tbuckley/cabot-search huggingface dataset:
Results of interval debulking surgery in advanced stage ovarian cancer: an exposed–non-exposed study
Authors: P. Morice, D. Brehier-Ollive, A. Rey, D. Atallah, C. Lhommé, P. Pautier, C. Pomel, S. Camatte, P. Duvillard, D. Castaigne
Journal: Annals of Oncology (2002)
Hepatocellular carcinoma: clinical frontiers and perspectives
Authors: Jordi Bruix, Gregory J Gores, Vincenzo Mazzaferro
Journal: Gut (2014)

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death and is currently the main event leading to death in patients with cirrhosis. Evolving information suggests that the metabolic syndrome with non-alcoholic liver disease may be an important cause of HCC in addition to viral hepatitis and alcohol-induced liver disease. The molecular pathogenesis is extremely complex and heterogeneous. To date the molecular information has not impacted on treatment decisions. Periodic surveillance imaging of patients with cirrhosis is widely practiced, especially because diagnostic, radiographic criteria for early-stage HCC have been defined (including nodules between 1 and 2 cm) and effective treatment is available for tumours detected at an early stage. Worldwide the approach to resection versus transplantation varies depending upon local resources, expertise and donor availability. The criteria for transplantation are discussed, and the controversial areas highlighted with evidence-based recommendations provided. Several approaches are available for intermediate stage disease, including radiofrequency ablation, transarterial chemoembolisation and radioembolisation; the rationale for these therapies is buttressed by appropriate outcome-based studies. For advanced disease, systemic therapy with sorafenib remains the option best supported by current data. Thus, while several trials have failed to improve the benefits of established therapies, studies assessing the sequential or combined application of those already known to be beneficial are needed. Also, new concepts are provided in regards to selecting and stratifying patients for second-line studies, which may help explain the failure of prior studies.
Lipid related consequences of intestinal malabsorption.
Authors: G R Thompson
Journal: Gut (1989)

The small intestine plays a key role in lipid metabolism by absorbing fat and synthesising apoproteins. Fat malabsorption secondary to intestinal disease results in abnormalities of lipoprotein concentration and composition and can lead to deficiency of essential fatty acids and fat-soluble vitamins. Malabsorption of fat can be induced by administration of neomycin and malabsorption of bile acids by administration of anion-exchange resins or by creating a partial ileal bypass. These induced forms of malabsorption are useful in the treatment of hyperlipidaemic patients liable to atherosclerosis.
FCGR3A and FCGR2A polymorphisms may not correlate with response to alemtuzumab in chronic lymphocytic leukemia
Authors: Thomas S. Lin, Ian W. Flinn, Rama Modali, Teresa A. Lehman, Jennifer Webb, Sharon Waymer, Mollie E. Moran, Margaret S. Lucas, Sherif S. Farag, John C. Byrd
Journal: Blood (2004)
Randomized Controlled Trial of Tamoxifen in Advanced Hepatocellular Carcinoma
Authors: Jean-Claude Barbare, Olivier Bouché, Franck Bonnetain, Jean-Luc Raoul, Philippe Rougier, Armand Abergel, Valérie Boige, Bernard Denis, Alain Blanchi, Alexandre Pariente, Chantal Milan, Laurent Bedenne
Journal: Journal of Clinical Oncology (2005)

