tbuckley/cabot-search huggingface dataset:
NFAT2 to regulate anergy induction in CLL through Lck.
Authors: Melanie Maerklin, Jonas S. Heitmann, Felicia Truckenmueller, Manuela Ganser, Hans-Georg Kopp, Stefan Wirths, Lothar Kanz, Anjana Rao, Martin Rudolf Mueller
Journal: Journal of Clinical Oncology (2015)

7019 Background: NFAT2 is a highly phosphorylated transcription factor which regulates developmental and activation programs in diverse cell types. CLL constitutes a heterogeneous disease with some patients exhibiting an indolent course for many years and others progressing rapidly and requiring early treatment. A defined subgroup of patients shows enhanced responsiveness to stimulation of the B cell receptor (BCR) complex and more aggressive disease. In contrast, another subset of CLL patients with more indolent course is characterized by an anergic B cell phenotype referring to B cell unresponsiveness to IgM ligation. Here, we analyzed the role of NFAT2 in the pathogenesis of CLL and in anergy induction in CLL cells. Methods: We crossed conditional CD19-Cre NFAT2 knock out mice with the Eµ-TCL1 transgenic mice, which develop a human-like CLL. We analyzed TCL1+NFAT2 ko mice and TCL1 mice without a NFAT2 deletion served as controls. We performed a comparative gene expression analysis, Ca2+mobilization assays and Western Blots for multiple downstream signaling molecules on both CLL cells. Results: Mice with NFAT2 ko exhibited a significantly more aggressive disease course with accelerated accumulation of CLL cells and a dramatically reduced life expectancy. We detected a substantially altered expression profile of genes associated with B cell anergy in the TCL1+NFAT2 ko mice. The vast majority of these genes was expressed significantly less in the absence of NFAT2 with Lck, Pacsin1 and Cbl representing the biggest hits. While anergic CLL cells from TCL1 mice exhibited an unresponsive phenotype with respect to Ca2+ flux upon IgM ligation, TCL1+NFAT2 ko mice showed a normal capacity to mobilize Ca2+and a normal activation of the downstream signaling. IgM stimulation did not activate normal phosphotyrosine induction in TCL1 mice. However TCL1 mice showed a strong activation of the anergy regulator Lck. Conclusions: Genetic loss NFAT2 leads aggressive disease and controls the expression of several important anergy-associated genes. We identified Lck as a critical target of NFAT2 in this context. Taken together, our data demonstrate that the NFAT2-Lck axis plays an essential role in the pathogenesis of CLL and implicate it as a potential target in its treatment.
Primary Resistance to Immune Checkpoint Inhibitors in Metastatic Colorectal Cancer—Beyond the Misdiagnosis—In Reply
Authors: Romain Cohen, Alex Duval, Magali Svrcek
Journal: JAMA Oncology (2019)

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 Oncology 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 Oncology journal
THU-488-Acquisition of stem-like features in cholangiocarcinoma is associated with an oxidative metabolism
Authors: Chiara Raggi, Nadia Navari, Maria Letizia Taddei, Elena Sacco, Margherita Correnti, Jesper B Andersen, Benedetta Piombanti, Matteo Ramazzotti, Ivan Orlandi, Paola Chiarugi, Fabio Marra
Journal: Journal of Hepatology (2019)
Alveolar Macrophage Transcriptional Programs Are Associated with Outcomes in Acute Respiratory Distress Syndrome
Authors: Eric D. Morrell, Pavan K. Bhatraju, Carmen R. Mikacenic, Frank Radella, Anne M. Manicone, Renee D. Stapleton, Mark M. Wurfel, Sina A. Gharib
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Serial measurements of alveolar macrophage (AM) transcriptional changes in patients with acute respiratory distress syndrome (ARDS) could identify cell-specific biological programs that are associated with clinical outcomes.
N-acetylcysteine (NAC) ameliorates radiocontrast-induced renal insufficiency in coronary-procedure patients by decreasing urinary F2-isoprostane (F2I) excretion: role of oxidative stress
Authors: Luciano Drager, Luiz A. M. Cesar, Lucia Andrade, A. C. Seguro, João F. B. Toledo
Journal: Journal of the American Society of Nephrology (2003)
TCTAP A-018 Association of Vitamin D Level with Severity of Angiographically Documented Coronary Artery Disease: Observations from Bangladeshi Patients
Authors: Ashraf Ur Rahman, Pradip Kumar Karmakar, STM Abu Azam, Shaila Nabi, Ahad Mahmiud Khan, Md Saqif Shahriar, Sabrina Jabeen
Journal: Journal of the American College of Cardiology (2019)
FRI-259-Characteristics and sustained virologic response of persons reporting illicit substance use in the past 6 months: Results from the CANUHC prospective patient registry
Authors: Daniel Smyth, Lisa Barrett, Sergio Borgia, Brian Conway, Curtis Cooper, Jordan Feld, Samuel Lee, Stefanie Materniak, Heidy Morales, Alnoor Ramji, Marie-Louise Vachon
Journal: Journal of Hepatology (2019)
Exploring Tenascin-C as a novel therapeutic target in pediatric brainstem glioma.
Authors: Amanda Muhs Saratsis
Journal: Journal of Clinical Oncology (2015)

