tbuckley/cabot-search huggingface dataset:
Abstract 1679: Genome-wide methylation analysis in Barrett's esophagus and esophageal adenocarcinoma
Authors: Enping xu, Jian Gu, Ernest T. Hawk, Maosheng Huang, Kenneth K. Wang, Jaffer A. Ajani, Xifeng Wu
Journal: Cancer Research (2012)

Abstract Esophageal carcinogenesis (EAC) is a multiple-step process involving the accumulation of multiple genetic and epigenetic changes. Barrett's esophagus (BE) is a precursor of EAC. In this study, we performed genome-wide methylation profiling of BE and EAC tissues to identify novel tumor suppressors involved in esophageal carcinogenesis and potential biomarkers for the malignant progression of EAC. Using Illumina's HumanMethylation27 BeadChip microarray, we examined the methylation status of 27,578 CpG sites in 94 normal tissues, 77 BE, and 117 EAC tissues. Hierarchical clustering analysis showed an excellent separation of normal tissues from BE and EAC tissues; however, the clustering of BE and EAC tissues was less clear, suggesting the methylation pattern of BE and EAC was similar and methylation occurs early during the progression of EAC. At the individual gene level, we recapitulated the major tumor suppressors that previously reported to be hypermethylated in BE and EAC, including SFRP1, APC, WIF1, etc. We also identified a large number of novel hypermethylated genes in BE and EAC tissues, in particular, genes of several family proteins, including ADAM peptidase proteins, cadherin and procadherin, and potassium voltage-gated channels. We used pyrosequencing to validate selected genes in these families. For example, in normal, BE and EAC tissue, the methylation frequency of PCDH9 was 0.20%, 24.6% and 29.5% respectively, and the methylation frequency of ADAMTS2 was 4.69%, 37.3% and 32% respectively. In general, there were significant correlations between array and pyrosequencing results. The identified differentially methylated genes may become potential biomarkers for the prediction and early detection EAC among BE patients and molecular targets for prevention and therapy of EAC. 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 1679. doi:1538-7445.AM2012-1679
Fibrous Dysplasia Associated with Primary Hyperparathyroidism in the Absence of the McCune-Albright Syndrome
Authors: SEONG-JANG KIM, JU-WON SEOK, IN-JU KIM, YONG-KI KIM, DAE-SOO JUNG, DONG-SOO KIM
Journal: Clinical Nuclear Medicine (2003)

KIM, SEONG-JANG M.D.; SEOK, JU-WON M.D.; KIM, IN-JU M.D.; KIM, YONG-KI M.D.; JUNG, DAE-SOO M.D.; KIM, DONG-SOO M.D. Author Information
Chemical structure, reactivity, and carcinogenicity of halohydrocarbons.
Authors: B L Van Duuren
Journal: Environmental Health Perspectives (1977)

