tbuckley/cabot-search huggingface dataset:
P13 Safety of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF): Integrated analysis of cumulative data from 5 clinical trials: Abstract P13 Table 1
Authors: PW Noble, C Albera, WZ Bradford, U Costabel, I Glaspole, MK Glassberg, DJ Lederer, Z Lin, SD Nathan, CA Pereira, JJ Swigris, D Valeyre, L Lancaster
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> IPF is a chronic, progressive and irreversible disease that requires long-term clinical management. To further evaluate the clinical safety of pirfenidone in patients with IPF, we performed a comprehensive integrated analysis of safety data from 5 clinical trials. <h3>Methods</h3> All patients assigned to receive pirfenidone (2403 mg/d) in the Phase 3 ASCEND (016) and CAPACITY (004/006) studies and all patients receiving ≥1 dose of pirfenidone in either of two ongoing open-label studies (studies 002 and 012) comprised the integrated population. EAP (002) is a compassionate use study in the U.S.; RECAP (012) is evaluating pirfenidone in patients who completed one of the Phase 3 studies. Analyses were based on the January 15, 2014 interim data cut. <h3>Results</h3> 1299 patients were included in the integrated population. The cumulative total exposure to pirfenidone was 3160 person exposure years (PEY). The median duration of exposure was 1.7 years (range, 1 week–9.9 years); 545 (42%) patients received pirfenidone for ≥2 years and 325 (25%) patients received pirfenidone for ≥4 years. The majority of patients (75.8%) received a mean daily dose of ≥1800 mg. Consistent with prior observations, gastrointestinal and skin-related events were among the most common treatment emergent adverse events (Table 1); these were almost always mild to moderate in severity, reversible with dose modification and rarely led to treatment discontinuation. Cough, dyspnoea and IPF were the most common respiratory adverse events in the integrated population—a finding that is consistent with expectations in patients with a chronic progressive respiratory disease followed over a long period of observation. Aminotransferase (ALT or AST) elevations (&gt;3 × ULN) occurred in 40/1299 (3.0%) patients in the integrated population. <h3>Conclusions</h3> A comprehensive integrated analysis of safety outcomes in a large, well–defined cohort of 1299 patients with IPF who were treated with pirfenidone for up to 9.9 years demonstrated that treatment with pirfenidone is safe and generally well tolerated. These observations provide further evidence to support the long-term clinical safety of pirfenidone in patients with IPF.
GW26-e4714 Impact of Postoperative Anemia on Exercise Capacity Recovery in Patients Underwent Coronary Artery Bypass Surgery
Authors: Yi-Ling Lai, Ching-Ling Hsu, Yu-Shan Lin, Fei-Hsin Cheng, Li-Ying Kuo, Bo-Yan Chen, Hui-Yu Tsai, Wei-Shan Ling, Hsin-Yi Huang
Journal: Journal of the American College of Cardiology (2015)
Towards evidence based research
Authors: Hans Lund, Klara Brunnhuber, Carsten Juhl, Karen Robinson, Marlies Leenaars, Bertil F Dorch, Gro Jamtvedt, Monica W Nortvedt, Robin Christensen, Iain Chalmers
Journal: BMJ (2016)

To avoid waste of research, no new studies should be done without a systematic review of existing evidence, argue  Hans Lund and colleagues
Auranofin to prevent progression of pancreatic ductal adenocarcinoma.
Authors: Mayrim V. Rios Perez, David Roife, Bing Bing Dai, Ya'an Kang, Xinqun Li, Michael Pratt, Jason B. Fleming
Journal: Journal of Clinical Oncology (2016)

236 Background: Auranofin, an FDA anti-rheumatic agent shown to have anticancer properties for lung and ovarian cancer has never been studied for pancreatic cancer. We hypothesize that Auranofin may prevent pancreatic ductal adenocarcinoma (PDAC) progression by induction of apoptosis. Methods: We performed in vitro and in vivo studies using human PDAC cell lines and patient-derived xenografts (PDX) to assess Auranofin anticancer activity. Sensitivity to the compound was determined based on IC 50 s. Western blot assay was used to interrogate mechanisms of apoptosis, autophagy, and resistance. Two PDAC orthotopic mouse models were designed to determine optimal dose (survival), and antitumor effect (non-survival). Results: We found more than half of PDAC cell lines (10/18) to be sensitive to Auranofin based on IC 50 s below 5µM. Ex vivo tissue growth inhibition greater than 44% was observed for 13 PDX tissue cases treated with 10 µM Auranofin. Treatment with low-dose Auranofin (0.5-1µM) was found to induce PARP cleavage and LC3B expression among sensitive cell lines when compared to control (0.1% DMSO). High Txnrd1 and low Nrf2 expression was observed for resistant cell lines. Survival study using MiaPaCa-2 Luc+ showed 15mg/kg IP as the optimal dose due to absence of gross solid organ metastasis up to 13 weeks post-treatment (median survival 8 and 12, respectively; p = 0.0953). Non-survival study using MDA-Patc53 Luc+ showed a decreased tumor bioluminescence (p = 0.1097) and a 9-fold decrease in mean tumor progression from baseline (p = 0.1640) 3 weeks post-treatment. Conclusions: We have demonstrated that Auranofin prevents PDAC progression using two animal models. In vitro studies suggest apoptosis and autophagy as possible mechanisms of action, and Txnrd1 as a biomarker of resistance. This study altogether demonstrates both primary and metastatic antitumor effect of Auranofin for PDAC, which could represent an advantageous therapeutic approach for a broad selection of patients in both neoadjuvant and adjuvant settings.
