tbuckley/cabot-search huggingface dataset:
Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting
Authors: Antonia Rotolo, Valentina S. Caputo, Monika Holubova, Nicoleta Baxan, Olivier Dubois, Mohammed Suhail Chaudhry, Xiaolin Xiao, Katerina Goudevenou, David S. Pitcher, Kyriaki Petevi, Carolina Kachramanoglou, Sandra Iles, Kikkeri Naresh, John Maher, Anastasios Karadimitris
Journal: Cancer Cell (2018)

Chimeric antigen receptor anti-CD19 (CAR19)-T cell immunotherapy-induced clinical remissions in CD19+ B cell lymphomas are often short lived. We tested whether CAR19-engineering of the CD1d-restricted invariant natural killer T (iNKT) cells would result in enhanced anti-lymphoma activity. CAR19-iNKT cells co-operatively activated by CD1d- and CAR19-CD19-dependent interactions are more effective than CAR19-T cells against CD1d-expressing lymphomas in vitro and in vivo. The swifter in vivo anti-lymphoma activity of CAR19-iNKT cells and their enhanced ability to eradicate brain lymphomas underpinned an improved tumor-free and overall survival. CD1D transcriptional de-repression by all-trans retinoic acid results in further enhanced cytotoxicity of CAR19-iNKT cells against CD19+ chronic lymphocytic leukemia cells. Thus, iNKT cells are a highly efficient platform for CAR-based immunotherapy of lymphomas and possibly other CD1d-expressing cancers.
P3.13-03 Real-World Anaplastic Lymphoma Kinase Testing Practices: Results from a Survey in the United States
Authors: K. Bloom, S. Sudarsanam, H. Hwang, F. Racke, S. Astrow, M. Moran, M. Chioda, J. Sheng, J. Ramage, J. Mardekian, A.J. Iafrate
Journal: Journal of Thoracic Oncology (2018)
Response to Comment on Andersen et al. Risk-Factor Trajectories Preceding Diabetic Polyneuropathy: ADDITION-Denmark. Diabetes Care 2018;41:1955–1962
Authors: Signe T. Andersen, Daniel R. Witte, Henning Andersen, Lasse Bjerg, Niels Henrik Bruun, Marit E. Jørgensen, Nanna B. Finnerup, Torsten Lauritzen, Troels S. Jensen, Hatice Tankisi, Morten Charles
Journal: Diabetes Care (2018)

We thank Rigalleau et al. (1) for their interest in our study (2) on risk-factor trajectories preceding a clinical diagnosis of diabetic polyneuropathy (DPN) 13 years after a diagnosis of type 2 diabetes by screening. Rigalleau et al. showed that in patients with long-standing diabetes, retrospectively analyzed strong declines in HbA1c levels over 6 years were associated with higher indices of DPN (vibration perception thresholds and skin autofluorescence) (1). Strong decline was defined as the quintile of patients experiencing the greatest decline in HbA1c in the 6 years preceding DPN assessments. Associations were studied in linear regression models adjusted for sex, age, diabetes duration, BMI, blood lipids, and arterial hypertension.

In our study (2), we hypothesized that the velocity of risk-factor changes during the course of diabetes might reflect distinct pathophysiological mechanisms and that the effect …
Abstract 18067: Serum Troponin In Patients Presenting With Acute Heart Failure and High BNP/NT-proBNP Without Electrocardiographic Evidence of ST-Elevation Myocardial Infarction
Authors: Ayman El-Menyar, Kadhim Sulaiman, Wael AlMahmeed, Rajvir Singh, Nidal Asaad, Jassim Al Suwaidi
Journal: Circulation (2016)

