tbuckley/cabot-search huggingface dataset:
Merkel Cell Polyomavirus Infection, Large T Antigen, Retinoblastoma Protein and Outcome in Merkel Cell Carcinoma
Authors: Harri Sihto, Heli Kukko, Virve Koljonen, Risto Sankila, Tom Böhling, Heikki Joensuu
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Merkel cell carcinoma (MCC) is rare skin cancer that is often associated with Merkel cell polyomavirus (MCPyV) infection. Polyomaviruses repress tumor suppressor proteins, thus influencing cell-cycle progression, but the effect of MCPyV on the key cell-cycle regulating proteins is poorly understood. Experimental Design: We evaluated expression of the MCPyV large T-antigen (LTA), Ki-67, and the key putative tumor suppressor proteins, the retinoblastoma protein (RB and phospho-RB) and p53, and their regulatory proteins (cyclin D1, cyclin E, p16, p21, p27, and MDM2) by using immunohistochemistry from tumors of 91 MCC patients identified from a population-based nationwide cohort. Tumor MCPyV DNA was measured by using quantitative PCR, and TP53 mutations were identified with sequencing. Results: MCPyV LTA expression was strongly associated with presence of MCPyV DNA in tumor, and it was almost invariably associated with tumor RB expression (P &amp;lt; 0.0001 for both comparisons). Both MCC LTA and RB expression were strongly associated with favorable MCC-specific and overall survival in univariable analyses (P ≤ 0.01 for all four analyses). Presence of MCPyV LTA was also associated with the female gender, the intermediate type of tumor histology, location of the tumor in a limb, cell proliferation rate, and absence of p53 expression. TP53 mutations were detected only in MCPyV DNA–negative tumors. Conclusions: MCPyV DNA–positive MCC has several clinical and molecular features that differ from MCPyV DNA-negative cancers. MCPyV-associated MCCs express RB, but may not harbor TP53 mutations. These findings provide further support that MCPyV causes the majority of MCCs. Clin Cancer Res; 17(14); 4806–13. ©2011 AACR.
IL-20 and IL-20R1 antibodies protect against liver fibrosis
Authors: Yi-Shu Chiu, Chi-Chen Wei, Yih-Jyh Lin, Yu-Hsiang Hsu, Ming-Shi Chang
Journal: Hepatology (2014)

Interleukin (IL)-20 is a proinflammatory cytokine of the IL-10 family and involved in rheumatoid arthritis, atherosclerosis, stroke, and osteoporosis. However, the pathophysiological roles of IL-20 in liver injury have not been extensively studied. We explored the involvement of IL-20 in liver injury and the therapeutic potential of IL-20 antagonists for treating liver fibrosis. Compared with normal liver tissue from healthy individuals, the amount of IL-20 was much higher in hepatocytes and hepatic stellate cells in liver biopsies from patients with fibrosis, cirrhosis, and hepatocellular carcinoma. Carbon tetrachloride (CCl 4 ) treatment induced IL-20 that further up-regulated the expression of transforming growth factor (TGF)-β1 and p21 WAF1 and resulted in cell cycle arrest in the Clone-9 rat hepatocyte cell line. IL-20 activated quiescent rat hepatic stellate cells (HSCs) and up-regulated TGF-β1 expression. IL-20 also increased TGF-β1, tumor necrosis factor (TNF)-α, and type I collagen (Col-I) expression, and promoted the proliferation and migration of activated HSCs. Serum IL-20 was significantly elevated in mice with short-term and long-term CCl 4 -induced liver injury. In mice with short-term liver injury, anti-IL-20 monoclonal antibody (7E) and anti-IL-20 receptor (IL-20R1) monoclonal antibody (51D) attenuated hepatocyte damage caused by CCl 4 , TGF-β1, and chemokine production. In mice with long-term liver injury, 7E and 51D inhibited CCl 4 -induced cell damage, TGF-β1 production, liver fibrosis, HSC activation, and extracellular matrix accumulation, which was caused by the reduced expression of tissue inhibitors of metalloproteinases as well as increased metalloproteinase expression and Col-I production. IL-20R1-deficient mice were protected from short-term and long-term liver injury. Conclusion : We identified a pivotal role of IL-20 in liver injury and showed that 7E and 51D may be therapeutic for liver fibrosis. (Hepatology 2014;60:1003–1014)
Hypertension as a Biomarker of Efficacy in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib
Authors: B. I. Rini, D. P. Cohen, D. R. Lu, I. Chen, S. Hariharan, M. E. Gore, R. A. Figlin, M. S. Baum, R. J. Motzer
Journal: JNCI Journal of the National Cancer Institute (2011)