Phase I/II Study of BI 6727 (volasertib), An Intravenous Polo-Like Kinase-1 (Plk1) Inhibitor, In Patients with Acute Myeloid Leukemia (AML): Results of the Dose Finding for BI 6727 In Combination with Low-Dose Cytarabine
Authors: Gesine Bug, Richard F. Schlenk, Carsten Müller-Tidow, Michael Lübbert, Alwin Krämer, Frank Fleischer, Tillmann Taube, Oliver G. Ottmann, Hartmut Doehner
Journal: Blood (2010)
Results of the Mantle Cell Lymphoma Subset from a Phase 2a Study of Copanlisib, a Novel PI3K Inhibitor, in Patients with Indolent and Aggressive Lymphoma
Authors: David Cunningham, Pier Luigi Zinzani, Sarit E. Assouline, Krimo Bouabdallah, Dominique Bron, Corinne Haioun, Luigina Mollica, Marius Giurescu, Igor Gorbatchevsky, Manoel Neves, Marta M. Lemos, Julia Grunert, Florian Hiemeyer, Barrett H. Childs, Martin H. Dreyling
Journal: Blood (2015)
Oral Fluoroquinolone Use and Retinal Detachment
Authors: Ian J. Douglas, Adrian Root, Bhaskaran Krishnan
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Secondary Resistance to Lenalidomide in Del(5q) MDS Is Associated with CDC25C &amp; PP2A Overexpression.
Authors: Alan F List, Kathy Rocha, Ling Zhang, Rami S. Komrokji, Justine Clark, Gisela Caceres, Debbie Billingsley, Lubomir Sokol, Jeffrey E Lancet, Jaroslaw P. Maciejewski, Mikkael A. Sekeres, Xianghong Chen, Sheng Wei
Journal: Blood (2009)
Predicting Autologous Stem Cell Mobilization Failure In Hematologic Malignancies
Authors: Pavan Bhamidipati, Mark A. Fiala, Stephanie Wang, Trisha Sturgill, Feng Gao, Camille N. Abboud, Amanda F Cashen, Meagan Jacoby, Iskra Pusic, Rizwan Romee, Mark A. Schroeder, Geoffrey L. Uy, Ravi Vij, Peter Westervelt, John F. DiPersio, Keith E. Stockerl-Goldstein
Journal: Blood (2013)
Loss of osteoglycin promotes angiogenesis in limb ischaemia mouse models via modulation of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 signalling pathway
Authors: Qi-Hong Wu, Yu Ma, Cheng-Chao Ruan, Yan Yang, Xin-He Liu, Qian Ge, Ling-Ran Kong, Ji-Wei Zhang, Chen Yan, Ping-Jin Gao
Journal: Cardiovascular Research (2016)

Osteoglycin (OGN) has been noted for its implication in cardiovascular disease in recent studies. However, the relationship between OGN and angiogenesis remains unknown. Therefore, we aimed to investigate the effect of OGN on ischaemia-induced angiogenesis and to address the underlying mechanisms.The expression of OGN was decreased in a limb ischaemia mouse model. OGN knockout (KO) mice were used to further understand the role of OGN after ischaemia. The perfusion recovery rate after femoral artery ligation was higher in OGN KO mice than in wild-type (WT) mice. The capillary density in the gastrocnemius muscle of the ischaemic limb was also higher in OGN KO mice. Moreover, ex vivo aortic ring explants from OGN KO mice exhibited stronger angiogenic sprouting than those from WT mice. In human umbilical vein endothelial cells (HUVECs), OGN knockdown enhanced endothelial cell (EC) activation, including tube formation, proliferation, and migration. In contrast, OGN overexpression inhibited HUVEC activation. Mechanistic studies revealed that OGN associates with vascular endothelial growth factor receptor 2 (VEGFR2) and negatively regulates the interaction of vascular endothelial growth factor (VEGF) and VEGFR2, thereby negatively modulating the activation of VEGFR2 and its downstream signalling pathways. Consistently, the pro-angiogenic effect of OGN KO was abrogated by VEGFR2 inhibition, supporting the critical role of VEGFR2 signalling in OGN-mediated regulation of angiogenic function.OGN plays a critical role in negatively regulating ischaemia-induced angiogenesis by inhibiting VEGF-VEGFR2 signalling and thereby attenuating EC tube formation, proliferation, and migration. Thus, OGN may be a novel therapeutic target for ischaemic vascular diseases.