Introduction: Serum troponins could increase in acute heart failure (AHF) but its clinical significance and correlation with BNP are not well explored. Hypothesis: We investigated the implication o...
Genotyping of circulating tumor DNA in biliary tract cancer reveals diagnostic and prognostic information
Authors: T.J. Ettrich, D. Schwerdel, A. Dolnik, F. Beuter, T. Blätte, S.A. Schmidt, N. Stanescu-Siegmund, J. Steinacker, R. Marienfeld, A. Kleger, L. Bullinger, T. Seufferlein, A.W. Berger
Journal: Annals of Oncology (2018)
Antigen discovery and specification of immunodominance hierarchies for MHCII-restricted epitopes
Authors: Daniel B. Graham, Chengwei Luo, Daniel J. O’Connell, Ariel Lefkovith, Eric M. Brown, Moran Yassour, Mukund Varma, Jennifer G. Abelin, Kara L. Conway, Guadalupe J. Jasso, Caline G. Matar, Steven A. Carr, Ramnik J. Xavier
Journal: Nature Medicine (2018)
Final results of a randomized phase III trial of nimotuzumab for the treatment of newly diagnosed glioblastoma in addition to standard radiation and chemotherapy with temozolomide versus standard radiation and temoziolamide.
Authors: Manfred Westphal, Ferdinand Bach
Journal: Journal of Clinical Oncology (2012)

2033 Background: The receptor for epidermal growth factor (EGF-R) has consistently been found expressed or overexpressed in human malignant glioma disease. Therapeutic targeting of the EGF-R has shown mixed responses which appear to be restricted by specific features of the tumor cells.Nimotuzumab binds preferentially to highly over expressing cells, a phase III trial was initiated to test efficacy in glioma. Methods: Nimotuzumab was tested in an open label, randomized, multicenter Phase III trial in patients with histologically confirmed, newly diagnosed glioblastoma. 12 consecutive weekly infusions of 400mg during standard radiotherapy with Temozolomide followed by biweekly infusions of 400mg arm A was randomized against standard radio chemotherapy alone arm B. Primary endpoint was PFS as determined by centralized neuro-imaging review. OS as secondary endpoint with quality of life, safety as additional parameters.MGMT and EGF-R were assessed where sufficient materials could be retrieved as well as tumor hypoxia. Results: Between 2007 and 2010, 149 patients were randomized and 142 were available for analysis. Stratification according to resection status resulted in 40 pts in the treatment arm and 41 in the control arm with residual tumor and 31 vs 30 pts without residual tumor. PFS: 12 month was 25.5% arm A vs 20.3% in arm B (p = 0.78) and OS: 679 days vs 596 days. For non - methylated MGMT the difference was most notable: OS arm A 28 pats: 19.6 months vs arm B 28 pats 15.0 months EGF-R amplification, gave no clear signal, neither was there a statistically significant treatment effect between with or without residual tumor. Tumor hypoxia does not appear to have predictive value in the overall group but possibly in subgroups.AEs and SAEs did not reveal a new specific toxicity profile beyond the known side effects from glioma treatment with current standard. Conclusions: Nimotuzumab shows a clear trend towards efficacy in MGMT non-methylated glioblastoma patients. Safety profile and indications for subgroup efficacy potentially justify focused evaluation of antibody therapy against glioblastoma.
Abstract 20137: A Novel Form of Familial Fibrotic Cardiomyopathy Associated With Homozygous Loss-of-Function SERPINE1 Mutation
Authors: Sadiya S Khan, Sanjiv J Shah, Ekaterina Klyachko, Panagiotis Flevaris, Daniel C Lee, Michael Cuttica, James C Carr, Brandon C Benefield, Lauren Nelson, Meadow Heiman, Sweta Gupta, Amy D Shapiro, Douglas E Vaughan
Journal: Circulation (2016)

Introduction: Inbred homozygous mice with complete genetic deficiency of plasminogen activator inhibitor-1 (PAI-1), but not heterozygous mice, develop age-dependent cardiac-specific fibrosis. A uni...
Safety of benzodiazepines and opioids in interstitial lung disease: a national prospective study
Authors: Sabrina Bajwah, Joanna M. Davies, Hanan Tanash, David C. Currow, Adejoke O. Oluyase, Magnus Ekström
Journal: European Respiratory Journal (2018)

