tbuckley/cabot-search huggingface dataset:
Stabilization of Notch1 by the Hsp90 Chaperone is Crucial for T-Cell Leukemogenesis
Authors: Zhaojing Wang, Yufeng Hu, Daibiao Xiao, Jingchao Wang, Chuntao Liu, Yisheng Xu, Xiaomeng Shi, Peng Jiang, Liang Huang, Peng Li, Hudan Liu, Guoliang Qing
Journal: Clinical Cancer Research (2017)

Purpose: Notch1 deregulation is assuming a focal role in T-cell acute lymphoblastic leukemia (T-ALL). Despite tremendous advances in our understanding of Notch1 transcriptional programs, the mechanisms by which Notch1 stability and turnover are regulated remain obscure. The goal of the current study is to identify intracellular Notch1 (ICN1, the activated form of Notch1) binding partner(s) regulating its stability and activity. Experimental Design: We employed immunoaffinity purification to identify ICN1-associating partner(s) and used coimmunoprecipitation to verify the endogenous protein interaction. Pharmacologic or short hairpin RNA-mediated inhibition was applied in loss-of-function assays to assess the role of tentative binding partner(s) in modulating ICN1 protein stability as well as affecting T-ALL cell expansion in vitro and in vivo Mechanistic analysis involved protein degradation and polyubiquitination assays. Results: We identify the Hsp90 chaperone as a direct ICN1-binding partner essential for its stabilization and transcriptional activity. T-ALL cells exhibit constitutive endogenous ICN1-Hsp90 interaction and Hsp90 depletion markedly decreases ICN1 levels. The Hsp90-associated E3 ubiquitin ligase Stub1 mediates the ensuring proteasome-dependent ICN1 degradation. Administration of 17-AAG or PU-H71, two distinct Hsp90 inhibitors, depletes ICN1, inhibits T-ALL cell proliferation, and triggers dramatic apoptotic cell death. Systemic treatment with PU-H71 reduces ICN1 expression and profoundly inhibits murine T-ALL allografts as well as human T-ALL xenografts. Conclusions: Our findings demonstrate Hsp90 blockade leads to ICN1 destabilization, providing an alternative strategy to antagonize oncogenic Notch1 signaling with Hsp90-selective inhibitors. Clin Cancer Res; 23(14); 3834-46. ©2017 AACR.
Cladribine Alone or in Combination with Cyclophosphamide or Cyclophosphamide and Mitoxantrone as First Line Treatment in Chronic Lymphocytic Leukemia: An Early Report of Prospective Randomized Study.
Authors: Tadeusz Robak, Jerzy Z. Blonski, Joanna Gora-Tybor, Marek Kasznicki, Jadwiga Dwilewicz-Trojaczek, Agnieszka Tomaszewska, Lech Konopka, Bernadeta Ceglarek, Janusz Kloczko, Jaroslaw Sokolowski, Anna Dmoszynska, Malgorzata Kowal, Krystyna Zawilska, Beata Stella-Holowiecka, Kazimierz Sulek, Kazimierz Kuliczkowski, Krzysztof Warzocha, Malgorzata Calbecka, Aleksander Skotnicki
Journal: Blood (2004)
Pathological Complete Response to Neoadjuvant Trastuzumab Is Dependent on HER2/CEP17 Ratio in HER2-Amplified Early Breast Cancer
Authors: Christian F. Singer, Yen Y. Tan, Florian Fitzal, Guenther G. Steger, Daniel Egle, Angelika Reiner, Margaretha Rudas, Farid Moinfar, Christine Gruber, Edgar Petru, Rupert Bartsch, Kristina A. Tendl, David Fuchs, Michael Seifert, Ruth Exner, Marija Balic, Zsuzsanna Bago-Horvath, Martin Filipits, Michael Gnant
Journal: Clinical Cancer Research (2017)

