tbuckley/cabot-search huggingface dataset:
MR/PET Imaging of the Cardiovascular System
Authors: Philip M. Robson, Damini Dey, David E. Newby, Daniel Berman, Debiao Li, Zahi A. Fayad, Marc R. Dweck
Journal: JACC. Cardiovascular imaging (2017)

Cardiovascular imaging has largely focused on identifying structural, functional, and metabolic changes in the heart. The ability to reliably assess disease activity would have major potential clinical advantages, including the identification of early disease, differentiating active from stable conditions, and monitoring disease progression or response to therapy. Positron emission tomography (PET) imaging now allows such assessments of disease activity to be acquired in the heart, whereas magnetic resonance (MR) scanning provides detailed anatomic imaging and tissue characterization. Hybrid MR/PET scanners therefore combine the strengths of 2 already powerful imaging modalities. Simultaneous acquisition of the 2 scans also provides added benefits, including improved scanning efficiency, motion correction, and partial volume correction. Radiation exposure is lower than with hybrid PET/computed tomography scanning, which might be particularly beneficial in younger patients who may need repeated scans. The present review discusses the expanding clinical literature investigating MR/PET imaging, highlights its advantages and limitations, and explores future potential applications.
Endothelial Activation and Blood–Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells
Authors: Juliane Gust, Kevin A. Hay, Laïla-Aïcha Hanafi, Daniel Li, David Myerson, Luis F. Gonzalez-Cuyar, Cecilia Yeung, W. Conrad Liles, Mark Wurfel, Jose A. Lopez, Junmei Chen, Dominic Chung, Susanna Harju-Baker, Tahsin Özpolat, Kathleen R. Fink, Stanley R. Riddell, David G. Maloney, Cameron J. Turtle
Journal: Cancer Discovery (2017)

Lymphodepletion chemotherapy followed by infusion of CD19-targeted chimeric antigen receptor-modified T (CAR-T) cells can be complicated by neurologic adverse events (AE) in patients with refractory B-cell malignancies. In 133 adults treated with CD19 CAR-T cells, we found that acute lymphoblastic leukemia, high CD19+ cells in bone marrow, high CAR-T cell dose, cytokine release syndrome, and preexisting neurologic comorbidities were associated with increased risk of neurologic AEs. Patients with severe neurotoxicity demonstrated evidence of endothelial activation, including disseminated intravascular coagulation, capillary leak, and increased blood-brain barrier (BBB) permeability. The permeable BBB failed to protect the cerebrospinal fluid from high concentrations of systemic cytokines, including IFNγ, which induced brain vascular pericyte stress and their secretion of endothelium-activating cytokines. Endothelial activation and multifocal vascular disruption were found in the brain of a patient with fatal neurotoxicity. Biomarkers of endothelial activation were higher before treatment in patients who subsequently developed grade ≥4 neurotoxicity.Significance: We provide a detailed clinical, radiologic, and pathologic characterization of neurotoxicity after CD19 CAR-T cells, and identify risk factors for neurotoxicity. We show endothelial dysfunction and increased BBB permeability in neurotoxicity and find that patients with evidence of endothelial activation before lymphodepletion may be at increased risk of neurotoxicity. Cancer Discov; 7(12); 1404-19. ©2017 AACR.See related commentary by Mackall and Miklos, p. 1371This article is highlighted in the In This Issue feature, p. 1355.