10037 Background: Diffuse intrinsic pontine glioma (DIPG) is the most deadly solid tumor of childhood. Histone 3 mutation occurs in up to 80% of DIPGs, causing global epigenetic aberration. Tenascin-C (TNC) is an extracellular matrix protein expressed during brain development by oligodendroglial progenitor cells (OPCs), the purported DIPG cell of origin. TNC is highly expressed in adult glioma, contributing to local invasion and poor survival. We report increased TNC in tumor tissue and cerebrospinal fluid (CSF) from children with high-grade glioma, including DIPG, and characterize TNC expression in relation to histone 3 mutation and DNA methylation. Methods: Tissue collected intraoperatively or post-mortem from children with brainstem (DIPG, n = 14), supratentorial (n = 7), and cerebellar astrocytoma (n = 2), and CSF from DIPG (n = 9) and supratentorial astrocytoma (n = 17), were subjected to MS/MS proteomic analysis. Tissue gene expression, DNA methylation, and H3F3A or HIST1H3B sequencing was performed. TNC expression was validated and correlated with tumor grade and H3K27M status via Western blot and immunohistochemistry. Data integration was performed via Partek Genomics Suite and Ingenuity Pathway Analysis. Results: TNC protein expression was significantly increased in 75% of glioma tissue specimens compared to normal tissue, including all DIPG specimens tested (fold change > 2, p < 0.05). Secreted TNC was detected in 7/9 DIPG CSF specimens (77.8%). Tumor-specific TNC expression was confirmed with Western blot and tissue immunohistochemistry. Greater relative TNC expression correlated with tumor grade and was associated with Notch pathway activation, H3K27M mutation, and TNC promoter hypomethylation. Conclusions: We report increased TNC expression in tissue and CSF of pediatric high-grade astrocytomas, including DIPGs, associated with promoter hypomethylation and H3K27M mutation. Given the effect of TNC on OPC proliferation, migration and differentiation, TNC could serve as a clinical biomarker of disease and rational therapeutic target for a substantial subgroup of DIPG patients. Further studies exploring the mechanism of TNC overexpression and effects of targeting TNC expression in DIPG are currently underway.
THU-211-Evaluation of point shearwave elastography using acoustic radiation force impulse imaging for non-invasive assessment of liver fibrosis in HBeAg-negative chronic HBV infection: A prospective longitudinal study
Authors: Christiana Graf, Viola Knop, Antonia Mondorf, Kai-Henrik Peiffer, Stefan Zeuzem, Christoph Sarrazin, Johannes Vermehren
Journal: Journal of Hepatology (2019)
My patient’s condition could affect their fitness to drive. What should I do?
Authors: Abi Rimmer
Journal: BMJ (2019)

My patient's condition could affect their fitness to drive. What should I do?It is often difficult to know what to do when a patient continues to drive despite medical advice but guidance is available, three experts tell Abi Rimmer Abi RimmerThe BMJ Consider how to support safe drivingDesmond O'Neill, consultant physician and director of the National Office for Traffic Medicine, Dublin, says, "The UK and Ireland have helpful and regularly updated guidelines on medical fitness to drive.These are supportive of continued safe driving and over recent decades have reduced restrictions on driving.This is recognition of better evidence and of how many medical interventions, from cataract surgery to therapy for obstructive sleep apnoea, can improve driving safety.
Dual DNA topoisomerase 1 and tyrosyl‐DNA phosphodiesterase 1 inhibition for improved anticancer activity
Authors: Alexandra Zakharenko, Nadezhda Dyrkheeva, Olga Lavrik
Journal: Medicinal Research Reviews (2019)

