tbuckley/cabot-search huggingface dataset:
The characteristics of MET exon 14 skipping mutations in Chinese non-small cell lung cancer: A retrospective analysis
Authors: Y. Zhu, C. Xu, W. Wang, Q. Zhang, W. Zhuang, G. Chen, M. Fang, T. Lv, Y. Song
Journal: Annals of Oncology (2019)

Background: MET exon 14 skipping is a potential driver alteration in lung cancer targetable. Treatment with crizotinib can cause dramatic responses in patients whose cancers have MET exon 14 skipping. The current study was aiming to determine the clinical and pathological characteristics in non-small cell lung cancers (NSCLC). Methods: A total of 2926 patients with NSCLC were recruited between July 2012 and 2015. The status of MET exon 14 skipping and other genes were detected by next generation sequencing. Results: MET exon 14 skipping rate was 1.06% (31/2926) in NSCLC, including X1009_spilce (10 patients), X963_spilce (6 patients), D1010H (5 patients), D1010N (3 patients), X1008_spilce (1 patient), X1006_spilce (1 patient), X1007_spilce (1 patient), D1010Y (1 patient), Y1003S (1 patient), D1002G (1 patient), P1008A (1 patient). Among them, EGFR mutations+ MET skipping [7 patients (2 patients with 19 del+ 5 patients with L858R)], ALK fusion+ MET skipping (2 patients) and ROS1 fusion+ MET skipping (1 patient). Conclusions: MET exon 14 skipping defined a new molecular subset of NSCLC with identifiable clinical characteristics. The therapeutic crizotinib might be an alternative treatment for patients with MET exon 14 skipping NSCLC. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Platelet reactivity in patients with advanced stage adenocarcinoma and healthy controls.
Authors: Arnab Basu, Rohit Gosain, Aman Opneja, Kenneth David Miller
Journal: Journal of Clinical Oncology (2015)

e22003 Background: Thrombocytosis has been associated with worse outcomes in cancer. Recent evidence has demonstrated multiple pathways for platelets to contribute to metastasis. We conducted a study of platelet activation and reactivity in patients with advanced adenocarcinomas (TNM Stage III or greater) in comparison to healthy controls. Methods: Citrated blood samples from patients with advanced adenocarcinomas and healthy controls were collected. Platelet rich plasma (PRP) was examined with light transmission aggregometry for primary aggregation in response to low dose agonists-1μMol , 2μMol , 5μMol ADP as well as 2μMol Arachidonic Acid (AA) and 4μMol Collagen. EDTA blood samples were collected for flow cytometry and PRP samples were stored for future analysis of inflammatory markers. Results: Among cases and healthy controls maximum platelet aggregation observed at 1 μmol, 2 μmol & 5 μmol ADP, Collagen and Arachidonic Acid were similar. These findings were reproduced with.Platelet aggregation velocity in response to ADP was however significantly more rapid in patients with cancer than controls. Conclusions: This study demonstrates possible differences in the rate of platelet aggregation in response to low dose ADP in patients with advanced adenocarcinoma in comparison to healthy controls though there does not appear to be a difference in maximal aggregation in this relatively small sample. Further studies are warranted to explain potential links to thrombotic risks. We are currently recruiting fifty patients for further analysis.
Cardiovascular Benefits of Fish-Oil Supplementation Against Fine Particulate Air Pollution in China
Authors: Zhijing Lin, Renjie Chen, Yixuan Jiang, Yongjie Xia, Yue Niu, Cuiping Wang, Cong Liu, Chen Chen, Yihui Ge, Weidong Wang, Guanjin Yin, Jing Cai, Viviane Clement, Xiaohui Xu, Bo Chen, Honglei Chen, Haidong Kan
Journal: Journal of the American College of Cardiology (2019)
Prognostic significance of human telomerase reverse transcriptase promoter region mutations C228T and C250T for overall survival in spinal chordomas
Authors: Chetan Bettegowda, Stephen Yip, Bowen Jiang, Wei-Lien Wang, Michelle J Clarke, Aron Lazary, Marco Gambarotti, Ming Zhang, Daniel M Sciubba, Jean-Paul Wolinsky, C Rory Goodwin, Edward McCarthy, Niccole M Germscheid, Arjun Sahgal, Ziya L Gokaslan, Stefano Boriani, Peter Pal Varga, Charles G Fisher, Laurence D Rhines
Journal: Neuro-Oncology (2019)

