tbuckley/cabot-search huggingface dataset:
Nitrate Intake Does Not Influence Bladder Cancer Risk: The Netherlands Cohort Study
Authors: Maurice P. Zeegers, Roel F.M. Selen, Jos C.S. Kleinjans, R. Alexandra Goldbohm, Piet A. van den Brandt
Journal: Environmental Health Perspectives (2006)

ObjectivesN-nitroso compounds, endogenously formed from nitrate-derived nitrite, are suspected to be important bladder carcinogens. However, the association between nitrate exposure from food or drinking water and bladder cancer has not been substantially investigated in epidemiologic studies.MethodsWe evaluated the associations between nitrate exposure and bladder cancer in the Netherlands Cohort Study, conducted among 120,852 men and women, 55–69 years of age at entry. Information on nitrate from diet was collected via a food frequency questionnaire in 1986 and a database on nitrate content of foods. Individual nitrate exposures from beverages prepared with tap water were calculated by linking the postal code of individual residence at baseline to water company data. After 9.3 years of follow-up and after excluding subjects with incomplete or inconsistent dietary data, 889 cases and 4,441 subcohort members were available for multivariate analyses. We calculated incidence rate ratios (RR) and corresponding 95% confidence intervals (CIs) using Cox regression analyses. We also evaluated possible effect modification of dietary intake of vitamins C and E (low/high) and cigarette smoking (never/ever).ResultsThe multivariate RRs for nitrate exposure from food, drinking water, and estimated total nitrate exposure were 1.06 (95% CI, 0.81–1.31), 1.06 (95% CI, 0.82–1.37), and 1.09 (95% CI, 0.84–1.42), respectively, comparing the highest to the lowest quintiles of intake. Dietary intake of vitamins C and E (low/high) and cigarette smoking (never/ever) had no significant impact on these results.ConclusionAlthough the association between nitrate exposure and bladder cancer risk is biologically plausible, our results in this study do not support an association between nitrate exposure and bladder cancer risk.
Reduced-Intensity Conditioning Compared With Conventional Allogeneic Stem-Cell Transplantation in Relapsed or Refractory Hodgkin's Lymphoma: An Analysis From the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation
Authors: Anna Sureda, Stephen Robinson, Carmen Canals, Angelo M. Carella, Marc A. Boogaerts, Dolores Caballero, Ann E. Hunter, Lothar Kanz, Shimon Slavin, Jan J. Cornelissen, Martin Gramatzki, Dietger Niederwieser, Nigel H. Russell, Norbert Schmitz
Journal: Journal of Clinical Oncology (2007)

To compare the clinical outcome in terms of nonrelapse mortality (NRM), relapse rate (RR), overall survival (OS), and progression-free survival (PFS) in patients with relapsed Hodgkin's lymphoma (HL) treated with reduced-intensity conditioning (RIC) or myeloablative conditioning followed by allogeneic stem-cell transplantation (alloSCT).A total of 168 patients with HL undergoing a first alloSCT (RIC, n = 89; myeloablative conditioning, n = 79) between January 1997 and December 2001 and registered in the European Group for Blood and Marrow Transplantation database were analyzed.NRM was significantly decreased in the RIC group (hazard ratio [HR], 2.85; 95% CI, 1.62 to 5.02; P < .001). OS was better in the RIC group (HR, 2.05; 95% CI, 1.27 to 3.29; P = .04) and there was a trend for better PFS in the RIC group (HR, 1.53; 95% CI, 0.97 to 2.40; P = .07). RR was higher in the RIC group in univariate but not in multivariate analysis. The development of chronic graft-versus-host disease (GVHD) significantly decreased the incidence of relapse, which translated into a trend for a better PFS.The lower incidence of NRM in the RIC group is encouraging, particularly because these patients experienced adverse pretransplantation characteristics more frequently. This analysis also indicates the existence of a graft-versus-HL effect correlated to the development of GVHD. Additional efforts to reduce the high RR seen in both groups of patients will be necessary to improve the modest PFS (31% v 27%) and OS (59% v 36%) for patients prepared with RIC or myeloablative conditioning.
Exploring the Occurrence of Classic Selective Sweeps in Humans Using Whole-Genome Sequencing Data Sets
Authors: Maud Fagny, Etienne Patin, David Enard, Luis B. Barreiro, Lluis Quintana-Murci, Guillaume Laval
Journal: Molecular Biology and Evolution (2014)

