tbuckley/cabot-search huggingface dataset:
Abstract 1326: Systems approach to identifying potential environmental exposures playing a role in ovarian carcinogenesis
Authors: J. Christopher States, Ming Ouyang, C. William Helm
Journal: Cancer Research (2011)

Abstract Other than an association of a small fraction with inherited mutations in BRCA1 and BRCA2, most cases of ovarian cancer (OvCa) are sporadic with cause unknown. Identifying environmental exposures that may contribute to ovarian carcinogenesis would provide the basis for epidemiological studies to determine other causes of OvCa. Environmental exposures are capable of inducing epigenetic changes that result in changes in gene expression. Most importantly, changes in microRNA expression may cause permanent changes in regulation of gene expression patterns leading to altered cellular phenotypes. These alterations in microRNAs represent dysregulation in the cancer cells and may be a manifestation of environmental exposures. Thus, we hypothesized that circulating microRNAs associated with OvCa are biomarkers of exposure and could be used to identify gene expression changes resulting from environmental exposures. We employed a systems approach utilizing publicly available data for elevated levels of circulating microRNAs associated with OvCa and for altered gene expression in ovarian cancers in conjunction with associations between chemical exposures and gene expression compiled in the Comparative Toxicogenomics Database (CTD) to identify chemicals that may play a role in ovarian carcinogenesis. Intersection of genes with altered expression in ovarian cancer and putative gene targets of microRNAs identified in plasmas of OvCa patients gave a list of candidate genes for chemical interactions. Ingenuity Pathway analyses of these genes show that they participate in pathways involved in cancer and other chronic diseases. This list of genes was submitted to the CTD and a list of chemicals with known interactions with these genes was collected. The list of chemicals interacting with the OvCa specific genes included known carcinogens (arsenic, asbestos, benzo[a]pyrene), co-carcinogens (tetrachlorodibenzodioxin, tetradecanoylphorbol acetate), peroxides, heavy metals (Cu, Zn), epigenotoxicants (hydralizine, valproic acid), inflammation inducers (zymosan, lipopolysaccharide), steroid hormones (estradiol, progesterone, dexamethasone), dietary chemopreventives (indole-3-carbinol, curcumin) and chemotherapeutics (doxorubicin, tamoxifen). While some of these chemicals and pathways have been implicated previously in ovarian carcinogenesis, many have not and their identification will enable the development of targeted epidemiological studies to determine the role of their exposure in inducing or preventing OvCa. This systems approach may be useful to identify environmental exposures contributing to cancer of other organs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1326. doi:10.1158/1538-7445.AM2011-1326
Efficacy and Toxicity of Belotecan for Relapsed or Refractory Small Cell Lung Cancer Patients
Authors: Gun Min Kim, Young Sam Kim, Young Ae Kang, Jae-Heon Jeong, Sun Mi Kim, Yun Kyoung Hong, Ji Hee Sung, Seung Taek Lim, Joo Hang Kim, Se Kyu Kim, Byoung Chul Cho
Journal: Journal of Thoracic Oncology (2012)
Balancing benefits and harms in health care
Authors: Jeff Aronson
Journal: BMJ (2004)

Some drugs yield more than one benefit. For instance, β blockers have antihypertensive, antianginal, and antiarrhythmic effects. They also have more than one adverse effect. So we can talk about their benefits and harms. It's all to do with how you count.

The Danish philologist Otto Jespersen expounded the concept of count and non-count nouns in an unpublished lecture to the Copenhagen Academy of Sciences in 1911. As he explained in The Philosophy of Grammar (1924), you can form plurals if you can collect two things alike. For example, two bananas (two of the same thing). Or two fruits, an apple and an orange (two of the same kind). But we have no plural word for a journal plus a stethoscope, except to call them …
Hepatic lentiviral gene transfer is associated with clonal selection, but not with tumor formation in serially transplanted rodents
Authors: Ina Rittelmeyer, Michael Rothe, Martijn H. Brugman, Marcus Iken, Axel Schambach, Michael P. Manns, Christopher Baum, Ute Modlich, Michael Ott
Journal: Hepatology (2012)

