tbuckley/cabot-search huggingface dataset:
Abstract 4910: Development of an antagonist to the TWEAK-Fn14 ligand-receptor interaction with enhanced efficacy/potency in glioblastoma cells
Authors: Bryan Harder, Chris Sereduk, Harshil Dhruv, Nghia Millard, Anthony Kim, Jeffrey Winkles, Graeme Woodworth, Holly Yin, Nhan L. Tran
Journal: Cancer Research (2018)

Abstract Glioblastoma multiforme (GBM) remains the most common and deadly primary brain tumor with minimal advances in therapeutic development for pharmacological treatment. Tumor resection followed by temozolomide (TMZ) and radiotherapy adds months to survival; however, tumor recurrence usually occurs. The fibroblast growth factor-inducible 14 (Fn14) receptor has been shown to be up-regulated in the GBM cells left behind after surgery and contributes to an invasive and pro-survival phenotype, providing a desirable molecule to target after removal of the primary tumor. Previously, L524-0366 was reported by our lab to be the first antagonist of Fn14 signaling; however, minimal efficacy/potency has limited this drug from progressing from a useful research tool to preclinical studies. Structure activity relationship (SAR) studies using the parent L524-0366 compound gave rise to K78, which was found to bind to Fn14 with enhanced affinity, while showing no binding to the structurally-related TNFα receptor. Furthermore, K78 was able to abate the downstream signaling effects initiated by the Fn14 ligand, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), as well as sensitize GBM cells to the cytotoxic effects of TMZ. TWEAK-induced cellular migration was also mitigated with co-treatment of K78 in GBM cells, compared to a vehicle control. It is anticipated that further development of Fn14 antagonists will be of great importance for the advancement of GBM patient treatment and warrant further investigation as primary and combination therapy, especially for the prevention of recurrent disease. Citation Format: Bryan Harder, Chris Sereduk, Harshil Dhruv, Nghia Millard, Anthony Kim, Jeffrey Winkles, Graeme Woodworth, Holly Yin, Nhan L. Tran. Development of an antagonist to the TWEAK-Fn14 ligand-receptor interaction with enhanced efficacy/potency in glioblastoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4910.
Abstract 727: A novel rMVA combination immunotherapy triggers potent innate and adaptive immune responses against established tumors
Authors: Jose Medina-Echeverz, Maria Hinterberger, Marco Testori, Marlene Geiger, Raphael Giessel, Paul Chaplin, Hubertus Hochrein, Henning Lauterbach
Journal: Cancer Research (2018)

Abstract Virus-based vaccines and appropriate costimulation enhance potent antigen-specific T cell immunity against cancer. However, the tumor microenvironment exerts intrinsic and extrinsic mechanisms to evade tumor destruction. In the present study we exploit both innate and adaptive immune responses triggered by a novel recombinant modified vaccinia virus Ankara (rMVA) encoding costimulatory CD40L against solid tumors in combination regimes to overcome tumor-induced resistance to immunotherapy. Therapeutic treatment with rMVA-CD40L resulted in strong antitumor effects in unrelated established tumor models. Tumor infiltration was composed of non-exhausted, antigen-specific CD8+ T cells with proliferative capacity after rMVA-CD40L immunization. Strikingly, this antitumor effect was not entirely dependent on cross-presenting CD8α+ DC -induced CD8+ T cell expansion, as experiments with MVA encoding for T. gondii profilin (TLR11 ligand) and using Batf3-/- tumor bearers depicted. Indeed, rMVA-CD40L-induced tumor control did not depend on cytosolic DNA sensor STING. Interestingly, rMVA-CD40L induced strong NK cell activation and thereby potent Antibody Dependent Cell Cytotoxicity (ADCC) against Tumor-Associated Antigen (TAA) targeting antibodies. Hence, the combination of TAA targeting antibodies and rMVA-CD40L resulted in increased therapeutic antitumor efficacy. We describe a novel and translationally relevant therapeutic synergy between viral vaccination and CD40L costimulation. We connect CD40 ligation to cross-presenting CD8α+ DC -mediated expansion of non-exhausted CD8+ T cells in the tumor microenvironment. Taking advantage from intrinsic MVA-induced NK cell activation and further improved NK cell function by CD40 ligation, we show strengthened antitumor immune responses when both rMVA-CD40L-induced innate and adaptive immune mechanisms are exploited by combining immunotherapeutic regimes. This finding has a direct potential impact in clinical trials where TAA targeting antibodies are currently under evaluation. Citation Format: Jose Medina-Echeverz, Maria Hinterberger, Marco Testori, Marlene Geiger, Raphael Giessel, Paul Chaplin, Hubertus Hochrein, Henning Lauterbach. A novel rMVA combination immunotherapy triggers potent innate and adaptive immune responses against established tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 727.
The Carbohydrate-Insulin Model of Obesity Is Difficult to Reconcile With Current Evidence
Authors: Kevin D. Hall, Stephan J. Guyenet, Rudolph L. Leibel
Journal: JAMA Internal Medicine (2018)