BackgroundHypertension (HTN) is an on-target effect of the vascular endothelial growth factor pathway inhibitor, sunitinib. We evaluated the association of sunitinib-induced HTN with antitumor efficacy and HTN-associated adverse events in patients with metastatic renal cell carcinoma.
Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes
Authors: Tami D Lieberman, Jean-Baptiste Michel, Mythili Aingaran, Gail Potter-Bynoe, Damien Roux, Michael R Davis, David Skurnik, Nicholas Leiby, John J LiPuma, Joanna B Goldberg, Alexander J McAdam, Gregory P Priebe, Roy Kishony
Journal: Nature Genetics (2011)
SWOG Cooperative Group Biorepository Resource: Access for Scientific Research Studies
Authors: Carolyn J. Hoban, Wilbur Franklin, Kenneth J. Kopecky, Laurence H. Baker
Journal: Clinical Cancer Research (2011)

SWOG (formerly the Southwest Oncology Group), a National Cancer Institute-supported cooperative group, conducts multi-institutional, multidisciplinary clinical trials for adult patients with cancer, covering a wide range of solid tumors and hematologic cancers. The group has amassed a large set of biospecimens, collected from patients in numerous studies over many years and linked to clinical data. SWOG is now actively promoting the use of this unique scientific resource by making it available to a much wider group of researchers. This biospecimen resource offers material for research on disease mechanisms, genomic changes associated with cancer progression, markers of response and resistance to therapies, diagnosis or detection of recurrence, and more. By collecting, storing, and distributing the specimens, SWOG provides the framework for translational scientists to complete the feedback loop from "bedside to bench." This article provides an overview of the group's biospecimen resources and guidelines for gaining access to them.
Endothelial Cell Protein C Receptor Opposes Mesothelioma Growth Driven by Tissue Factor
Authors: Shiva Keshava, Sanghamitra Sahoo, Torry A. Tucker, Steven Idell, L. Vijaya Mohan Rao, Usha R. Pendurthi
Journal: Cancer Research (2013)

Abstract The procoagulant protein tissue factor (F3) is a powerful growth promoter in many tumors, but its mechanism of action is not well understood. More generally, it is unknown whether hemostatic factors expressed on tumor cells influence tissue factor-mediated effects on cancer progression. In this study, we investigated the influence of tissue factor, endothelial cell protein C receptor (EPCR, PROCR), and protease activated receptor-1 (PAR1, F2R) on the growth of malignant pleural mesothelioma (MPM), using human MPM cells that lack or express tissue factor, EPCR or PAR1, and an orthotopic nude mouse model of MPM. Intrapleural administration of MPM cells expressing tissue factor and PAR1 but lacking EPCR and PAR2 (F2RL1) generated large tumors in the pleural cavity. Suppression of tissue factor or PAR1 expression in these cells markedly reduced tumor growth. In contrast, tissue factor overexpression in nonaggressive MPM cells that expressed EPCR and PAR1 with minimal levels of tissue factor did not increase their limited tumorigenicity. More importantly, ectopic expression of EPCR in aggressive MPM cells attenuated their growth potential, whereas EPCR silencing in nonaggressive MPM cells engineered to overexpress tissue factor increased their tumorigenicity. Immunohistochemical analyses revealed that EPCR expression in tumor cells reduced tumor cell proliferation and enhanced apoptosis. Overall, our results enlighten the mechanism by which tissue factor promotes tumor growth through PAR1, and they show how EPCR can attenuate the growth of tissue factor-expressing tumor cells. Cancer Res; 73(13); 3963–73. ©2013 AACR.
Functional heartburn: the stimulus, the pain, and the brain
Authors: R Fass, G Tougas
Journal: Gut (2002)

Functional heartburn is a common disorder and appears to be composed of several distinct subgroups. Identifying the different subgroups based on clinical history only is not achievable at present. The mechanisms responsible for pain, clinical characteristics, and the optimal therapeutic approach remain poorly understood. Response to potent antireflux treatment is relatively limited. Current and future treatment strategies for functional heartburn patients who have failed standard dose proton pump inhibitors (PPIs) include increased PPI dose in some, as well as addition of pain modulators in others.
Regional Myocardial Blood Flow in Lambs with Concentric Right Ventricular Hypertrophy
Authors: JOSEPH P. ARCHIE, DAVID E. FIXLER, DANIEL J. ULLYOT, GERALD D. BUCKBERG, JULIEN I. E. HOFFMAN
Journal: Circulation Research (1974)