Abstract Purpose: To evaluate whether pathologic complete response (pCR) to neoadjuvant trastuzumab is dependent on the level of HER2 amplification. Experimental Design: 114 HER2-overexpressing early breast cancer patients who had received neoadjuvant trastuzumab were included in this study. Absolute HER2 and chromosome 17 centromere (CEP17) were measured by in situ hybridization analysis, and associations were examined between HER2/CEP17 ratio and tumor pCR status (commonly defined by ypT0 ypN0, ypT0/is ypN0, and ypT0/is). Results: In trastuzumab-treated patients, ypT0 ypN0 was achieved in 69.0% of patients with high-level amplification (HER2/CEP17 ratio &amp;gt; 6), but only in 30.4% of tumors with low-level amplification (ratio ≤ 6; P = 0.001). When pCR was defined by ypT0/is ypN0 or ypTis, 75.9% and 82.8% of tumors with high-level amplification had a complete response, whereas only 39.1%, and 38.3% with low-level amplification achieved pCR (P = 0.002 and P &amp;lt; 0.001, respectively). Logistic regression revealed that tumors with high-level amplification had a significantly higher probability achieving ypT0 ypN0 (OR, 5.08; 95% confidence interval, 1.86–13.90; P = 0.002) than tumors with low-level amplification, whereas no other clinicopathologic parameters were predictive of pCR. The association between high-level HER2 amplification and pCR was almost exclusively confined to hormone receptor (HR)–positive tumors (ypT0 ypN0: 62.5% vs. 24.0%, P = 0.014; ypT0/is ypN0: 75.0% vs. 28.0%, P = 0.005; and ypT0/is: 87.5% vs. 28.0%, P &amp;lt; 0.001), and was largely absent in HR-negative tumors. Conclusions: An HER2/CEP17 ratio of &amp;gt;6 in the pretherapeutic tumor biopsy is associated with a significantly higher pCR rate, particularly in HER2/HR copositive tumors, and can be used as a biomarker to predict response before neoadjuvant trastuzumab is initiated. Clin Cancer Res; 23(14); 3676–83. ©2017 AACR.
Myelodysplasia with Trisomy 8 Is Associated with a Cytotoxic CD8 T Cell Immune Response to Wilms Tumor-1 Protein (WT1).
Authors: Elaine M. Sloand, Katayoun Rezvani, John Barrett, Lori Mainwaring, Roger Kurlander, Emma Gostick, Shakti Ramkissoon, Yong Tang, Daniel Douek, David Price, Neal S. Young
Journal: Blood (2004)
Self-assembling complexes between binary mixtures of lipids with different linkers and nucleic acids promote universal mRNA, DNA and siRNA delivery
Authors: Thibault Colombani, Pauline Peuziat, Laurence Dallet, Thomas Haudebourg, Mathieu Mével, Mathieu Berchel, Olivier Lambert, Damien Habrant, Bruno Pitard
Journal: Journal of Controlled Release (2017)
Short-term CTLA-4 blockade directly followed by PD-1 blockade in advanced melanoma patients: a single-center experience
Authors: A. Meerveld-Eggink, E.A. Rozeman, F. Lalezari, J.V. van Thienen, J.B.A.G. Haanen, C.U. Blank
Journal: Annals of Oncology (2017)
Long Term Follow-up of 107 Patients with Essential Thrombocythemia: Role of Cardiovascular Events
Authors: Eleonora Arboscello, Elisa Molinari, Andrea Bellodi, Lisette Del Corso, Serena Favorini, Vera Sicbaldi, Jacopo Agnelli Giacchello, Chiara Salvetti, Enrico Balleari, Riccardo Ghio, Maria Teresa Van Lint
Journal: Blood (2014)
GS-9219 - A Novel Prodrug of the Acyclic Nucleotide PMEG Demonstrates Significant Therapeutic Activity Against Spontaneous Non-Hodgkin’s Lymphoma as Modeled in Pet Dogs.
Authors: David M. Vail, Douglas H. Thamm, Daniel B. Tumas, Hans Reiser, Adrian S. Ray, Grushenka H.I. Wolfgang, Darius Babusis, Ilene D. Kurzman, Robert Jeraj, Susan Plaza, Christie Anderson, Mackenzie A. Wessel, Cecilia Robat, Jessica Lawrence
Journal: Blood (2007)
Petechiae, Purpura, and Hemorrhagic Vesicles
Authors: Jennifer Scott, Christina Clarke, Richard Marchell
Journal: JAMA Dermatology (2017)