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that catalyzes the hydrolysis of the phosphodiester bond in the DNA-topoisomerase 1 (Top1) covalent complex and repairs some other 3'-end DNA adducts. Currently, Tdp1 functions as an important target in cancer drug design owing to its ability to break down various DNA adducts induced by chemotherapeutics. Tdp1 inhibitors may sensitize tumor cells to the action of Top1 poisons, thereby potentiating their effects. This mini-review summarizes findings from studies reporting the combined inhibition of Top1 and Tdp1. Two different approaches have been considered for developing such drug precursors.
Evidence base of mind body intervention in palliative care.
Authors: Afsar imam Zaidi
Journal: Journal of Clinical Oncology (2015)

e20747 Background: The diagnosis of cancer is taken as life threatening issue and creates violent emotional strain. It results in anxiety , depresson , fatigue, fear of recurrence and insomnia. Hence it is logical that for a fruitful cancer care , physical , mental and spiritual aspects are treated as a whole . That is why interest towards integrative palliative care is shown by growing number of cancer patients . However, the effects of MBSR on telomere length (TL) and telomerase activity (TA), known markers of cellular aging are not known. We assess correct evidence base about the benefits and risks of Mindfulness based stress reduction [MBSR]. Methods: 50 women with breast cancer [BC] were recruited from a cancer center in Pakistan. They were rnadomized after 6 weeks of radiotherapy, to an MBSR group [N = 25] and a control group. The MBSR group took MBSR practice for 8 weeks as twice weekly practice while control group was left as such. Quality of life [QoL] was assesed at baseline in both groups for mental symptoms at end of treatment, after 1 month and after 3 months. Results: Compared to controls, the MBSR group reported large post-intervention reducations as assessed by effect size (d). In analyses adjusted for baseline TA and psychological status, TA increased steadily over 12 weeks in the MBSR(BC) group (approximately 17%) compared to essentially no increase in the control group (approximately 3%, p < .01). In contrast, no between-group difference was observed for TL (p = .92). These results provide preliminary evidence that MBSR(BC) increases TA in peripheral blood mononuclear cells from BC patients and have implications for understanding how MBSR(BC) may extend cell longevity at the cellular level. Conclusions: The results show moderate to high evidence of MBSR effect in palliative care and further studies are warrented.
Typical and Atypical 18FDG PET/CT Findings in Two Cases of Cat Scratch Disease
Authors: Wei Zhou, Lianggeng Gong, Changjing Zuo, Jian Zhang
Journal: Clinical Nuclear Medicine (2019)

Cat scratch disease (CSD) is a rare zoonotic infection disease, and the imaging performance for evaluation varies. We present FDG PET/CT images of two cases of CSD. In one case, images showed typical findings of regional lymph node enlargement. In another case, images showed atypical findings of extensive superficial and deep lymph node enlargement.
Tumor Suppressors RB1 and CDKN2a Cooperatively Regulate Cell-Cycle Progression and Differentiation During Cardiomyocyte Development and Repair
Authors: Konstantinos E. Hatzistergos, Adam R. Williams, Derek Dykxhoorn, Michael A. Bellio, Wendou Yu, Joshua M. Hare
Journal: Circulation Research (2019)