Spinal chordomas, a subtype of primary spinal column malignancies (PSCM), are rare tumors with poor prognosis, and we have limited understanding of the molecular drivers of neoplasia. Study design was a retrospective review of prospectively collected data with cross-sectional survival. Archived paraffin embedded pathologic specimens were collected for 133 patients from 6 centers within Europe and North America between 1987 and 2012. Tumor DNA was extracted and the human telomerase reverse transcriptase (hTERT) promoter was sequenced. The hTERT mutational status was correlated with overall survival (OS) and time to first local recurrence. Ninety-two chordomas, 26 chondrosarcomas, 7 osteosarcomas, 3 Ewing's sarcomas, and 5 other malignant spinal tumors were analyzed. Median OS following surgery was 5.8 years (95% CI: 4.6 to 6.9) and median time to first local recurrence was 3.9 years (95% CI: 2.5 to 6.7). Eight chordomas, 2 chondrosarcomas, 1 Ewing's sarcoma, and 1 other malignant spinal tumor harbored either a C228T or C250T mutation in the hTERT promoter. In the overall cohort, all patients with hTERT mutation were alive at 10 years postoperative with a median OS of 5.1 years (95% CI: 4.5 to 6.6) (P = 0.03). hTERT promoter mutation was observed in 8.7% of spinal chordomas, and 100% of chordoma patients harboring the mutation were alive at 10 years postoperative compared with 67% patients without the mutation (P = 0.05). We report for the first time that hTERT promoter mutations C228T and C250T are present in approximately 8.7% of spinal chordomas. The presence of hTERT mutations conferred a survival benefit and could potentially be a valuable positive prognostic molecular marker in spinal chordomas.
TCTAP A-120 Management of Silent Coronary Ischemia in Patients with Symptomatic Peripheral Vascular Disease Who Require Surgery
Authors: Indulis Kumsars, Dainis Krievins, Sandra Jegere, Gustavs Latkovskis, Karlis Strenge, Edgars Zellans, Eva Strike, Roberts Rumba, Peteris Stradins, Ligita Zvaigzne, Inga Narbute, Christopher K. Zarins, Andrejs Erglis
Journal: Journal of the American College of Cardiology (2019)
A signature of circulating inflammatory proteins and development of end-stage renal disease in diabetes
Authors: Monika A. Niewczas, Meda E. Pavkov, Jan Skupien, Adam Smiles, Zaipul I. Md Dom, Jonathan M. Wilson, Jihwan Park, Viji Nair, Andrew Schlafly, Pierre-Jean Saulnier, Eiichiro Satake, Christopher A. Simeone, Hetal Shah, Chengxiang Qiu, Helen C. Looker, Paolo Fiorina, Carl F. Ware, Jennifer K. Sun, Alessandro Doria, Matthias Kretzler, Katalin Susztak, Kevin L. Duffin, Robert G. Nelson, Andrzej S. Krolewski
Journal: Nature Medicine (2019)
Immunohistochemical characteristics of neuron-glial relationships in human astrocytic brain tumors of different grades of malignancy.
Authors: Galina Vitalyevna Zhukova, Evgenia Kirichenko, Aleksandr Sukhov, Dmitriy P. Atmachidi, Anastasia Grankina, Alla I Shikhliarova, Pavel G. Sakun, Elena Alekseevna Shirnina, Marina Igorevna Bragina, Tatiana Albertovna Barteneva
Journal: Journal of Clinical Oncology (2015)