A man presented with encephalopathy, recent falls, leukocytosis, nausea, and arthralgias, and progressing cutaneous eruption, scattered petechiae and hemorrhagic vesicles on the hands and feet, and palpable purpura were noted across the extremities. What is your diagnosis?
Graft T Cells Retard Stem Cell Derived Lymphoid Organ Reconstitution and Immune Function After Allogeneic Transplantation,
Authors: Antonia MS Mueller, Holbrook E Kohrt, Sumana Shashidhar, Mareike Florek, Natascha J Kuepper, Janice (Wes) M. Brown, Judith A Shizuru
Journal: Blood (2011)
Concomitant Diagnosis of Chronic Myeloid Leukemia and B-Cell Chronic Lymphocytic Leukemia in a 57-Year-Old Female Patient, with Good Therapeutic Response Exclusively to Imatinib in Both Myeloid and Lymphoid Clones.
Authors: Arthur Moellmann-Coelho, Luise Otero, Ricardo S. Bigni, Denise Azambuja, Claudio G. Stefanoff, Jane A. Dobbin, Ilana Zalczberg
Journal: Blood (2007)
“Incidental Carcinomas” Detected by PET/CT Scans In the Patients with Malignant Lymphoma: A Single-Center Experience with 363 Patients
Authors: Kazuya Sato, Katsutoshi Ozaki, Tomohiro Matsuyama, Ken Ohmine, Takahiro Suzuki, Masaki Mori, Tadashi Nagai, Kazuo Muroi, Keiya Ozawa
Journal: Blood (2010)
Helicobater Pylori Infection and Clinical Response to Eradication Therapy in Patients with Immune Thrombocytopenic Purpura (ITP).
Authors: Fabrizio Fabris, Emanuele Allemand, Raffaella Scandellari, Silvia Vettore, Maria Luigia Randi, Guido Luzzatto
Journal: Blood (2005)
A New Human CD20 Spliced mRNA as a Potential Molecular Marker for the Follow-up of B-Cell Malignancies.
Authors: Marina Deschamps, Carole Henry, Eric Robinet, Francine Garnache-Ottou, Jean-Paul Remy-Martin, Christophe Borg, Pierre-Simon Rohrlich, Eric Deconinck, Pierre Tiberghien, Christophe Ferrand
Journal: Blood (2008)
Reconstitution of Regulatory T Cells Involves in the Development of Acute Graft-Versus-Host Disease after Hematopoietic Stem Cell Transplantation.
Authors: Shuhei Karakawa, Kazuhiro Nakamura, Keiichi Hara, Yoko Mizoguchi, Mizuka Miki, Hiroshi Kawaguchi, Takashi Sato, Shin-ichiro Nishimura, Masao Kobayashi
Journal: Blood (2008)
Bowel preparation in diabetic patients undergoing colonoscopy
Authors: Alba Panarese
Journal: Endoscopy (2017)

We read with interest the article by Alvarez-Gonzalez et al. regarding bowel preparation in patients with diabetes mellitus undergoing colonoscopy. In these patients, who can be difficult to prepare, the proposed multifactorial strategy improved bowel preparation compared with the conventional bowel preparation protocol (CBP) without differences in safety or tolerability (P = 0.014; risk ratio 3.1, 95 % confidence interval [Cl] 1.2 – 8) [1].
Stroke Caused by Extracranial Disease
Authors: Kevin M. Barrett, Thomas G. Brott
Journal: Circulation Research (2017)

Extracranial internal carotid artery atherosclerotic occlusive disease is a common ischemic stroke mechanism. Vascular risk factor control remains the cornerstone of stroke prevention in patients with both asymptomatic and symptomatic carotid occlusive diseases. Intensive medical therapy refers to the contemporary approach of antiplatelet therapy, blood pressure control, low-density lipoprotein reduction, and lifestyle modification to reduce stroke risk. Carotid revascularization with endarterectomy or angioplasty and stenting are established treatments for patients with symptomatic carotid stenosis ≥70%. Previously accepted ischemic stroke preventative strategies, such as carotid revascularization for asymptomatic carotid stenosis, require reassessment given advances in both medical therapy and surgical techniques. The purpose of this review is to describe contemporary approaches to the management of extracranial carotid atherosclerotic occlusive disease and the basis of these recommendations. Results from recently published clinical trials will be highlighted in addition to updated information from clinical trials addressing knowledge gaps in prevention of stroke caused by extracranial disease.
THE BOKSMART SAFE SIX: FUNCTIONAL WARM-UP TO REDUCE INJURIES IN RUGBY UNION. DESIGN OF A CLUSTER RCT
Authors: Nicola Sewry, Evert Verhagen, Mike Lambert, Willem van Mechelen, James Brown
Journal: British Journal of Sports Medicine (2017)