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
Abstract 16552: Hydrogen Sulfide-Mediated Reduction of Enos Tyrosine Phosphorylation:Implications for Cardioprotection
Authors: Sofia-Iris Bibli, Athanasia Chatzianastasiou, Andreas Papapetropoulos
Journal: Circulation (2016)

Introduction: Hydrogen sulfide (H2S) exhibits beneficial effects in the cardiovascular system. Many of its actions have been shown to depend on endogenously produced nitric oxide (NO) and extensive...
Abstract 15886: Depressive Symptoms, Anxiety, and Perceived Social Support Do Not Predict Weight Change in Overweight and Obese Rural Adults With Low Education Attainment
Authors: Demetrius Abshire, Terry Lennie, Celestina Barbosa-Leiker, Ekaterina Burduli, Debra Moser
Journal: Circulation (2016)

Introduction:  Barriers to achieving weight loss in overweight and obese rural dwelling adults with low education attainment include limited resources and the effects of poor psychosocial health on obesity risk. Improving psychosocial health may be one strategy to promote weight loss in this population. However, it is currently unknown whether psychosocial factors predict body weight change in rural residents with excess body weight and low education attainment.   Purpose:  To determine if psychosocial factors of depressive symptoms, anxiety, and perceived social support predict weight change in overweight and obese rural adults with a high school education or less.   Methods:  This secondary analysis includes rural adults in Kentucky having a body mass index ≥25kg/m 2  (n = 172, age = 56 ± 13; 71% female; 99% Caucasian) who participated in a comprehensive lifestyle intervention to reduce cardiovascular disease risk. Participants completed baseline assessments of depressive symptoms, anxiety, and social support using the 9-item Patient Health Questionnaire, Brief Symptom Inventory Anxiety subscale, and the Perceived Social Support scale, respectively. Body weight was assessed at baseline and approximately 4-6 months using professional-grade digital scales. Multivariable linear and binary logistic regressions were used to determine if baseline psychosocial factors predicted weight change controlling for age, sex, income, and baseline weight.   Results:  Average percent weight change for the sample was -0.2 ± 3.5%. Average percent weight change was -2.8 ± 2.2% among those who maintained/lost weight and 2.6 ± 2.3% among those who gained weight. Psychosocial factors did not predict body weight change in any regression model. Older age predicted weight loss in all models.   Conclusions:  These findings suggest that baseline depressive symptoms, anxiety, and poor social support do not interfere with weight loss in overweight and obese rural residents with low education attainment.
Terlipressin versus norepinephrine as infusion in patients with septic shock: a multicentre, randomised, double-blinded trial
Authors: Zi-Meng Liu, Juan Chen, Qiuye Kou, Qinhan Lin, Xiaobo Huang, Zhanhong Tang, Yan Kang, Ke Li, Lixin Zhou, Qing Song, Tongwen Sun, Ling Zhao, Xue Wang, Xiandi He, Chunting Wang, Benquan Wu, Jiandong Lin, Shiying Yuan, Qin Gu, Kejian Qian, Xianqing Shi, Yongwen Feng, Aihua Lin, Xiaoshun He, Xiang-Dong Guan
Journal: Intensive Care Medicine (2018)
Abortion-Related Adverse Events by Facility Type
Authors: Carolyn L. Westhoff, Anne R. Davis
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
포스터발표 : 컨벤션홀 특설 발표장 ; 유전자 1형 만성 C형간염에서 리바비린 용량에 따른 페그인터페론 알파-2a와 리바비린 병합요법 치료 결과
Authors: 윤기태, 김도영, 최종원, 박준용, 안상훈, 전재윤, 한광협
Journal: Clinical and Molecular Hepatology (2008)
Assessing the cost-effectiveness of hepatitis C screening strategies in France
Authors: Sylvie Deuffic-Burban, Alexandre Huneau, Adeline Verleene, Cécile Brouard, Josiane Pillonel, Yann Le Strat, Sabrina Cossais, Françoise Roudot-Thoraval, Valérie Canva, Philippe Mathurin, Daniel Dhumeaux, Yazdan Yazdanpanah
Journal: Journal of Hepatology (2018)
Expression of Long Noncoding RNA <i>YIYA</i> Promotes Glycolysis in Breast Cancer
Authors: Zhen Xing, Yanyan Zhang, Ke Liang, Liang Yan, Yu Xiang, Chunlai Li, Qingsong Hu, Feng Jin, Vasanta Putluri, Nagireddy Putluri, Cristian Coarfa, Arun Sreekumar, Peter K. Park, Tina K. Nguyen, Shouyu Wang, Jianwei Zhou, Yan Zhou, Jeffrey R. Marks, David H. Hawke, Mien-Chie Hung, Liuqing Yang, Leng Han, Haoqiang Ying, Chunru Lin
Journal: Cancer Research (2018)

