tbuckley/cabot-search huggingface dataset:
Extensive Molecular and Clinical Heterogeneity in Patients With Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children’s Oncology Group Randomized ACNS0332 Trial
Authors: Eugene I. Hwang, Marcel Kool, Peter C. Burger, David Capper, Lukas Chavez, Sebastian Brabetz, Chris Williams-Hughes, Catherine Billups, Linda Heier, Alok Jaju, Jeff Michalski, Yimei Li, Sarah Leary, Tianni Zhou, Andreas von Deimling, David T.W. Jones, Maryam Fouladi, Ian F. Pollack, Amar Gajjar, Roger J. Packer, Stefan M. Pfister, James M. Olson
Journal: Journal of Clinical Oncology (2018)

Purpose Children with histologically diagnosed high-risk medulloblastoma, supratentorial primitive neuroectodermal tumor of the CNS (CNS-PNET), and pineoblastoma (PBL) have had poor survival despite intensive treatment. We included these patients in this Children’s Oncology Group trial. Molecular profiling later revealed tumor heterogeneity that was not detectable at protocol inception. Enrollment of patients with CNS-PNET/PBL was subsequently discontinued, and outcomes for this part of the study are reported here. Patients and Methods In this phase III, four-arm prospective trial, consenting children age 3-22 years with newly diagnosed CNS-PNET were randomly assigned (1:1) to receive carboplatin during radiation and/or adjuvant isotretinoin after standard intensive therapy. Primary outcome measure was event-free survival (EFS) in the intent-to-treat population. Molecular tumor classification was retrospectively completed using DNA methylation profiling. Results Eighty-five participants with institutionally diagnosed CNS-PNETs/PBLs were enrolled. Of 60 patients with sufficient tissue, 31 were nonpineal in location, of which 22 (71%) represented tumors that were not intended for trial inclusion, including 18 high-grade gliomas (HGGs), two atypical teratoid rhabdoid tumors, and two ependymomas. Outcomes across tumor types were strikingly different. Patients with supratentorial embryonal tumors/PBLs exhibited 5-year EFS and overall survival of 62.8% (95% CI, 43.4% to 82.2%) and 78.5% (95% CI, 62.2% to 94.8%), respectively, whereas patients with molecularly classified HGG had EFS and overall survival of 5.6% (95% CI, 0% to 13.0%) and 12.0% (95% CI, 0% to 24.7%), respectively. Neither carboplatin, nor isotretinoin significantly altered outcomes for all patients. Survival for patients with HGG was similar to that of historic studies that avoid craniospinal irradiation and intensive chemotherapy. Conclusion For patients with CNS-PNET/PBL, prognosis is considerably better than previously assumed when molecularly confirmed HGGs are removed. Identification of molecular HGGs may spare affected children from unhelpful intensive treatment. This trial highlights the challenges of a histology-based diagnosis for pediatric brain tumors and indicates that molecular profiling should become a standard component of initial diagnosis.
