participants of European ancestry treated for major depression with escitalopram (N=394) or nortriptyline (N=312) over a 12-week period in the Genome-Based Therapeutic Drugs for Depression (GENDEP) project, a partially randomized open-label pharmacogenetic trial. Results Single nucleotide polymorphisms in two intergenic regions containing copy number variants on chromosomes 1 and 10 were associated with the outcome of treatment with escitalopram or nortriptyline at suggestive levels of significance and with a high posterior likelihood of true association. Drug-specific analyses revealed a genome-wide significant association between marker rs2500535 in the uronyl 2-sulphotransferase gene and response to nortriptyline. Response to escitalopram was best predicted by a marker in the interleukin-11 (IL11) gene. A set of 72 a priori-selected candidate genes did not show pharmacogenetic associations above a chance level, but an association with response to escitalopram was detected in the interleukin-6 gene, which is a close homologue of IL11. Conclusions While limited statistical power means that a number of true associations may have been missed, these results suggest that efficacy of antidepressants may be predicted by genetic markers other than traditional candidates. Genome-wide studies, if properly replicated, may thus be important steps in the elucidation of the genetic basis of pharmacological response.