tbuckley/cabot-search huggingface dataset:
Abstract IA22: Non-coding RNA from discovery to therapy
Authors: Phillip Sharp
Journal: Cancer Research (2017)

Abstract The central roles of non-coding RNAs in both normal and malignant cells offer new approaches to detection and treatment of cancer. Changes in microRNA levels have illuminated epigenetic processes that appear to maintain an embryonic malignant state in some adult cancer cells. This epigenetic network involves a small set of oncofetal genes, also expressed in early embryos, conferring malignant properties. This same set is also part of a larger network that integrates nutrient level data according to the size of the vertebrates where it is found. Further, the existence of the biosynthetic pathway for microRNAs in all adult cells allows introduction of small interfering RNAs to silence genes. This is now highly effective for silencing genes in the liver of patients and may become a general new therapeutic modality. Finally, many long non-coding RNAs are synthetized from promoters and enhancers by divergent transcription. The importance of these non-coding RNAs in regulation of nearby genes is being investigated but there is no question that enhancers stimulate promoters through processes involving the action of RNA polymerase. It is critical to understand the mechanism of enhancer action because many new drug agents preferentially target super-enhancer associated genes. This type of enhancer is frequently associated with oncogenes in cancer cells. Citation Format: Phillip Sharp. Non-coding RNA from discovery to therapy. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr IA22.
Abstract 5017: Visualization of the mechanisms of metastasis within a biomimetic engineered tumor microenvironment encompassing a perfusable cylindrical 3D microvessel
Authors: Andrew D. Wong, Vanesa Silvestri, Anderw J. Ewald, Peter C. Searson
Journal: Cancer Research (2017)

Abstract Metastasis is responsible for the majority of cancer related deaths; however, many of the biological and physical details surrounding the critical steps (e.g. invasion and intravasation) are largely unknown, in part due to the difficulty in recapitulating and visualizing these dynamic processes. To elucidate these mechanisms, we have developed an in vitro model of invasion and intravasation that comprises tumor cells embedded within an extracellular matrix (ECM) surrounding an engineered microvessel. The microvessel is cylindrical, 150 µm in diameter, and lined with endothelial cells forming a functional barrier that is maintained under constant perfusion at a shear stress of 2-8 dyne cm-2. Using this biomimetic tumor-microvessel platform, we have previously visualized invasion and intravasation of single MDA-MB-231 breast cancer cells into the microvessel and escape into flow. Here, we present mechanistic details of intravasation from both single tumor cells (MDA-MB-231) and mouse mammary tumor organoids (MMTV-PyMT). For single cells, we observe a mitosis-mediated mechanism of intravasation where tumor cell entry into flow is prefaced by cell division at the ECM-vessel interface. For tumor organoids, we see vascular deformation and destabilization from growing tumors that impinge upon proximal vessels, and that bulk intravasation is mediated by shear stress and tumor cell adhesion. As we characterize the various ways in which tumor cells interact with the vessel endothelium and intravasate, we can explore strategies involving the tumor vasculature and clinically relevant drugs to inhibit critical steps in the metastatic cascade. Citation Format: Andrew D. Wong, Vanesa Silvestri, Anderw J. Ewald, Peter C. Searson. Visualization of the mechanisms of metastasis within a biomimetic engineered tumor microenvironment encompassing a perfusable cylindrical 3D microvessel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5017. doi:10.1158/1538-7445.AM2017-5017
Implicit Bias in Academic Medicine
Authors: Molly Cooke
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
Abstract P6-09-38: Interaction between body mass index and hormone receptor status as a prognostic factor in node-positive breast cancer
Authors: IY Chung, JW Lee, JS Lee, YR Park, Y Lee, SB Lee, HJ Kim, BS Ko, BH Son, SH Ahn
Journal: Cancer Research (2017)