Genome-wide scans for selection have identified multiple regions of the human genome as being targeted by positive selection. However, only a small proportion has been replicated across studies, and the prevalence of positive selection as a mechanism of adaptive change in humans remains controversial. Here we explore the power of two haplotype-based statistics—the integrated haplotype score (iHS) and the Derived Intraallelic Nucleotide Diversity (DIND) test—in the context of next-generation sequencing data, and evaluate their robustness to demography and other selection modes. We show that these statistics are both powerful for the detection of recent positive selection, regardless of population history, and robust to variation in coverage, with DIND being insensitive to very low coverage. We apply these statistics to whole-genome sequence data sets from the 1000 Genomes Project and Complete Genomics. We found that putative targets of selection were highly significantly enriched in genic and nonsynonymous single nucleotide polymorphisms, and that DIND was more powerful than iHS in the context of small sample sizes, low-quality genotype calling, or poor coverage. As we excluded genomic confounders and alternative selection models, such as background selection, the observed enrichment attests to the action of recent, strong positive selection. Further support to the adaptive significance of these genomic regions came from their enrichment in functional variants detected by genome-wide association studies, informing the relationship between past selection and current benign and disease-related phenotypic variation. Our results indicate that hard sweeps targeting low-frequency standing variation have played a moderate, albeit significant, role in recent human evolution.
Treatment of Kaposi's sarcoma after solid organ transplantation.
Authors: F A Shepherd, E Maher, C Cardella, E Cole, P Greig, J A Wade, G Levy
Journal: Journal of Clinical Oncology (1997)

This retrospective review of all patients who developed Kaposi's sarcoma (KS) after solid organ transplantation at a single institution was undertaken to define the clinical presentation of this malignancy in the setting of iatrogenic immunodeficiency, and to determine the most appropriate treatment for patients in this clinical setting.The records of 2,099 patients who underwent heart, lung, liver, or kidney transplantation at The Toronto Hospital between January 1, 1981 and June 30, 1995, were reviewed. Twelve patients were identified who developed biopsy-proven KS in the posttransplantation period. Five patients who had disseminated KS who had not responded to either reduction or withdrawal of immunosuppression or to local radiotherapy were treated with combination chemotherapy consisting of doxorubicin 20 to 30 mg/m2, bleomycin 10 mg/m2, and vincristine 2 mg (ABV) administered intravenously every 3 weeks.Eight of 12 patients were male and nine were of Italian origin. KS was limited to a localized area of the skin for only six patients, all after kidney transplantation. Visceral KS was present in three patients. Four of five patients responded to ABV chemotherapy (two complete and two partial remissions). The fifth patient responded to second-line etoposide and cisplatin. The median duration of response was in excess of 13 months (range, 8+ to 45+ months). Toxicity was limited to grade 1 neurotoxicity and grade 1 skin toxicity.KS is an uncommon but recognized complication of solid organ transplantation. Combination chemotherapy is a safe and effective treatment for patients with disseminated or visceral KS that fails to respond to changes in immunosuppression.
Geographic Variation in Diagnosis Frequency and Risk of Death Among Medicare Beneficiaries
Authors: H. Gilbert Welch
Journal: JAMA (2011)

Because diagnosis is typically thought of as purely a patient attribute, it is considered a critical factor in risk-adjustment policies designed to reward efficient and high-quality care.To determine the association between frequency of diagnoses for chronic conditions in geographic areas and case-fatality rate among Medicare beneficiaries.Cross-sectional analysis of the mean number of 9 serious chronic conditions (cancer, chronic obstructive pulmonary disease, coronary artery disease, congestive heart failure, peripheral artery disease, severe liver disease, diabetes with end-organ disease, chronic renal failure, and dementia) diagnosed in 306 hospital referral regions (HRRs) in the United States; HRRs were divided into quintiles of diagnosis frequency. Participants were 5,153,877 fee-for-service Medicare beneficiaries in 2007.Age/sex/race-adjusted case-fatality rates.Diagnosis frequency ranged across HRRs from 0.58 chronic conditions in Grand Junction, Colorado, to 1.23 in Miami, Florida (mean, 0.90 [95% confidence interval {CI}, 0.89-0.91]; median, 0.87 [interquartile range, 0.80-0.96]). The number of conditions diagnosed was related to risk of death: among patients diagnosed with 0, 1, 2, and 3 conditions the case-fatality rate was 16, 45, 93, and 154 per 1000, respectively. As regional diagnosis frequency increased, however, the case fatality associated with a chronic condition became progressively less. Among patients diagnosed with 1 condition, the case-fatality rate decreased in a stepwise fashion across quintiles of diagnosis frequency, from 51 per 1000 in the lowest quintile to 38 per 1000 in the highest quintile (relative rate, 0.74 [95% CI, 0.72-0.76]). For patients diagnosed with 3 conditions, the corresponding case-fatality rates were 168 and 137 per 1000 (relative rate, 0.81 [95% CI, 0.79-0.84]).Among fee-for-service Medicare beneficiaries, there is an inverse relationship between the regional frequency of diagnoses and the case-fatality rate for chronic conditions.
Vitamin D metabolism and mechanisms of calcium transport.
Authors: R Kumar
Journal: Journal of the American Society of Nephrology (1990)