Chronically hypertrophied right ventricles function normally under high systolic pressures, whereas normal right ventricles fail when they are acutely subjected to similar pressures. This phenomenon may be partly due to adaptation of the coronary circulation as well as to hypertrophy. Knowledge of the magnitude and distribution of coronary blood flow and the degree of coronary vascular reserve are important in understanding the function of hypertrophied myocardium. We studied these variables in 16 awake, 5-12-week-old, tranquilized lambs; 9 of the lambs had had their main pulmonary artery banded at 2 days of age. Pressures, cardiac output, and coronary blood flow (radioactive microsphere method) were measured at rest and during two stress states--isoproterenol and dextran infusion. Ventricular function was similar in control and banded lambs. We found significant right ventricular hypertension and both right ventricular and septal hypertrophy in the banded lambs. Total coronary blood flow per gram was slightly higher in banded lambs in all states, and right ventricular flow per gram was significantly elevated at rest and during isoproterenol infusion. Right ventricular coronary resistance per gram was significantly lower in banded lambs in all states. These changes demonstrate that hypertrophied right ventricular tissue is not ischemic at rest, since there is vascular reserve. The changes also raise the question of increased vascularity in hypertrophied myocardium. Right ventricular oxygen supply per unit oxygen demand was increased in banded lambs at rest and during isoproterenol infusion. This finding suggests that hypertrophied myocardium has inefficient oxygen utilization, low oxygen extraction, or both.
Cognitive Outcomes of Preschool Children With Prenatal Cocaine Exposure
Authors: Lynn T. Singer, Sonia Minnes, Elizabeth Short, Robert Arendt, Kathleen Farkas, Barbara Lewis, Nancy Klein, Sandra Russ, Meeyoung O. Min, H. Lester Kirchner
Journal: JAMA (2004)

Because of methodological limitations, the results of the few prospective studies assessing long-term cognitive effects of prenatal cocaine exposure are inconsistent.To assess effects of prenatal cocaine exposure and quality of caregiving environment on 4-year cognitive outcomes.Longitudinal, prospective, masked comparison cohort study from birth (September 1994-June 1996) to 4 years.Research laboratory of a US urban county teaching hospital.A total of 415 consecutively enrolled infants identified from a high-risk population screened for drug use through clinical interview, urine, and meconium screens. Ninety-three percent retention for surviving participants at 4 years of age resulted in 376 children (190 cocaine-exposed and 186 nonexposed).The Wechsler Preschool and Primary Scales of Intelligence-Revised.After control for covariates, prenatal cocaine exposure was not related to lower full-scale IQ (cocaine exposed [80.7] vs nonexposed [82.9]; P =.09) scores or summary verbal (cocaine exposed [79.9] vs nonexposed [81.9]; P =.11) or performance (cocaine exposed [85.5] vs nonexposed [87.5]; P =.18) IQ scores at age 4 years. However, prenatal cocaine exposure was related to small but significant deficits on several subscales (mean [SE]): visual-spatial skills (cocaine exposed [7.3 (0.22)] vs nonexposed [8.2 (0.22)]; P =.01), general knowledge (cocaine exposed [6.1 (0.18)] vs nonexposed [6.7 (0.17)]; P =.04), and arithmetic skills (cocaine exposed [6.2 (0.20)] vs nonexposed [6.8 (0.20)]; P =.05). Prenatal cocaine exposure was also associated with a lower likelihood of achievement of IQ above normative means (odds ratio, 0.26 [95% confidence interval, 0.10-0.65]; P =.004). The quality of the caregiving environment was the strongest independent predictor of outcomes. Cocaine-exposed children placed in nonrelative foster or adoptive care lived in homes with more stimulating environments and had caregivers with better vocabulary scores, and they attained full-scale and performance IQ scores (83 and 87, respectively) similar to nonexposed children in biological maternal or relative care (full-scale IQ, 82; performance IQ, 88) and higher than cocaine-exposed children in biological maternal or relative care (full-scale IQ, 79; performance IQ, 84).Prenatal cocaine exposure was not associated with lower full-scale, verbal, or performance IQ scores but was associated with an increased risk for specific cognitive impairments and lower likelihood of IQ above the normative mean at 4 years. A better home environment was associated with IQ scores for cocaine-exposed children that are similar to scores in nonexposed children.
Cutaneous field stimulation of sensory nerve fibers reduces itch without affecting contact dermatitis
Authors: J. Wallengren
Journal: Allergy (2002)