Multicenter study to evaluate the efficacy and standardize radiofrequency ablation therapy for early breast cancer (RAFAELO study)
Authors: T. Kinoshita, S. Ohtani, H. Doihara, M. Takahashi, T. Fujisawa, N. Yamamoto, K. Aogi, T. Hojo
Journal: Annals of Oncology (2018)

Background: Given the increasing number of early-stage breast cancers detected by screening mammography, we aim to establish RFA as a minimally invasive, cost-efficient, and cosmetically acceptable local treatment. In our Phase I study, localized tumors with a maximum diameter of 2 cm, preoperatively diagnosed by imaging and histopathology, were treated with RFA. A 90% complete ablation rate was confirmed histopathologically. Trial design: The objective of our study is to demonstrate the non-inferiority of RFA compared with standard treatment in terms of local recurrence-free survival, which is the best index of local control. The inclusion criteria are untreated pts with histologically confirmed ductal carcinoma with a single localized tumor of 1.5 cm or less in the greatest dimension on preoperative imaging, no prior treatment for breast cancer. RFA is defined as a procedure in which a radiofrequency electrode needle is inserted into the breast lesion from the surface of the body under imaging guidance and thermal ablation with radiofrequency waves is performed. The Cool-tip™ RF Ablation Single Electrode Kit (Medtronic, Boulder, CO, USA) is recommended to standardize the evaluation of the effect of ablation. All pts receive RT and systemic therapy according to the ER, HER2, tumor grade and lymph node status of the primary breast cancer after RFA. Residual lesions after RFA will be assessed in all patients approximately 3 months after RT using imaging studies and pathological examination. VAB will be performed in all patients regardless of imaging results. If biopsy specimens reveals suspicious of viable tumor, additional excision will be performed. Follow-up evaluation for residual tumor every 12 months after RFA included clinical breast examination, diagnostic imagings (ultrasound, magnetic resonance, and mammography). The primary endpoint is 5-year local recurrence-free survival, and the secondary endpoints are residual lesion rate after treatment, overall survival, distant recurrence-free survival and adverse events of RFA. The pts accrual was started in August 2013. From 9 participating institutions, enrollment of 372 pts is planned over a 5-year accrual period. Clinical trial identification: UMIN-CTR: UMIN000005586. Legal entity responsible for the study: Takayuki Kinoshita. Funding: The Japan Agency for Medical Research and Development. Disclosure: All authors have declared no conflicts of interest.
Validation of Time in Range as an Outcome Measure for Diabetes Clinical Trials
Authors: Roy W. Beck, Richard M. Bergenstal, Tonya D. Riddlesworth, Craig Kollman, Zhaomian Li, Adam S. Brown, Kelly L. Close
Journal: Diabetes Care (2018)

OBJECTIVE This study evaluated the association of time in range (TIR) of 70–180 mg/dL (3.9–10 mmol/L) with the development or progression of retinopathy and development of microalbuminuria using the Diabetes Control and Complications Trial (DCCT) data set in order to validate the use of TIR as an outcome measure for clinical trials. RESEARCH DESIGN AND METHODS In the DCCT, blood glucose concentrations were measured at a central laboratory from seven fingerstick samples (seven-point testing: pre- and 90-min postmeals and at bedtime) collected during 1 day every 3 months. Retinopathy progression was assessed every 6 months and urinary microalbuminuria development every 12 months. Proportional hazards models were used to assess the association of TIR and other glycemic metrics, computed from the seven-point fingerstick data, with the rate of development of microvascular complications. RESULTS Mean TIR of seven-point profiles for the 1,440 participants was 41 ± 16%. The hazard rate of development of retinopathy progression was increased by 64% (95% CI 51–78), and development of the microalbuminuria outcome was increased by 40% (95% CI 25–56), for each 10 percentage points lower TIR (P &amp;lt; 0.001 for each). Results were similar for mean glucose and hyperglycemia metrics. CONCLUSIONS Based on these results, a compelling case can be made that TIR is strongly associated with the risk of microvascular complications and should be an acceptable end point for clinical trials. Although hemoglobin A1c remains a valuable outcome metric in clinical trials, TIR and other glycemic metrics—especially when measured with continuous glucose monitoring—add value as outcome measures in many studies.