Characterization of the Average Daily Ischemic and Bleeding Risk After Primary PCI for STEMI
Authors: Gennaro Giustino, Roxana Mehran, George D. Dangas, Ajay J. Kirtane, Björn Redfors, Philippe Généreux, Sorin J. Brener, Jayne Prats, Stuart J. Pocock, Efthymios N. Deliargyris, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2017)
Overall survival and immunologic responses in metastatic pancreatic adenocarcinoma (PDAC) on PEGylated human IL-10 (AM0010) with 5-FU/LV and oxaliplatin (FOLFOX)
Authors: J.R. Hecht, A. Naing, G. Falchook, M.R. Patel, J.R. Infante, R. Aljumaily, D.J. Wong, K. Autio, Z.A. Wainberg, M. Javle, J.C. Bendell, S. Pant, A. Hung, P. Van Vlasselaer, G. Brown, M. Oft, K. Papadopoulos
Journal: Annals of Oncology (2017)
PD-L1 Detection and Assay Performance in Squamous Cell Carcinoma of the Head and Neck Using PD-L1 IHC 28-8 pharmDx
Authors: S. Alvarez, J. Chan, J. William, C. Felten, D.A. Hanks, A. Northrup, D. Jaiswal, M. Jansson, T. Phillips, A. Segal, I. Satnick, H. McDonald, H. Little, C. Pierce, B. Wynne, J. Carnahan, S.Y. Reddy, H.D. Inzunza, E. Oroudjev
Journal: Annals of Oncology (2017)
Impact of prior treatment on palbociclib plus letrozole (P+L) efficacy and safety in patients (pts) with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2–) first-line advanced breast cancer (ABC): A PALOMA-2 subgroup analysis
Authors: R.S. Finn, K.A. Gelmon, J. Ettl, J. Asselah, A. Castrellon, A. Ruiz Simón, A.A. Joy, D. Lu, E.R. Gauthier, A. Mori, H.S. Rugo, V. Diéras
Journal: Annals of Oncology (2017)
Interim results from a phase 1 first-in-human study of flotetuzumab, a CD123 x CD3 bispecific DART molecule, in AML/MDS
Authors: N. Vey, J. Davidson-Moncada, G.L. Uy, M. Foster, D. Rizzieri, J. Godwin, M. Topp, F. Ciceri, M. Carrabba, G. Martinelli, G.A. Huls, A. Wegener, M. Shannon, K. Tran, J. Sun, E. Bonvini, B. Löwenberg, J. Wigginton, J.F. Dipersio
Journal: Annals of Oncology (2017)
Phase I studies of the novel carcinoembryonic antigen T-cell bispecific (CEA-CD3 TCB) antibody as a single agent and in combination with atezolizumab: Preliminary efficacy and safety in patients (pts) with metastatic colorectal cancer (mCRC)
Authors: N.H. Segal, J. Saro, I. Melero, W. Ros, G. Argiles, A. Marabelle, M.E. Rodriguez Ruiz, J. Albanell, E. Calvo, V. Moreno, J.M. Cleary, J.P. Eder, V. Karanikas, S. Bouseida, F. Sandoval, D. Sabanes, S. Sreckovic, H.I. Hurwitz, L. Paz-Ares, J. Tabernero
Journal: Annals of Oncology (2017)
The role of ethnicity in the upper airway in a Belgian paediatric population with obstructive sleep apnoea
Authors: Monique Slaats, Wim Vos, Cedric Van Holsbeke, Jan De Backer, Dieter Loterman, Wilfried De Backer, An Boudewyns, Stijn Verhulst
Journal: European Respiratory Journal (2017)

Obstructive sleep apnoea (OSA) occurs in up to 4% of children in the general population [1]. The pathophysiology is likely to be multifactorial because of the high incidence of residual OSA after adenotonsillectomy. There are several risk factors such as obesity, a family history of OSA, male sex, sickle-cell disease, cerebral palsy, and other conditions that may lead to narrowing of the upper airway (UA), such as Down syndrome [2]. Numerous studies of different samples have shown an association between craniofacial skeletal morphology and UA dimension in patients with OSA compared to patients without OSA [3, 4]. A growing body of literature around the world also reports substantial ethnic disparities in the prevalence, degree and treatment of