e22096 Background: At present, the development of glial tumors is associated with abnormalities in cell-cell interactions through gap junctions (GJ). Data on changes in GJ in the development of human glial brain tumors are fragmentary and contradictory. Virtually it is known nothing about the expression of connexin-36, the structural protein of neuronal GJ. Meanwhile, these data are necessary to clarify the role of changes in neuro-glial relationships in the pathogenesis of glial tumors. The research aim was to study the expression of connexin 36 and its relation with expression of neuroglial antigens in human astrocytic brain tumors of Grade II - Grade IV. Methods: The fragments of resected human astrocytic brain tumors (Grade II, Grade III and Grade IV – 3, 6 and 7 cases, respectively), and of peritumoral area tissues served as the material for the study. The tumors localized predominantly in frontal lobes. The expression of connexin 36, synaptophysin, neurofilament protein and glial fibrillary acidic protein (GFAP) was investigated by methods of immunohistochemistry (IHC). The primary mouse monoclonal and rabbit polyclonal antibodies (Dako, Denmark and Invitrogen, USA) were applied. The visualization system Dako EnVision System + Peroxidase (DAB) and the morphometry program Leica Application Suite 4.3 (Leica, Germany) were used. Results: New data on the expression of neuronal connexin 36, as well as the relation of this parameter with the expression of synaptophysin, neurofilament protein and GFAP in human astrocytic brain tumors and in peritumoral area were obtained. It was shown that in sequence of tumors Grade II - Grade III - Grade IV reduction of expression of studied neuronal proteins was accompanied by disorganization of the coexpression of synaptophysin / neurofilament protein and connexin 36. IHC heterogeneity of glioblastomas in the level of expression of synaptophysin and neurofilament protein and in their combination was revealed. Conclusions: The results deepen submission about the pathogenesis of gliomas and determine the direction of the future research. Data on IHC heterogeneity of glioblastomas may have prognostic significance.
THU-186-Progress towards achieving hepatitis C elimination in the country of Georgia, April 2015-August 2018
Authors: Tengiz Tsertsvadze, Amiran Gamkrelidze, Nikoloz Chkhartishvili, Akaki Abutidze, Lali Sharvadze, Vakhtang Kerashvili, Maia Butsashvili, David Metreveli, Lia Gvinjilia, Shaun Shadaker, Muazzam Nasrullah, Valeri Kvaratskhelia, Maia Lagvilava, Ekaterine Adamia, Stefan Zeuzem, Nezam Afdhal, Sanjeev Arora, Karla Thornton, Francisco Averhoff
Journal: Journal of Hepatology (2019)
THU-115-Effects of health-related quality of life of interferon-free antiviral therapy for chronic hepatitis C infection-Results from the GermanhHepatitis C-Registry (DHC-R)
Authors: Schäfer Arne, Stefan Christensen, Renate Heyne, Uwe Naumann, Ralph Link, Christoph Herold, Willibold Schiffelholz, Rainer Guenther, Markus Cornberg, Yvonne Serfert, Heiner Wedemeyer, Michael R. Kraus
Journal: Journal of Hepatology (2019)
Abstract 18451: Palliative Care Education in Cardiology: A National Survey of Fellows and Faculty
Authors: Daniela R Crousillat, Brieze R Keeley, Hui R Zheng, Donna M Polk, Mary K Buss, Kristen G Schaefer
Journal: Circulation (2017)

Introduction: Cardiologists increasingly care for patients nearing the end of life. Little is known about how well cardiology fellowships prepare trainees to effectively use palliative care (PC) in the management of advanced cardiovascular disease. Methods: We conducted an online cross-sectional national survey study of cardiology fellows and faculty to assess the quantity and quality of teaching received in essential PC competencies as outlined by the American College of Cardiology 2015 Core Cardiovascular Training Statement 4 (COCATS 4). Results: Thirty-nine percent (47/121) of fellows and twenty-six percent (34/120) of faculty surveyed participated in the study. The majority of fellows and faculty agreed that PC training is important, though most faculty (72.4%) and fellows (52.5%) reported that cardiologists lack knowledge about PC. There was significantly less teaching on goals of care discussions compared to general cardiology concepts, including rare cardiac disease (p=0.05, Figure 1). On a scale o...
Comment on: ‘Idiopathic inflammatory myopathies and antisynthetase syndrome: contribution of antisynthetase antibodies to improve current classification criteria’ by Greco <i>et al</i>
Authors: Johannes Knitza, Lorenzo Cavagna, Georg Schett, Jörg H W Distler
Journal: Annals of the Rheumatic Diseases (2019)

With great interest, we read the letter titled ‘Idiopathic inflammatory myopathies and antisynthetase syndrome: contribution of antisynthetase antibodies to improve current classification criteria’ by Greco et al 1 published in the Annals of the Rheumatic Diseases .