Safety concerns are a barrier to prescribing benzodiazepines (BDZs) and opioids in interstitial lung disease (ILD). We therefore examined the association of BDZs and opioids on risk of admission to hospital and death. We conducted a population-based longitudinal cohort study of fibrotic ILD patients starting long-term oxygen therapy in Sweden between October 2005 and December 2014. Effects of BDZs and opioids on rates of admission to hospital and mortality were analysed using Fine–Gray and Cox regression while adjusting for potential confounders. We included 1603 patients (61% females). BDZs were used by 196 (12%) patients and opioids were used by 254 (15%) patients. There was no association between BDZs and increased admission. Treatment with high- versus low-dose BDZs was associated with increased mortality (subdistribution hazard ratio (SHR) 1.46, 95% CI 1.08–1.98 versus 1.13, 95% CI 0.92–1.38). Opioids showed no association with increased admission. Neither low-dose opioids (≤30 mg·day −1 oral morphine equivalent) (SHR 1.18, 95% CI 0.96–1.45) nor high-dose opioids (&gt;30 mg·day −1 oral morphine equivalent) (SHR 1.11, 95% CI 0.89–1.39) showed association with increased mortality. This first ever study to examine associations between BDZ and opioid use and harm in ILD supports the use of opioids and low-dose BDZs in severely ill patients with respiratory compromise.
Predictive significance of tumour angiogenic and anti-angiogenic VEGF-A splice variants in patients with metastatic colorectal cancer
Authors: G. Pentheroudakis, V. Kotoula, G.-A. Koliou, K. Papadopoulou, E. Samantas, T. Makatsoris, V. Karavasilis, D. Mauri, I. Efstratiou, D. Bafaloukos, P. Papakostas, A. Psyrri, G. Papatsibas, G. Zarkavelis, A. Goussia, I. Bompolaki, G. Oikonomopoulos, A.N. Christopoulou, D.G. Pectasides, G. Fountzilas
Journal: Annals of Oncology (2018)
Efficacy of an Education Program for People With Diabetes and Insulin Pump Treatment (INPUT): Results From a Randomized Controlled Trial
Authors: Dominic Ehrmann, Bernhard Kulzer, Melanie Schipfer, Bernhard Lippmann-Grob, Thomas Haak, Norbert Hermanns
Journal: Diabetes Care (2018)

OBJECTIVE Continuous subcutaneous insulin infusion (CSII) is the most advanced form of insulin delivery, but it requires structured education to provide users with the necessary knowledge/skills and to support their motivation. Currently, no structured education program designed to provide this training has been evaluated. We developed a CSII-specific, structured education program (Insulin Pump Treatment [INPUT]) and evaluated its impact on glycemic control, behavior, and psychosocial status. RESEARCH DESIGN AND METHODS This was a multicenter, randomized, parallel trial with a 6-month follow-up. Eligible participants (age 16–75 years) currently were treated with insulin pump therapy. Participants were randomly assigned (1:1) to the INPUT program or to usual care using a computer-generated algorithm, with study center as the stratification factor. The primary outcome was HbA1c change from baseline to 6 months. Secondary outcomes were incidence of severe hypoglycemia and changes in behavioral and psychosocial measures. RESULTS Between 1 April 2016 and 26 April 2016, 268 people with diabetes and a mean duration of CSII therapy of 9.5 years were randomly assigned to the INPUT group (n = 135) or control group (n = 133). At 6 months, HbA1c improved in the INPUT group (8.33 ± 0.8 vs. 8.04 ± 0.9; P &amp;lt; 0.0001) but not in the control group (8.33 ± 1.0 vs. 8.27 ± 1.0; P = 0.11). The between-group difference in HbA1c reduction was significant, favoring INPUT (−0.28% vs. −0.06%, Δ −0.22%, 95% CI −0.38 to −0.06; P = 0.0029). The incidence rate ratio of severe hypoglycemia was 3.55 times higher for participants in the control group than for those in the INPUT group (95% CI 1.50–8.43; P = 0.0041). CONCLUSIONS The INPUT education program led to a significant improvement in glycemic control and incidence of severe hypoglycemia in insulin pump users.
Hypermetabolism Caused by Seizure Mimicking Tumor Recurrence
Authors: Jingnan Wang, Yiwei Zhang, Heyang Sun, Ruixue Cui
Journal: Clinical Nuclear Medicine (2018)

A 41-year-old man had a right frontal grade I glioma resection 17 years ago. He was tumor free since. However, 1 month ago, he presented with an uncontrollable seizure, which raised the possibility of recurrent tumor. The FDG PET/CT brain scan showed increased tracer uptake at the margin of the previous resected tumor, suggesting the possibility of tumor recurrence. However, on a repeat FDG PET brain scan confirmed by electroencephalography monitory as an interictal study, no elevated FDG uptake was revealed at this site. These results indicate that the elevated F-FDG activity on the original study was a result of seizure.
After surgery for stage II or III colorectal cancer, more vs less frequent follow-up did not differ for 5-year mortality
Authors: William T. Clarke, Joseph D. Feuerstein
Journal: Annals of Internal Medicine (2018)