Purpose Randomized studies on tamoxifen treatment of hepatocellular carcinoma (HCC) produced conflicting results. The aim of this study was to assess the efficacy of tamoxifen administration in improving overall survival of patients with advanced HCC. Patients and Methods A total of 420 patients with HCC who were not suitable for surgery or local treatment were randomly assigned between April 1995 and May 2000: 210 in the control group and 210 in the tamoxifen group (20 mg/d orally). Patients with WHO performance status greater than 2, belonging to Child-Pugh class C, or with serum creatinine greater than 130 μmol/L were not eligible. Results Tolerance was good and the main reported adverse effects were thrombophlebitis (three patients), nausea (two patients), and hot flushes (three patients). Outcome did not differ between the two treatment arms: estimated median survival was 4.8 and 4.0 months in the tamoxifen and in the control groups, respectively (P = .25). Univariate analysis showed significant association of survival with age, Okuda stage, WHO performance status, Child-Pugh class, intrahepatic tumor stage, alpha-fetoprotein serum concentration, and presence of extrahepatic spread, portal vein thrombosis, hepatomegaly, or hepatalgia. In a Cox proportional hazards model we found a significant beneficial effect of tamoxifen on survival in patients belonging to Okuda I or II stages. Conclusion In this large study, tamoxifen did not improve the survival of patients with advanced HCC, but there is a suggestion that patients without major hepatic insufficiency seem to have some survival benefit. New trials involving this specific population are warranted.
Effects of Electronegative VLDL on Endothelium Damage in Metabolic Syndrome
Authors: Chu-Huang Chen, Jonathan Lu, Shu-Hua Chen, Roger Y. Huang, H. Ramazan Yilmaz, Jianwen Dong, MacArthur A. Elayda, Richard A.F. Dixon, Chao-Yuh Yang
Journal: Diabetes Care (2012)

Biochemical heterogeneity governs functional disparities among lipoproteins. We examined charge-defined VLDL subfractions in metabolic syndrome (MetS) to determine whether their increased electronegativity is associated with increased cytotoxicity and whether high concentrations of highly electronegative subfractions render VLDL harmful to the vascular endothelium.
Concealment of Information in Clinical Practice: Is Lying Less Stressful Than Telling the Truth?
Authors: Efharis Panagopoulou, Gesthimani Mintziori, Anthony Montgomery, Dorothea Kapoukranidou, Alexis Benos
Journal: Journal of Clinical Oncology (2008)

From the Lab of Hygiene; Lab of Physi-ology, Medical School, Aristotle Univer-sity, Thessaloniki, Greece.Submitted May 31, 2007; acceptedJune 21, 2007.The ﬁrst and second author haveconducted the same amount of workand share ﬁrst authorship.Authors’ disclosures of potential con-ﬂicts of interest and author contribu-tions are found at the end of thisarticle.Corresponding author: E. Panagopoulou,Lab of Hygiene, 54124, Medical School,Aristotle University, Thessaloniki, Greece;e-mail: efharis@the.forthnet.gr.© 2008 by American Society of ClinicalOncology0732-183X/08/2607-1175/$20.00DOI: 10.1200/JCO.2007.12.8751
Localization of the gene for Cowden disease to chromosome 10q22–23
Authors: M.R. Nelen, G.W. Padberg, E.A.J. Peeters, A.Y. Lin, B. van den Helm, R.R. Frants, V. Goulon, A.M. Goldstein, M.M.M van Reen, D.F. Eastern, R.A. Eeles, S. Hodgson, J.J. Mulvihill, V.A. Murday, M.A. Tucker, E.C.M. Mariman, T.M. Starink, B.A.J. Ponder, H.H. Ropers, H. Kremer, M. Longy, C. Eng
Journal: Nature Genetics (1996)
Is 1-year follow-up adequate for adult tuberculosis contacts?
Authors: Jia-Yih Feng, San-Chi Chen, Ming-Che Lee, Wen-Chien Fan, Wei-Juin Su, Yu-Wen Hu, Chiu-Mei Yeh, Tzeng-Ji Chen, Chia-Jen Liu
Journal: European Respiratory Journal (2015)