OSA [5–13]. Several US studies concluded that African American (AA) children were associated with more severe OSA in children [5–12]. Buxbaum et al . [11] investigated the difference in OSA severity between Caucasians and AA families (children and adults, n=1915), and showed that there is an underlying genetic basis for OSA in AA children (independent of the contribution of body mass index (BMI)). Stepanski et al . [12] investigated sleep and respiratory parameters in 198 children with and without sleep-disordered breathing (SBD). They reported that AA children with SBD had more severe oxygen desaturation with obstructive events and increased risk of cardiovascular consequences compared to Caucasian children. Marcus et al . [7] concluded that AA children are more likely to have residual disease after surgery than Caucasian children. Tamanyan et al . [13] determined whether demographic or clinical factors predict OSA severity in 301 Australian children. They concluded that non-Caucasian children were more likely to be diagnosed with moderate-to-severe OSA than Caucasian children. Furthermore, there are no studies that compared Asian with Caucasian children with OSA. Upper airway volume between the uvula and epiglottis is smaller in African compared to European children with OSA <http://ow.ly/AgoR30evNCu>
Abstract 16040: Corin Reduces Myocardial Infarction and Protects Against Cardiomyocyte Apoptosis
Authors: Dong Wang, Ryan D Sullivan, Inna P Gladysheva, Aiilyan Houng, Ranjana Tripathi, Tai-Hwang M Fan, Guy L Reed
Journal: Circulation (2015)

Corin is a cardiac-selective membrane protease that activates pro-ANP and pro-BNP. Emerging evidence suggests that corin may be a key biomarker and modulator of heart failure in dilated cardiomyopathy, but there is little known about the role of corin in myocardial infarction (MI). In acute MI in mice, we found that corin transcript and protein levels were significantly decreased when compared to non-MI controls 24 hrs post MI (1.0±0.1 vs 0.6±0.1, p=0.01; 1.0±0.04 vs 0.5±0.1, p&lt;0.01). To examine the functional role of corin, we studied effect of transgenic overexpression of corin (corin-Tg) on cardiomyocyte survival in acute MI and we explored the effects of corin on cardiomyocyte survival in vitro. Compared to control, wild-type mice, there was a significant decrease in infarct size in corin-Tg mice (infarct area:left ventricle area, 44±3 % vs 25±3%, p=0.01) and in the ratio of infarct area:area at risk (102±8% vs 63±4%, p&lt;0.001) 24 hrs post MI. Apoptosis was also significantly reduced in the infarcted left ventricle of corin-Tg mice vs. control (TUNEL-positive cells/myocardium mm 2 , 261±13 vs 106±16, p&lt;0.0001). In the HL-1 mouse cardiomyocyte cell line, overexpression of corin protected HL-1 cells from staurosporine -induced apoptosis by blocking cytochrome c release and caspase 3 cleavage; whereas siRNA knock down of corin in HL-1 cells promoted caspase 3 activation, as evaluated by immunofluorescence staining and Western-blotting. We conclude that experimental myocardial infarction is associated with marked reductions of corin transcript and protein levels in the heart. Overexpression of corin significantly reduces infarct size and protects against cardiomyocyte apoptosis, both in vivo and in vitro. Taken together these data suggest that corin promotes cardiomyocyte survival after MI. Corin appears to mediate its protective role in part by blocking the cytochrome c-caspase 3 mediated apoptotic pathway.