Vitamin D3 undergoes sequential hydroxylations in the liver and kidney to form 1,25-dihydroxyvitamin D3, the biologically active form of the vitamin. 1,25-dihydroxyvitamin D3 is metabolized by several processes in various target tissues that decrease the biological activity of the sterol. In addition, 1,25-dihydroxyvitamin D3 is excreted in the bile as polar metabolites, such as glucuronides and, possibly sulfates and neutral polar steroids. These compounds undergo an enterohepatic recirculation in both man and experimental animals. 1,25-dihydroxyvitamin D3 increases the absorption of calcium in the intestine and the reabsorption of calcium in the kidney. It induces the synthesis of several proteins, the most notable of which is calcium binding protein that is thought to play a role in the absorption of calcium. The vitamin D-dependent calcium binding proteins and the calcium-magnesium ATPase calcium pump are co-localized in several tissues that play a role in the absorption of calcium.
New Colorimetric Cytotoxicity Assay for Anticancer-Drug Screening
Authors: P. Skehan, R. Storeng, D. Scudiero, A. Monks, J. McMahon, D. Vistica, J. T. Warren, H. Bokesch, S. Kenney, M. R. Boyd
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article New Colorimetric Cytotoxicity Assay for Anticancer-Drug Screening Get access Philip Skehan, Philip Skehan * Developmental Therapeutics Program, Division of Cancer Treatment * Correspondence to: Philip Skehan, M.D., Developmental Therapeutics Program, Division of Cancer Treatment, Bldg. 560, Rm. 3260, National Cancer Institute, Frederick Cancer Research Facility, Frederick, MD 21701 Search for other works by this author on: Oxford Academic PubMed Google Scholar Ritsa Storeng, Ritsa Storeng Developmental Therapeutics Program, Division of Cancer Treatment Search for other works by this author on: Oxford Academic PubMed Google Scholar Dominic Scudiero, Dominic Scudiero Program Resources, Inc., National Cancer Institute, Frederick Cancer Research FacilityFrederick, MD. Search for other works by this author on: Oxford Academic PubMed Google Scholar Anne Monks, Anne Monks Program Resources, Inc., National Cancer Institute, Frederick Cancer Research FacilityFrederick, MD. Search for other works by this author on: Oxford Academic PubMed Google Scholar James McMahon, James McMahon Developmental Therapeutics Program, Division of Cancer Treatment Search for other works by this author on: Oxford Academic PubMed Google Scholar David Vistica, David Vistica Developmental Therapeutics Program, Division of Cancer Treatment Search for other works by this author on: Oxford Academic PubMed Google Scholar Jonathan T. Warren, Jonathan T. Warren Developmental Therapeutics Program, Division of Cancer Treatment Search for other works by this author on: Oxford Academic PubMed Google Scholar Heidi Bokesch, Heidi Bokesch Program Resources, Inc., National Cancer Institute, Frederick Cancer Research FacilityFrederick, MD. Search for other works by this author on: Oxford Academic PubMed Google Scholar Susan Kenney, Susan Kenney Developmental Therapeutics Program, Division of Cancer Treatment Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael R. Boyd Michael R. Boyd Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer InstituteBethesda, MD. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 13, 4 July 1990, Pages 1107–1112, https://doi.org/10.1093/jnci/82.13.1107 Published: 04 July 1990 Article history Received: 05 September 1980 Revision received: 11 December 1989 Accepted: 15 March 1990 Published: 04 July 1990
Risk of injury and concussion associated with team performance and penalty minutes in competitive youth ice hockey
Authors: Carolyn A Emery, Jian Kang, Kathryn J Schneider, Willem H Meeuwisse
Journal: British Journal of Sports Medicine (2011)