Background: A new technique, cutaneous field stimulation (CFS), which activates electrically unmyelinated C‐fibers, is used to treat localized itch. Its action is similar to that of capsaicin, the pungent agent in hot peppers, which enhances delayed allergic reactions. The aim of the study was to investigate how experimental contact dermatitis responds to CFS. Methods: Twelve patients with contact dermatitis in response to nickel were treated by CFS for 1 h each for four consecutive days. A flexible plate containing electrodes was applied to a test area on the upper arm and was stimulated by a constant current (0.8 mA). On the fifth day, patients were provoked by epicutaneous application of nickel sulfate (allergic contact dermatitis) and benzalkonium chloride (irritant contact dermatitis), and by intradermal tuberculin (delayed immunologic reaction). Twelve other patients with IgE‐mediated allergy were treated by CFS on the lower arm for 1 h and were then pricked with histamine and allergen extracts (wheal volume was measured) and were tested using benzoic acid (nonimmunologic contact urticaria; closed test). Ten of these patients were also treated by CFS for four days, and experiments were performed on the fifth day. Results: Test reactions to nickel, benzalkonium, and tuberculin were found to be unaffected by CFS treatment. Although allergic prick test reactions were enhanced (by 28%) after a single CFS treatment, the associated itch was significantly reduced both after single and repeated CFS treatments (by 65% and 38%, respectively). Conclusions: Repeated use of CFS to reduce itch has no adverse effects on contact dermatitis.
Degenerate Tetraploidy Was Established Before Bdelloid Rotifer Families Diverged
Authors: J. H. Hur, K. Van Doninck, M. L. Mandigo, M. Meselson
Journal: Molecular Biology and Evolution (2008)

Rotifers of Class Bdelloidea are abundant freshwater invertebrates known for their remarkable ability to survive desiccation and their lack of males and meiosis. Sequencing and annotation of approximately 50-kb regions containing the four hsp82 heat shock genes of the bdelloid Philodina roseola, each located on a separate chromosome, have suggested that its genome is that of a degenerate tetraploid. In order to determine whether a similar structure exists in a bdelloid distantly related to P. roseola and if degenerate tetraploidy was established before the two species separated, we sequenced regions containing the hsp82 genes of a bdelloid belonging to a different family, Adineta vaga, and the histone gene clusters of P. roseola and A. vaga. Our findings are entirely consistent with degenerate tetraploidy and show that it was established before the two bdelloid families diverged and therefore probably before the bdelloid radiation.
99 PROGENITOR CELL ACTIVATION AND LIVER REPAIR IS ALTERED IN NOTCH2- AND RBP-Jκ-DEFECTIVE MICE EXPOSED TO CHOLESTATIC INJURIES
Authors: R. Fiorotto, C. Spirli, R. Scirpo, T. Gridley, S. Huppert, B. Torcello, C. Ferrero, M. Strazzabosco
Journal: Journal of Hepatology (2010)
Discovery and Validation of Biomarkers that Respond to Treatment with Brivanib Alaninate, a Small-Molecule VEGFR-2/FGFR-1 Antagonist
Authors: Mark Ayers, Joseph Fargnoli, Anne Lewin, Qiuyan Wu, J. Suso Platero
Journal: Cancer Research (2007)

The process of neovascularization from preexisting blood vessels, referred to as angiogenesis, plays a critical role in both tumor growth and dissemination in multiple cancer types. Currently, there exists a need to identify biomarkers that can both indicate biological activity and predict efficacy at the molecular level for antiangiogenesis drugs which are anticipated to result in tumor stasis rather than regression. To identify such biomarkers, athymic mice bearing L2987 human tumor xenografts were treated with the antiangiogenic agent brivanib alaninate, which is currently under clinical evaluation. This is an orally available and selective tyrosine kinase inhibitor that targets the key angiogenesis receptors vascular endothelial growth factor receptor 2 (VEGFR-2) and fibroblast growth factor receptor 1. In the described studies, tumor samples were collected from these xenografts and RNA was extracted for gene expression profiling on Affymetrix 430A mouse GeneChips. Statistical analysis was done using a defined set of genes identified to be coexpressed with VEGFR-2 from a clinical tumor gene expression profiling database and between tumor samples isolated from brivanib alaninate-treated and untreated mice. Tyrosine kinase receptor 1 (Tie-1), collagen type IV alpha1 (Col4a1), complement component 1, q subcomponent receptor 1 (C1qr1), angiotensin receptor-like 1 (Agtrl1), and vascular endothelial-cadherin (Cdh5) were all identified to be significantly modulated by treatment with brivanib alaninate. These genes, which may be potentially useful as markers of brivanib alaninate activity, were further studied at the protein level in two separate in vivo human colon tumor xenograft models, HCT116 and GEO, using immunohistochemistry-based approaches.
Proteomic Approaches to Analyze the Dynamic Relationships Between Nucleocytoplasmic Protein Glycosylation and Phosphorylation
Authors: Stephen A. Whelan, Gerald W. Hart
Journal: Circulation Research (2003)