ICON7: Ovarian cancer, platinum second-line chemotherapy and overall survival
Authors: A. Cook, A. Embleton, G. Jayson, R. Kaplan, G. Kristensen, M.K. Parmar, J. Pfisterer, E. Pujade-Lauraine, A.M. Oza, T. Perren
Journal: Annals of Oncology (2017)
Vaccination Coverage for Selected Vaccines, Exemption Rates, and Provisional Enrollment Among Children in Kindergarten — United States, 2016–17 School Year
Authors: Ranee Seither, Kayla Calhoun, Erica J. Street, Jenelle Mellerson, Cynthia L. Knighton, Ashley Tippins, J. Michael Underwood
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

State and local school vaccination requirements help protect students and communities against vaccine-preventable diseases (1). CDC reports vaccination coverage and exemption data for children attending kindergarten (kindergartners) collected by federally funded immunization programs in the United States.* The typical age range for kindergartners is 4-6 years. Although vaccination requirements vary by state (the District of Columbia [DC] is counted as a state in this report.), the Advisory Committee on Immunization Practices recommends that children in this age range have received, among other vaccinations, 5 doses of diphtheria, tetanus, and acellular pertussis vaccine (DTaP), 2 doses of measles, mumps, and rubella vaccine (MMR), and 2 doses of varicella vaccine (2). This report summarizes 2016-17 school year MMR, DTaP, and varicella vaccination coverage reported by immunization programs in 49 states, exemptions in 50 states, and kindergartners provisionally enrolled or within a grace period in 27 states. Median vaccination coverage† was 94.5% for the state-required number of doses of DTaP; 94.0% for 2 doses of MMR; and 93.8% for 2 doses of varicella vaccine. The median percentage of kindergartners with an exemption from at least one vaccine§ was 2.0%, similar to 2015-16 (1.9%). Median grace period and provisional enrollment was 2.0%. Vaccination coverage remains consistently high and exemptions low at state and national levels. Local-level vaccination coverage data provide opportunities for immunization programs to identify schools, districts, counties, or regions susceptible to vaccine-preventable diseases and for schools to address undervaccination through implementation of existing state and local vaccination policies (1) to protect communities through increased coverage.
Docetaxel (D) with androgen suppression (AS) for high-risk localized prostate cancer (HrPC) patients (pts) who relapsed PSA after radical prostatectomy (RP) and/or radiotherapy (RT): A randomized phase III trial
Authors: S. Oudard, I. Latorzeff, A. Caty, L. Miglianico, E. Sevin, A-C. Hardy Bessard, R. Delva, F. Rolland, C. Chevreau, F. Priou, P. Beuzeboc, G. Gravis, C. Linassier, P. Gomez, E. Voog, P. Chinet, X. Muracciole, C. Abraham Jaillon, R. Elaidi, S. Culine
Journal: Annals of Oncology (2017)
Endoscopic ultrasound-guided gallbladder drainage to facilitate biliary rendezvous for the management of cholangitis due to choledocholithiasis
Authors: Ryan Law, Todd Baron
Journal: Endoscopy (2017)

An 81-year-old man presented with upper abdominal pain, nausea, and vomiting, with elevated liver test results. Abdominal computed tomography demonstrated mild intra- and extrahepatic biliary ductal dilation (common bile duct 11 mm), with choledocholithiasis, layering gallstones, and enhancement and thickening of the gallbladder wall. Endoscopic retrograde cholangiopancreatography (ERCP) was attempted, but biliary cannulation of an intradiverticular papilla failed, despite precut sphincterotomy. Endoscopic ultrasonography (EUS)-guided gallbladder drainage provided initial biliary decompression. Subsequently, biliary rendezvous via the gallbladder conduit facilitated conventional ERCP with sphincterotomy and stone extraction, as described below ([Video 1]).