Abstract Purpose: The aim of this study was to investigate the interaction between BMI at breast cancer diagnosis and the various factors including hormone-receptor, menopausal and nodal status, and to find a specific subgroup where BMI has an effect on breast cancer prognosis. Methods: We retrospectively analyzed the data of 8,763 non-metastatic invasive breast cancer patients from the Asan Medical Center's research database. Overall survival (OS) and breast cancer-specific survival (BCSS) among BMI groups were compared using the Kaplan-Meier method and Cox proportional hazard model with interaction term. Results: Only in node-positive breast cancer, there was a significant interaction between obesity (BMI ≥ 30.0 kg/m2) at diagnosis and positive hormone receptor which showed worse overall survival (OS) and breast cancer specific survival (BCSS) than normal weight patients (adjusted hazard ratio [HR] = 1.65, 95% confidence interval [CI] = 1.01 to 2.69 and HR = 1.90, 95% CI = 1.15 to 3.15, respectively). Underweight (BMI&amp;lt;18.50 kg/m2) which interacted with negative hormone receptor status in node-positive breast cancer was associated with decreased OS (HR = 2.01, 95% CI = 1.02 to 3.98) and BCSS (HR = 2.15, 95% CI = 1.08 to 4.26). There was no significant interaction between BMI and hormone receptor status in node-negative setting and BMI did not interact with menopausal status in any population. Conclusions: BMI interacts with hormone receptor status in node positive setting, thereby playing a role in the breast cancer prognosis. Citation Format: Chung IY, Lee JW, Lee JS, Park YR, Lee Y, Lee SB, Kim HJ, Ko BS, Son BH, Ahn SH. Interaction between body mass index and hormone receptor status as a prognostic factor in node-positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-38.
Haploidentical Allogeneic Hematopoietic Cell Transplantation as Salvage Therapy for Engraftment Failure After Unrelated and Autologous Cell Transplantation.
Authors: Yamin Tan, Huarui Fu, Yi Luo, Xiujin Ye, Li Li, Yanlong Zheng, Jimin Shi, Jie Sun, Liqun Zhou, Haowen Xiao, Yongxian Hu, He Huang
Journal: Blood (2010)
Obatoclax and LY3009120 Efficiently Overcome Vemurafenib Resistance in Differentiated Thyroid Cancer
Authors: Wei-Jun Wei, Zhen-Kui Sun, Chen-Tian Shen, Hong-Jun Song, Xin-Yun Zhang, Zhong-Ling Qiu, Quan-Yong Luo
Journal: Theranostics (2017)

Although the prognosis of differentiated thyroid cancer (DTC) is relatively good, 30-40% of patients with distant metastases develop resistance to radioactive iodine therapy due to tumor dedifferentiation. For DTC patients harboring BRAFV600E mutation, Vemurafenib, a BRAF kinase inhibitor, has dramatically changed the therapeutic landscape, but side effects and drug resistance often lead to termination of the single agent treatment. In the present study, we showed that either LY3009120 or Obatoclax (GX15-070) efficiently inhibited cell cycle progression and induced massive death of DTC cells. We established that BRAF/CRAF dimerization was an underlying mechanism for Vemurafenib resistance. LY3009120, the newly discovered pan-RAF inhibitor, successfully overcame Vemurafenib resistance and suppressed the growth of DTC cells in vitro and in vivo. We also observed that expression of anti-apoptotic Bcl-2 increased substantially following BRAF inhibitor treatment in Vemurafenib-resistant K1 cells, and both Obatoclax and LY3009120 efficiently induced apoptosis of these resistant cells. Specifically, Obatoclax exerted its anti-cancer activity by inducing loss of mitochondrial membrane potential (ΔΨm), dysfunction of mitochondrial respiration, reduction of cellular glycolysis, autophagy, neutralization of lysosomes, and caspase-related apoptosis. Furthermore, the cancer killing effects of LY3009120 and Obatoclax extended to two more Vemurafenib-resistant DTC cell lines, KTC-1 and BCPAP. Taken together, our results highlighted the potential value of LY3009120 for both Vemurafenib-sensitive and -resistant DTC and provided evidence for the combination therapy using Vemurafenib and Obatoclax for radioiodine-refractory DTC.
Tropism and innate host responses of influenza A/H5N6 virus: an analysis of<i>ex vivo</i>and<i>in vitro</i>cultures of the human respiratory tract
Authors: Kenrie P. Y. Hui, Louisa L. Y. Chan, Denise I. T. Kuok, Chris K. P. Mok, Zi-feng Yang, Run-feng Li, Geraldine S. M. Luk, Elaine F. Lee, Jimmy C. C. Lai, Hui-ling Yen, Huachen Zhu, Yi Guan, John M. Nicholls, J. S. Malik Peiris, Michael C. W. Chan
Journal: European Respiratory Journal (2017)