Abstract Long noncoding RNA (lncRNA) is yet to be linked to cancer metabolism. Here, we report that upregulation of the lncRNA LINC00538 (YIYA) promotes glycolysis, cell proliferation, and tumor growth in breast cancer. YIYA is associated with the cytosolic cyclin-dependent kinase CDK6 and regulated CDK6-dependent phosphorylation of the fructose bisphosphatase PFK2 (PFKFB3) in a cell-cycle–independent manner. In breast cancer cells, these events promoted catalysis of glucose 6-phosphate to fructose-2,6-bisphosphate/fructose-1,6-bisphosphate. CRISPR/Cas9-mediated deletion of YIYA or CDK6 silencing impaired glycolysis and tumor growth in vivo. In clinical specimens of breast cancer, YIYA was expressed in approximately 40% of cases where it correlated with CDK6 expression and unfavorable survival outcomes. Our results define a functional role for lncRNA in metabolic reprogramming in cancer, with potential clinical implications for its therapeutic targeting. Significance: These findings offer a first glimpse into how a long-coding RNA influences cancer metabolism to drive tumor growth. Cancer Res; 78(16); 4524–32. ©2018 AACR.
Abstract 2051: Perfusable 3D angiogenesis in a high-throughput microfluidic culture platform
Authors: K M. Bircsak, V van Duinen, S J. Trietsch, A J. van Zonneveld, T Hankemeier, A Saleh, P Vulto
Journal: Cancer Research (2018)

Abstract The transition from 2D to 3D cell culture is a first step towards more physiologically relevant in vitro cancer models. To adequately capture the complex tissue architectures observed in vivo, 3D microfluidic techniques incorporate and achieve long-term gradient stability, continuous perfusion and patterning of cancer cell layers as stratified co-cultures. We used a standardized high-throughput (n=40) microfluidic 3D tissue culture platform called the OrganoPlate® to generate precisely controlled gradients, without pumps, ideal for growing blood vessels and inducing controlled 3D angiogenic sprouting. The blood vessel is grown against an extracellular matrix (ECM) gel with cancer cells and is subsequently exposed to pro- and antiangiogenic compounds to direct sprouting towards 3D cancer cell clusters. Utilizing high-content confocal time-lapse imaging and analysis, angiogenic potential was measured in various cancer models. The exposed vasculature shows many of the important hallmarks of cancer angiogenesis found in vivo, including tip cells induction and migration and stalk cells formation. Importantly, the stalk cells develop a perfusable lumen that is connected to the parental vessel as demonstrated with perfusion of high-molecular-weight (150KD) fitc-dextran through microvascular structures. This model will be used as an in vitro cancer screening platform to unravel the important drivers in angiogenesis and vasculogenesis and the mechanism of action of antiangiogenic compounds. By combining this culture platform with mural cells, cell-cell interactions can be studied. In parallel, we will combine this 3D cancer angiogenesis platform with our current Tumor-on-a-Chip models to create tissue models with integrated vasculature. Citation Format: K M. Bircsak, V van Duinen, S J. Trietsch, A J. van Zonneveld, T Hankemeier, A Saleh, P Vulto. Perfusable 3D angiogenesis in a high-throughput microfluidic culture platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2051.
Overexpression of Sirt1 in mesenchymal stem cells protects against bone loss in mice by FOXO3a deacetylation and oxidative stress inhibition
Authors: Wen Sun, Wanxin Qiao, Bin Zhou, Zixuan Hu, Quanquan Yan, Jun Wu, Rong Wang, Qian Zhang, Dengshun Miao
Journal: Metabolism (2018)
Association of Heparin-Induced Thrombocytopenia With Bacterial Infection in Trauma Patients
Authors: Areg Grigorian, Sebastian Schubl, Cristobal Barrios, Victor Joe, Matthew Dolich, Michael Lekawa, Jeffry Nahmias
Journal: JAMA Surgery (2018)