This review summarizes studies concerning the covalent binding of [14C]TCE to rat liver microsomal protein and exogenous DNA, in vitro, the enhancement of this binding by inducers of mixed-function oxidases, and inhibition of binding by inhibitors of these enzymes. Furthermore, recent studies on this type of binding in various strains of mice and rats of both sexes and using microsomal preparations from various organs are briefly reviewed. Other work reviewed here concerns the synthesis of TCE epoxide and its reaction with nucleophiles since it is believed that TCE epoxide is the activated carcinogenic intermediate of TCE. The utility of structural prognostication of carcinogenic activity and the importance of considering possible metabolic pathways for other chlorinated olefins is also discussed.
THU0114 Efficacy and Safety of Spironolactone in the Treatment of Rheumatoid Arthritis and Ankylosing Spondylitis
Authors: A. Syngle, I. Verma, P. Krishan
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Synthetic disease-modifying antirheumatic drugs (DMARDs) though effective have limitations often requiring use of expensive parenteral biologic DMARDs in Rheumatoid Arthritis (RA) and Ankylosing Spondylitis (AS). Hence there is a need for safe, efficacious economical therapies for management of disease and co-morbidities. Given the TNF inhibiting potential of spironolactone (SPIR)<sup>1</sup>, we decided to investigate its use as a novel therapy in RA and AS. <h3>Objectives</h3> A randomized, placebo-controlled, open label study to evaluate the efficacy and safety of spironolactone in patients with RA and AS. <h3>Methods</h3> A total 73 patients of which 44 of RA (22 in SPIR and 22 in placebo arm) and 29 patients with AS (15 in SPIR and 14 in placebo arm) were randomized to oral SPIR (2 mg/kg/day) or placebo for 12 weeks as an adjunct to existing DMARDs. Patients with active disease (DAS-28 ≥3.2 in RA and BASDAI score ≥4 in AS) with stable doses of conventional DMARDs for at least 6 months were investigated. Clinical response was assessed after 12 weeks by the Disease Activity Score in 28 joints (DAS28), simple disease activity index (SDAI) and American College of Rheumatology (ACR) response criteria for RA and the Bath Ankylosing Spondylitis Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) for AS patients. Quality of life was assessed using HAQ-DI. <h3>Results</h3> The spironolactone and placebo groups were well matched in both RA and AS. After treatment with spironolactone, there was significant reduction (p&lt;0.05) in inflammatory markers (CRP and ESR) and disease activity measures in (DAS-28, SDAI in RA and BASDAI and ASDAS in AS) RA and AS patients (Fig.1A). HAQ-DI score was significantly improved in both RA and AS patients (p&lt;0.02 and p&lt;0.001 respectively) as compared to placebo group. At week 12, ACR 20 and ACR 50 responses were achieved by 68% (n=15) and 27% (n=6) of RA patients respectively in the spironolactone treated group (Fig. 1B), while 18% (n=4) of patients in the placebo group achieved ACR 20 response. There were minor side effects which did not mandate stopping of spironolactone. No change in any biochemical profile was noted after spironolactone treatment. <h3>Conclusions</h3> This study suggests that spironolactone significantly reduces inflammatory biomarkers and disease severity and improves physical function assessed by HAQ-DI, which is an excellent predictor of work disability, morbidity. The results suggest spironolactone is a safe, effective adjunctive treatment for RA and AS. <h3>References</h3> Bendtzen K et al. Clin Exp Immunol. 2003;134:151–158. <h3>Acknowledgements</h3> This study has been supported by a Research Fellowship from University Grant Commission, New Delhi (Govt. of India) [No. F.10-15/2007 (SA-I)]. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5165
Abstract 3241: Multipotential PTEN−/− p53−/− prostate tumor initiating cells give rise to adenocarcinoma which displays epithelial-to-mesenchymal transition, metastasis, and androgen independent growth
Authors: Rachel M. Pierce, Philip L. Martin, Kathy Kelly
Journal: Cancer Research (2010)

Abstract Determining the cell lineage and differentiation potential of tumor initiating cells is fundamental to understanding mechanisms of progression and metastasis. We describe the differentiative, tumorigenic, and metastatic properties of primary, transplanted secondary, and clonally-derived tumors in a model of prostate cancer initiated by prostate epithelial cell specific deletion of the tumor suppressors, PTEN and p53. Although adenocarcinoma is the majority tumor type that develops in this mouse model, other histological tumor types, including a late developing sarcomatoid carcinoma were observed. The heterogeneity displayed in transgenic mouse prostate tumors may be due to the transformation of multiple lineage specific tumor initiating cells, or a common tumor progenitor/stem cell capable of plasticity in differentiation potential. Orthotopic transplantation of PTEN−/− p53−/−prostate carcinoma cells was undertaken to determine whether a single tumor initiating cells is capable of giving rise to the diversity of tumor phenotypes observed in the parental prostate carcinoma. Direct orthotopic transplantation of mixed populations of PTEN−/− p53−/− tumor cells favored the development of adenocarcinomas, while transplantation of cells grown as protospheres in matrigel favored the development of basal/squamous carcinomas. This indicates a developmental plasticity in transplantable tumor initiating cells that can be influenced by extracellular matrix components. Transplantation of clonal cell lines that were derived from orthotopic carcinomas produced adenocarcinomas with lesser amounts basal/squamous carcinoma with one line undergoing EMT to form sarcomatoid carcinomas. Lung and lymph node metastases were common. Tumor growth, metastasis, and response to androgen deprivation were assayed with in-vivo bioluminescent imaging. The orthotopic tumors recapitulated the diversity of tumor phenotypes observed in the probasin-cre, PTEN fl/fl p53 fl/fl transgenic donor mouse including: adenocarcinoma, spindle cell carcinoma, urothelial carcinoma, and basal/squamous carcinoma. In a pattern that mimics a phenotype observed in metastatic human prostate carcinoma, CK8+ adenocarcinomas displayed heterogeneous labeling for the neuroendocrine marker synaptophysin. Our data suggests that a multi-potential CK8+/CK5+ tumor stem cell can be a progenitor for CK8+ adenocarcinoma. 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 3241.
P150GLP-1 (7-36) prevents palmitate-induced oxidative stress in HL-1 cardiomyocytes
Authors: S Ravassa Albeniz, J Beaumont, A Gonzalez, J Diez
Journal: Cardiovascular Research (2014)