Fingolimod Expands Human Umbilical Cord Blood Cells (UCB) in Vitro and Improves Engraftment Rate of Human UCB in Sublethally Irradiated NOD SCID Gamma (NSG) Mice
Authors: Basem M. William, Stephen Moreton, Jane Reese, Pingfu Fu, Julia V. Busik, Marcos de Lima, David N. Wald
Journal: Blood (2014)
An Evolutionary Framework for Carpel Developmental Control Genes
Authors: Kai C. Pfannebecker, Matthias Lange, Oliver Rupp, Annette Becker
Journal: Molecular Biology and Evolution (2016)

Carpels are the female reproductive organs of flowering plants (angiosperms), enclose the ovules, and develop into fruits. The presence of carpels unites angiosperms, and they are suggested to be the most important autapomorphy of the angiosperms, e.g., they prevent inbreeding and allow efficient seed dispersal. Many transcriptional regulators and coregulators essential for carpel development are encoded by diverse gene families and well characterized in Arabidopsis thaliana. Among these regulators are AGAMOUS (AG), ETTIN (ETT), LEUNIG (LUG), SEUSS (SEU), SHORT INTERNODE/STYLISH (SHI/STY), and SEPALLATA1, 2, 3, 4 (SEP1, 2, 3, 4). However, the timing of the origin and their subsequent molecular evolution of these carpel developmental regulators are largely unknown. Here, we have sampled homologs of these carpel developmental regulators from the sequenced genomes of a wide taxonomic sampling of the land plants, such as Physcomitrella patens, Selaginella moellendorfii, Picea abies, and several angiosperms. Careful phylogenetic analyses were carried out that provide a phylogenetic background for the different gene families and provide minimal estimates for the ages of these developmental regulators. Our analyses and published work show that LUG-, SEU-, and SHI/STY-like genes were already present in the Most Recent Common Ancestor (MRCA) of all land plants, AG- and SEP-like genes were present in the MRCA of seed plants and their origin may coincide with the ξ Whole Genome Duplication. Our work shows that the carpel development regulatory network was, in part, recruited from preexisting network components that were present in the MRCA of angiosperms and modified to regulate gynoecium development.
Urinary Cadmium and Breast Cancer: A Prospective Danish Cohort Study
Authors: Kirsten T. Eriksen, Jane A. McElroy, James M. Harrington, Keith E. Levine, Camilla Pedersen, Mette Sørensen, Anne Tjønneland, Jaymie R. Meliker, Ole Raaschou-Nielsen
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: Cadmium is a human lung carcinogen, and recent evidence suggests it may play a role in hormone-related cancers because of its estrogenic activity. Case-control studies consistently show higher cadmium concentrations in urine from women diagnosed with breast cancer compared with control women. Our aim was to investigate the association between urinary cadmium and breast cancer in a prospective design. Methods: We conducted a case-cohort study using the population-based Danish Diet Cancer and Health Cohort. Women age 50 to 64 years were recruited in 1993–1997 and provided urine for analysis. We identified 900 incident case patients in the Danish Cancer Registry and compared with 898 individuals in a subcohort. Urine samples collected at enrollment into the cohort were analyzed for cadmium and creatinine. We estimated incidence rate ratios (IRRs) for breast cancer in Cox proportional hazards models with age as time axis and calculated 95% confidence intervals (CIs). Results: The linear analysis showed no association between urinary cadmium and risk for breast cancer (IRR = 1.00, 95% CI = 0.81 to 1.24 per ng Cd/mL urine). The categorical analyses showed a slightly higher risk for breast cancer for the second (IRR = 1.10, 95% CI = 0.86 to 1.42) and third (IRR = 1.14, 95% CI = 0.83 to 1.55) exposure tertiles compared with the lowest tertile. Results were similar in analyses of breast cancer subtypes defined by estrogen and progesterone receptor status and by histology, and analyses stratified by years from baseline to diagnosis. Conclusions: This large prospective study showed no association between urinary concentration of cadmium and subsequent risk for development of postmenopausal breast cancer.