To eliminate tuberculosis (TB) on a global scale, the identification and neutralisation of latently infected high-risk individuals is of paramount importance [1]. Active TB contacts are well documented with an increased risk for both latent TB infection (LTBI) and the development of active TB disease [2]. Contact investigation is an important and effective active case-finding strategy, but also requires abundant public health resources [3]. Risk of active TB after the first year should not be ignored: extended follow-up in adult TB contacts is needed <http://ow.ly/I9t28>
Frizzled7 controls vascular permeability through the Wnt-canonical pathway and cross-talk with endothelial cell junction complexes
Authors: Nancy Ferreira Tojais, Claire Peghaire, Nathalie Franzl, Frédéric Larrieu-Lahargue, Béatrice Jaspard, Annabelle Reynaud, Catherine Moreau, Thierry Couffinhal, Cécile Duplàa, Pascale Dufourcq
Journal: Cardiovascular Research (2014)

Vascular permeability is essential for the health of normal tissues and is an important characteristic of many disease states. The role of the Wnt/frizzled pathway in vascular biology has recently been reported. The objectives of this study are to analyse the role of Frizzled7 (Fzd7) receptor in the control of vascular integrity. Fzd7 is expressed in endothelial cells and accumulates at the points of cell–cell contact in association with VE-cadherin and β-catenin, two major adherens junction molecules. To selectively delete fzd7 in the vasculature, we developed gene targeting approaches using CreLox strategy in mice. Genetic fzd7 inhibition in the endothelium increases vascular permeability in basal and factor-induced conditions. On the cellular level, fzd7 knockdown or depletion leads to an increase in paracellular permeability with a loss of adherens junction organization. These impairments are associated with a decrease in both VE-Cadherin and β-catenin expression, a decrease in their association and an increase of tyrosine phosphorylation of VE-cadherin/β-catenin. Fzd7 transduces a Wnt/β-catenin signalling cascade that is required to regulate β-catenin and canonical target gene expression. Finally, LiCl, a GSK3 inhibitor, and β-catenin overexpression rescued endothelial integrity and adherens junction organization, induced by fzd7 deletion. These findings establish that Fzd7 is a new partner of adherens junctional complex and represents a novel molecular switch for the control of vascular permeability via activation of the Wnt-canonical pathway.
Clinical, radiographic, and thermographic assessment of osteoarthritis in the knee joints
Authors: H Warashina
Journal: Annals of the Rheumatic Diseases (2002)

It has been reported that thermography enables the evaluation of non-steroidal anti-inflammatory drugs for the treatment of rheumatic synovitis.1,2 However, few reports mentioned the relation between skin temperature and symptoms, physical signs, and radiographic features in patients with osteoarthritis (OA). In this study we evaluated the correlation between radiographic and clinical findings and skin temperature measured by thermography for the assessment of OA in the knee joints in the Comprehensive Health Examination Programme at Y-town, Japan in 1999.3

The assessments were performed on 974 knees of 169 men and 318 women who had a mean (SD) age of 57.6 (4.3). The following physical examinations of the knees were carried out: local tenderness, joint swelling, local heat, McMurray test, Lachmann test, instability of collateral ligaments, patellofemoral joint (PFJ) grinding test, range of joint motion, and thigh girth. Walking and stair climbing ability were graded using the Hospital for Special Surgery (HSS) knee rating scores and Lysholm knee scoring scale.4 Present or past pain continuing for more than one month …
Siomycin A targets brain tumor stem cells partially through a MELK-mediated pathway
Authors: I. Nakano, K. Joshi, K. Visnyei, B. Hu, M. Watanabe, D. Lam, E. Wexler, K. Saigusa, Y. Nakamura, D. R. Laks, P. S. Mischel, M. Viapiano, H. I. Kornblum
Journal: Neuro-Oncology (2011)