The authors analysed if the detection of anti-aminoacyl transfer RNA synthetase (ARS) autoantibodies other than anti-Jo1 could improve the European League Against Rheumatism/Amercian College of Rheumatology (EULAR/ACR) classification criteria2 for adult and juvenile idiopathic inflammatory …
Respiratory virus infection among hospitalized adult patients with or without clinically apparent respiratory infection: a prospective cohort study
Authors: K.K.W. To, K.-H. Chan, J. Ho, P.K.P. Pang, D.T.Y. Ho, A.C.H. Chang, C.W. Seng, C.C.Y. Yip, V.C.C. Cheng, I.F.N. Hung, K.-Y. Yuen
Journal: Clinical Microbiology and Infection (2019)
Pharmacogenetic markers for efficacy and toxicity of chemotherapy in osteosarcoma patients.
Authors: Hanneke I. Vos, Marieke J.H. Coenen, Hans Gelderblom, Tahar van der Straaten, Eveline S.J.M de Bont, Winette TA van der Graaf, H.W.B. Schreuder, Frank N. van Leeuwen, Henk-jan Guchelaar, Dunja Maroeska W.M. Te Loo
Journal: Journal of Clinical Oncology (2015)

10054 Background: Despite multiagent chemotherapeutic treatment, osteosarcoma patients relapse frequently and survival has reached a plateau in the past decades. A poor response to chemotherapy is considered as risk factor for an unfavourable outcome. We have previously identified genetic markers predictive of treatment outcome in genes of cisplatin and doxorubicin metabolic pathways. However, the complex metabolism of the drugs used in osteosarcoma treatment involves a broader range of drug metabolic enzymes and transporters. Therefore we have performed large scale screening of 1,936 genetic variants in 231 genes known to be involved in drug metabolism and transport. Methods: From two cohorts of osteosarcoma patients (n = 139 and n = 177), germline DNA was genotyped using the DMET Plus array. Associations between genetic variants and ototoxicity (SIOP grade 1-4), histological response (HR) to preoperative cisplatin and doxorubicin based chemotherapy, and 5-year Disease Free Survival (DFS) were assessed by logistic regression models in PLINK and Cox proportional hazards models in GenABEL respectively. Results: 689 markers and 136 patients (cohort 1), and 669 markers and 174 patients (cohort 2) passed quality control (call rates > 0.9, minor allele frequency > 0.01). Upon meta-analysis, 16 markers were significantly associated (P< 0.05) with ototoxicity, including AOX1 encoding a protein involved in homeostasis of reactive oxygen species. A total of 14 variants showed association with HR, and 23 markers with 5-year DFS, with an overlapping marker in the energy metabolism gene SLC25A27. In addition, a previously detected association between an ABCC5 variant and DFS was confirmed. Conclusions: To the best of our knowledge, this is the first pharmacogenetic study in osteosarcoma patients studying a large number of drug metabolism and transporter genes. We have detected significant associations of treatment response and ototoxicity with genes previously unknown to be related to cisplatin and doxorubicin metabolism and transport. Upon replication, biological validation and prospective testing, these markers are of potential interest for the development of new treatment strategies and optimizing current therapy.
Racial disparities in characteristics and prognosis in Asian versus white patients receiving atezolizumab: An ancillary analysis of POPLAR and OAK studies
Authors: J. Qian, W. Nie, J. Lu, L. Zhang, Y. Zhang, B. Zhang, S. Wang, M. Hu, J. Xu, Y. Lou, Y. Dong, Y. Niu, B. Yan, R. Zhong, W. Zhang, T. Chu, H. Zhong, B.-H. Han
Journal: Annals of Oncology (2019)