Although rare cardiomyogenesis is reported in the adult mammalian heart, whether this results from differentiation or proliferation of cardiomyogenic cells remains controversial. The tumor suppressor genes RB1 (retinoblastoma) and CDKN2a (cyclin-dependent kinase inhibitor 2a) are critical cell-cycle regulators, but their roles in human cardiomyogenesis remains unclear.We hypothesized that developmental activation of RB1 and CDKN2a cooperatively cause permanent cell-cycle withdrawal of human cardiac precursors (CPCs) driving terminal differentiation into mature cardiomyocytes, and that dual inactivation of these tumor suppressor genes promotes myocyte cell-cycle reentry.Directed differentiation of human pluripotent stem cells (hPSCs) into cardiomyocytes revealed that RB1 and CDKN2a are upregulated at the onset of cardiac precursor specification, simultaneously with GATA4 (GATA-binding protein 4) homeobox genes PBX1 (pre-B-cell leukemia transcription factor 1) and MEIS1 (myeloid ecotropic viral integration site 1 homolog), and remain so until terminal cardiomyocyte differentiation. In both GATA4+ hPSC cardiac precursors and postmitotic hPSC-cardiomyocytes, RB1 is hyperphosphorylated and inactivated. Transient, stage-specific, depletion of RB1 during hPSC differentiation enhances cardiomyogenesis at the cardiac precursors stage, but not in terminally differentiated hPSC-cardiomyocytes, by transiently upregulating GATA4 expression through a cell-cycle regulatory pathway involving CDKN2a. Importantly, cytokinesis in postmitotic hPSC-cardiomyocytes can be induced with transient, dual RB1, and CDKN2a silencing. The relevance of this pathway in vivo was suggested by findings in a porcine model of cardiac cell therapy post-MI, whereby dual RB1 and CDKN2a inactivation in adult GATA4+ cells correlates with the degree of scar size reduction and endogenous cardiomyocyte mitosis, particularly in response to combined transendocardial injection of adult human hMSCs (bone marrow-derived mesenchymal stromal cells) and cKit+ cardiac cells.Together these findings reveal an important and coordinated role for RB1 and CDKN2a in regulating cell-cycle progression and differentiation during human cardiomyogenesis. Moreover, transient, dual inactivation of RB1 and CDKN2a in endogenous adult GATA4+ cells and cardiomyocytes mediates, at least in part, the beneficial effects of cell-based therapy in a post-MI large mammalian model, a finding with potential clinical implications.
Environmental Health Sciences in a Translational Research Framework: More than Benches and Bedsides
Authors: Joel D. Kaufman, Cynthia L. Curl
Journal: Environmental Health Perspectives (2019)

Background: Environmental health scientists may find it challenging to fit the structure of the questions addressed in their discipline into the prevailing paradigm for translational research. Objective: We aim to frame the translational science paradigm to address the stages of scientific discovery, knowledge acquisition, policy development, and evaluation in a manner relevant to the environmental health sciences. Our intention is to characterize differences between environmental health sciences and clinical medicine, and to orient this effort towards public health goals. Discussion: Translational research is usually understood to have evolved from the bench-to-bedside framework by which basic science transitions to clinical treatment. Although many health-related fields have incorporated the terminology and context of translational science, environmental health research has not always found a clear fit into this paradigm. We describe a translational research framework applicable to environmental health sciences that retains the basic structure that underlies the original bench-to-bedside paradigm. We propose that scientific discovery (T1) in environmental health research frequently occurs through epidemiological or clinical observations. This discovery often involves understanding the potential for human health effects of exposure to a given environmental chemical or chemicals. The practical applications of this discovery evolve through an understanding of exposure–response relationships (T2) and identification of potential interventions to reduce exposure and improve health (T3). These stages of translation require an interdisciplinary partnership between exposure sciences, exposure biology, toxicology, epidemiology, biostatistics, risk assessment, and clinical sciences. Implementation science then plays a crucial role in the development of environmental and public health practice and policy interventions (T4). Outcome evaluation (T5) often takes the form of accountability research, as environmental health scientists work to quantify the costs and benefits of these interventions. Conclusion: We propose an easily visualized framework for translation of environmental health science knowledge–from discovery to public health practice–that reflects the crucial interactions between multiple disciplines in our field. https://doi.org/10.1289/EHP4067
Study of genetic translocations in children with acute lymphoblastic leukemia using qualitative Multiplex Reverse Transcriptase Polymerase chain reaction.
Authors: Arathi Srinivasan, Julius Xavier Scott
Journal: Journal of Clinical Oncology (2015)