The epigallocatechin gallate derivative Y6 reverses drug resistance mediated by the ABCB1 transporter both in vitro and in vivo
Authors: Yan Wen, Ruiqiang Zhao, Pranav Gupta, Yingfang Fan, Yunkai Zhang, Zhenguang Huang, Xiaohui Li, Yuangang Su, Lijuan Liao, Yu-An Xie, Donghua Yang, Zhe-Sheng Chen, Gang Liang
Journal: Acta Pharmaceutica Sinica B (2018)

Previously, we reported that Y6, a new epigallocatechin gallate derivative, is efficacious in reversing doxorubicin (DOX)--mediated resistance in hepatocellular carcinoma BEL-7404/DOX cells. In this study, we evaluated the efficacy of Y6 in reversing drug resistance both in vitro and in vivo by determining its effect on the adenosine triphosphate-binding cassette protein B1 transporter (ABCB1 or P-glycoprotein, P-gp). Our results showed that Y6 significantly sensitized cells overexpressing the ABCB1 transporter to anticancer drugs that are ABCB1 substrates. Y6 significantly stimulated the adenosine triphosphatase activity of ABCB1. Furthermore, Y6 exhibited a higher docking score as compared with epigallocatechin gallate inside the transmembrane domain of ABCB1. In addition, in the nude mouse tumor xenograft model, Y6 (110 mg/kg, intragastric administration), in combination with doxorubicin (2 mg/kg, intraperitoneal injection), significantly inhibited the growth of BEL-7404/DOX cell xenograft tumors, compared to equivalent epigallocatechin gallate. In conclusion, Y6 significantly reversed ABCB1-mediated multidrug resistance and its mechanisms of action may result from its competitive inhibition of the ABCB1 drug efflux function.
Abstract 13789: Prediction of Angioedema Among 12,557 Patients Receiving Enalapril
Authors: William J Kostis, Javier Cabrera, Julian Daeumer, Yuvraj S Chowdhury, Mrinali Shetty, Abel E Moreyra, John B Kostis
Journal: Circulation (2017)

Introduction: Angioedema is a rare but potentially life-threatening complication of ACE inhibition. We have published on the occurrence of angioedema with enalapril among 12,557 participants in the...
Analysis of the relationship between heading N / L and survival in patients treated with immunotherapy in lung cancer
Authors: N. De Dios Alvare, M. Costa Rivas, S. Agraso Busto, A. Alonso Herrero, M.J. Villanueva Silva, D. Pereiro Corbacho, C. GarcÍa Benito
Journal: Annals of Oncology (2018)
Recessive XLI: high prevalence of neurological disorders
Authors: B. Rodrigo-Nicolás, E. Bueno-Martínez, A. Martín-Santiago, J. Cañueto, A. Vicente, A. Torrelo, L. Noguera-Morel, A. Duat-Rodríguez, C. Jorge-Finnigan, I. Palacios-Álvarez, J.L. García-Hernández, D.F. Sebaratnam, R. González-Sarmiento, A. Hernández-Martín
Journal: British Journal of Dermatology (2018)
Impact of hormone receptor status in HER2+ early breast cancer: A paradigm shift in the trastuzumab era
Authors: A. De Nonneville, A. Gonçalves, J.-M. Boher, M. Cohen, F. Reyal, J.-M. Classe, S. Giard, P.-E. Colombo, X. Muracciol, E. Darai, E. Jouve, C. Mazouni, P. Gimbergues, A.-S. Azuar, E. Barranger, R. Rouzier, R. Villet, N. Chopin, E. Lambaudie, G. Houvenaeghel
Journal: Annals of Oncology (2018)
P3.09-22 Correlation Between Maximum Tumour Diameter Measurement on CT-Scan and Histopathological Specimen: An Indian Experience
Authors: M. Gowda, B. Bansal, V. Kumar, S. Deo, S. Bhoriwal, D. Jain, P. Malik, S. Jee Bharati, S. Kumar
Journal: Journal of Thoracic Oncology (2018)
The role of oxidatively generated DNA fragments in the formation of nucleic acid adducts
Authors: Amanda Bryant-Friedrich
Journal: Cancer Research (2008)

2253  The oxidation of nucleic acids plays a significant role in the development of cancer. The direct products of oxidative events are derived from all nucleic acid constituents: the base, sugar and the phosphate linkage. It has long been accepted that base adduction is a primary player resulting from the reaction of endogenous and exogenous substrates with DNA. Evidence has accumulated which reveals the formation of several electrophilic substrates from the oxidative damage of DNA when the target is the 2-deoxyribose moiety. The degradation of sugar based radicals; especially in the presence of oxygen, often results in the formation of small molecules capable of reacting with cellular nucleophiles. Through the study of the C-3’-thymidinyl radical in ssDNA using photocleavable precursors, we have determined that the aerobic degradation of this reactive intermediate results in the formation of several DNA damage fragments capable of forming adducts with nucleophilic cellular inhabitants. This work revealed that due to the flexibility of the single stranded oligonucleotide and the reactivity of the peroxylradical formed by the trapping of oxygen, several different degradation pathways are observed, each leading to a unique electrophilic sugar fragment. The work presented here will elucidate the reactions of several of these fragments with DNA bases and other cellular nucleophiles. The utility of these DNA adducts as biomarkers of oxidative stress will also be investigated.