EZH2 Modulates the DNA Methylome and Controls T Cell Adhesion Through Junctional Adhesion Molecule A in Lupus Patients
Authors: Pei‐Suen Tsou, Patrick Coit, Nathan C. Kilian, Amr H. Sawalha
Journal: Arthritis & Rheumatology (2017)

EZH2 is an epigenetic regulator that mediates H3K27 trimethylation (H3K27me3) and modulates DNA methylation. The aim of this study was to characterize the role of EZH2 in CD4+ T cells in the pathogenesis of systemic lupus erythematosus.EZH2 expression levels were determined in CD4+ T cells isolated from lupus patients and healthy controls. The epigenetic effects of EZH2 overexpression in CD4+ T cells were evaluated using a genome-wide DNA methylation approach. Gene expression profiles and microRNAs (miRNAs) were assessed by quantitative polymerase chain reaction, while protein expression was examined by Western blotting. A cell adhesion assay was used to assess adhesion of CD4+ T cells to human microvascular endothelial cells.EZH2 and H3K27me3 levels were increased in CD4+ T cells from lupus patients compared to healthy controls. T cell production of EZH2 was down-regulated in the presence of miR-26a and miR-101, and levels of both miRNAs were reduced in lupus CD4+ T cells. Overexpression of EZH2 induced in CD4+ T cells resulted in significant DNA methylation changes. Genes involved in leukocyte adhesion and migration, including F11R (which encodes junctional adhesion molecule A [JAM-A]), became hypomethylated in CD4+ T cells when EZH2 was overexpressed. Overexpression of EZH2 resulted in increases in JAM-A expression and CD4+ T cell adhesion. Preincubation of EZH2-transfected CD4+ T cells with neutralizing antibodies against JAM-A significantly blunted cell adhesion. Similarly, CD4+ T cells from lupus patients overexpressed JAM-A and adhered significantly more to endothelial cells than to T cells from healthy controls. Blocking JAM-A or EZH2 significantly reduced the capacity of lupus CD4+ T cells to adhere to endothelial cells.The results of this study identify a novel role of EZH2 in T cell adhesion mediated by epigenetic remodeling and up-regulation of JAM-A. Blockade of EZH2 or JAM-A might have therapeutic potential by acting to reduce T cell adhesion, migration, and extravasation in patients with lupus.
Cancer incidence and mortality trends in Crete, Greece during the last two decades (1992-2013): Results from the cancer registry of Crete
Authors: V-E. Chatzea, D. Sifaki-Pistolla, F. Koinis, E. Saloustros, L. Vamvakas, G. Pitsoulis, N. Tzanakis, D. Mavroudis, V. Georgoulias, C. Lionis
Journal: Annals of Oncology (2017)
The Lung Immune Prognostic Index (LIPI), a predictive score for immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC) patients
Authors: L. Mezquita, E. Auclin, M. Charrier, R. Ferrara, J. Remon Masip, D. Planchard, S. Ponce Aix, L. Paz-Ares, J. Lahmar, L. Leroy, C. Audigier-Valette, J. Zeron-Medina Cuairan, P. Garrido Lopez, S. Brosseau, J. Mazieres, C. Caramella, J. Adam, N. Chaput, J.-C. Soria, B. Besse
Journal: Annals of Oncology (2017)
Intracranial efficacy of brigatinib (BRG) in patients (Pts) With crizotinib (CRZ)-refractory anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) and baseline CNS metastases
Authors: S.-H.I. Ou, M. Tiseo, R. Camidge, M.-J. Ahn, R.M. Huber, M.J. Hochmair, S.-W. Kim, H.L. West, K.L. Reckamp, J.R. Molina, G. Liu, A. Delmonte, S. Viteri, A. Bearz, Y. Summers, W. Reichmann, D. Kerstein, S.N. Gettinger, D.-W. Kim
Journal: Annals of Oncology (2017)
A phase II, open label study of tucatinib (ONT-380) combined with trastuzumab in patients with HER2+ metastatic colorectal cancer (mCRC)(MOUNTAINEER).