e21006 Background: Despite the high rate of cure, ALL is one of the leading causes of death in children. The chromosomal translocations which have a therapeutic and prognostic significance ETV6-RUNX1 t(12;21) cryptic translocation, known as TEL-AML1, Philadelphia chromosome t(9;22) translocation, MLL translocations t(4;11), TCF3-PBX1 t(1;19) translocations were studied by qualitative multiplex RT-PCR in children with acute lymphoblastic leukemia (ALL) in our population. Methods: This is a single institution prospective study of 22 children from 0 to 18 years newly diagnosed as acute lymphoblastic leukemia by flow cytometry from January 2014 to December 2015. We used a multiplex RT-PCR to detect genetic abnormalities from peripheral blood of these ALL patients. They were initially risk stratified as per the NCI risk criteria by age and leucocyte counts. Based on the genetic abnormalities detected they were re-stratified as standard risk or high risk. Children detected to have TEL/AML1 fusion were classified as low risk and those with BCR/ABL fusion, MLL gene rearrangements, and t (1;19) translocations were classified as high risk. Results: A total of 22 samples were analysed for the genetic aberrations. The male:female ratio was 15:7. There were 4 (18%) with gene fusion and 18 (82%) without any gene fusions. There were 3 children with positivity for t (12, 21)/ETV6-RUNX1, 1 with t(9,22)/ BCR-ABL1 and none with t(1,19)/TCF-PBX1 and MLL. The t(12,21) fusion correlated with younger age, initial total count of < 50000/mm3 and hyperdiploidy stratifying them as standard risk where as one child with t(9;22) normal counts and young age was re stratified as high risk after fusion detection. Conclusions: Detection of gene fusions by RT PCR helped in refining our risk stratification and tailoring ALL therapy based on biological features. However a larger sample size in our population will help in defining the prognostic and therapeutic implications of various genetic aberrations.
Abstract 17206: Identification of Coronary Vascular Dysfunction by Contrast Density Difference Measured From Coronary CT Angiography
Authors: Yuka Otaki, Michaela Hell, Annika Schuhbaeck, Luis E Juarez-Orozco, Heidi Gransar, Stephan Achenbach, Guido Germano, Daniel Berman, Aloha Meave, Piotr Slomka, Erick Alexanderson, Damini Dey
Journal: Circulation (2016)

Introduction: Contrast density difference (CDD), which can be measured by semi-automated software in coronary CT angiography (CTA), has been shown to predict lesion-specific ischemia. We investigat...
Argentine Multicentric Experience of Carfilzomib Use in Relapsed / Refractory Multiple Myeloma. Report from the GAMM (Grupo Argentino de Mieloma Multiple)
Authors: Natalia Paola Schutz, Patricio Duarte, Claudia Shanley, Agustina Cia, Paola Ochoa, Ariel Corzo, Luis Dario Quiroga, Sergio Mario Orlando, Romina Mariano, Alicia Enrico, Dardo Riveros, Guillermina Remaggi, Dorotea Beatriz Fantl
Journal: Blood (2017)
FRI-172-Outcomes of response guided therapy with pegylated interferon alpha 2a in chronic hepatitis B and D
Authors: George Sebastian Gherlan, Stefan Lazar, Augustina Culinescu, Smadu Daniela, Andreea Ruxandra Cazan, Corneliu Petre Popescu, Adelina Paunescu, Laurentiu Filip, simin florescu, Petre Calistru, Emanoil Ceausu
Journal: Journal of Hepatology (2019)
GS-03-Global real world evidence of sofosbuvir/velpatasvir as a simple, effective regimen for the treatment of chronic hepatitis C patients: Integrated analysis of 12 clinical practice cohorts
Authors: Alessandra Mangia, Scott Milligan, Mandana Khalili, Stefano Fagiuoli, Stephen Shafran, Fabrice Carrat, Denis Ouzan, George Papatheodoridis, Alnoor Ramji, Sergio Borgia, Heiner Wedemeyer, Valeria Piazzolla, Francisco Andrés Pérez Hernández, Nicole Wick, Dawn Fishbein, Pietro Lampertico, Karen Doucette, Michael Mertens, Kim Vanstraelen, Juan Turnés
Journal: Journal of Hepatology (2019)
Abstract 16905: Regional Myocardial Work by Magnetic Resonance Imaging and Noninvasive Left Ventricular Pressure: A Feasibility Study in Left Bundle Branch Block
Authors: Camilla K Larsen, John Aalen, Caroline Stokke, Jan G Fjeld, Erik Kongsgaard, Otto A Smiseth, Einar Hopp
Journal: Circulation (2016)

Introduction: We have recently innovated and validated a noninvasive estimate of the left ventricular (LV) pressure curve. This study investigates the feasibility of calculating regional myocardial...