tbuckley/cabot-search huggingface dataset:
Tivozanib versus sorafenib as initial targeted therapy for patients with advanced renal cell carcinoma: Results from a phase III randomized, open-label, multicenter trial.
Authors: Robert John Motzer, Dmitry Nosov, Tim Eisen, Igor N. Bondarenko, Vladmir Lesovoy, Oleg N. Lipatov, Piotr Tomczak, Alexey A. Lyulko, Anna Alyasova, Mihai Harza, Mikhail Kogan, Boris Y. Alexeev, Cora N. Sternberg, Cezary Szczylik, Joshua Zhang, Andrew Louis Strahs, Brooke Esteves, William J. Slichenmyer, Anna Berkenblit, Thomas E. Hutson
Journal: Journal of Clinical Oncology (2012)

4501 Background: Tivozanib, a potent, selective, long half-life tyrosine kinase inhibitor targeting all three VEGF receptors, showed activity and tolerability in a Phase II trial (JCO 2011;29[18S]:4550). Methods: Patients (pts) with clear cell advanced renal cell carcinoma (RCC), prior nephrectomy, RECIST-defined measurable disease, and Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 were randomized 1:1 to tivozanib (T) 1.5 mg once daily for 3 weeks (wks) followed by 1 wk rest, or sorafenib (S) 400 mg twice daily continuously in a 4-wk cycle. Pts were treatment naïve or received no more than 1 prior systemic therapy for metastatic disease; pts receiving prior VEGF- or mTOR-targeted therapy were excluded. The primary endpoint was progression-free survival (PFS) per blinded, independent radiological review. 500 pts were to be enrolled to observe 310 events, yielding 90% power to detect medians of 9.7 and 6.7 months (m) with 5% type I error (2-sided). Results: A total of 517 pts were randomized to T (n=260) or S (n=257). Demographics were well balanced between the 2 groups, except ECOG 0 (T: 45% vs S: 54%, p=0.035). Median PFS was 11.9 m for T vs 9.1 m for S (HR=0.797, 95% CI 0.639–0.993; p=0.042). In the treatment-naïve stratum (70% of pts enrolled in each arm), the median PFS was 12.7 m for T vs 9.1 m for S (HR 0.756, 95% CI 0.580–0.985; p=0.037). In all pts, objective response rate (ORR) for T was 33% vs 23% for S (p=0.014). The most common adverse event (AE; all grades/≥grade 3) for T was hypertension (T: 46%/26% vs S: 36%/18%) and for S was hand-foot syndrome (T: 13%/2% vs S: 54%/17%). Other important AEs included diarrhea (T: 22%/2% vs S: 32%/6%), fatigue (T: 18%/5% vs S: 16%/4%), and neutropenia (T: 10%/2% vs S: 9%/2%). Patient-reported outcome data are being analyzed. Overall survival data are not mature. Conclusions: Tivozanib demonstrated significant improvement in PFS and ORR compared with sorafenib as initial targeted treatment for advanced RCC. The safety profile of tivozanib is favorable, and includes a low incidence of fatigue, diarrhea, myelosuppression, and hand-foot syndrome.
ULTRASOUND TISSUE TEXTURE-BASED ANALYSIS OF MYOCARDIAL FIBROSIS: RADIOMICS AND MACHINE LEARNING APPROACH
Authors: Nobuyuki Kagiyama, Sirish Shrestha, Jung Sun Cho, Muhammad Khalil, Yashbir Singh, Abhiram Challa, Grace Casaclang-Verzosa, Partho P. Sengupta
Journal: Journal of the American College of Cardiology (2020)
METOTHREXATE DECREASES CARDIOMYOCYTE HYPERTROPHY AND INFLAMMATORY CYTOKINE EXPRESSION IN A HF MODEL
Authors: Omar Lozano, Eduardo Vázquez-Garza, Martín Ramos, Héctor Chapoy-Villanueva, Gerardo García-Rivas, Guillermo Torre-Amione
Journal: Journal of the American College of Cardiology (2020)
DOES STUDY SUBJECT RACE, ETHNICITY OR SEX INFLUENCE CARDIOLOGY RESEARCH SITE PERFORMANCE
Authors: Wayne B. Batchelor, Abdulla Damluji, Mona Fluzat, David E. Kandzari, Scott Barnett, Dominic Allocco, Kristine Roy, Matthew William Sherwood, Behnam Tehrani, Kelly Epps, Christopher O'Connor, Roxana Mehran
Journal: Journal of the American College of Cardiology (2020)
ATHEROSCLEROTIC BURDEN AND PROGRESSION IN THE LEFT CIRCUMFLEX ARTERY VERSUS THE OTHER MAJOR CORONARY ARTERIES: INSIGHTS FROM THE PROGRESSION OF ATHEROSCLEROTIC PLAQUE DETERMINED BY COMPUTED TOMOGRAPHIC ANGIOGRAPHY IMAGING (PARADIGM) STUDY
Authors: Maxim Bax, Alexander R. van Rosendael, Inge J. van den Hoogen, Xiaoyue Ma, Umberto Gianni, Sara W. Tantawy, Daniel S. Berman, Hyuk-Jae Chang, Jagat Narula, Jonathon Leipsic, Martin Hadamitzky, Matthew J. Budoff, Peter Howard Stone, Sang-Eun Lee, Sanghoon Shin, Yong-Jin Kim, James Min, Fay Lin, Leslee J. Shaw
Journal: Journal of the American College of Cardiology (2020)
Reverse TCR repertoire evolution toward dominant low-affinity clones during chronic CMV infection
Authors: Kilian Schober, Florian Voit, Simon Grassmann, Thomas R. Müller, Joel Eggert, Sebastian Jarosch, Bianca Weißbrich, Patrick Hoffmann, Lisa Borkner, Enzo Nio, Lorenzo Fanchi, Christopher R. Clouser, Aditya Radhakrishnan, Lorenz Mihatsch, Philipp Lückemeier, Justin Leube, Georg Dössinger, Ludger Klein, Michael Neuenhahn, Jennifer D. Oduro, Luka Cicin-Sain, Veit R. Buchholz, Dirk H. Busch
Journal: Nature Immunology (2020)
EFFICACY AND SAFETY OF ALIROCUMAB IN A REAL-LIFE SETTING IN PATIENTS WITH OR WITHOUT FAMILIAL HYPERCHOLESTEROLEMIA: THE ODYSSEY APPRISE STUDY
Authors: Daniel Gaudet, José Luis López-Sendón, Maurizio Averna, Gregory Bigot, Maciej Banach, Alexia Letierce, Megan Loy, Rita Samuel, Isabela Batsu, Patrick Henry
Journal: Journal of the American College of Cardiology (2020)
A Feed-Forward Mechanosignaling Loop Confers Resistance to Therapies Targeting the MAPK Pathway in BRAF-Mutant Melanoma
Authors: Christophe A. Girard, Margaux Lecacheur, Rania Ben Jouira, Ilona Berestjuk, Serena Diazzi, Virginie Prod'homme, Aude Mallavialle, Frédéric Larbret, Maéva Gesson, Sébastien Schaub, Sabrina Pisano, Stéphane Audebert, Bernard Mari, Cédric Gaggioli, Eleonora Leucci, Jean-Christophe Marine, Marcel Deckert, Sophie Tartare-Deckert
Journal: Cancer Research (2020)