Lentiviral (LV) vectors are promising tools for long-term genetic correction of hereditary diseases. In hematopoietic stem cell gene therapies adverse events in patients due to vector integration-associated genotoxicity have been observed. Only a few studies have explored the potential risks of LV gene therapy targeting the liver. To analyze hepatic genotoxicity in vivo, we transferred the fumarylacetoacetate hydrolase (FAH) gene by LV vectors into FAH((-/-)) mice (n = 97) and performed serial hepatocyte transplantations (four generations). The integration profile (4,349 mapped insertions) of the LV vectors was assessed by ligation-mediated polymerase chain reaction and deep sequencing. We tested whether the polyclonality of vector insertions was maintained in serially transplanted mice, linked the integration sites to global hepatocyte gene expression, and investigated the effects of LV liver gene therapy on the survival of the animals. The lifespan of in vivo gene-corrected mice was increased compared to 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) control animals and unchanged in serially transplanted animals. The integration profile (4,349 mapped insertions) remained polyclonal through all mouse generations with only mild clonal expansion. Genes close to the integration sites of expanding clones may be associated with enhanced hepatocyte proliferation capacity.We did not find evidence for vector-induced tumors. LV hepatic gene therapy showed a favorable risk profile for stable and long-term therapeutic gene expression. Polyclonality of hepatocyte regeneration was maintained even in an environment of enforced proliferation.
CLOPIDOGREL ALTERS THROMBUS QUANTITY AND QUALITY IN PATIENTS WITH TYPE II DIABETES MELLITUS AND STABLE CORONARY ARTERY DISEASE
Authors: Girish Viswanathan, Kath White, Karthik Balasubramaniam, Juan Badimon, Azfar Zaman, Sally Marshall
Journal: Journal of the American College of Cardiology (2013)
Postoperative Craniotomy Infections
Authors: Arthur A. Ward
Journal: JAMA (1966)

We might anticipate that advances in operating room techniques and postoperative care would reduce the hazards of infection. The experience here reported does not bear this out. In the Massachusetts General Hospital, in 2,148 clean intracranial operations, the overall infection rate was 5.7%, rising to 15% for operations on meningiomas. This modern experience does not compare favorably with the experience of Harvey Cushing, who reported an infection rate of about 1% for operations on meningiomas and an even lower rate for all intracranial operations. The MGH series is broken down into clean intradural procedures, posterior fossa craniotomies, and extradural procedures. The infection rates in each group are further analyzed and each series is accompanied by long, illustrative case protocols. The infection rate goes up in association with the number of times a wound is re-explored and, to a lesser degree, the length of the surgical procedure. Prophylactic antibiotics do not
Hyperlipidemia Following Treatment With Antipsychotic Medications
Authors: Mark Olfson, Steven C. Marcus, Patricia Corey-Lisle, A.V. Tuomari, Patricia Hines, Gilbert J. L’Italien
Journal: American Journal of Psychiatry (2006)

Objective: This study attempted to estimate the relative risk of developing hyperlipidemia after treatment with antipsychotics in relation to no antipsychotic treatment. Method: A matched case-control analysis was performed with pharmacy and claims data from California Medicaid (Medi-Cal). Patients were excluded if they were treated for medical disorders or prescribed medications known to increase their risk of hyperlipidemia. Cases were ages 18 to 64 years with schizophrenia, major depression, bipolar disorder, or other affective psychoses and incident hyperlipidemia. Cases were matched to up to six control subjects by age, sex, race, and psychiatric diagnosis. Both groups were prescribed either no antipsychotic medication or had two or more prescriptions for one and only one antipsychotic medication during the 60 days prior to the first indication of hyperlipidemia (cases) or matched index date (controls) in the billing record. Conditional logistic regressions were used to derive odds ratios and 95% confidence intervals (95% CIs) of each antipsychotic medication in relation to no antipsychotic medication. Results: A total of 13,133 incident cases of hyperlipidemia were matched to 72,140 control subjects. As compared with no antipsychotic medication, treatment with clozapine (odds ratio: 1.82, 95% CI: 1.61–2.05), risperidone (odds ratio: 1.53, 95% CI: 1.43–1.64), quetiapine (odds ratio: 1.52, 95% CI: 1.40–1.65), olanzapine (odds ratio: 1.56, 95% CI: 1.47–1.67), ziprasidone (odds ratio: 1.40, 95% CI: 1.19–1.65), and first-generation antipsychotics (odds ratio: 1.26, 95% CI: 1.14–1.39), but not aripiprazole (odds ratio: 1.19, 95% CI: 0.94–1.52) was associated with a significant increase in risk of incident hyperlipidemia. Conclusions: These findings suggest that most commonly prescribed antipsychotic medications increase the risk of developing hyperlipidemia in patients with schizophrenia or mood disorders.
Expression of an Estrogen Receptor by Human Coronary Artery and Umbilical Vein Endothelial Cells
Authors: Seunghee Kim-Schulze, Kelly A. McGowan, Susan C. Hubchak, Maria C. Cid, Mary Beth Martin, Hynda K. Kleinman, Geoffrey L. Greene, H. William Schnaper
Journal: Circulation (1996)

