tbuckley/cabot-search huggingface dataset:
Phase III trial of dovitinib (TKI258) versus sorafenib in patients with metastatic renal cell carcinoma after failure of anti-angiogenic (VEGF-targeted and mTOR inhibitor) therapies.
Authors: Robert John Motzer, Camillo Porta, Georg A. Bjarnason, Cezary Szcylik, Sun Young Rha, Emilio Esteban, Ugo De Giorgi, Mary J. MacKenzie, Paul N. Mainwaring, Scott North, Roberto Sabbatini, Istvan Bodrogi, Fairooz Kabbinavar, Giacomo Carteni, Cora N. Sternberg, Nicholas J. Vogelzang, Michael Shi, Gladys Urbanowitz, Bernard J. Escudier
Journal: Journal of Clinical Oncology (2012)

TPS4683 Background: Standard first- and second-line treatments in metastatic renal cell carcinoma (mRCC) target the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) signaling pathways. However, signaling through other pathways, including the fibroblast growth factor receptor (FGFR) pathway, may account for tumor resistance to these standard therapies. Dovitinib (TKI258) is an oral FGF, VEGF, and platelet-derived growth factor (PDGF) receptor tyrosine kinase inhibitor, with IC 50 values of ≈ 10 nM. In a phase II study of 59 RCC patients, many of whom had failed prior VEGF-targeted and mTOR inhibitor therapies, dovitinib (500 mg/day on a 5-days-on/2-days-off schedule) was well tolerated and demonstrated promising anti-tumor effects, with progression-free survival (PFS) of 5.5 months (Angevin et al, ASCO 2011). Methods: Approximately 550 patients from over 26 countries will be randomized 1:1 in this multicenter, open-label, randomized phase III trial (NCT01223027) to receive dovitinib (500 mg/day on a 5-days-on/2-days-off schedule) or sorafenib (400 mg twice daily). Eligible mRCC patients must have failed 1 VEGF-targeted therapy and 1 mTOR inhibitor (disease progression on or within 6 months of stopping the prior treatment). Patients will remain on study until disease progression, unacceptable toxicity, death, or discontinuation for any other reason. No treatment crossover is planned. The primary endpoint is PFS as determined by central radiology assessment according to RECIST v1.1, with evaluations performed every 8 weeks. Secondary endpoints include overall survival, overall response rate, safety, patient-reported outcomes, and pharmacokinetics. The pharmacodynamic effects of dovitinib on plasma/serum biomarkers will also be explored. The data monitoring committee last reviewed the trial on 20 December 2011 and recommended that the trial continue as planned. This is the first third-line randomized clinical trial in mRCC to evaluate a multitargeted inhibitor of FGFR.
Randomized, Open-Label Phase II Study Evaluating the Efficacy and Safety of Talimogene Laherparepvec in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced, Unresectable Melanoma
Authors: Jason Chesney, Igor Puzanov, Frances Collichio, Parminder Singh, Mohammed M. Milhem, John Glaspy, Omid Hamid, Merrick Ross, Philip Friedlander, Claus Garbe, Theodore F. Logan, Axel Hauschild, Celeste Lebbé, Lisa Chen, Jenny J. Kim, Jennifer Gansert, Robert H.I. Andtbacka, Howard L. Kaufman
Journal: Journal of Clinical Oncology (2017)