Source Citation Wille-Jørgensen P, Syk I, Smedh K, et al; COLOFOL Study Group. Effect of more vs less frequent follow-up testing on overall and colorectal cancer-specific mortality in patients with stage II or III colorectal cancer: the COLOFOL randomized clinical trial. JAMA. 2018;319:2095-103. 29800179
Treatment sequences in metastatic renal cell carcinoma: Efficacy results from the Czech registry (RENIS)
Authors: J. Finek, R. Demlova, K. Kopeckova, T. Buchler, B. Melichar, J. Prausova, A. Poprach, T. Hrnciarova, T. Mlcoch, T. Dolezal
Journal: Annals of Oncology (2018)
Implementation research: new imperatives and opportunities in global health
Authors: Sally Theobald, Neal Brandes, Margaret Gyapong, Sameh El-Saharty, Enola Proctor, Theresa Diaz, Samuel Wanji, Soraya Elloker, Joanna Raven, Helen Elsey, Sushil Bharal, David Pelletier, David H Peters
Journal: The Lancet (2018)
GW29-e1451 Sodium Intake Reduction in Shandong Province in China: A Qualitative evaluation of Shandong-Ministry of Health Action on Salt and Hypertension (2011-2015)
Authors: Ying Cai, Xing Zhang, Jixiang Ma, Xiaolei Guo, Jing Dong, Xinying Sun
Journal: Journal of the American College of Cardiology (2018)
Genetic diversity between mouse strains allows identification of the CC027/GeniUnc strain as an orally reactive model of peanut allergy
Authors: Kelly Orgel, Johanna M. Smeekens, Ping Ye, Lauren Fotsch, Rishu Guo, Darla R. Miller, Fernando Pardo-Manuel de Villena, A. Wesley Burks, Martin T. Ferris, Michael D. Kulis
Journal: Journal of Allergy and Clinical Immunology (2018)
A phase I trial of vorolanib (X-82t vascular endothelial growth factor receptor (VEGFR) inhibitor, in patients (pts) with advanced solid tumors
Authors: J. Bendell, K.N. Moore, M.R. Patel, C. Chua, H.-T. Arkenau, G. Dukart, K. Harrow, C. Liang
Journal: Annals of Oncology (2018)
Genetic signatures always suggest undertreatment? Experience with PAM50
Authors: C. Sales, I. Vieira, M. Cassiano, C. Oliveira, C. Vieira, M. Ferreira, A. Rodrigues, A. Ferreira, M.I. Pousa, R. Couto, C. Leal, J. Abreu, M. Teixeira, D. Pereira, S. Sousa, M.H. Abreu
Journal: Annals of Oncology (2018)
Smoking and Risk of Colorectal Cancer Sub-Classified by Tumor-Infiltrating T Cells
Authors: Tsuyoshi Hamada, Jonathan A Nowak, Yohei Masugi, David A Drew, Mingyang Song, Yin Cao, Keisuke Kosumi, Kosuke Mima, Tyler S Twombly, Li Liu, Yan Shi, Annacarolina da Silva, Mancang Gu, Wanwan Li, Katsuhiko Nosho, NaNa Keum, Marios Giannakis, Jeffrey A Meyerhardt, Kana Wu, Molin Wang, Andrew T Chan, Edward L Giovannucci, Charles S Fuchs, Reiko Nishihara, Xuehong Zhang, Shuji Ogino
Journal: JNCI Journal of the National Cancer Institute (2018)

Evidence indicates not only carcinogenic effect of cigarette smoking but also its immunosuppressive effect. We hypothesized that the association of smoking with colorectal cancer risk might be stronger for tumors with lower anti-tumor adaptive immune response.
Brain-derived neurotrophic factor, a new soluble biomarker for malignant pleural mesothelioma involved in angiogenesis
Authors: Patrick Smeele, Sènan Mickaël d’Almeida, Clément Meiller, Anne-Laure Chéné, Charly Liddell, Laurent Cellerin, François Montagne, Sophie Deshayes, Sarah Benziane, Marie-Christine Copin, Paul Hofman, Françoise Le Pimpec-Barthes, Henri Porte, Arnaud Scherpereel, Marc Grégoire, Didier Jean, Christophe Blanquart
Journal: Molecular Cancer (2018)