Objective To determine if there is an association between the risk of all injury or concussion and win–loss records or penalty minutes in competitive youth ice hockey players (ages 11–14). Design, setting, participants This is a secondary data analysis of a 2-year cohort study in Alberta and Quebec on the 2007/2008 (Pee Wee) and 2008/2009 (Bantam) seasons. Main outcome measures Incidence rate ratios (IRRs) were estimated based on Poisson regression for game-related injury and concussion and adjusted for cluster by team. Results A total of 140 teams from Alberta (n=2081) and 137 teams (n=2018) from Quebec were included in the analysis. There were 451 game-related injuries (121 concussions) from Alberta and 280 (62 concussions) from Quebec. For game-related injuries, the IRR between players from teams with more than 50% wins and players with less or equal to 50% wins was 0.78 (95% CI 0.64–0.95) for all injuries, 0.75 (95% CI 0.52–1.08) for concussions, 0.64 (95% CI 0.47–0.88) for injuries resulting in time loss of more than 7 days, and 0.74 (95% CI 0.39–1.40) for concussions resulting in time loss of more than 10 days; adjusting for clustering by team and other important risk factors (ie, province, age, level of play, previous injury, weight and position). There was no association found between the total penalty minutes per game and game-related injury or concussion. Conclusions There was a significant association found between team performance (ie, win/loss/tie record) and injury risk with a 22% lower injury rate and 36% lower injury rate resulting in less than 7 days time loss in Pee Wee and Bantam ice hockey teams winning more than 50% of all season games. Total penalty minutes per game were not associated with injury or concussion rates.
Eplerenone
Authors: Nancy J. Brown
Journal: Circulation (2003)

Data from animal studies and clinical trials indicate that aldosterone causes cardiovascular and renal injury through mineralocorticoid receptor-dependent mechanisms. However, although aldosterone receptor antagonism reduces mortality in patients with congestive heart failure, the progestational and antiandrogenic side effects of the nonspecific aldosterone receptor antagonist, spironolactone, have limited its usefulness in the treatment of hypertension. This review provides an overview of the pharmacology, efficacy, and safety of a new, more selective aldosterone receptor antagonist, eplerenone, in the context of emerging concepts of the role of aldosterone in cardiovascular toxicity.
Inhibition of angiogenesis and suppression of colorectal cancer metastatic to the liver using the Sleeping Beauty Transposon System
Authors: Lalitha R Belur, Kelly M Podetz-Pedersen, Brent S Sorenson, Alice H Hsu, Josh B Parker, Cathy S Carlson, Daniel A Saltzman, S Ramakrishnan, R Scott McIvor
Journal: Molecular Cancer (2011)

Metastatic colon cancer is one of the leading causes of cancer-related death worldwide, with disease progression and metastatic spread being closely associated with angiogenesis. We investigated whether an antiangiogenic gene transfer approach using the Sleeping Beauty (SB) transposon system could be used to inhibit growth of colorectal tumors metastatic to the liver. Liver CT26 tumor-bearing mice were hydrodynamically injected with different doses of a plasmid containing a transposon encoding an angiostatin-endostatin fusion gene (Statin AE) along with varying amounts of SB transposase-encoding plasmid. Animals that were injected with a low dose (10 μg) of Statin AE transposon plasmid showed a significant decrease in tumor formation only when co-injected with SB transposase-encoding plasmid, while for animals injected with a higher dose (25 μg) of Statin AE transposon, co-injection of SB transposase-encoding plasmid did not significantly affect tumor load. For animals injected with 10 μg Statin AE transposon plasmid, the number of tumor nodules was inversely proportional to the amount of co-injected SB plasmid. Suppression of metastases was further evident in histological analyses, in which untreated animals showed higher levels of tumor cell proliferation and tumor vascularization than animals treated with low dose transposon plasmid. These results demonstrate that hepatic colorectal metastases can be reduced using antiangiogenic transposons, and provide evidence for the importance of the transposition process in mediating suppression of these tumors.
S-Nitrosation of β-Catenin and p120 Catenin
Authors: Natalie Marín, Patricia Zamorano, Rodrigo Carrasco, Patricio Mujica, Francisco G. González, Claudia Quezada, Cynthia J. Meininger, Mauricio P. Boric, Walter N. Durán, Fabiola A. Sánchez
Journal: Circulation Research (2012)