Aberrant extracellular matrix (ECM) deposition and stiffening is a physical hallmark of several solid cancers and is associated with therapy failure. BRAF-mutant melanomas treated with BRAF and MEK inhibitors almost invariably develop resistance that is frequently associated with transcriptional reprogramming and a de-differentiated cell state. Melanoma cells secrete their own ECM proteins, an event that is promoted by oncogenic BRAF inhibition. Yet, the contribution of cancer cell-derived ECM and tumor mechanics to drug adaptation and therapy resistance remains poorly understood. Here, we show that melanoma cells can adapt to targeted therapies through a mechanosignaling loop involving the autocrine remodeling of a drug-protective ECM. Analyses revealed that therapy-resistant cells associated with a mesenchymal dedifferentiated state displayed elevated responsiveness to collagen stiffening and force-mediated ECM remodeling through activation of actin-dependent mechanosensors Yes-associated protein (YAP) and myocardin-related transcription factor (MRTF). Short-term inhibition of MAPK pathway also induced mechanosignaling associated with deposition and remodeling of an aligned fibrillar matrix. This provided a favored ECM reorganization that promoted tolerance to BRAF inhibition in a YAP- and MRTF-dependent manner. Matrix remodeling and tumor stiffening were also observed in vivo upon exposure of BRAF-mutant melanoma cell lines or patient-derived xenograft models to MAPK pathway inhibition. Importantly, pharmacologic targeting of YAP reversed treatment-induced excessive collagen deposition, leading to enhancement of BRAF inhibitor efficacy. We conclude that MAPK pathway targeting therapies mechanically reprogram melanoma cells to confer a drug-protective matrix environment. Preventing melanoma cell mechanical reprogramming might be a promising therapeutic strategy for patients on targeted therapies. SIGNIFICANCE: These findings reveal a biomechanical adaptation of melanoma cells to oncogenic BRAF pathway inhibition, which fuels a YAP/MRTF-dependent feed-forward loop associated with tumor stiffening, mechanosensing, and therapy resistance. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/10/1927/F1.large.jpg.
Difference in outcome of adolescents (14–17 years) with acute lymphoblastic leukemia (ALL) enrolled in the Italian pediatric (AIEOP) and adult (GIMEMA) multicenter protocols
Authors: A. Testi
Journal: Journal of Clinical Oncology (2006)