Correlation of ctDNA and response in patients (pts) with PDGFRα D842 GIST treated with avapritinib
Authors: S. George, S. Bauer, R.L. Jones, C. Serrano, M. von Mehren, Y.-K. Kang, P. Schöffski, P. Cassier, F.A. Eskens, O. Mir, W.D. Tap, S.P. Chawla, P. Rutkowski, H. Shi, O. Schmidt-Kittler, B. Mar, M. Heinrich
Journal: Annals of Oncology (2018)
GW29-e0136 O-GlcNAc-Modified SNAP29 Inhibits Autophagy Degradation via the Disturbed SNAP29-STX17-VAMP8 Complex and Exacerbates Myocardial Injury in TypeⅠ Diabetic Rats
Authors: Lin Huang, Ping Yuan, Qiling Kong, Kui Hong
Journal: Journal of the American College of Cardiology (2018)
A Randomized Trial of Binocular Dig Rush Game Treatment for Amblyopia in Children Aged 7 to 12 Years
Authors: Jonathan M. Holmes, Ruth E. Manny, Elizabeth L. Lazar, Eileen E. Birch, Krista R. Kelly, Allison I. Summers, Stacy R. Martinson, Aparna Raghuram, Jeffrey D. Colburn, Christine Law, Justin D. Marsh, Derek P. Bitner, Raymond T. Kraker, David K. Wallace
Journal: Ophthalmology (2018)
Cardiac Computed Tomography in Troponin-Positive Chest Pain
Authors: Antonio Esposito, Anna Palmisano, Maurizio Barbera, Davide Vignale, Giulia Benedetti, Roberto Spoladore, Marco Bruno Ancona, Francesco Giannini, Michele Oppizzi, Alessandro Del Maschio, Francesco De Cobelli
Journal: JACC. Cardiovascular imaging (2018)
P3.07-14 Collaborations of Pharmacists with Lung Cancer Treatment by Prepared Patients Controlled Analgesia (PCA) for Perioperative Pain Control
Authors: K. Tani, H. Houchi, S. Kosaka, M. Kaji, S. Tsuji, K. Higuchi, Y. Isobe, Y. Honda, M. Kouzai, S. Yamashita
Journal: Journal of Thoracic Oncology (2018)
Abstract 20697: An Intracostal Pacing System: A Novel Alternative to Leadless Pacing
Authors: Martin C Burke, Alan Marcovechio, Rick Sanghera, Adrian Ebner
Journal: Circulation (2017)

Introduction: A novel extracardiac lead delivery method may offer the potential to provide pacing and defibrillation therapy while eliminating complications from vascular access and endocardial (le...