Background: Racial differences in characteristics and prognosis of Asiatic and White patients receiving immunotherapy have not been well described. Methods: We studied 390 patients from the POPLAR and OAK studies who received atezolizumab with evaluable biomarker parameters retrieved from a subsequent blood-based study. The differences of Asians versus Whites in baseline characteristics, outcomes and genetic mutations of atezolizumab therapy were assessed. Results: Asiatic and White patients differed in characteristics including smoking history, baseline sum of the longest diameters (BLSLD), EGFR mutation frequency, programmed death-ligand 1 (PD-L1) expression and blood-based tumor mutational burden (bTMB) level. Overall survival (OS) was longer in Asians compared with Whites before (median OS: 18.7 vs. 11.1 mo; P = 0.005) and after (median OS: 20.9 vs. 12.6 mo; P = 0.005) propensity score matching (PSM). Race was an independent prognostic factor for OS (Asian vs White: HR 0.647, 95% CI 0.447-0.936, P = 0.021) in addition to performance status (PS), histology, BLSLD, and number of metastatic sites. The objective response rate (ORR) for Asians and Whites was 8.2% and 17.1%, respectively and disease control rate (DCR) was 51.2% and 47.7%, respectively. The blood-based mutational landscape differentiated between Asians and Whites. In the overall population, mutations of STK11, EGFR, KEAP1, POLE, GRM3, ATM and STAG2 were associated with treatment response while mutations of TP53, KEAP1, APC, RB1, CREBBP, EPHA5 and STAG2 were associated with OS. Comparing the frequency of efficacy- or prognosis- related mutations, Asians had more EGFR mutations and less TP53 and STK11 mutations than Whites. Conclusions: Asians and Whites differed in the clinicopathological features and mutational landscape which may explain the superior efficacy of atezolizumab in Asiatic patients with NSCLC. This study conveys implications for further studies on racial disparity in the treatment of immunotherapy. Legal entity responsible for the study: The authors. Funding: Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Support (No. 20161434). Disclosure: All authors have declared no conflicts of interest.
Abstract 20851: Incidence of Appropriate ICD Therapies After Elective Generator Replacement in Patient With Heart Failure Initially Implanted for Primary Prevention: A Systematic Literature Review and Metanalysis
Authors: Stefano Cornara, Roberto Rordor, Andrea Borin, Simone Savastano, Antonio Sanzo, Alessandro Vicentini, Barbara Petracci, Chiara Rebuffi, Catherine Klersy, Gaetano M De Ferrari
Journal: Circulation (2017)

Implantable cardioverter-defibrillator (ICD) is an effective therapy to reduce overall mortality in heart failure. When the ICD generator approaches the end of life, the majority of the patients un...
SAT-107-Effect of a multifactorial intervention (non-alcoholic beer, diet and exercise) on endothelial function, nutritional status and quality of life in patients with cirrhosis
Authors: Astrid Ruiz-Margain, May E. Espin-Nasser, Silvia L. Ríos-Torres, Berenice M. Román-Calleja, Elizabeth Moreno-Tavarez, Gabriela Fernández-del Rivero, Nayelli C. Flores-Garcia, Gretel Galicia_Hernández, Aldo Torre, Samantha González-Rodríguez, Osvely Méndez-Guerrero, Jose Luis Rodriguez, Ricardo Macias-Rodriguez
Journal: Journal of Hepatology (2019)
Natural killer group 2D receptor and its ligands in cancer immune escape
Authors: Shixin Duan, Weihua Guo, Zuxing Xu, Yunbo He, Chuting Liang, Yongzhen Mo, Yian Wang, Fang Xiong, Can Guo, Yong Li, Xiaoling Li, Guiyuan Li, Zhaoyang Zeng, Wei Xiong, Fuyan Wang
Journal: Molecular Cancer (2019)