Premenopausal women have much lower susceptibility to coronary artery disease than do men or postmenopausal women. It has been proposed that estrogen plays a role in cardioprotection, but little information is available regarding the mechanism by which estrogen may help to protect the vasculature. Here, we describe an estrogen receptor (ER) in human coronary artery and umbilical vein endothelial cells.Human umbilical vein endothelial cells and human coronary artery endothelial cells were cultured in hormone-free medium for 48 hours before experiments. Estradiol (3.7 nmol/L) added to cultures promoted proliferation by a mechanism that is inhibited by the specific ER antagonist ICI182,780. Estradiol-treated cells incorporated twice the [3H]thymidine of hormone-free cells; this increase was prevented by ICI182,780. Endothelial cells from both sources stained in a nuclear pattern with an ER-specific antibody. Ribonuclease protection assay detected mRNA for the ER. Ligand-binding studies estimated 2 x 10(4) to 8 x 10(4) receptors per cell and a Kd of approximately 5 nmol/L. Interaction of ERs with a consensus estrogen response element was shown by an electrophoretic mobility shift assay. In addition, an antibody against the ER supershifted the protein-DNA complex.These studies define the presence of an ER in human coronary artery and umbilical vein endothelial cells. They support the hypothesis that cardioprotective effects of estrogen are mediated, at least in part, through a classic steroid hormone receptor mechanism.
Easy assessment of axial spondyloarthritis (early ankylosing spondylitis) at the bedside
Authors: M Rudwaleit, E Feldtkeller, J Sieper
Journal: Annals of the Rheumatic Diseases (2006)

Making a diagnosis of ankylosing spondylitis in patients with chronic back pain can be difficult at an early stage—that is, before radiographic sacroiliitis is definitely present (also referred to as axial spondyloarthritis (SpA) at the preradiographic state). We recently proposed to diagnose patients at this early stage by probability estimations1 based on a pretest probability (ppre) of 5% in patients with chronic back pain.2 To facilitate the probability calculation in each patient, we subsequently3 proposed the use of likelihood ratios (LR).4 We suggested that the diagnosis could be considered definite if the post-test probability (ppost) is ⩾90% (LR product ⩾171), probable if the post-test probability is 80–90% (LR product …
270 CD4+CD25+FOXP3+ TREGS: DO THEY INHIBIT HCV CLEARANCE IN CHRONIC HCV GENOTYPE 1 INFECTION?
Authors: A.L. Bellou, A. Sarantopoulos, E. Gigi, A. Sykia, A. Beltsis, P. Boura, M. Raptopoulou-Gigi
Journal: Journal of Hepatology (2011)
1137 THE HLA CLASS I B*1801 ALLELE INFLUENCES HEPATOCELLULAR EXPRESSION OF AMOXICILLIN-CLAVULANATE LIVER DAMAGE AND OUTCOME IN SPANISH PATIENTS
Authors: C. Stephens, M.A. Lopez-Nevot, M.I. Lucena, F. Ruiz-Cabello, E. Ulzurrun, M.R. Cabello, M.C. Fernandez, C. Guarner, G. Soriano, M. Romero-Gomez, J.M. Navarro, J.L. Solís-Herruzo, A. Castiella, J. Costa, R. Planas, F. Pons, M. Moreno, J.L. Calleja, R. Perez Álvarez, R. Solá Lamoglia, O. Lo lacono, J. Salmerón, Y. Borraz, R.J. Andrade
Journal: Journal of Hepatology (2010)
Autologous Translocation of the Choroid and Retinal Pigment Epithelium in Patients with Geographic Atrophy
Authors: Antonia M. Joussen, Sandra Joeres, Nader Fawzy, Florian M.A. Heussen, Helene Llacer, Jan C. van Meurs, Bernd Kirchhof
Journal: Ophthalmology (2007)
CS-27 * IDH1/2 MUTATIONS INFLUENCE ZEB1 EXPRESSION IN GRADES II AND III GLIOMAS
Authors: C. Nesvick, C. Zhang, B. Montgomery, M. Lee, C. Yang, H. Wang, M. Merrill, J. Heiss, A. Ray-Chaudhury, Z. Zhuang
Journal: Neuro-Oncology (2014)