Association between glutathione s-transferase P1 polymorphisms and time to tumor progression in small cell lung cancer patients.
Authors: P. Saip, F. Sen, B. Vural, E. Ugurel, A. Demirkan, D. Derin, Y. Eralp, H. Camlica, Z. Ustuner, U. Ozbek
Journal: Journal of Clinical Oncology (2010)

e12041 Background: Many of commonly used chemotherapeutics in lung cancer treatment are metabolized by glutathione-S transferases (GST). Placental isoform of GST (GSTP1) is the most abundant isoform in the lung. Polymorphisms within the GSTP1 may result in alterations in enzyme activity and change sensitivity to platinum based chemotherapy. We investigated whether the polymorphism within the exon 5 and exon 6 of GSTP1 gene may change response to therapy, time to tumor progression (TTP) and overall survival in small cell lung cancer (SCLC) patients. Methods: Ninety four histologically confirmed patients with SCLC were enrolled in this study during 1995-2006. GSTP1 Ile105Val polymorphism in exon 5 and GSTP1 Ala114Val polymorphism in exon 6 were determined by using PCR-RFLP techniques. Associations between the GSTP1 polymorphisms and treatment response were evaluated using the chi-square tests. Associations between the GSTP1 polymorphisms and TTP and overall survival were compared using Kaplan-Meier survival curves. Results: We found no significant associations between exon 5 and exon 6 GSTP1 gene polymorphisms and response to therapy or overall survival. Patients carrying both variant exon 5 (Ile/Val or Val/Val) and variant exon 6 (Ala/Val) genotypes had significantly short TTP (5 months vs 8 months). Moreover, patients with heterozygote exon 6 variant had presented with extensive stage disease. Conclusions: No individual effect of variant alleles was found on chemotherapy response, median TTP and overall survival. The carriage of both types of variant alleles may predict worse outcome. No significant financial relationships to disclose.
Amonafide + ara-C in secondary acute myeloid leukemia (sAML): Consistent efficacy in poor risk populations
Authors: D. A. Rizzieri, H. P. Erba, M. O'Donnell, B. L. Powell, A. S. Lundberg, J. M. Bennett, R. L. Capizzi
Journal: Journal of Clinical Oncology (2008)

7027 Background: The poor prognosis for sAML (prior MDS or leukemogenic therapy, i.e., tAML) relates to disease (unfavorable cytogenetics and multidrug resistance (MDR) phenotype) and patient (pt) characteristics (elderly w/comorbid illnesses). Amonafide (Xanafide), a topoisomerase II inhibitor, is not a substrate or inhibitor of the MDR efflux pump, P-glycoprotein (Pgp) (Chau 2007 Leuk Res in press; O'Loughlin 2007 Blood 110:702a; Lundberg 2008 ASCO, submitted). A 42% CR rate in this Phase 2 trial was previously reported (Erba 2007 Proc Am Soc Clin Onc 25:373s). We report updated results & long-term follow up. Methods: sAML pts received amonafide 600 mg/m2 days 1–5 + ara-C 200 mg/m2 CIV days 1–7. A 2nd course could be given for persistent leukemia on day 14. CR pts received either stem cell transplant or intermediate/high dose ara-C depending on age. Centralized pathology review and DSMB were utilized. Primary endpoint was complete remission (CR) with or without (CRi) hematologic recovery. Median duration of follow-up is 208 days. Results: Enrollment 88 pts; median age 63 yrs (range 23–87); prior MDS, 45.5%; tAML 54.5%; unfavorable cytogenetics, 47%. Overall CR was 42%, 34 CR + 3 CRp (CR without recovery of platelets). CR rate was consistent across poor risk subgroups: age <60yrs, 39.4%; >60yrs, 43.6%. MDS → AML without and with prior therapy for MDS (mostly azacytidine), 43.5% & 36%; tAML, 40%; intermediate & unfavorable cytogenetics, 60% & 22%. 6 of 10 CR pts with informative cytogenetics achieved cytogenetic CR. 30 pts received post-remission therapy with ara-C (21), BMT (7), or both (2). Median duration of CR is >10 months, among age > 60 is > 9 months, with pts continuing on study. Kaplan-Meier estimate of continuous CR at 12 months is 43%, 47%, 64% and 57% for all pts, older pts (>60), pts with tAML, and pts with poor risk cytogenetics. Median overall survival (OS) is 7 months, and median OS for CR pts is >11 months. Safety profile was acceptable, death within 28 days was 20.5%. Conclusions: This study demonstrated robust and durable CR across poor-risk subsets of sAML, including older pts, tAML, and previously treated MDS → AML. Amonafide and ara-C may be a promising alternative for pts with sAML, especially those with over- expression of Pgp. This is being tested in a Phase 3 clinical trial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Xanthus Pharmaceuticals Xanthus Pharmaceuticals Xanthus Pharmaceuticals