Glioblastoma multiforme (GBM) is a devastating disease, and the current therapies have only palliative effect. Evidence is mounting to indicate that brain tumor stem cells (BTSCs) are a minority of tumor cells that are responsible for cancer initiation, propagation, and maintenance. Therapies that fail to eradicate BTSCs may ultimately lead to regrowth of residual BTSCs. However, BTSCs are relatively resistant to the current treatments. Development of novel therapeutic strategies that effectively eradicate BTSC are, therefore, essential. In a previous study, we used patient-derived GBM sphere cells (stemlike GBM cells) to enrich for BTSC and identified maternal embryonic leucine-zipper kinase (MELK) as a key regulator of survival of stemlike GBM cells in vitro. Here, we demonstrate that a thiazole antibiotic, siomycin A, potently reduced MELK expression and inhibited tumor growth in vivo. Treatment of stemlike GBM cells with siomycin A resulted in arrested self-renewal, decreased invasion, and induced apoptosis but had little effect on growth of the nonstem cells of matched tumors or normal neural stem/progenitor cells. MELK overexpression partially rescued the phenotype of siomycin A-treated stemlike GBM cells. In vivo, siomycin A pretreatment abraded the sizes of stemlike GBM cell-derived tumors in immunodeficient mice. Treatment with siomycin A of mice harboring intracranial tumors significantly prolonged their survival period compared with the control mice. Together, this study may be the first model to partially target stemlike GBM cells through a MELK-mediated pathway with siomycin A to pave the way for effective treatment of GBM.
Differential Involvement of Vascular Endothelial Growth Factor in the Survival of Hypoxic Colon Cancer Cells
Authors: Maura Calvani, Daniela Trisciuoglio, Cristina Bergamaschi, Robert H. Shoemaker, Giovanni Melillo
Journal: Cancer Research (2008)

Abstract The recent approval of bevacizumab (Avastin), a humanized anti–vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with chemotherapy for the treatment of patients with metastatic colorectal cancer, has provided proof of principle of the efficacy of antiangiogenic strategies for cancer therapy. The activity of bevacizumab is primarily attributed to its ability to inhibit endothelial cell survival. Whether anti-VEGF strategies may also have a direct effect on cancer cell survival is poorly understood. We show that serum-starved colon cancer cells differentially respond to autocrine production of VEGF with the induction of hypoxia inducible factor-1α (HIF-1α) and survival under hypoxic conditions. Inhibition of VEGF or VEGF receptor 2 (VEGFR2)/KDR, but not VEGFR1/Flt-1, was sufficient to abrogate VEGF-mediated induction of HIF-1α and survival in sensitive HCT116, but not in resistant HT29, colon cancer cells. These results provide evidence that a VEGF/KDR/HIF-1α autocrine loop differentially mediates survival of hypoxic colon cancer cells, and they suggest that colon cancer cells may be intrinsically sensitive or resistant to anti-VEGF strategies, which may determine the therapeutic efficacy of bevacizumab. [Cancer Res 2008;68(1):285–91]
Funny Current Downregulation and Sinus Node Dysfunction Associated With Atrial Tachyarrhythmia
Authors: Yung-Hsin Yeh, Brett Burstein, Xiao Yan Qi, Masao Sakabe, Denis Chartier, Philippe Comtois, Zhiguo Wang, Chi-Tai Kuo, Stanley Nattel
Journal: Circulation (2009)