The immune system plays important roles in tumor development. According to the immune-editing theory, immune escape is the key to tumor survival, and exploring the mechanisms of tumor immune escape can provide a new basis for the treatment of tumors. In this review, we describe the mechanisms of natural killer group 2D (NKG2D) receptor and NKG2D ligand (NKG2DL) in tumor immune responses. Natural killer (NK) cells are important cytotoxic cells in the immune system, and the activated NKG2D receptor on the NK cell surface can bind to NKG2DL expressed in tumor cells, enabling NK cells to activate and kill tumor cells. However, tumors can escape the immune clearance mediated by NKG2D receptor/NKG2DL through various mechanisms. The expression of NKG2D receptor on NK cells can be regulated by cells, molecules, and hypoxia in the tumor microenvironment. Tumor cells regulate the expression of NKG2DL at the level of transcription, translation, and post-translation and thereby escape recognition by NK cells. In particular, viruses and hormones have special mechanisms to affect the expression of NKG2D receptor and NKG2DL. Therefore, NKG2D\NKG2DL may have applications as targets for more effective antitumor therapy.
The role of chemotherapy in hormone receptor-positive and HER2-positive breast cancer patients over age 70.
Authors: Vincent Caggiano, Carol Parise
Journal: Journal of Clinical Oncology (2013)

e12511 Background: Standard adjuvant therapy for HER2 positive female breast cancer patients that are estrogen receptor (ER) positive is chemotherapy, trastuzumab, and endocrine therapy. For patients older than 70 years of age, the combination of chemotherapy and trastuzumab may increase the toxicity profile. The purpose of this study was to evaluate the role of chemotherapy in for the ER+/PR+/HER- and ER+/PR+/HER+ subtypes in patients over age 70. These subtypes differ only by HER2 status. Methods: We identified 13,167 cases of patients over age 70 with stages 1-3 first primary invasive breast cancer from the California Cancer Registry diagnosed between January 1, 2000 and December 31, 2010. Of these, 9,710 were ER+/PR+/HER- and 988 were ER+/PR+/HER+. Cox regression analysis adjusted for race/ethnicity, socioeconomic status, grade, and year of diagnosis was used to compare risk of mortality for combination endocrine and chemotherapy versus endocrine therapy alone. Analyses were conducted separately for each stage. Results: For the ER+/PR+/HER- subtype, there was no difference in the risk of mortality for patients given endocrine and chemotherapy versus endocrine therapy alone for stages 1 and 2. For stage 3, there was a 57% reduced risk of mortality (HR = 0.43; 95%CI: 0.27-0.69) for patients given combination chemo and endocrine therapy. For the ER+/PR+/HER+ subtype, there were no differences in risk of mortality in any stage due to treatment. Conclusions: With the exception of stage 3 patients with the ER+/PR+/HER- subtype, chemotherapy appears to add little or no benefit to risk of mortality for patients over 70 years of age. These results support the use of endocrine therapy and anti-HER2 therapy without chemotherapy in elderly patients with early stage, estrogen receptor positive, HER2 positive breast cancer.
A novel <i>de novo</i> mutation substantiates <i> <scp>KDF</scp> 1 </i> as a gene causing ectodermal dysplasia
Authors: C. Manaspon, S. Thaweesapphithak, T. Osathanon, K. Suphapeetiporn, T. Porntaveetus, V. Shotelersuk
Journal: British Journal of Dermatology (2019)
6-Month Outcomes of Tricuspid Valve Reconstruction for Patients With Severe Tricuspid Regurgitation
Authors: Georg Nickenig, Marcel Weber, Robert Schueler, Jörg Hausleiter, Michael Näbauer, Ralph S. von Bardeleben, Efthymios Sotiriou, Ulrich Schäfer, Florian Deuschl, Karl-Heinz Kuck, Felix Kreidel, Jean-Michel Juliard, Eric Brochet, Azeem Latib, Eustachio Agricola, Stephan Baldus, Kai Friedrichs, Prashanthi Vandrangi, Patrick Verta, Rebecca T. Hahn, Francesco Maisano
Journal: Journal of the American College of Cardiology (2019)