Abstract IA06: Influence of macrophage metabolism on vessel shape: Implications for cancer
Authors: Massimiliano Mazzone
Journal: Cancer Research (2016)

Abstract Cancer typically has an inflammatory nature. Of all immune cells invading the tumor, the role of macrophages remains controversial because of their functionally distinct differentiation states. Classically activated (M1-like) macrophages and alternatively activated (M2-like) macrophages represent the two extremities of a continuum, in which the former are proinflammatory and tumoricidal, whereas the latter display pro-angiogenic and protumoral activities. This heterogeneity reflects the plasticity and versatility of these cells in response to microenvironmental signals. The tumor environment is constituted of cancer cells and stromal cells that coexist under different oxygen tensions and the influence of soluble factors. A plethora of (hypoxia-induced) cytokines and chemokines can define the macrophage phenotype and their positioning within the tumor. We have elucidated an elegant mechanism by which macrophages are recruited and retained in avascular hypoxic niches of the tumor, where they exert their immunosuppressive and pro-angiogenic activity. Hypoxia by itself indeed strongly affects macrophage function, as the cells are forced to adapt and alter their metabolism, which is accompanied by a drastic change in their transcriptome and proteome. We have found that the resultant metabolic changes drive macrophages towards a pro-angiogenic phenotype in an attempt to restore oxygenation. Soluble factors derived from the tumor exacerbate this macrophage shift by further enforcing this metabolic adaptation. As a consequence, tumor blood vessels are abnormal and dysfunctional, thus perpetuating hypoxia, which in turn fosters metastasis. By using genetic tools in mice, we show that inhibiting macrophage recruitment in hypoxic niches, or altering their metabolic and energetic state can break this feed-forward loop, resulting in normalized blood vessels and thus, strongly reducing metastatic dissemination. Citation Format: Massimiliano Mazzone. Influence of macrophage metabolism on vessel shape: Implications for cancer. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr IA06.
SRAS : étude rétrospective de la cohorte allemande ayant séjourné à l'hôtel 'M', Hong-Kong
Authors: D Radun, M Niedrig, A Ammon, K Stark
Journal: Eurosurveillance (2003)

Hong Kong a joue un role central dans la diffusion internationale du Syndrome Respiratoire Aigu Severe (SRAS) : un medecin ayant sejourne la nuit du 21-22 fevrier 2003 a l'hotel 'M' a ete identifie comme etant le cas index de quatre cas groupes de SRAS, nationaux et internationaux. Parallelement a l'etude collaborative internationale menee par l'OMS et les Etats-Unis, une etude retrospective sur la cohorte de ressortissants allemands ayant sejourne a l'hotel 'M' a ete realisee. Les criteres d'inclusion couvraient la periode du 21 fevrier au 3 mars 2003 afin de permettre la detection des cas dus a une possible contamination environnementale. Vingt-et-un Allemands ayant sejourne a l'hotel 'M' au cours de cette periode ont ainsi ete inclus, dont un cas de SRAS confirme microbiologiquement. L'histoire de ce cas suggere qu'une forte proximite avec le cas index a pu jouer un role dans la transmission. D'apres les resultats des investigations environnementales menees dans l'hotel, la contamination environnementale devrait etre consideree comme une source possible d'infection.
Pulmonary effects of immediate versus deferred antiretroviral therapy in HIV-positive individuals: a nested substudy within the multicentre, international, randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial
Authors: Ken M Kunisaki, Dennis E Niewoehner, Gary Collins, Bitten Aagaard, Nafisah B Atako, Elzbieta Bakowska, Amanda Clarke, Giulio Maria Corbelli, Ernest Ekong, Sean Emery, Elizabeth B Finley, Eric Florence, Rosa M Infante, Cissy M Kityo, Juan Sierra Madero, Daniel E Nixon, Ellen Tedaldi, Jørgen Vestbo, Robin Wood, John E Connett
Journal: The Lancet Respiratory Medicine (2016)