Epithelial-mesenchymal transition (EMT) is a cell program that crucially regulates polarity and enhances invasion in normal epithelia and carcinomas. It has been recently demonstrated that EMT-promoting transcription factors (EMT-TFs) also govern cell invasion in glioblastoma, but the role of these proteins in lower-grade gliomas has not yet been investigated. We investigated the impact of EMT-TF expression on overall survival in World Health Organization (WHO) grades II and III gliomas using the National Cancer Institute Repository for Molecular Brain Neoplasis Data (REMBRANDT) and Cancer Genome Atlas Network Lower-Grade Glioma (CGAN LGG) datasets. Surprisingly, while expression of EMT-promoting transcription factors were generally associated with a decrease in overall survival, high ZEB1 expression was associated with an increase in overall survival in both datasets (log-rank test on all grade II and III gliomas: for REMBRANDT, median overall survival (OS) 54.2 months ZEB1-high vs. 19.6 months ZEB1-low, p = 0.0016; for CGAN, median OS 134.3 months ZEB1-high vs. 63.6 months ZEB1-low, p = 0.0038). Mutations in the genes coding for Isocitrate Dehydrogenases 1 and 2 (IDH1/2) are found in 85-90% of grades II and III gliomas and confer a favorable prognosis in these tumors. Using the CGAN LGG dataset, we found that ZEB1 is upregulated in IDH1/2-mutant versus IDH1/2-wild type tumors (unpaired t-test on all grade II and III gliomas: t = 10.292, p < 0.0001). Moreover, IDH1/2-mutant gliomas express lower levels of genes that are suppressed by ZEB1 including MIR200B and MIR200C (unpaired t-test on all grade II and III gliomas: p < 0.0001 for both targets). We further validated these findings in an independent set of 37 grade II and III gliomas using quantitative real-time PCR, Western blot and immunohistochemistry. These findings reveal that ZEB1 not only has an unexpected prognostic significance in grades II and III gliomas but also may play an important role in IDH1/2-mutant tumors.
Radionuclide Therapy of HER2-Positive Microxenografts Using a 177Lu-Labeled HER2-Specific Affibody Molecule
Authors: Vladimir Tolmachev, Anna Orlova, Rikard Pehrson, Joakim Galli, Barbro Baastrup, Karl Andersson, Mattias Sandström, Daniel Rosik, Jörgen Carlsson, Hans Lundqvist, Anders Wennborg, Fredrik Y. Nilsson
Journal: Cancer Research (2007)

Abstract A radiolabeled anti-HER2 Affibody molecule (ZHER2:342) targets HER2-expressing xenografts with high selectivity and gives good imaging contrast. However, the small size (∼7 kDa) results in rapid glomerular filtration and high renal accumulation of radiometals, thus excluding targeted therapy. Here, we report that reversible binding to albumin efficiently reduces the renal excretion and uptake, enabling radiometal-based nuclide therapy. The dimeric Affibody molecule (ZHER2:342)2 was fused with an albumin-binding domain (ABD) conjugated with the isothiocyanate derivative of CHX-A″-DTPA and labeled with the low-energy β-emitter 177Lu. The obtained conjugate [CHX-A″-DTPA-ABD-(ZHER2:342)2] had a dissociation constant of 18 pmol/L to HER2 and 8.2 and 31 nmol/L for human and murine albumin, respectively. The radiolabeled conjugate displayed specific binding to HER2-expressing cells and good cellular retention in vitro. In vivo, fusion with ABD enabled a 25-fold reduction of renal uptake in comparison with the nonfused dimer molecule (ZHER2:342)2. Furthermore, the biodistribution showed high and specific uptake of the conjugate in HER2-expressing tumors. Treatment of SKOV-3 microxenografts (high HER2 expression) with 17 or 22 MBq 177Lu-CHX-A″-DTPA-ABD-(ZHER2:342)2 completely prevented formation of tumors, in contrast to mice given PBS or 22 MBq of a radiolabeled non–HER2-binding Affibody molecule. In LS174T xenografts (low HER2 expression), this treatment resulted in a small but significant increase of the survival time. Thus, fusion with ABD improved the in vivo biodistribution, and the results highlight 177Lu-CHX-A″-DTPA-ABD-(ZHER2:342)2 as a candidate for treatment of disseminated tumors with a high level of HER2 expression. [Cancer Res 2007;67(6):2773–82]
A Novel EML4-ALK Variant: Exon 6 of EML4 Fused to Exon 19 of ALK
Authors: Roland Penzel, Peter Schirmacher, Arne Warth
Journal: Journal of Thoracic Oncology (2012)