Psychological distress and health-related quality of life in women recently diagnosed with breast cancer in the Epi-GEICAM study
Authors: N. Fernández-De-Larrea, B. Pérez-Gómez, A. Ruiz, A.M. Casas, B. Bermejo, J.M. Baena-Cañada, S. Antolin, P. Sánchez Rovira, M. Ramos Vázquez, J.A. Garcia-Saénz, A. Anton Torres, M. Muñoz, C. Jara, M. Gil-Gil, E. Adrover, A. Oltra, J. Brunet, S. Bezares, M. Martín, M. Pollán
Journal: Annals of Oncology (2018)
Impact of different programmed cell death ligand-1 (PD-L1) expression algorithms on patient selection and durvalumab efficacy in urothelial carcinoma (UC)
Authors: J. Walker, M. Zajac, J. Ye, M. Scott, M. Ratcliffe, P. Scorer, C. Barker, H. Al-Masri, M.C. Rebelatto, A. Gupta, P. Mukhopadhay, S. Ferro, T. Powles, J.A. Williams
Journal: Annals of Oncology (2018)
GW29-e0300 Establishment of a predicting model for inpatient sudden cardiac death in a Chinese cardiac department population: a retrospective study
Authors: Luxiang Shang, Xianhui Zhou, Jianghua Zhang, Wenhui Zhang, ZuKela TuErHong, Yang Zhao, Wenkui Lv, Yaodong Li, Hongli Wang, Qina Zhou, Umesh Yadav, Baopeng Tang
Journal: Journal of the American College of Cardiology (2018)
Device Approved to Seal Coronary Artery Perforations
Authors: Rebecca Voelker
Journal: JAMA (2018)

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Aortic Stenosis (Japanese Version)
Authors: Faisal G. Bakaeen, Todd K. Rosengart, Blase A. Carabello
Journal: Annals of Internal Medicine (2017)

In the Clinic3 January 2017Aortic Stenosis (Japanese Version)Correction(s) for this article:CorrectionsNov 2022Correction: Japanese Translations of In the ClinicFREEFaisal G. Bakaeen, MD, Todd K. Rosengart, MD, and Blase A. Carabello, MDFaisal G. Bakaeen, MDSearch for more papers by this author, Todd K. Rosengart, MDSearch for more papers by this author, and Blase A. Carabello, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/IsTranslatedFrom_AITC201701030_Japanese SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Editors' Note: This article (available in PDF format) is the translated Japanese version of In the Clinic: Aortic Stenosis (Bakaeen FG, Rosengart TK, Carabello BA. Aortic Stenosis. Ann Intern Med. 2017;166:ITC1-ITC16. doi:10.7326/AITC201701030). Author, Article, and Disclosure InformationAffiliations: Correction: This article was updated on 1 November 2022 to remove the glossary of terms, which was not present on the original publication, and to indicate the translators of the article.Funding Source: American College of Physicians.Disclosures: Drs. Bakaeen, Rosengart, and Carabello, ACP Contributing Authors, have nothing to disclose. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-2270.With the assistance of additional physician writers, the editors of Annals of Internal Medicine develop In the Clinic using MKSAP and other resources of the American College of Physicians.In the Clinic does not necessarily represent official ACP clinical policy. For ACP clinical guidelines, please go to https://www.acponline.org/clinical_information/guidelines/. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAortic Stenosis Faisal G. Bakaeen , Todd K. Rosengart , and Blase A. Carabello Correction: Japanese Translations of In the Clinic Metrics Cited byCorrection: Japanese Translations of In the ClinicThe Clinical Value of Heart Rate Monitoring Using an Apple Watch 3 January 2017Volume 166, Issue 1Page: JITC1-JITC16 ePublished: 16 October 2018 Issue Published: 3 January 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
GW29-e0030 Potassium Supplement blunts the effects of high sodium intake on serum retinol-binding protein 4 levels in humans
Authors: Fuqiang Liu, Yong Zhang, Ronghuai Zhang, Zhongwei Liu, Shuo Pan, Li Hu, Qingyu Wang, Junkui Wang
Journal: Journal of the American College of Cardiology (2018)
Cell surface polysaccharides of <i>Bifidobacterium bifidum</i> induce the generation of Foxp3 <sup>+</sup> regulatory T cells
Authors: Ravi Verma, Changhon Lee, Eun-Ji Jeun, Jaeu Yi, Kwang Soon Kim, Ambarnil Ghosh, Seohyun Byun, Choong-Gu Lee, Hye-Ji Kang, Gi-Cheon Kim, Chang-Duk Jun, Gwenaël Jan, Chang-Hee Suh, Ju-Yang Jung, Jonathan Sprent, Dipayan Rudra, Cristina De Castro, Antonio Molinaro, Charles D. Surh, Sin-Hyeog Im
Journal: Science Immunology (2018)

Cell wall components of probiotic bacterium Bifidobacterium bifidum drive induction of regulatory T cells in the gut.