Background— Sinoatrial node (SAN) dysfunction is frequently associated with atrial tachyarrhythmias (ATs). Abnormalities in SAN pacemaker function after termination of ATs can cause syncope and require pacemaker implantation, but underlying mechanisms remain poorly understood. This study examined the hypothesis that ATs impair SAN function by altering ion channel expression. Methods and Results— SAN tissues were obtained from 28 control dogs and 31 dogs with 7-day atrial tachypacing (400 bpm). Ionic currents were measured from single SAN cells with whole-cell patch-clamp techniques. Atrial tachypacing increased SAN recovery time in vivo by ≈70% ( P &lt;0.01), a change which reflects impaired SAN function. In dogs that underwent atrial tachypacing, SAN mRNA expression (real-time reverse-transcription polymerase chain reaction) was reduced for hyperpolarization-activated cyclic nucleotide-gated subunits (HCN2 and HCN4) by &gt;50% ( P &lt;0.01) and for the β-subunit minK by ≈42% ( P &lt;0.05). SAN transcript expression for the rapid delayed-rectifier ( I Kr ) α-subunit ERG, the slow delayed-rectifier ( I Ks ) α-subunit KvLQT1, the β-subunit MiRP1, the L-type ( I CaL ) and T-type ( I CaT ) Ca 2+ -current subunits Cav1.2 and Cav3.1, and the gap-junction subunit connexin 43 (were unaffected by atrial tachypacing. Atrial tachypacing reduced densities of the HCN-related funny current ( I f ) and I Ks by ≈48% ( P &lt;0.001) and ≈34% ( P &lt;0.01), respectively, with no change in voltage dependence or kinetics. I Kr , I CaL , and I CaT were unaffected. SAN cells lacked Ba 2+ -sensitive inward-rectifier currents, irrespective of AT. SAN action potential simulations that incorporated AT-induced alterations in I f accounted for slowing of periodicity, with no additional contribution from changes in I Ks . Conclusions— AT downregulates SAN HCN2/4 and minK subunit expression, along with the corresponding currents I f and I Ks . Tachycardia-induced remodeling of SAN ion channel expression, particularly for the “pacemaker” subunit I f , may contribute to the clinically significant association between SAN dysfunction and supraventricular tachyarrhythmias.
Murine Anti-GD2 Monoclonal Antibody 3F8 Combined With Granulocyte-Macrophage Colony-Stimulating Factor and 13-<i>Cis</i>-Retinoic Acid in High-Risk Patients With Stage 4 Neuroblastoma in First Remission
Authors: Nai-Kong V. Cheung, Irene Y. Cheung, Brian H. Kushner, Irina Ostrovnaya, Elizabeth Chamberlain, Kim Kramer, Shakeel Modak
Journal: Journal of Clinical Oncology (2012)