Purpose We evaluated the combination of talimogene laherparepvec plus ipilimumab versus ipilimumab alone in patients with advanced melanoma in a phase II study. To our knowledge, this was the first randomized trial to evaluate addition of an oncolytic virus to a checkpoint inhibitor. Methods Patients with unresectable stages IIIB to IV melanoma, with no more than one prior therapy if BRAF wild-type, no more than two prior therapies if BRAF mutant, measurable/injectable disease, and without symptomatic autoimmunity or clinically significant immunosuppression were randomly assigned 1:1 to receive talimogene laherparepvec plus ipilimumab or ipilimumab alone. Talimogene laherparepvec treatment began in week 1 (first dose, ≤ 4 mL × 106 plaque-forming units/mL; after 3 weeks, ≤ 4 mL × 108 plaque-forming units/mL every 2 weeks). Ipilimumab (3 mg/kg every 3 weeks; up to four doses) began week 1 in the ipilimumab alone arm and week 6 in the combination arm. The primary end point was objective response rate evaluated by investigators per immune-related response criteria. Results One hundred ninety-eight patients were randomly assigned to talimogene laherparepvec plus ipilimumab (n = 98), or ipilimumab alone (n = 100). Thirty-eight patients (39%) in the combination arm and 18 patients (18%) in the ipilimumab arm had an objective response (odds ratio, 2.9; 95% CI, 1.5 to 5.5; P = .002). Responses were not limited to injected lesions; visceral lesion decreases were observed in 52% of patients in the combination arm and 23% of patients in the ipilimumab arm. Frequently occurring adverse events (AEs) included fatigue (combination, 59%; ipilimumab alone, 42%), chills (combination, 53%; ipilimumab alone, 3%), and diarrhea (combination, 42%; ipilimumab alone, 35%). Incidence of grade ≥ 3 AEs was 45% and 35%, respectively. Three patients in the combination arm had fatal AEs; none were treatment related. Conclusion The study met its primary end point; the objective response rate was significantly higher with talimogene laherparepvec plus ipilimumab versus ipilimumab alone. These data indicate that the combination has greater antitumor activity without additional safety concerns versus ipilimumab.
UNICANCER: Prospective cohort study of treatment related chronic toxicities in patients with localized breast cancer (CANTO).
Authors: Ines Maria Vaz Duarte Luis, Paul H. Cottu, Christel Mesleard, Anne-Laure Martin, Agnes Dumas, Sarah Dauchy, Olivier Tredan, Christelle Levy, Johan Adnet, Marina Rousseau-Tsangaris, Fabrice Andre, Patrick Arveux
Journal: Journal of Clinical Oncology (2017)

TPS10125 Background: Corresponding with improved survival among breast cancer patients an awareness of the long term effects of cancer treatments has increased. There is now a call for better coordination of care and management of these patients to focus on their survivorship. This study will identify factors associated with the development and persistence of long term toxicities in patients treated for Stage I-III breast cancer. In addition, it will characterize their incidence as well as, psychological, social and economic impacts. Methods: This is a prospective cohort study enrolling newly diagnosed invasive cT0-cT3, cN0-3, M0 breast cancer patients of 26 French comprehensive cancer centers. All patients will be followed for a minimum of 5 years. Patients will be assessed at diagnosis, 3-6 (M0), 12 (M12), 36 (M36), 48 (M48), 60 (M60), months after treatment completion. Treatment completion is defined as completion of primary surgery, chemotherapy or radiotherapy, whichever comes last. Adjuvant trastuzumab, endocrine therapy or participation in clinical trials can be ongoing. CANTO collects an extensive list of clinical, treatment, and toxicity data including validated patient reported outcomes questionnaires ( Hospital Anxiety and Depression scale [HADS], Scheier et Carver’s Questionnaire, Life Orientation Test-Revised [LOT-R], Beck Depression Inventory [BDI-SF], European Organization for Research and Treatment-QOL questionnaire for breast cancer [EORTC QLQC30-BR23], EORTC-FA13, 12 Item Short Form Survey [SF12], Global physical activity questionnaire [GPAQ]6, impact of cancer questionnaire [IOCv2], economic and social questionnaires). Blood collection is available for all patients at diagnosis, M0, M12, M36 and M60. Genotyping will be performed in all samples. Biologic substudies are ongoing (e.g, microbiotic and cognitive substudy). CANTO aggregates a multidisciplinary team of French investigators and created a dedicated national network. Enrolment started in 2012 and by December 2016, 10030 patients were already enrolled, with a goal of 12.000 patients. Clinical trial information: NCT01993498.
Desenvolvimento de uma rede de investigação de agentes patogénicos emergentes de origem alimentar na Alemanha
Authors: D Werber, A Ammon
Journal: Eurosurveillance (2000)