Association of Heparin-Induced Thrombocytopenia With Bacterial Infection in Trauma PatientsHeparin-induced thrombocytopenia (HIT) is a rare complication that has been reported to occur in 0.36% of trauma patients and is caused by antibody formation to complexes between heparin and platelet-factor 4 (PF4), leading to platelet activation and subsequent thrombosis. 1,2An earlier report demonstrated that PF4 can bind to bacteria, inducing an autoimmune response similar to the major antigen in HIT. 3 We hypothesized that trauma patients with HIT have a higher incidence of bacterial infection during their hospitalization compared with patients without HIT.In addition, we provide a descriptive analysis of HIT in trauma patients.Methods | This study was approved by the institutional review board of the University of California, Irvine.The need for informed consent was waived by the institutional review board of the University of California, Irvine.We queried the National Trauma Data Bank from 2008 through 2015 to identify patients with HIT using the International Classification of Diseases, Ninth Revision (289.84).Because of the observed imbalance in the sample size, we used a 1:2 ratio propensity score model to match patients with HIT to those without HIT using demographic and injury profile parameters (Table ).Our analysis included only cases that were within 0.001 of the estimated logit. 4 If a patient with HIT did not have a close match, they were excluded.A Student t test was used to compare continuous variables, and the χ 2 test was used to compare categorical variables for bivariate analysis.The primary outcomes were incidence of bacterial infection, urinary tract infection, and pneumonia.Bacterial infection was defined as gastrointestinal tract bacterial infection or bacteremia.Analysis of outcomes was performed using a logistic regression model and reported with odds ratios (ORs) and 95% CIs; the statistical significance level was set at a 2-sided P < .05.
Patient safety is compromised by understaffing, physicians warn
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Unfilled vacancies and rota gaps are increasingly threatening patient safety in UK hospitals, consultant physicians have warned.

Of the 8579 consultants and trainees (response rate: 37% of consultants and 51% of trainees) who replied to the Royal College of Physicians’ (RCP) annual census,1 over half (53%) of consultants and two thirds (68%) of trainees reported frequent gaps in trainee rotas, while one in five (20%) said that rota gaps were causing significant problems for patient safety.

Three quarters of respondents (75%) described regularly having to find solutions to minimise the impact …
A Multicentre Study of 5-year Outcomes Following Focal Therapy in Treating Clinically Significant Nonmetastatic Prostate Cancer
Authors: Stephanie Guillaumier, Max Peters, Manit Arya, Naveed Afzal, Susan Charman, Tim Dudderidge, Feargus Hosking-Jervis, Richard G. Hindley, Henry Lewi, Neil McCartan, Caroline M. Moore, Raj Nigam, Chris Ogden, Raj Persad, Karishma Shah, Jan van der Meulen, Jaspal Virdi, Mathias Winkler, Mark Emberton, Hashim U. Ahmed
Journal: European Urology (2018)