Afatinib dose intensity and clinical efficacy in advanced EGFR-mutated non-small cell lung cancer: UK multicentre real-life data
Authors: C. Escriu, M. Sallam, L.P. del Carpio, N. Tokaca, L. Solway, R. Shah, A. Fouzia, Q. Ghafoor, S. Popat, P.E. Postmus
Journal: Annals of Oncology (2018)
The role of comprehensive evaluation for clinical complete response in predicting pathologic complete response in patients treated with neoadjuvant chemoradiation for esophageal squamous cell carcinoma (ESCC)
Authors: H.-S. Im, J. Kang, Y.-H. Kim, H.R. Kim, J.H. Kim, H.-Y. Jung, G.-H. Lee, H.J. Song, D.H. Kim, K.D. Choi, J.H. Lee, J.Y. Ahn, J.-S. Ryu, K.-J. Cho, S.-B. Kim, S.R. Park
Journal: Annals of Oncology (2018)
GW29-e1129 Clinical Outcomes Associated with Medical Management versus Coronary Intervention in Patients with Acute Coronary Syndrome
Authors: Alessandro Lupi, Dajun Chai, Amr Elhadidy, Cetin Erol, Yaling Han, Chunjian Li, Yihong Sun, Shuyang Zhang, Dara Paek, Michael del Aguila, Shalini Girotra
Journal: Journal of the American College of Cardiology (2018)
GW29-e1123 Computed Tomography Angiography-Derived Fractional Flow Reserve (CT-FFR) for the Detection of Myocardial Ischemia-with Invasive Fractional Flow Reserve as Reference: Systematic Review and Meta-Analysis
Authors: Baiyan Zhuang, Shuli Wang, Shihua Zhao, Arlene Sirajuddin, Arai E. Andrew, Minjie Lu
Journal: Journal of the American College of Cardiology (2018)
Enhancing Abiraterone Acetate Efficacy in Androgen Receptor–positive Triple-negative Breast Cancer: Chk1 as a Potential Target
Authors: Thomas Grellety, Celine Callens, Elodie Richard, Adrien Briaux, Valérie Vélasco, Marina Pulido, Anthony Gonçalves, Pierre Gestraud, Gaetan MacGrogan, Hervé Bonnefoi, Bruno Cardinaud
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Our aim was to identify predictive factors of abiraterone acetate efficacy and putative new druggable targets in androgen receptor (AR)-positive triple-negative breast cancer (TNBC) treated in the UCBG 2012-1 trial. Experimental Design: We defined abiraterone acetate response as either complete or partial response, or stable disease at 6 months. We sequenced 91 general and breast cancer–associated genes from the tumor DNA samples. We analyzed transcriptomes from the extracted RNA samples on a NanoString platform and performed IHC using tissue microarrays. We assessed abiraterone acetate and Chk1 inhibitors (GDC-0575 and AZD7762) efficacies, either alone or in combination, on cell lines grown in vitro and in vivo. Results: Classic IHC apocrine markers including AR, FOXA1, GGT1, and GCDFP15, from patients' tumors allowed identifying abiraterone acetate-responders and nonresponders. All responders had clear apocrine features. Transcriptome analysis revealed that 31 genes were differentially expressed in the two subgroups, 9 of them being linked to proliferation and DNA damage repair. One of the most significant differences was the overexpression, in nonresponders, of CHEK1, a gene encoding Chk1, a protein kinase that can be blocked by specific inhibitors. On the basis of cell line experiments, abiraterone acetate and Chk1 inhibitor combination showed at least additive effect on cell viability, cell cycle, apoptosis, and accumulation of DNA damages. In vivo, orthotopic xenograft experiments confirmed the efficacy of this combination therapy. Conclusions: This study suggests that apocrine features can be helpful in the identification of abiraterone acetate-responders. We identified Chk1 as a putative drug target in AR-positive TNBCs.