Na Alemanha, esta a ser desenvolvida uma rede de epidemiologistas, microbiologistas, veterinarios e medicos de clinica geral, com o objectivo de apoiar os departamentos de saude local e estatal e as autoridades veterinarias nas respectivas pesquisas e investigacoes epidemiologicas sobre os agentes patogenicos de origem alimentar. Este artigo descreve os metodos que estao a ser utilizados para investigar a Escherichia coli enterohemorragica (ECEH) e o sindroma hemolitico-uremico (SHU).
Integration of Cancer Survivorship Care and Primary Care Practice
Authors: Emily S. Tonorezos, Joseph Conigliaro
Journal: JAMA Internal Medicine (2017)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
After the Mass Shooting in Las Vegas — Finding Common Ground on Gun Control
Authors: Edward W. Campion, Stephen Morrissey, Debra Malina, Chana A. Sacks, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2017)

We've seen so many mass shootings -in theaters, in churches, in nightclubs, in schools -that each new episode of the mass slaughter of Americans induces a weary sense of déjà vu. 1,2ut some realities of the recent mass shooting in Las Vegas, the largest in modern history, might help produce action, rather than the paralysis we've seen for so many years.What's different this time is the unprecedented magnitude of the killing.It appears that a single, heavily armed man was able to kill at least 58 people and wound nearly 500 more.He was untrained and unskilled but could direct his high-powered automatic and semiautomatic guns down on a crowd of some 22,000 people at the Route 91 Harvest country music festival.He fired thousands of rounds of ammunition from the 32nd floor of his hotel, a quarter mile from the concert venue.This 64-year-old man had no known political, racial, or religious agenda, and there was no history of known mental illness or criminal behavior.But he used his large arsenal of weapons to kill and maim more innocent Americans than anyone else has ever done.A couple of lessons are clear from the Las Vegas shooting.First, few security measures within any venue can protect against assault from outside the venue.Second, readily available high-powered modern weaponry makes mass killing easy for a determined killer, even an inexperienced one.Third, the magnitude of the killing could have been far greater.Given his position and his firepower, the shooter could have killed thousands, if not for the courageous, coordinated assault by the highly trained Las Vegas law-enforcement team.
La surveillance des maladies transmissibles dans le Nord du Portugal pendant la coupe d’Europe de football EURO 2004
Authors: G Gonçalves, L Castro, A M Correia, Laurinda Queirós
Journal: Eurosurveillance (2005)

La coupe d’Europe de football, l’EURO 2004, s’est tenue au Portugal du 12 juin au 4 juillet 2004. La population couverte par le Service regional de Sante publique du Nord du Portugal represente 3,2 millions de personnes. Cette region a accueilli 12 matchs, plus que toute autre region. L’article decrit les activites de surveillance des maladies transmissibles dans cette region pendant l’EURO 2004. Dix epidemies de toxi-infections alimentaires, sept cas d’infections a meningocoque et un cas de legionellose ont ete detectes. Les visiteurs n’ont pas ete affectes, et les cas survenus chez les residents ne semblent pas avoir ete influences par la presence de milliers de visiteurs. Une situation similaire a ete observee lors d’autres rassemblements de masse ou des activites de surveillance specifiques avaient ete mises en place. Cela ne diminue pas pour autant l’importance d’une surveillance en sante publique lors de telles manifestations. De plus, l’evaluation de ces activites specifiques devrait representer une occasion de remettre a l’ordre du jour des points tels que les ressources, les priorites, l’organisation et la formation en matiere de surveillance des maladies transmissibles.
FRIEND: A randomized pilot study to compare the efficacy and tolerability of fulvestrant 500mg with exemestane as first line endocrine therapy for post-M ER positive HER2 negative ABC patients relapse after adjuvant non-steroidal aromatase inhibitors (NSAI)
Authors: J. Wang, B. Xu, Q. Li, P. Zhang, P. Yuan, F. Ma, Y. Luo, R. Cai, Y. Fan, S. Chen, Q. Li
Journal: Annals of Oncology (2017)
Primary care improvement in Wales “over reliant” on key individuals
Authors: Anne Gulland
Journal: BMJ (2017)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Primary care improvement in Wales “over reliant” on key individuals Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Monitoring multiple myeloma by idiotype-specific peptide binders of tumor-derived exosomes
Authors: Enrico Iaccino, Selena Mimmi, Vincenzo Dattilo, Fabiola Marino, Patrizio Candeloro, Antonio Di Loria, Danilo Marimpietri, Antonio Pisano, Francesco Albano, Eleonora Vecchio, Simona Ceglia, Gaetanina Golino, Antonio Lupia, Giuseppe Fiume, Ileana Quinto, Giuseppe Scala
Journal: Molecular Cancer (2017)