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The discovery of soluble biomarkers with diagnostic/prognostic and/or therapeutic properties would improve therapeutic care of MPM patients. Currently, soluble biomarkers described present weaknesses preventing their use in clinic. This study aimed at evaluating brain-derived neurotrophic factor (BDNF), we previously identified using transcriptomic approach, in MPM. We observed that high BDNF expression, at the mRNA level in tumors or at the protein level in pleural effusions (PE), was a specific hallmark of MPM samples. This protein presented significant but limited diagnostic properties (area under the curve (AUC) = 0.6972, p < 0.0001). Interestingly, high BDNF gene expression and PE concentration were predictive of shorter MPM patient survival (13.0 vs 8.3 months, p < 0.0001, in PE). Finally, BDNF did not affect MPM cell oncogenic properties but was implicated in PE-induced angiogenesis. In conclusion, BDNF appears to be a new interesting biomarker for MPM and could also be a new therapeutic target regarding its implication in angiogenesis.
Loss of TNFAIP3 enhances MYD88L265P-driven signaling in non-Hodgkin lymphoma
Authors: Kerstin Wenzl, Michelle K. Manske, Vivekananda Sarangi, Yan W. Asmann, Patricia T. Greipp, Hanna R. Schoon, Esteban Braggio, Matthew J. Maurer, Andrew L. Feldman, Thomas E. Witzig, Susan L. Slager, Stephen M. Ansell, James R. Cerhan, Anne J. Novak
Journal: Blood Cancer Journal (2018)

MYD88 mutations are one of the most recurrent mutations in hematologic malignancies. However, recent mouse models suggest that MYD88L265P alone may not be sufficient to induce tumor formation. Interplay between MYD88L265P and other genetic events is further supported by the fact that TNFAIP3 (A20) inactivation often accompanies MYD88L265P. However, we are still lacking information about the consequence of MYD88L265P in combination with TNFAIP3 loss in human B cell lymphoma. Review of our genetic data on diffuse large B cell lymphoma (DLBCL) and Waldenstrom macroglobulinemia (WM), found that a large percentage of DLBCL and WM cases that have a MYD88 mutation also harbor a TNFAIP3 loss, 55% DLBCL and 28% of WM, respectively. To mimic this combination of genetic events, we used genomic editing technology to knock out TNFAIP3 in MYD88L265P non-Hodgkin's lymphoma (NHL) cell lines. Loss of A20 expression resulted in increased NF-κB and p38 activity leading to upregulation of the NF-κB target genes BCL2 and MYC. Furthermore, we detected the increased production of IL-6 and CXCL10 which led to an upregulation of the JAK/STAT pathway. Overall, these results suggest that MYD88L265P signaling can be enhanced by a second genetic alteration in TNFAIP3 and highlights a potential opportunity for therapeutic targeting.
GW29-e1128 Comparison of Dual Antiplatelet Therapy with Clopidogrel and Ticagrelor in Patients with Acute Coronary Syndrome at High Risk of Bleeding
Authors: Yafeng Zhou, Ning Guo, Wei Liu, Dara Paek, Toby Sayre, Shalini Girotra
Journal: Journal of the American College of Cardiology (2018)
<i>Mycobacterium tuberculosis</i>–induced IFN-β production requires cytosolic DNA and RNA sensing pathways
Authors: Yong Cheng, Jeffrey S. Schorey
Journal: The Journal of Experimental Medicine (2018)