Authors: John H. Strickler, Donna Niedzwiecki, Tyler Zemla, Andrea Cercek, Marwan Fakih, Kimmie Ng, Federico Augusto Sanchez, Christina Sing-Ying Wu, Scott Peterson, Lorelei Bandel, Axel Grothey, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2017)

TPS3624 Background: To improve survival for patients with mCRC, efforts are needed to identify and treat actionable genomic alterations. HER2 is amplified in approximately 5-8% of patients with KRAS and NRAS (RAS) wild-type mCRC. HER2 functions as an oncogenic driver and a mediator of EGFR antibody (Ab) resistance. Although prior studies have shown that anti-HER2 therapies are active in patients with HER2+ (HER2 IHC 3+ or HER2 amplified) mCRC, there are no HER2-directed therapies approved for these patients. Tucatinib is a potent and highly selective oral small molecule tyrosine kinase inhibitor of HER2, currently being developed to treat metastatic breast cancer. In HER2+ CRC patient derived xenograft models, tucatinib has substantial anti-tumor activity. The addition of the anti-HER2 monoclonal Ab trastuzumab augments tumor growth inhibition. Methods: This single-arm phase II study will test the combination of tucatinib and trastuzumab in patients with HER2+ mCRC. Eligible patients include those with RAS wild-type mCRC who have been previously treated with 5-FU, oxaliplatin, irinotecan, and an anti-VEGF monoclonal Ab. Patients must have HER2+ disease by IHC, FISH, or NGS. Prior treatment with anti-HER2 targeting therapy is excluded. The primary objective is to assess the objective response rate for the combination. Secondary objectives are to evaluate the efficacy (PFS, OS, clinical benefit rate), safety, and tolerability of the combination. Correlation between tissue and blood-based biomarkers and clinical outcomes will be explored. Blood will be collected at baseline and each restaging to determine if the combination eliminates HER2 amplified circulating tumor DNA. Subjects will receive tucatinib at a dose of 300mg by mouth daily, and trastuzumab will be administered every 3 weeks (8 mg/kg IV day 1 of cycle 1, then 6 mg/kg IV Q3 weeks). Response will be assessed every 3 cycles (9 weeks) per RECIST version 1.1. Both agents will be provided by the study. This study was initiated in February 2017. Recruitment is ongoing at 8 sites in the Academic and Community Cancer Research United (ACCRU) network. Clinical trial information: NCT03043313.
Studies on Hepatomas. I. Size and Spacing of Multiple Doses in the Induction of Carbon Tetrachloride Hepatomas
Authors: Allen B. Eschenbrenner, Eliza Miller
Journal: JNCI Journal of the National Cancer Institute (1944)

Journal Article Studies on Hepatomas. I. Size and Spacing of Multiple Doses in the Induction of Carbon Tetrachloride Hepatomas Get access Allen B. Eschenbrenner, Allen B. Eschenbrenner passed assistant surgeon National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Eliza Miller Eliza Miller National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 4, February 1944, Pages 385–388, https://doi.org/10.1093/jnci/4.4.385 Published: 01 February 1944
Docetaxel, 5-fluorouracil and nedaplatin as second-line chemotherapy for patients with esophageal cancer after esophagectomy: A pilot study
Authors: K. Mafune, K. Yamada, K. Imamura, K. Kubota, M. Kaminishi
Journal: Journal of Clinical Oncology (2006)

14140 Background: We investigated the combination of docetaxel, 5-fluorouracil (5FU) and cisplatin analog, nedaplatin (CDGP) as second-line chemotherapy after esophagectomy. Methods: Eight patients with recurrent esophageal cancer who had undergone adjuvant 5FU/cisplatin after esophagectomy were included this study (7 male, 1 female; median ECOG performance status: 1). Histologic type of all esophageal cancer was squamous cell carcinoma. Patients received docetaxel 60 mg/m 2 on day 1, 5FU 600 mg/m 2 on days 1–5, and CDGP60 mg/m 2 on day 4 every 3 weeks. A total of 17 chemotherapy cycles was administered. The median number of cycles was 2 (range 1–5). Results: The overall response rate was 62.5%. The median overall survival was 42 weeks, and the median progression-free survival was 26 weeks. Hematological and non-hematological toxicities were moderate (neutropenia WHO grade III/IV: 62.5%, alopecia grade II/III: 75%, nausea/vomiting grade II/III: 50%, neurotoxicity grade II: 12.5%). Conclusions: The combination of docetaxel, 5FU and CDGP is an active regimen with moderate toxicity in the treatment of patients with recurrent esophageal cancer. This pilot study suggests the feasibility of a combination treatment containing a taxan, 5FU and cisplatin or its analog in esophageal squmaous cell carcinoma. No significant financial relationships to disclose.