Tumor-derived exosomes (TDEs) play a pivotal role in tumor establishment and progression, and are emerging biomarkers for tumor diagnosis in personalized medicine. To date, there is a lack of efficient technology platforms for exosome isolation and characterization. Multiple myeloma (MM) is an incurable B-cell malignancy due to the rapid development of drug-resistance. MM-released exosomes express the immunoglobulin B-cell receptor (Ig-BCR) of the tumor B-cells, which can be targeted by Idiotype-binding peptides (Id-peptides). In this study, we analyzed the production of MM-released exosomes in the murine 5T33MM multiple myeloma model as biomarkers of tumor growth. To this end, we selected Id-peptides by screening a phage display library using as bait the Ig-BCR expressed by 5T33MM cells. By FACS, the FITC-conjugated Id-peptides detected the MM-released exosomes in the serum of 5T33MM-engrafted mice, levels of which are correlated with tumor progression at an earlier time point compared to serum paraprotein. These results indicate that Id-peptide-based recognition of MM-released exosomes may represent a very sensitive diagnostic approach for clinical evaluation of disease progression.
What caused the decline in breast cancer incidence rates?
Authors: A. B. Chagpar, K. M. McMasters
Journal: Journal of Clinical Oncology (2007)

1513 Background: Recently, a sharp 7% decline in breast cancer incidence rates among women over the age of 50 was noted in 2003. It has been speculated that this may be due to changes in mammographic screening or in the use of hormone replacement therapy (HRT). The purpose of this study is to elucidate the cause of the decline in breast cancer incidence rate. Methods: The National Health Interview Survey (NHIS) is a population-based personal interview survey conducted annually by the Centers of Disease Control. In 2000 and 2005, a cancer supplement was administered containing information regarding behaviors which may affect breast cancer incidence. These data were analyzed using SAS-callable SUDAAN software to determine trends in the use of mammography, HRT use, and chemoprevention over this period of time in women older than 50. Results: 7147 and 7396 women over 50 were surveyed in 2000 and 2005 respectively. There was a significant drop in the proportion of women reporting current use of HRT between 2000 and 2005 (27.66% vs. 12.09%, p&lt;0.0001). While there was also a drop in the proportion of women reporting current use of tamoxifen (1.34% vs. 0.74%, p&lt;0.0001), there was an increase in the proportion of women reporting current use of raloxifene (0.92% vs. 1.27%, p&lt;0.0001). Overall, there was a slight decrease in the use of chemoprevention between 2000 and 2005 (2.18% vs. 1.99%, p&lt;0.0001). There was a reduction in the proportion of women over the age of 50 reporting ever having had a mammogram (83.85% vs. 82.76%, p&lt;0.0001) or clinical breast examination (81.63% vs. 75.34%, p&lt;0.0001) between 2000 and 2005. Fewer women over the age of 50 reported that their last mammogram was within the preceding 2 years (87.33% vs. 84.68%, p=0.0002). Similar results were seen for clinical breast examination within the preceding 2 years (88.98% vs. 86.22%, p&lt;0.0001). Conclusions: The decline in breast cancer incidence rate is multifactorial, due in part to declining rates of early detection and chemoprevention. The principal etiologic factor, however, is likely the dramatic reduction in the use of HRT. No significant financial relationships to disclose.
Improving patient outcomes after surgery
Authors: Clare Marx, Derek Alderson
Journal: BMJ (2017)

Abstract  Genome-scale metabolic models provide a valuable context for analyzing data from diverse high-throughput experimental techniques. Models can quantify the activities of diverse pathways and cellular functions. Since some metabolic reactions are only catalyzed in specific environments, several algorithms exist that build context-specific models. However, these methods make differing assumptions that influence the content and associated predictive capacity of resulting models, such that model content varies more due to methods used than cell types. Here we overcome this problem with a novel framework for inferring the metabolic functions of a cell before model construction. For this, we curated a list of metabolic tasks and developed a framework to infer the activity of these functionalities from transcriptomic data. We protected the data-inferred tasks during the implementation of diverse context-specific model extraction algorithms for 44 cancer cell lines. We show that the protection of data-inferred metabolic tasks decreases the variability of models across extraction methods. Furthermore, resulting models better capture the actual biological variability across cell lines. This study highlights the potential of using biological knowledge, inferred from omics data, to obtain a better consensus between existing extraction algorithms. It further provides guidelines for the development of the next-generation of data contextualization methods.
Respuesta a un caso sospechoso de difteria en Dordrecht, Países Bajos
Authors: J. E. van Steenbergen, A Leentvaar-Kuijpers, J H C T van den Kerkhof
Journal: Eurosurveillance (1996)