Aims: Lipotoxicity increases oxidative stress and induces mitochondrial alterations in cardiomyocytes, contributing to left ventricular dysfunction in diabetic cardiomyopathy. GLP-1 is an incretin reported to have anti-oxidant actions in different cellular models. We investigated whether GLP-1 inhibits oxidative stress, mitochondrial dysfunction and DNA oxidative damage in murine HL-1 cardiomyocytes stimulated with palmitate.
High Blood Alcohol Levels in Women
Journal: New England Journal of Medicine (1990)

Abstract After consuming comparable amounts of ethanol, women have higher blood ethanol concentrations than men, even with allowance for differences in size, and are more susceptible to alcoholic liver disease. Recently, we documented significant   of ethanol due to its oxidation by gastric tissue. We report a study of the possible contribution of this metabolism to the sex-related difference in blood alcohol concentrations in 20 men and 23 women. Six in each group were alcoholics. The first-pass metabolism was determined on the basis of the difference in areas under the curves of blood alcohol concentrations after intravenous and oral administration of ethanol (0.3 g per kilogram of body weight). Alcohol dehydrogenase activity was also measured in endoscopic gastric biopsies. In nonalcoholic subjects, the first-pass metabolism and gastric alcohol dehydrogenase activity of the women were 23 and 59 percent, respectively, of those in the men, and there was a significant correlation (rs...
Muscular and Myocardial Involvement in Sarcoidosis
Authors: YOSHIO TANABE, YASUFUMI OHUCHI, TOSHIHIDE OGAWA
Journal: Clinical Nuclear Medicine (2002)

From the Department of Radiology, Faculty of Medicine, Tottori University, Tottori, Japan Received for publication September 13, 2000. Revision accepted February 13, 2002. Correspondence: Yoshio Tanabe, Department of Radiology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago City, Tottori 683-8504, Japan. E-mail: [email protected]
Abstract 1353: Inactivation of ribosomal protein L22 promotes transformation by induction of Lin28B
Authors: Shuyun Rao, Sangyun Lee, Alejandro Guitierrez, Jacqueline Jacqueline Perrigoue, Roshan Thapa, Zhigang Tu, John Jeffers, Michele Rhodes, Stephen Hunger, James Downing, Rugang Zhang, Siddharth Balachandran, Gerard Zambetti, Joseph Testa, A. Thomas Look, David Wiest
Journal: Cancer Research (2012)

Abstract The molecular basis by which mutations in some ribosomal proteins (RP) predispose to development of hematologic malignancies remains unclear. We show here that germline inactivation of the ribosomal protein L22 (Rpl22), which selectively blocks T cell development, also predisposes T lineage progenitors to transformation. Indeed, RPL22 was found to be inactivated in ∼9% of human T-acute lymphoblastic leukemias (T-ALL). Moreover, mono-allelic loss of Rpl22 accelerates development of thymic lymphoma in a mouse model of T cell malignancy and in acute transformation assays in vitro. Furthermore, we show that Rpl22 inactivation enhances transformation potential through induction of Lin28B. These findings represent the first mechanistic insight into how an RP mutation promotes transformation.Our finding that Rpl22 inactivation promotes transformation by inducing expression of Lin28B provides insight into the mechanistic basis by which mutations in Rpl22, and perhaps other RP genes, increase cancer risk. In addition, because we have determined that Lin28B induction is dependent upon NF-kB activity, our findings may provide new opportunities for therapeutic intervention both in aggressive forms of T-ALL, where we have found Rpl22 to be inactivated, and perhaps in other diseases caused by mutations in RP genes. 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 1353. doi:1538-7445.AM2012-1353
Combined Tc-99m MIBI and Tc-99m RBC for Anatomic Localization of Ectopic Mediastinal Parathyroid Adenomas
Authors: SUZANNE T. MASTIN, NANETTE M. MANCUSO, J. WILLIAM KISER, MICHAEL W. NICOLE, WALTER E. DRANE
Journal: Clinical Nuclear Medicine (1996)