O-linked β- N -acetylglucosamine (O-GlcNAc) is both an abundant and dynamic posttranslational modification similar to phosphorylation that occurs on serine and threonine residues of cytosolic and nuclear proteins in all metazoans and cell types examined, including cardiovascular tissue. Since the discovery of O-GlcNAc more than 20 years ago, the elucidation of O-GlcNAc as a posttranslational modification has been slow, albeit similar to the rate of acceptance of phosphorylation, because of the lack of tools available for its study. Identifying O-GlcNAc posttranslational modifications on proteins is a major challenge to proteomics. The recent development of mild β-elimination followed by Michael addition with dithiothreitol has significantly improved the site mapping of both O-GlcNAc and O -phosphate in functional proteomics. β-Elimination followed by Michael addition with dithiothreitol facilitates the study of the labile O-GlcNAc modification in the etiology of disease states. We discuss how recent technological innovations will expand our present understanding of O-GlcNAc and what the implications are for diabetes and cardiovascular complications.
Production of Arterial Lesions by a Humoral Factor in Parabiotic Rats
Authors: PAUL R. PATEK, SOL BERNICK, DONALD K. MACCALLUM
Journal: Circulation Research (1963)

The experimental production of arteriosclerosis and atherosclerosis by RES blocking agents such as colloidal carbon and thorium dioxide has implicated the RES as a factor in the etiology of these diseases. Holtzman strain male rats each received a single intravenous injection of colloidal carbon (5 mg/100 g animal body wt). Three days later the injected animals were united by parabiosis to non-injected animals of the same sex, weight and genetic strain. Carbon granules were found in the RES of injected rats, but few or no granules were found in Kupffer cells of their non-injected parabiotic partners. Coronary arteries of both injected and non-injected animals showed thickening and fragmentation of the internal elastic membrane after two months. After four to six months the lesions included degenerative changes of muscle cells just external to the internal elastic membrane and thickening of the intima. Hyperplasia of the thyroid was found in both parabionts. Addition of 1% cholesterol-5% fat to the diet caused deposition of lipid in endothelial cells and intimal macrophages of the damaged arteries of both parabionts. Distribution of lipid within the hepatic parenchymal cells was also altered in the experimental animals but not in controls. It is suggested that uptake of particulate matter by cells of the RES causes them to release a substance capable of producing arterial lesions.
Effect of pH changes on the cardiac sphincter
Authors: G. R. Giles, C. Humphries, M. C. Mason, C. G. Clark
Journal: Gut (1969)

In 16 normal subjects the pressure characteristics of the cardiac sphincter have been examined. The effect of perfusing the gastric aspect of the sphincter mucosa has been studied by comparing the effects of saline with those of solutions where pH ranged from 1.0 to 8.0. Acid perfusion produced an increase in sphincteric pressure, particularly at pH 3.0. This suggests that a physiological mechanism exists which can increase the barrier pressure to gastrooesophageal reflux during periods of active secretion of the stomach, as occurs in digestion.
Effect of visceral fat accumulation on uric acid metabolism in male obese subjects: Visceral fat obesity is linked more closely to overproduction of uric acid than subcutaneous fat obesity
Authors: Fumihiko Matsuura, Shizuya Yamashita, Tadashi Nakamura, Makoto Nishida, Shuichi Nozaki, Tohru Funahashi, Yuji Matsuzawa
Journal: Metabolism (1998)
Alternative Processing of Growth Hormone Receptor Transcripts*
Authors: Alexander Edens, Frank Talamantes
Journal: Endocrine Reviews (1998)

I. Introduction: GH Receptor and GH-Binding Protein II. The GHR Gene III. GHR Transcript Heterogeneity A. 5′-UTR heterogeneity B. Deletions and truncations of the transmembrane or intracellular domain C. Deletions in the hormone-binding domain-encoding region IV. Summary of GHR Alternative Processing and Possible Future Studies