Alrededor de 25.000-50.000 refugiados piden asilo cada ano en los Paises Bajos. Tras una evaluacion juridica inmediata, del 85% al 90% de los mismos es trasladado a uno de los 14 centros de acogida donde se les somete a pruebas para detectar la tuberculosis y los ninos y ancianos son reconocidos clinicamente por un medico. Se comprueban las vacunas recibidas por los ninos menores de 18 anos y se actualiza su inmunizacion de acuerdo con el estandar holandes (difteria-pertussis-tetanos, vacuna de polio inactivada, sarampion-parotiditis-rubeola y, para refugiados, antituberculosa -BCG-). Pasados cuatro meses, los refugiados son trasladados a uno de los 14 centros u hostales para refugiados, donde pueden permanecer de uno a dos anos hasta que se les declara oficialmente refugiados. De ahi en adelante, se les ayuda a encontrar un alojamiento adecuado.
Copper Chelation Inhibits BRAFV600E-Driven Melanomagenesis and Counters Resistance to BRAFV600E and MEK1/2 Inhibitors
Authors: Donita C. Brady, Matthew S. Crowe, Danielle N. Greenberg, Christopher M. Counter
Journal: Cancer Research (2017)

MEK1/2 and BRAFV600E inhibitors are used to treat BRAFV600E-positive melanoma, with other cancers under evaluation. Genetic perturbation of copper import or pharmacologic reduction of copper with the clinical copper chelator TTM inhibits MEK1/2 kinase activity and reduces BRAFV600E-driven tumorigenesis. In this study, we report that TTM inhibited transformed growth of melanoma cell lines resistant to BRAF or MEK1/2 inhibitors and enhanced the antineoplastic activity of these inhibitors. TTM also provided a survival advantage in a genetically engineered mouse model of melanoma, and when accounting for putative overdosing, trended toward an increase in the survival benefit afforded by BRAF inhibition. This effect was phenocopied by genetically inhibiting copper import in tumors, which was linked to a reduction in MAPK signaling. Thus, TTM reduces copper levels and MAPK signaling, thereby inhibiting BRAFV600E-driven melanoma tumor growth. These observations inform and support clinical evaluation of TTM in melanoma. Cancer Res; 77(22); 6240-52. ©2017 AACR.
Abstract 17693: The Effect of Interventricular Delay on AV Optimization for Cardiac Resynchronization Therapy
Authors: Michael R Gold, Yinghong Yu, Jagmeet P Singh, Kenneth M Stein, Ulrika Birgersdotter-Green, Nicholas Wold, Timothy E Meyer, Kenneth A Ellenbogen
Journal: Circulation (2016)

Introduction: Left ventricular (LV) delay, as measured by the QLV interval, at the LV pacing site predicts a number of outcomes with CRT including the magnitude of reverse remodeling. It also ident...
CD169 <sup>+</sup> macrophages orchestrate innate immune responses by regulating bacterial localization in the spleen
Authors: Oriana A. Perez, Stephen T. Yeung, Paola Vera-Licona, Pablo A. Romagnoli, Tasleem Samji, Basak B. Ural, Leigh Maher, Masato Tanaka, Kamal M. Khanna
Journal: Science Immunology (2017)

CD169 + macrophages in the spleen play an essential role in the clearance of Listeria monocytogenes .
Prospective cohort study of bevacizumab plus standard platinum based chemotherapy as front-line treatment for advanced epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer: Japanese Gynecologic Oncology Group study (JGOG3022)
Authors: K. Kato, S. Komiyama, N. Takeshima, H. Takano, A. Inoue, A. Hongo, M. Asai-Sato, A. Arakawa, K. Kubushiro, S. Kamiura, T. Sugiyama
Journal: Annals of Oncology (2017)