Since their first isolation in 2013, influenza A/H5N6 viruses have spread amongst poultry across multiple provinces in China and to Laos, Vietnam and Myanmar. So far, there have been 14 human H5N6 infections with 10 fatalities.We investigated the tropism, replication competence and cytokine induction of one human and two avian H5N6 isolates in ex vivo and in vitro cultures derived from the human respiratory tract. Virus tropism and replication were studied in ex vivo cultures of human nasopharynx, bronchus and lung. Induction of cytokines and chemokines was measured in vitro in virus-infected primary human alveolar epithelial cells.Human H5N6 virus replicated more efficiently than highly pathogenic avian influenza (HPAI) H5N1 virus and as efficiently as H1N1pdm in ex vivo human bronchus and lung and was also able to replicate in ex vivo cultures of human nasopharynx. Avian H5N6 viruses replicated less efficiently than H1N1pdm in human bronchial tissues and to similar titres as HPAI H5N1 in the lung. While the human H5N6 virus had affinity for avian-like receptors, the two avian isolates had binding affinity for both avian- and human-like receptors. All three H5N6 viruses were less potent inducers of pro-inflammatory cytokines compared with H5N1 virus.Human H5N6 virus appears better adapted to infect the human airways than H5N1 virus and may pose a significant public health threat.
Circulating gluten-specific FOXP3 + CD39 + regulatory T cells have impaired suppressive function in patients with celiac disease
Authors: Laura Cook, C. Mee Ling Munier, Nabila Seddiki, David van Bockel, Noé Ontiveros, Melinda Y. Hardy, Jana K. Gillies, Megan K. Levings, Hugh H. Reid, Jan Petersen, Jamie Rossjohn, Robert P. Anderson, John J. Zaunders, Jason A. Tye-Din, Anthony D. Kelleher
Journal: Journal of Allergy and Clinical Immunology (2017)

Celiac disease is a chronic immune-mediated inflammatory disorder of the gut triggered by dietary gluten. Although the effector T-cell response in patients with celiac disease has been well characterized, the role of regulatory T (Treg) cells in the loss of tolerance to gluten remains poorly understood.We sought to define whether patients with celiac disease have a dysfunction or lack of gluten-specific forkhead box protein 3 (FOXP3)+ Treg cells.Treated patients with celiac disease underwent oral wheat challenge to stimulate recirculation of gluten-specific T cells. Peripheral blood was collected before and after challenge. To comprehensively measure the gluten-specific CD4+ T-cell response, we paired traditional IFN-γ ELISpot with an assay to detect antigen-specific CD4+ T cells that does not rely on tetramers, antigen-stimulated cytokine production, or proliferation but rather on antigen-induced coexpression of CD25 and OX40 (CD134).Numbers of circulating gluten-specific Treg cells and effector T cells both increased significantly after oral wheat challenge, peaking at day 6. Surprisingly, we found that approximately 80% of the ex vivo circulating gluten-specific CD4+ T cells were FOXP3+CD39+ Treg cells, which reside within the pool of memory CD4+CD25+CD127lowCD45RO+ Treg cells. Although we observed normal suppressive function in peripheral polyclonal Treg cells from patients with celiac disease, after a short in vitro expansion, the gluten-specific FOXP3+CD39+ Treg cells exhibited significantly reduced suppressive function compared with polyclonal Treg cells.This study provides the first estimation of FOXP3+CD39+ Treg cell frequency within circulating gluten-specific CD4+ T cells after oral gluten challenge of patients with celiac disease. FOXP3+CD39+ Treg cells comprised a major proportion of all circulating gluten-specific CD4+ T cells but had impaired suppressive function, indicating that Treg cell dysfunction might be a key contributor to disease pathogenesis.
Pacing as a Treatment for Reflex-Mediated (Vasovagal, Situational, or Carotid Sinus Hypersensitivity) Syncope: A Systematic Review for the 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society
Authors: Paul D. Varosy, Lin Y. Chen, Amy L. Miller, Peter A. Noseworthy, David J. Slotwiner, Venkatesh Thiruganasambandamoorthy
Journal: Circulation (2017)