RNA sensing pathways are key elements in a host immune response to viral pathogens, but little is known of their importance during bacterial infections. We found that Mycobacterium tuberculosis (M.tb) actively releases RNA into the macrophage cytosol using the mycobacterial SecA2 and ESX-1 secretion systems. The cytosolic M.tb RNA induces IFN-β production through the host RIG-I/MAVS/IRF7 RNA sensing pathway. The inducible expression of IRF7 within infected cells requires an autocrine signaling through IFN-β and its receptor, and this early IFN-β production is dependent on STING and IRF3 activation. M.tb infection studies using Mavs−/− mice support a role for RNA sensors in regulating IFN-β production and bacterial replication in vivo. Together, our data indicate that M.tb RNA is actively released during an infection and promotes IFN-β production through a regulatory mechanism involving cross-talk between DNA and RNA sensor pathways, and our data support the hypothesis that bacterial RNA can drive a host immune response.
Metformin use was linked to hospitalization for acidosis at 6 y only in patients with eGFR &lt; 30 mL/min/1.73 m<sup>2</sup>
Authors: Alexander A. Leung, Raj S. Padwal
Journal: Annals of Internal Medicine (2018)

Source Citation Lazarus B, Wu A, Shin JI, et al. Association of metformin use with risk of lactic acidosis across the range of kidney function: a community-based cohort study. JAMA Intern Med. 2018;178:903-10. 29868840
Abstract 12933: Increased Lipid Tissue in the Neointima of Late Restenosis after Stent Implantation: Integrated Backscatter Intravascular Ultrasound Analysis for In-Stent Restenosis
Authors: Yusaku Shimbo, Hirohiko Ando, Kazuhiro Harada, Katsuhide Kitagawa, Ayako Kunimura, Akihiro Suzuki, Ken Harada, Tomohiro Yoshida, Bunichi Kato, Tadayuki Uetani, Masataka Kato, Nobuyuki Marui, Hiroaki Takashima, Tetsuya Amano, Tatsuaki Matsubara, Hideki Ishii, Toyoaki Murohara
Journal: Circulation (2012)

Background: Although late restenosis is one of the long-term complications after stent implantation, the pathogenesis has not been fully elucidated. The purpose of this study is to compare the tissue characterization of neointima between early restenosis and late restenosis using integrated backscatter intravascular ultrasound (IB-IVUS). Methods: A total of 73 consecutive patients with in-stent restenosis (ISR) after bare-metal stent (BMS, n=48) or sirolimus-eluting stent (SES, n=25) implantation were enrolled. All enrolled patients underwent initial follow-up angiography from 6 to 12 months after stent implantation. When ISR was detected at initial follow-up angiography, this lesion was classified as the early restenosis group. On the other hand, when ISR was detected at 13 months or later without ISR at initial follow-up angiography, this lesion was classified as the late restenosis group. Volumetric evaluation of neointima within the stented segment using IB-IVUS was performed. Results: Late restenosis...
DNA Polymerase Eta Prevents Tumor Cell-Cycle Arrest and Cell Death during Recovery from Replication Stress
Authors: Ryan P. Barnes, Wei-Chung Tsao, George-Lucian Moldovan, Kristin A. Eckert
Journal: Cancer Research (2018)

: Neoplastic transformation and genome instability are enhanced by replication stress, conditions that slow or stall DNA replication forks. Consequently, cancer cells require multiple enzymes and checkpoint signaling pathways to mitigate replication stress for their viability and proliferation. Targeting proteins that enhance cancer cell survival during replication stress is a recent approach in clinical strategies, especially when targets produce synthetic lethality. DNA polymerase eta (Pol η) has many key functions in genome stability, particularly for translesion synthesis. Here we demonstrate that endogenous Pol η displays significant protein induction and forms intense foci throughout the nucleus in response to replication stress induced by drugs that do not directly form DNA adducts. During replication stress, Pol η-deficient cells displayed hyperactivation of the ATR replication checkpoint and arrested late in the cell cycle. During recovery from replication stress, Pol η-deficient cells continue to display aberrant phenotypes, including delayed cell-cycle progression, apoptosis, and cell survival. Depletion or inhibition of ATR was synthetically lethal with Pol η deficiency, particularly when tumor cells were treated with replication stress-inducing drugs. Together our data expand knowledge of the cellular environments that increase endogenous Pol η expression beyond DNA damaging agents and demonstrate that Pol η regulation is central to the replication stress response. Because Pol η is aberrantly expressed in several tumor types, our results are critical for developing more effective chemotherapy approaches and identify coinhibition of Pol η and ATR as a potential therapeutic strategy. SIGNIFICANCE: This study demonstrates that replication stress upregulates Pol η (POLH) in tumor cells and reveals a role for Pol η in tumor cell recovery following replication stress.