9024 Background: Progress in the treatment of acute lymphoblastic leukemia (ALL) has led to better survival rates; however, this benefit has not extended in the same proportion to adolescents who retain a lower cure rate, compared to younger patients. Based on some recent reports, adolescents treated on pediatric ALL trials seem to have a significantly better event free-survival (EFS) than those treated on adult trials. Methods: We retrospectively compared the results obtained in 242 adolescents enrolled either in the national cooperative pediatric (AIEOP; n=150) or adult (GIMEMA; n=92) ALL trials, between 4/1996 and 10/2003. Results: The characteristics of the patients at diagnosis in the two groups under examination were comparable except for age (median age: 15 in the AIEOP vs 16 in the GIMEMA trials). Adolescents in the AIEOP protocols had a better complete remission (CR) rate (97%) compared to those treated with the GIMEMA protocols (89%). Overall treatment results estimated at 2 years were significantly superior for patients treated in the pediatric trials: survival 81% vs 71% and EFS 78% vs 47%. This difference was significant also at the multivariate analysis. Conclusions: Our results support, in keeping with other studies, the concept that adolescents with ALL have a better outcome if treated in pediatric trials. No significant financial relationships to disclose.
Prognostic stratification of k-RAS wild type colorectal cancer patients receiving irinotecan-cetuximab treatment: Preliminary results of a prospective study.
Authors: Mario Scartozzi, Riccardo Giampieri, Alessandra Mandolesi, Khaled Mahmoud Abouelkhair, Cristian Loretelli, Michela Del Prete, Luca Faloppi, Alessandro Bittoni, Maristella Bianconi, Luca Cecchini, Ezzeldin M. Ibrahim, Italo Bearzi, Stefano Cascinu
Journal: Journal of Clinical Oncology (2013)