Endothelial adherens junction proteins constitute an important element in the control of microvascular permeability. Platelet-activating factor (PAF) increases permeability to macromolecules via translocation of endothelial nitric oxide synthase (eNOS) to cytosol and stimulation of eNOS-derived nitric oxide signaling cascade. The mechanisms by which nitric oxide signaling regulates permeability at adherens junctions are still incompletely understood.We explored the hypothesis that PAF stimulates hyperpermeability via S-nitrosation (SNO) of adherens junction proteins.We measured PAF-stimulated SNO of β-catenin and p120-catenin (p120) in 3 cell lines: ECV-eNOSGFP, EAhy926 (derived from human umbilical vein), and postcapillary venular endothelial cells (derived from bovine heart endothelium) and in the mouse cremaster muscle in vivo. SNO correlated with diminished abundance of β-catenin and p120 at the adherens junction and with hyperpermeability. Tumor necrosis factor-α increased nitric oxide production and caused similar increase in SNO as PAF. To ascertain the importance of eNOS subcellular location in this process, we used ECV-304 cells transfected with cytosolic eNOS (GFPeNOSG2A) and plasma membrane eNOS (GFPeNOSCAAX). PAF induced SNO of β-catenin and p120 and significantly diminished association between these proteins in cells with cytosolic eNOS but not in cells wherein eNOS is anchored to the cell membrane. Inhibitors of nitric oxide production and of SNO blocked PAF-induced SNO and hyperpermeability, whereas inhibition of the cGMP pathway had no effect. Mass spectrometry analysis of purified p120 identified cysteine 579 as the main S-nitrosated residue in the region that putatively interacts with vascular endothelial-cadherin.Our results demonstrate that agonist-induced SNO contributes to junctional membrane protein changes that enhance endothelial permeability.
ADP-ribose polymer - a novel and general biomarker of human cancers of head &amp; neck, breast, and cervix
Authors: Rennie O Lakadong, Amal C Kataki, Rajeshwar N Sharan
Journal: Molecular Cancer (2010)

Abstract Background Poly-ADP-ribosylation, a reversible post-translational modification of primarily chromosomal proteins, is involved in various cellular and molecular processes including carcinogenesis. ADP-ribose polymer or poly-ADP-ribose adducts are enzymatically added onto or stripped off the target chromosomal proteins during this metabolic process. Due to this, the chromatin superstructure is reversibly altered, which significantly influences the pattern of gene expression. We hypothesize that a decrease in the concentration of total poly-ADP-ribose adducts of peripheral blood lymphocyte (PBL) proteins strongly correlates with the incidence of human cancer. Results Using a novel immunoprobe assay, we show a statistically significant (P ≤ 0.001) reduction (~ 42 to 49%) in the level of poly-ADP-ribose adducts of PBL proteins of patients with advanced cancers of head &amp; neck (H &amp; N) region (comprising fourteen distinct cancers at different sites), breast and cervix in comparison to healthy controls. Conclusions These findings imply potential utility of the poly-ADP-ribose adducts of PBL proteins as a novel and general biomarker of human cancers with potentials of significant clinical and epidemiological applications.
Aging-Associated Reductions in AMP-Activated Protein Kinase Activity and Mitochondrial Biogenesis
Authors: Richard M. Reznick, Haihong Zong, Ji Li, Katsutaro Morino, Irene K. Moore, Hannah J. Yu, Zhen-Xiang Liu, Jianying Dong, Kirsty J. Mustard, Simon A. Hawley, Douglas Befroy, Marc Pypaert, D. Grahame Hardie, Lawrence H. Young, Gerald I. Shulman
Journal: Cell Metabolism (2007)

Recent studies have demonstrated a strong relationship between aging-associated reductions in mitochondrial function, dysregulated intracellular lipid metabolism, and insulin resistance. Given the important role of the AMP-activated protein kinase (AMPK) in the regulation of fat oxidation and mitochondrial biogenesis, we examined AMPK activity in young and old rats and found that acute stimulation of AMPK-α2 activity by 5′-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) and exercise was blunted in skeletal muscle of old rats. Furthermore, mitochondrial biogenesis in response to chronic activation of AMPK with β-guanidinopropionic acid (β-GPA) feeding was also diminished in old rats. These results suggest that aging-associated reductions in AMPK activity may be an important contributing factor in the reduced mitochondrial function and dysregulated intracellular lipid metabolism associated with aging.