Preoperative localization of abnormal parathyroid tissue in patients with persistent or recurrent hyperparathyroidism is recommended as a standard of care. A high percentage of these patients have ectopic tissue in the mediastinum. Tc-99m MIBI imaging alone for detection of ectopic parathyroid tissue in the mediastinum does not provide a sufficient number of anatomic landmarks, which makes communication regarding the exact location of any area of abnormal uptake difficult. We report the use of concomitant Tc-99m RBC and Tc-99m MIBI imaging for precise anatomic localization of ectopic mediastinal parathyroid tissue in 4 patients. It is thought that this combination of studies allows improved communication with referring physicians, surgeons, and radiologists for planning both surgical approach and correlative imaging studies. It is hoped that in the future this combination of studies may obviate the need for other imaging studies.
Multiple myeloma–derived MMP-13 mediates osteoclast fusogenesis and osteolytic disease
Authors: Jing Fu, Shirong Li, Rentian Feng, Huihui Ma, Farideh Sabeh, G. David Roodman, Ji Wang, Samuel Robinson, X. Edward Guo, Thomas Lund, Daniel Normolle, Markus Y. Mapara, Stephen J. Weiss, Suzanne Lentzsch
Journal: Journal of Clinical Investigation (2016)

Multiple myeloma (MM) cells secrete osteoclastogenic factors that promote osteolytic lesions; however, the identity of these factors is largely unknown. Here, we performed a screen of human myeloma cells to identify pro-osteoclastogenic agents that could potentially serve as therapeutic targets for ameliorating MM-associated bone disease. We found that myeloma cells express high levels of the matrix metalloproteinase MMP-13 and determined that MMP-13 directly enhances osteoclast multinucleation and bone-resorptive activity by triggering upregulation of the cell fusogen DC-STAMP. Moreover, this effect was independent of the proteolytic activity of the enzyme. Further, in mouse xenograft models, silencing MMP-13 expression in myeloma cells inhibited the development of osteolytic lesions. In patient cohorts, MMP-13 expression was localized to BM-associated myeloma cells, while elevated MMP-13 serum levels were able to correctly predict the presence of active bone disease. Together, these data demonstrate that MMP-13 is critical for the development of osteolytic lesions in MM and that targeting the MMP-13 protein - rather than its catalytic activity - constitutes a potential approach to mitigating bone disease in affected patients.
MYOCARDIAL REMODELLING AND FIBROSIS IN NONISCHAEMIC DILATED CARDIOMYOPATHY: INSIGHTS FROM CARDIOVASCULAR MAGNETIC RESONANCE
Authors: Andrea Barison, Alessandro Ortalda, Giancarlo Todiere, Giuseppe Vergaro, Chrysanthos Grigoratos, Gianluca Mirizzi, Alessandro Valleggi, Sara Chiappino, Luigi Pastormerlo, Claudio Passino, Giovanni Donato Aquaro, Michele Emdin
Journal: Journal of the American College of Cardiology (2016)
Case 40-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Kenneth McIntosh, Judith A. Ferry
Journal: New England Journal of Medicine (1990)

Presentation of CaseA 16-year-old boy was admitted to the hospital because of rapidly progressive hepatic failure.There was a history of seizures that began at the age of 12 years, with partial complex and generalized tonic-clonic episodes; the seizures became controlled during carbamazepine treatment. Thereafter the patient was in his usual state of health until 13 months before admission, when he began to experience fatigue, fever, arthralgia, and headache. A serologic test for infectious mononucleosis was reported to be positive. Four weeks later, in the presence of his father, the boy had a 75-minute bout of intermittent generalized tonic-clonic . . .
Secretin-Mediated Gene Delivery, a Specific Targeting Mechanism with Potential for Treatment of Biliary and Pancreatic Disease in Cystic Fibrosis
Authors: Tristan McKay, Paul Reynolds, Sarah Jezzard, David Curiel, Charles Coutelle
Journal: Molecular Therapy (2002)

Gene therapy directed to the gastroenterological manifestations of cystic fibrosis (CF) would ideally be administered systemically. Such delivery would require efficient targeting at the cellular level to achieve a safe and effective therapy. Here we describe gene delivery using the secretin receptor (SR) as a basolateral target specific to the biliary and pancreatic epithelia affected in CF patients. We describe here targeting of a polycation-based nonviral gene delivery vector and retargeting of an adenoviral vector to cells expressing the SR <i>in vitro</i>. We were able to transfect cells expressing the SR up to 10-fold more efficiently than those not expressing the SR with a targeted polycation, SecGGC–lPEI. This targeting effect was secretin-specific and substantially reduced by competing secretin. SR-retargeted adenovirus transduced SR-expressing cells at more than sixfold higher levels than adenovirus alone. The SR may be an effective target for targeting systemically applied viral and nonviral gene delivery constructs to disease-affected tissues in CF patients.
A Comparison of Three Months of Anticoagulation with Extended Anticoagulation for a First Episode of Idiopathic Venous Thromboembolism
Authors: Clive Kearon, Michael Gent, Jack Hirsh, Jeffrey Weitz, Michael J. Kovacs, David R. Anderson, Alexander G. Turpie, David Green, Jeffrey S. Ginsberg, Philip Wells, Betsy MacKinnon, Marilyn Johnston, James Douketis, Robin Roberts, Paul van Nguyen, Jeannine Kassis, Sean Dolan, Christine Demers, Louis Desjardins, Susan Solymoss, Arthur Trowbridge, Jim A. Julian
Journal: New England Journal of Medicine (1999)