3591 Background: Translational research identified numerous putative markers for a “beyond-k-RAS” selection of colorectal cancer patients receiving cetuximab, but none of these entered clinical practice mainly because prospective validation is lacking. The aim of our study was to evaluate whether a panel of biomarkers, prospectively analysed may be able to predict patients’ clinical outcome more accurately than k-RAS status alone. Methods: Metastatic, K-RAS wild type colorectal cancer patients, candidate to receive second/third-line cetuximab with chemotherapy have been prospectively allocated, after informed consent, into 2 groups on the basis of their genetic profile: favourable (BRAF and PIK3CA exon 20 wild type, EGFR GCN ≥ 2.6, HER-3 Rajkumar score ≤ 8, IGF-1 immunostaining &lt; 2) and unfavourable (any of the previous markers altered or mutated). All patients received cetuximab treatment as planned by treating physician who was unaware of biomarkers results. To detect a difference in terms of response rate (RR) among patients with an unfavourable profile (estimated around 25%) and patients with a favourable profile (estimated around 60%), assuming a probability alpha of 0.05 and beta of 0.05, required sample size will be 46 patients. Results: 31 patients have been enrolled, most patients (27, 86%) received cetuximab as third-line. Eleven patients (35%) were allocated to the favourable profile and 20 patients (75%) to the unfavourable profile. Patients with the unfavourable profile showed 1 BRAF mutation, 2 PIK3CA exon 20 mutations, 12 cases of EGFR GCN &lt; 2.6, 13 cases of HER-3 and 11 cases of IGF-1 overexpression respectively. RR in the favourable and unfavourable group was 7/11 (64%) and 1/20 (5%) (p= 0.008) respectively. The favourable group also showed an improved median TTP (8 months vs. 2.6 months, p = 0.0007) and OS (16 months vs. 6 months, p = 0.0002). Conclusions: Our results suggest that prospective selection of candidates for cetuximab may be able to improve clinical outcome in patients with a favourable profile. This approach, if confirmed, may also allow an early switch to alternative treatment in patients with an unfavourable profile.
SINGLE VS. SERIAL ASSESSMENTS OF ARTERIAL HEMODYNAMICS TO PREDICT THORACIC AORTIC ANEURYSM EXPANSION
Authors: Owais Mian, Munir Boodhwani, Luc Beauchesne, Kwan-Leung Chan, Carole Dennie, George Wells, Thais Coutinho
Journal: Journal of the American College of Cardiology (2020)
GENOME-WIDE ASSOCIATION STUDY OF PERIPHERAL ARTERY DISEASE AND CAROTID ARTERY DISEASE IDENTIFIES NOVEL GENETIC LOCI AND COAGULATION PATHWAYS
Authors: Chayakrit Krittanawong, Jagat Narula, Kipp Johnson, Navneet Narula, Ha My Vy, Fahd Al-Mulla, Ebaa Al-Ozairi, Jeffrey Berger, Jeffrey W. Olin, Ron Do, Girish Nadkarni
Journal: Journal of the American College of Cardiology (2020)
International Measles Vaccination Campaign to Reach Millions
Authors: Bridget M. Kuehn
Journal: JAMA (2020)

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SAFETY AND COMPLICATIONS OF CATHETER ABLATION FOR ATRIAL FIBRILLATION IN THE UNITED STATES: AN UPDATED ANALYSIS FROM THE NATIONAL INPATIENT SAMPLE DATABASE
Authors: Lingling Wu, Bharat Narasimhan, Faris Haddadin, Kam Ho, Yingying Zheng, Bharat Kantharia
Journal: Journal of the American College of Cardiology (2020)
Interim results of phase II trial of the cyclin-dependent kinase 4/6 inhibitor PD-0332991 in refractory retinoblastoma protein positive germ cell tumors.
Authors: David J. Vaughn, Maryann Gallagher, Priti Lal, Mark Alan Rosen, Wei-Ting Hwang, Lawrence H. Einhorn, Peter J. O'Dwyer
Journal: Journal of Clinical Oncology (2012)