To determine, using systematic review of the biomedical literature, whether pacing reduces risk of recurrent syncope and relevant clinical outcomes among adult patients with reflex-mediated syncope.MEDLINE (through PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (through October 7, 2015) were searched for randomized trials and observational studies examining pacing and syncope, and the bibliographies of known systematic reviews were also examined. Studies were rejected for poor-quality study methods and for the lack of the population, intervention, comparator, or outcome(s) of interest.Of 3188 citations reviewed, 10 studies met the inclusion criteria for systematic review, including a total of 676 patients. These included 9 randomized trials and 1 observational study. Of the 10 studies, 4 addressed patients with carotid sinus hypersensitivity, and the remaining 6 addressed vasovagal syncope. Among the 6 open-label (unblinded) studies, we found that pacing was associated with a 70% reduction in recurrent syncope (relative risk [RR]: 0.30; 95% confidence interval [CI]: 0.15-0.60). When the 2 analyzable studies with double-blinded methodology were considered separately, there was no clear benefit (RR: 0.73; 95% CI: 0.25-2.1), but confidence intervals were wide. The strongest evidence was from the randomized, double-blinded ISSUE-3 (Third International Study on Syncope of Uncertain Etiology) trial, which demonstrated a benefit of pacing among patients with recurrent syncope and asystole documented by implantable loop recorder.There are limited data with substantive evidence of outcome ascertainment bias, and only 2 studies with a double-blinded study design have been conducted. The evidence does not support the use of pacing for reflex-mediated syncope beyond patients with recurrent vasovagal syncope and asystole documented by implantable loop recorder.
Pure Red Cell Aplasia after ABO-Mismatched Allogeneic Stem Cell Transplantation Treated with Therapeutic Plasma Exchange and Rituximab
Authors: Rebecca Karp, Jon E. Arnason, Jacalyn Rosenblatt, David Avigan, Robin Joyce, Myrna Rita Nahas, Erik Uhlmann, Ayad Hamdan
Journal: Blood (2015)
Regional Cerebral Blood Flow SPECT and MRI in Logopenic Variant Primary Progressive Aphasia
Authors: Aristeidis H. Katsanos, Spyridon Tsiouris, Chrissa Sioka, Anastasia Zikou, Andreas Fotopoulos
Journal: Clinical Nuclear Medicine (2017)

We report a 61-year-old woman who presented because of gradually progressive speech disorders. MRI scan revealed left temporal lobe atrophy with ex vacuo dilatation of the temporal horn and atrophy of the left inferior frontal gyrus and the left inferior parietal lobe. These findings in brain perfusion SPECT corresponded to a generalized hypoperfusion of the left hemisphere, particularly prominent on the rear parietal cortex and the temporal lobe. After taking into consideration the clinical presentation and imaging findings on MRI and SPECT, the diagnosis of the logopenic variant of primary progressive aphasia was finally reached.
P53 and p21waf1— Expression by Immunohistochemistry in Diffuse Large B-Cell Lymphoma Has a Strong and Independent Impact on Survival of Patients with Germinal Center Phenotype.
Authors: Carlo Visco, Fabio Canal, Annalisa Andreoli, Claudia Parolini, Maurizio Lestani, Achille Ambrosetti, Mauro Krampera, Giovanni Pizzolo, Marco Chilosi
Journal: Blood (2005)
Highly potent antimicrobial polyionenes with rapid killing kinetics, skin biocompatibility and in vivo bactericidal activity
Authors: Shaoqiong Liu, Robert J. Ono, Hong Wu, Jye Yng Teo, Zhen Chang Liang, Kaijin Xu, Musan Zhang, Guansheng Zhong, Jeremy P.K. Tan, Michelle Ng, Chuan Yang, Julian Chan, Zhongkang Ji, Chang Bao, Kiran Kumar, Shujun Gao, Ashlynn Lee, Mareva Fevre, Huihui Dong, Jackie Y. Ying, Lanjuan Li, Weimin Fan, James L. Hedrick, Yi Yan Yang
Journal: Biomaterials (2017)
Liver enzymes elevation due to concurrent dexamethasone and lapatinib: Clinical and in vitro evidence.
Authors: Yi Ling Teo, Manit Saetaew, Suthan Chanthawong, Yoon Sim Yap, Eric Chun Yong Chan, Han Kiat Ho, Alexandre Chan
Journal: Journal of Clinical Oncology (2012)