Patients who have a first episode of venous thromboembolism in the absence of known risk factors for thrombosis (idiopathic thrombosis) are often treated with anticoagulant therapy for three months. Such patients may benefit from longer treatment, however, because they appear to have an increased risk of recurrence after anticoagulant therapy is stopped.
Novel application of catheter probe EUS for mediastinal lymph node
Authors: Nishimura Makoto, Shono Takashi, Ochiai Yasutoshi, Nakao Masamitsu, Togawa Osamu, Ishikawa Keiko, Arai Shin, Kita Hiroto
Journal: Endoscopy (2011)

Accurate evaluation of mediastinal lymphadenopathy of esophageal cancer or lung cancer is important for determining the appropriate therapy. Radial type endoscopic ultrasound (radial-EUS), computed tomography (CT), and positron emission tomography (PET) scanning are widely used, but there are no data regarding the use of catheter probe EUS for evaluation of mediastinal lymph node.
THE IMPACT OF ENDOTHELIAL DYSFUNCTION IN THE DEVELOPMENT OF DIABETIC RETINOPATHY: ROLE OF INFLAMMATION
Authors: Gerasimos Siasos, Nikolaos Gouliopoulos, Marilita Moschos, Evangelos Oikonomou, Christina Kollia, Marina Zaromitidou, Konstantinos Zisimos, Konstantinos Mourouzis, Sotirios Tsalamandris, Georgia Siasou, Theodore Paraskevopoulos, Savvas Mazaris, Theodosia Konsola, Christodoulos I Stefanadis, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2015)
Synergisitic inhibition of DNA repair by combining ß-lapachone with Nu7026 as a strategy for killing primary and metastatic breast cancers.
Authors: EA Bey, C Kessinger, E Blanco, R Bachoo, N Williams, DA Boothman
Journal: Cancer Research (2009)

Abstract Abstract #3078 The primary tumors of most breast cancer patients are removed via resection or complete mastectomy. However, years after having their primary tumors removed many patients will need chemotherapy for metastatic disease that arises in distal sites such as lung and brain. It has been reported that many breast cancers overexpress the 2 electron oxidoreducase NQO1, a marker of tumorigenesis for a variety of cancers. Since NQO1 expression levels are low in normal tissue but elevated 10-100 fold in breast cancers, we hypothesized that NQO1 levels could be exploited for chemotherapy with ß-lapachone. ß-lapachone is a naturally derived plant product that is bioactivated by NQO1. In this study we show that ß-lapachone (a DNA repair inhibitor) synergizes with the DNA-PK inhibitor Nu7026 to kill human breast cancer cell lines that express NQO1. Normal human breast tissues and breast cancer cell lines that did not express NQO1 were not affected by ß-lapachone. In addition by using in vivo breast cancer models we demonstrated that ß-lapachone effectively inhibited breast tumor growth in athymic mice. We also showed that ß-lap was efficacious against lung tumors derived from MDA-MB-231 breast cancer cell lines. Finally, our simulated brain metastatic model showed that ß-lap accumulated in brain tumors derived from MDA-MB-2331 cells. Together these data suggest that ß-lap and ß-lap in combination Nu7026 may be a potent combination for treating primary and metastatic breast cancer disease. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3078.
Misleading Ga-67 Uptake in a Patient with Hodgkin’s Disease, Mediastinal Deviation, and Pulmonary Compression
Authors: Pinhas Stark, Adam Steinmetz, Marina Hefetz, Ruth Hardoff
Journal: Clinical Nuclear Medicine (2002)

STARK, PINHAS M.D.*; STEINMETZ, ADAM M.D.†; HEFETZ, MARINA M.D.‡; HARDOFF, RUTH M.D., D.Sc.† Author Information