4596 Background: Deregulation of the retinoblastoma pathway in germ cell tumors (GCT) has been well documented. We previously reported that PD-0332991, a selective oral inhibitor of cyclin-dependent kinase 4/6, led to prolonged disease control in 3 patients (pts) with unresectable growing teratoma syndrome (NEJM, 2009). For these reasons, we initiated a phase II trial of PD-0332991 in pts with refractory retinoblastoma protein (Rb) positive (+) GCT. Methods: Pts with incurable refractory GCT that expressed Rb by immunohistochemistry were treated with PD-0332991 125 mg orally daily for 21 days followed by a 7 day break (cycle = 28 days). Tumor assessments were performed every 2 cycles. The primary endpoint was 6-month progression-free survival (PFS) rate. Results: As of 1/12/2012, archived tumors from 36 pts with refractory GCT were stained for Rb and 35 had ≥ 1+ staining. 18 of planned 24 pts have been enrolled and treated. Pt characteristics: 17 male, 1 female; median age, 31 years (range, 17-56); median ECOG performance status, 1 (range, 0-1); median number of prior chemotherapy regimens, 2 (range, 1-6); median number prior surgeries, 3 (range, 1-6). Pt pathology: mature teratoma (MT), 7; teratoma with malignant transformation (TMT), 7; mixed GCT, 2; late relapse (LR), 2. 16 pts are evaluable; 2 pts are too early to evaluate. 5 of 16 evaluable pts achieved 6-month PFS (3 MT, 1 TMT, 1 LR). Median PFS was 2 months (range, 0-17). No objective radiological responses were observed; 7 patients had best response of stable disease by RECIST criteria (3 MT, 3 TMT, 1 LR). Grade 3 toxicity included neutropenia (4 pts), thrombocytopenia (3 pts), anemia (1 pt), mucositis (1 pt). No grade 4 toxicity was seen. Analysis of archival tumor for predictive biomarkers including Rb and p16 expression is being performed. Conclusions: PD-0332991 has resulted in 6-month PFS in pts with refractory Rb + GCT, including pts with incurable teratomas.
DEVELOPMENT OF A NOVEL COMPUTATIONAL FLUID DYNAMICS MODEL APPLIED ON CARDIAC COMPUTED TOMOGRAPHY FOR ASSESSMENT OF REGIONAL HEMODYNAMIC CHANGES IN THE LEFT ATRIAL APPENDAGE DURING ATRIAL FIBRILLATION OR SINUS RHYTHM
Authors: Ioanna Kosmidou, Grigoris Grigoriadis, Antonis Sakellarios, Mengdan Liu, Katerina Naka, Lampros K. Michalis, Dimitris Fotiadis, Christopher R. Ellis
Journal: Journal of the American College of Cardiology (2020)
Daniel Porte Jr.: A Leader in Our Understanding of the Role of Defective Insulin Secretion and Action in Obesity and Type 2 Diabetes
Authors: Jerry P. Palmer, Steven E. Kahn, Michael W. Schwartz, Gerald J. Taborsky, Stephen C. Woods
Journal: Diabetes Care (2020)

Daniel Porte Jr. was born in New York City in 1931, and with his father being a clinical cardiologist, medicine was part of his life from very early on. After completing his undergraduate studies at Brown University, he commenced his migration west by first attending medical school at the University of Chicago, where he graduated with honors in 1957. Completing his westward migration, Dan moved to San Francisco for his internship and residency training in medicine in the University of California system. During that time, he spent 2 years performing research with Richard Havel at the Cardiovascular Research Institute at the University of California, San Francisco. It was during this period that Dan published his first scientific article describing cholesterol-labeled lipoproteins as a tracer for examining the fate of plasma cholesterol (1), as well as a clinical research study of an unusual patient with McArdle syndrome causing defective muscle phosphorylase leading to defective exercise tolerance (2).



Daniel Porte Jr. at medical school graduation, University of Chicago, 1957



Based on this early experience, it became clear to Dan that his future lay in academia and clinical research, so he decided to travel north to the University of Washington (UW) in Seattle for fellowship training in endocrinology and metabolism. One of the academic attractants at the time was Robert H. Williams, who was a leading national force in endocrinology and Chairman of Medicine at UW. As lipids were an important area of investigation in Seattle as well as in San Francisco at the time, Dan continued to work in this area during his fellowship and early faculty years. Following the development of the insulin radioimmunoassay, however, a whole new field opened up and he moved his research in a completely new direction.

Dan commenced his research in glucose metabolism and diabetes …
Macrophage lineages in heart valve development and disease
Authors: Andrew J Kim, Na Xu, Katherine E Yutzey
Journal: Cardiovascular Research (2020)