Introduction:Cytotoxic chemotherapy remains the mainstay of treatment for most patients with advanced disease. Recently, anaplastic lymphoma kinase (ALK) expression as a major target for successful treatment with ALK inhibitors was detected in a subset of non–small-cell lung carcinomas, usually as a result of echinoderm microtubule-associated protein-like 4 (EML4)-ALK rearrangements. Although the chromosomal breakpoint within the EML4 gene varied, the breakpoint within ALK was most frequently reported within intron 19 or rarely in exon 20. Therefore, the different EML4-ALK variants so far contain the same 3′ portion of ALK starting with exon 20.Methods:Here, we report a novel EML4-ALK variant detected by reverse transcription polymerase chain reaction analysis.Results:Subsequent sequencing revealed an EML4-ALK fusion variant in which exon 6 of EML4 was fused to exon 19 of ALK. It occurred in a predominant solid pulmonary adenocarcinoma of a 65-year-old woman with a clear split signal of ALK in fluorescence in situ hybridization analysis and a weakly homogeneous ALK expression in immunohistochemical staining.Conclusions:Because of the growing number of fusion variants a primary reverse transcription polymerase chain reaction-based screening for ALK-positive non–small-cell lung carcinoma patients may not be sufficient for predictive diagnostics but transcript-based approaches and sequencing of ALK fusion variants might finally contribute to an optimized selection of patients.
Priorities and rationing: pragmatism or principles?
Authors: R. Klein
Journal: BMJ (1995)

Time for Britain to follow the Netherlands, New Zealand, and Sweden's lead and get serious

There is always the danger of assuming that the NHS's problems are unique: that they reflect either the special characteristics of Britain's health care system or the government's niggardliness in funding it. The issue of priority setting--or, more emotively, rationing--is a case in point. This is not some peculiar British obsession. All health care systems have to grapple with the problem of how best to allocate scarce resources. The real difference is between how different health care systems have tried to address this issue: between those countries that, like Britain, tend to diffuse responsibility and those that have sought to develop a national framework for the decisions of health authorities and clinicians.

Britain's Department of Health issues an annual set of priorities, but these are largely a shopping list reflecting the department's current concerns. In contrast, other countries have sought to develop explicit criteria for guiding decisions about allocating resources. While Britain relies (as usual) on pragmatic incrementalism, with policy emerging almost as a byproduct of individual decisions, others have sought to devise a set of principles designed to shape those individual decisions. So which is the right way forward? Should policy be guided by pragmatism or principle? And, in making this choice, what can be learnt from other countries?

In trying to answer these questions we can now draw on the experience of three attempts by governments to devise national criteria for priority setting. In 1992 the Dutch government's Committee on Choices in Health Care produced what has since become known as the Dunning report, named after its chairman.1 The same year …
Survivor Costs in Cost-Effectiveness Analysis
Authors: Afschin Gandjour
Journal: Annals of Internal Medicine (2006)

Letters4 April 2006Survivor Costs in Cost-Effectiveness AnalysisAfschin Gandjour, MD, PhDAfschin Gandjour, MD, PhDFrom Institute of Health Economics and Clinical Epidemiology, University of Cologne, 50935 Köln, Germany.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-144-7-200604040-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Golan and colleagues (1) present a cost-effectiveness analysis of several anti-Candida strategies for high-risk patients in the intensive care unit. They evaluate treatment effectiveness by the number of life-years that are gained from reduced hospital mortality rates. The authors included initial hospitalization costs in their calculations. This approach, however, overestimates treatment cost-effectiveness and provides unduly favorable cost-effectiveness ratios. When treatment effectiveness is assessed by the number of life-years gained, costs for health care services that are required to provide this gain must also be included (2). After all, the anti-Candida therapy and the initial hospital stay are ...References1. Golan Y, Wolf MP, Pauker SG, Wong JB, Hadley S. Empirical anti-Candida therapy among selected patients in the intensive care unit: a cost-effectiveness analysis. Ann Intern Med. 2005;143:857-69. [PMID: 16365467] LinkGoogle Scholar2. Nyman JA. Should the consumption of survivors be included as a cost in cost-utility analysis? Health Econ. 2004;13:417-27. [PMID: 15127422] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Institute of Health Economics and Clinical Epidemiology, University of Cologne, 50935 Köln, Germany.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEmpirical Anti-Candida Therapy among Selected Patients in the Intensive Care Unit: A Cost-Effectiveness Analysis Yoav Golan , Michael P. Wolf , Stephen G. Pauker , John B. Wong , and Susan Hadley Survivor Costs in Cost-Effectiveness Analysis Yoav Golan , John B. Wong , and Stephen G. Pauker Metrics Cited byFuture costs in cost-effectiveness analysis: an empirical assessment 4 April 2006Volume 144, Issue 7Page: 534-535KeywordsConflicts of interestDeath ratesHealth careHospitalizationsIntensive care unitsLife expectancyMedical servicesSurvival analysis ePublished: 4 April 2006 Issue Published: 4 April 2006 Copyright & PermissionsCopyright © 2006 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...