e13023 Background: Concomitant usage of lapatinib (L) and dexamethasone (D), which are cytochrome P450 (CYP) 3A4 substrate and inducer respectively, may increase the formation of potentially hepatotoxic reactive L metabolites. This study aims to evaluate the effect of D on the occurrence of liver enzyme elevation and to ascertain its role using a parallel in vitro experiment. Methods: Clinical effects of D on L-induced liver enzyme elevation were evaluated in a nested case-control study. Liver enzyme elevation is defined as the first clinically significant change (from baseline) of either total bilirubin (TB), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) by at least 1 grade, based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.02. In the in vitro study, metabolically-competent transforming growth factor α mouse hepatocytes (TAMH) cells were treated with L and viabilities were compared in the presence or absence of D. Results: Among 97 patients, liver enzyme elevation episodes (87.5% vs. 60.3%, p=0.01) and ALT elevation (41.7% vs. 19.2%, p=0.03) occurred more frequently among patients receiving concomitant L+D comparing to L only. After adjusting for confounders (age, liver and brain metastasis, baseline liver function test (TB, AST, ALT, alkaline phosphatase), underlying liver disease, concurrent use of hepatotoxic medications), patients receiving concomitant L+D were 3.48 times (95% CI 1.24-9.80, p=0.02) and 4.57 times (95% CI 1.23-16.88, p=0.02) more likely to develop a change in ALT and among all liver enzymes respectively. Parallel to our clinical findings, treatment of TAMH cells with L reduced viability in a concentration-dependent manner. The introduction of D further reduced the viability. At 5 µM of L, the introduction of 10 µM and 20 µM of D resulted in a 19% and 59% decrease in viability respectively. Conclusions: The concomitant usage of L+D was associated with an increased occurrence of liver enzyme elevation. The in vitro findings have provided commensurating evidence on the role of D that increases the formation of L-derived hepatotoxic metabolites.
Allogeneic Stem Cell Transplantation for Refractory Acute Myeloid Leukemia in Pediatric Patients: The UK Experience
Authors: Patricia M O'Hare, Giovanna Lucchini, Michelle Cummins, Paul Veys, Mike Potter, Sarah Lawson, Ajay J. Vora, Robert Wynn, Andrew Peniket, Keiren Kirkland, Rachel Pearce, Julia Perry, Persis Jal Amrolia
Journal: Blood (2015)
Abstract P3-14-01: International validation of the EORTC patient-reported outcome measure (PROM) in breast reconstruction (BRR): The EORTC QLQ-BRECON23 evaluating the psychometric properties and clinical effectiveness
Authors: ZE Winters, M Afzal, C Rutherford, B Holzner, G Rumpold, RA da Costa Vieira, S Hartnup, K Filcroft, V Bjelic-Radisic, A Oberguggenburger, M Panouilleres, MR Mani, G Catanuto, M Douek, J Kokan, MT King
Journal: Cancer Research (2017)

Abstract This abstract was withdrawn by the authors.
Immunochemotherapy with Low-Dose Subcutaneous Alemtuzumab (A) Plus Oral Fludarabine and Cyclophosphamide (FC) Is Safe and Induces More and Deeper Complete Remissions in Untreated Patients with High-Risk Chronic Lymphocytic Leukemia (CLL) Than Chemotherapy with FC Alone. An Early Analysis of the Randomized Phase-III HOVON68 CLL Trial
Authors: Christian H Geisler, Mars MB van 't Veer, Wim van Putten, Jesper Jurlander, Jan Walewski, Geir Tjonnfjord, Maija Itälä-Remes, Eva Kimby, Tomas Kozak, Aaron Polliack, Shulamiet Wittebol, Fokje Spoelstra, Marinus H.J. Van Oers
Journal: Blood (2011)