Abstract Heterogeneous macrophage lineages are present in the aortic and mitral valves of the heart during development and disease. These populations include resident macrophages of embryonic origins and recruited monocyte-derived macrophages prevalent in disease. Soon after birth, macrophages from haematopoietic lineages are recruited to the heart valves, and bone marrow transplantation studies in mice demonstrate that haematopoietic-derived macrophages continue to invest adult valves. During myxomatous heart valve disease, monocyte-derived macrophages are recruited to the heart valves and they contribute to valve degeneration in a mouse model of Marfan syndrome. Here, we review recent studies of macrophage lineages in heart valve development and disease with discussion of clinical significance and therapeutic applications.
Immune Checkpoint Inhibitors in Thoracic Malignancies: Review of the Existing Evidence by an IASLC Expert Panel and Recommendations
Authors: Jordi Remon, Francesco Passiglia, Myung-Ju Ahn, Fabrice Barlesi, Patrick M. Forde, Edward B. Garon, Scott Gettinger, Sarah B. Goldberg, Roy S. Herbst, Leora Horn, Kaoru Kubota, Shun Lu, Laura Mezquita, Luis Paz-Ares, Sanjay Popat, Kurt A. Schalper, Ferdinandos Skoulidis, Martin Reck, Alex A. Adjei, Giorgio V. Scagliotti
Journal: Journal of Thoracic Oncology (2020)
Recombinant adenoviral human p53 gene combined with chemoradiotherapy in treatment of advanced unresectable head and neck cancer.
Authors: Jihong Shu
Journal: Journal of Clinical Oncology (2012)

e16011 Background: In head and neck cancer, p53 mutations are present in up 60% of head and neck cancers. Studies indicated p53 gene could increase both radio- and chemo-sensitivities. In this study, we investigate the effectiveness of recombinant adenoviral human p53 gene (rAd-p53) combined with chemoradiotherapy in treatment of advanced unresectable head and neck cancer. Methods: From May 2008 to Dec. 2011, 48 patients with an advanced unresectable head and neck cancer, 29 males and 18 females with an average of 61.3 years old, were included this study. Those patients were treated with intratumoral injection of rAd-p53 at a dose 1-3 ×10 12 viral particles (VP) , once every 3 days for 6 times. Chemotherapy regimen consisted of cisplatin 60 mg/m 2 on d1 and 5-Fu 600 mg/m 2 on d1-5, given intravenously every 3 weeks for 3 cycles. Radiation were given at a dose of 2Gy/f, five fractions a week for a total dose 50~70Gy. Patients were monitored for response, long-term efficacy and adverse events. Results: The median follow-up time was 21.2 months (6~39 months). Overall response rate was 91.7% (44/48), 47.9% (23/48) of complete responses and 43.8% (23/48) of partial responses. One-year overall survival was 79.2% and local progression-free survival was 70.8%. At the last follow-up, the overall survival was 72.9%. Forty-six patients experienced self-limited fever after administration of p53. Conclusions: rAd-p53 gene therapy as a component of comprehensive treatment for advanced unresectable head and neck cancer showed significant beneficial effects.
LIVING WITH CONGENITAL AORTIC STENOSIS: EXERCISE RESTRICTION, PATTERNS OF ADHERENCE, AND QUALITY OF LIFE
Authors: Laura Mansfield, Jeffrey Reichman, David Crowley, Jonathan Flyer, Kaitlyn Freeman, Kimberlee Gauvreau, Stewart Mackie, Bradley Marino, Jane Newburger, Sonja Ziniel, David Brown
Journal: Journal of the American College of Cardiology (2020)
REPEATED ULTRASOUND TARGETED DELIVERY OF EXOSOMES DERIVED FROM BONE MESENCHYMAL STEM CELLS STIMULATE ANGIOGENESIS AND REDUCE ADVERSE REMODELING AFTER MYOCARDIAL INFARCTION
Authors: Qing Deng, Qing Zhou, Dan Jia, Hao Wang, Yuanting Yang, Ye Xiong, Yijia Wang
Journal: Journal of the American College of Cardiology (2020)
EVALUATION OF THE RIGHT VENTRICULAR SYSTOLIC FUNCTION RECOVERY AND RIGHT VENTRICULAR REMODELING AFTER PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH INFERIOR WALL MYOCARDIAL INFARCTION BY SPECKLE TRACK IMAGING
Authors: Xue Yao, Bo Hu, Tuantuan Tan, Jinling Chen, Qing Zhou
Journal: Journal of the American College of Cardiology (2020)
ASSOCIATION OF ECG MEASURES AND BIOMARKERS OF INFLAMMATION AND CARDIAC INJURY (GDF-15 AND HS-CTNT) IN MIDDLE-AGED AND OLDER ADULTS: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS
Authors: Leonard Ilkhanoff, Stephen Seliger, Henry Tran, Marco Sbolli, Joao A.C. Lima, Christopher R. DeFilippi
Journal: Journal of the American College of Cardiology (2020)