Purpose Anti-GD2 monoclonal antibody (MoAb) combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown efficacy against neuroblastoma (NB). Prognostic variables that could influence clinical outcome were explored. Patients and Methods One hundred sixty-nine children diagnosed with stage 4 NB (1988 to 2008) were enrolled onto consecutive anti-GD2 murine MoAb 3F8 ± GM-CSF ± 13-cis-retinoic acid (CRA) protocols after achieving first remission (complete remission/very good partial remission). Patients enrolled in regimen A (n = 43 high-risk [HR] patients) received 3F8 alone; regimen B (n = 41 HR patients), 3F8 + intravenous GM-CSF + CRA, after stem-cell transplantation (SCT); and regimen C (n = 85), 3F8 + subcutaneous GM-CSF + CRA, 46 of 85 after SCT, whereas 28 of 85 required additional induction therapy and were deemed ultra high risk (UHR). Marrow minimal residual disease (MRD) was measured by quantitative reverse transcription polymerase chain reaction. Survival probability was calculated by the Kaplan-Meier method, and prognostic variables were analyzed by multivariate Cox regression model. Results At 5 years from the start of immunotherapy, progression-free survival (PFS) improved from 44% for HR patients receiving regimen A to 56% and 62% for those receiving regimens B and C, respectively. Overall survival (OS) was 49%, 61%, and 81%, respectively. PFS and OS of UHR patients were 36% and 75%, respectively. Relapse was mostly at isolated sites. Independent adverse prognostic factors included UHR (PFS) and post–cycle two MRD (PFS and OS), whereas the prognostic factors for improved outcome were missing killer immunoglobulin-like receptor ligand (PFS and OS), human antimouse antibody response (OS), and regimen C (OS). Conclusion Retrospective analysis of consecutive trials from a single center demonstrated that MoAb 3F8 + GM-CSF + CRA is effective against chemotherapy-resistant marrow MRD. Its positive impact on long-term survival can only be confirmed definitively by randomized studies.
Noninvasive Versus Invasive Microbial Investigation in Ventilator-associated Pneumonia
Authors: MAURICIO RUIZ, ANTONI TORRES, SANTIAGO EWIG, MARIA ANGELES MARCOS, AMALIA ALCÓN, RAFAEL LLEDÓ, MIGUEL ANGEL ASENJO, ABEL MALDONALDO
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Noninvasive and invasive diagnostic techniques have been shown to achieve comparable performances in the evaluation of suspected ventilator-associated pneumonia (VAP). We studied the impact of both approaches on outcome in a prospective, open, and randomized study in three intensive care units (ICUs) of a 1,000-bed tertiary care university hospital. Patients with suspected VAP were randomly assigned to noninvasive (Group 1) versus invasive (Group 2) investigation (tracheobronchial aspirates [TBAS] versus bronchoscopically retrieved protected specimen brush [PSB] and bronchoalveolar lavage [BAL]. Samples were cultured quantitatively, and BAL fluid (BALF) was examined for intracellular organisms (ICO) additionally. Initial empiric antimicrobial treatment was administered following the guidelines of the American Thoracic Society (ATS) and adjusted according to culture results (and ICO counts in Group 2). Outcome variables included length of ICU stay and mechanical ventilation as well as mortality. Overall, 76 patients (39 noninvasive, 37 invasive) were investigated. VAP was microbiologically confirmed in 23 of 39 (59%) and 23 of 37 (62%) (p = 0.78). There were no differences with regard to the frequencies of community-acquired and potentially drug-resistant microorganisms (PDRM). Antimicrobial treatment was changed in seven patients (18%) of Group 1 and 10 patients (27%) of Group 2 because of etiologic findings (including five of 17 with ICO = 2% (p = not significant [NS]). Length of ICU stay and mechanical ventilation were also not significantly different in both groups. Crude 30-d mortality was 31 of 76 (41%), and 18 of 39 (46%) in Group 1 and 14 of 37 (38%) in Group 2 (p = 0.46). Adjusted mortality was 16% versus 11% (p = 0.53), and mortality of microbiologically confirmed pneumonia 10 of 23 (44%) in both groups (p = 1.0). We conclude that the outcome of VAP was not influenced by the techniques used for microbial investigation.
Productivity Costs of Cancer Mortality in the United States: 2000–2020
Authors: Cathy J. Bradley, K. Robin Yabroff, Bassam Dahman, Eric J. Feuer, Angela Mariotto, Martin L. Brown
Journal: JNCI Journal of the National Cancer Institute (2008)

A model that predicts the economic benefit of reduced cancer mortality provides critical information for allocating scarce resources to the interventions with the greatest benefits. We developed models using the human capital approach, which relies on earnings as a measure of productivity, to estimate the value of productivity lost as a result of cancer mortality. The base model aggregated age- and sex-specific data from four primary sources: 1) the US Bureau of the Census, 2) US death certificate data for 1999–2003, 3) cohort life tables from the Berkeley Mortality Database for 1900–2000, and 4) the Bureau of Labor Statistics Current Population Survey. In a model that included costs of caregiving and household work, data from the National Human Activity Pattern Survey and the Caregiving in the U.S. study were used. Sensitivity analyses were performed using six types of cancer assuming a 1% decline in cancer mortality rates. The values of forgone earnings for employed individuals and imputed forgone earnings for informal caregiving were then estimated for the years 2000–2020. The annual productivity cost from cancer mortality in the base model was approximately $115.8 billion in 2000; the projected value was $147.6 billion for 2020. Death from lung cancer accounted for more than 27% of productivity costs. A 1% annual reduction in lung, colorectal, breast, leukemia, pancreatic, and brain cancer mortality lowered productivity costs by $814 million per year. Including imputed earnings lost due to caregiving and household activity increased the base model total productivity cost to $232.4 billion in 2000 and to $308 billion in 2020. Investments in programs that target the cancers with high incidence and/or cancers that occur in younger, working-age individuals are likely to yield the greatest reductions in productivity losses to society.