Clinically significant nonmetastatic prostate cancer (PCa) is currently treated using whole-gland therapy. This approach is effective but can have urinary, sexual, and rectal side effects. To report on 5-yr PCa control following focal high-intensity focused ultrasound (HIFU) therapy to treat individual areas of cancer within the prostate. This was a prospective study of 625 consecutive patients with nonmetastatic clinically significant PCa undergoing focal HIFU therapy (Sonablate) in secondary care centres between January 1, 2006 and December 31, 2015. A minimum of 6-mo follow-up was available for599 patients. Intermediate- or high-risk PCa was found in 505 patients (84%). Disease was localised using multiparametric magnetic resonance imaging (mpMRI) combined with targeted and systematic biopsies, or transperineal mapping biopsies. Areas of significant disease were treated. Follow-up included prostate-specific antigen (PSA) measurement, mpMRI, and biopsies. The primary endpoint, failure-free survival (FFS), was defined as freedom from radical or systemic therapy, metastases, and cancer-specific mortality. The median follow-up was 56 mo (interquartile range [IQR] 35–70). The median age was 65 yr (IQR 61–71) and median preoperative PSA was 7.2 ng/ml (IQR 5.2–10.0). FFS was 99% (95% confidence interval [CI] 98–100%) at 1 yr, 92% (95% CI 90–95%) at 3 yr, and 88% (95% 85–91%) at 5 yr. For the whole patient cohort, metastasis-free, cancer-specific, and overall survival at 5 yr was 98% (95% CI 97–99%), 100%, and 99% (95% CI 97–100%), respectively. Among patients who returned validated questionnaires, 241/247 (98%) achieved complete pad-free urinary continence and none required more than 1 pad/d. Limitations include the lack of long-term follow-up. Focal therapy for select patients with clinically significant nonmetastatic prostate cancer is effective in the medium term and has a low probability of side effects. In this multicentre study of 625 patients undergoing focal therapy using high-intensity focused ultrasound (HIFU), failure-free survival, metastasis-free survival, cancer-specific survival, and overall survival were 88%, 98%, 100%, and 99%, respectively. Urinary incontinence (any pad use) was 2%. Focal HIFU therapy for patients with clinically significant prostate cancer that has not spread has a low probability of side effects and is effective at 5 yr.
Abstract 3659: Detection and validation of cancer immunotherapy biomarkers in blood
Authors: Feng Xie, Jianjun Yu, Shidong Jia
Journal: Cancer Research (2018)

Abstract Immunotherapy response varies widely, making it difficult for physicians to know whether immunotherapy will be effective for a given patient. Indeed, ~80% or more patients with cancer fail to respond to checkpoint inhibitor immunotherapy. In addition to PD-L1 IHC staining, recent studies reported that patients with deleterious mutations in mismatch repair (MMR) genes, high tumor mutation burden (TMB) or microsatellite instability (MSI) are also associated with better clinical response. As tissue biopsy represents a practical challenge due to its insufficient quantity or lack of access, non-invasive molecular has emerged as an efficient complementary test and attracted increasing attention in clinical development of cancer immunotherapy. With Predicine's gene RARDAR technology, we developed a blood-based PrediSeq NGS panel to capture genomic alterations in 180 cancer genes including tumor mutation burden (TMB) and microsatellite instability (MSI) and a Predi-CI (Cancer Immunotherapy) panel to measure dynamic expression change of 212 genes related to immune cells or immune responses. Technical validation was performed to evaluate assay sensitivity, specificity and accuracy using reference samples with known genetic profiling. The panels have been further tested using tissue biopsy and plasma samples from cancer patients. The development of PrediSeq Panel and Predi-CI RNA gene expression tests offer a comprehensive solution to stratify and monitor cancer patients who may benefit from cancer immunotherapy. Citation Format: Feng Xie, Jianjun Yu, Shidong Jia. Detection and validation of cancer immunotherapy biomarkers in blood [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3659.
The Long Noncoding RNA CAREL Controls Cardiac Regeneration
Authors: Benzhi Cai, Wenya Ma, Fengzhi Ding, Lai Zhang, Qi Huang, Xiuxiu Wang, Bingjie Hua, Juan Xu, Jiamin Li, Chongwei Bi, Shuyuan Guo, Fan Yang, Zhenbo Han, Yuan Li, Gege Yan, Ying Yu, Zhengyi Bao, Meixi Yu, Faqian Li, Ye Tian, Zhenwei Pan, Baofeng Yang
Journal: Journal of the American College of Cardiology (2018)