Background Exercise-based interventions have consistently been associated with a reduction in injury rates in sports such as football. Although the injury burden in rugby union (‘rugby’) is high, such interventions have not been evaluated in rugby. Objective To evaluate the effectiveness of the BokSmart Safe Six on (i) the injury risk profile and burden in junior rugby players in South Africa, and (ii) the injury prevention behavioural determinants of the coaches of these players. Design A pragmatic cluster-randomised controlled trial, with no blinding of groups. Setting Male youth rugby players from two geographically-separated locations in South Africa over the 2017 rugby playing season. Patients (or Participants) Youth rugby players (14–16 year old) (n=160 players in the intervention group; n=160 in the control group) will be recruited from the Western Cape Schools Premier Division. This sample size provides sufficient power to detect meaningful differences. Interventions (or Assessment of Risk Factors) The teams will be randomly allocated to groups that either: (i) have the BokSmart Safe Six coach-delivered exercise intervention in their warm-up (experimental group), or (ii) continue with their usual warm-up (control group). Injury risk profiles will be assessed on all players through musculoskeletal screening performed at the beginning, middle and end of the trial. Epidemiological measurements include injury surveillance at all matches and training sessions, and exposure to the various warm-up exercises (including BokSmart Safe Six exercises). Behavioural determinants of coaches will be assessed before and after the intervention through standardised theory of planned behaviour questionnaires and focus groups. Main Outcome Measurements Comparison in injury risk profiles and burden of injury between the intervention and control groups. Changes in the behavioural determinants of coaches.
Prospective study of genetic mutations in matched tumor and plasma specimens in colorectal cancer patients.
Authors: G. Perkins, J. Dukes, T. A. Yap, R. Riisnaes, L. Pope, A. Cassidy, K. A. Denholm, D. Gonzalez de Castro, I. Chau, J. S. De Bono
Journal: Journal of Clinical Oncology (2011)

356 Background: Circulating free DNA (cfDNA) represents a minimally-invasive resource for detecting mutations in advanced cancer patients. The primary objective of this study was to determine if cfDNA is representative of tumor tissue for multiplex mutation detection utilizing Sequenom MassARRAY. Methods: Samples were spiked with dilutions (10ng/μl to 0.01ng/μl) of HCT116 DNA containing KRAS G13D mutations to determine assay sensitivity and specificity. Metastatic colorectal cancer patients referred to the Drug Development Unit at the Royal Marsden Hospital between 9/09-8/10 gave their consent to provide DNA from matched archival formalin fixed paraffin-embedded (FFPE) tumor and plasma. Samples had ∼200 described gene mutations genotyped using Sequenom MassARRAY (OncoCarta Panel). Results: Serial dilution spiking experiments revealed that the KRAS G13D mutation was reproducibly detectable to 40ng/mL of HCT116 DNA; 26 patient samples were then analyzed. KRAS, BRAF and PIK3CA mutations were detected in 8 (31%), 3 (12%) and 3 (12%) tumor specimens respectively; 100% concordance for KRAS status was observed between multiple FFPE biopsies from the same patient and analysis by Amplification Refractory Mutation System (ARMS)-Scorpion PCR. The median quantity of cfDNA was 353ng/ml (range 106-4603). Concordance between matched FFPE and cfDNA was 88% for KRAS and 100% for BRAF mutations. No patients with wildtype KRAS or BRAF tumor genotypes had mutations in their respective cfDNA confirming the high specificity of cfDNA analysis. Three patients had detectable PIK3CA mutations; 1 patient had a E346K mutation detected in both FFPE tissue and plasma; 1 patient had E545K detected only in FFPE and the other had E542K detected in a liver metastasis but not in the colorectal primary or plasma. The recently reported oncogenic AKT1 E17K mutation was detected in 1 patient in tissue and plasma. No mutations in any of the other tested oncogenes studied were detected. Conclusions: A high concordance in detected mutations was observed between FFPE tumor and matched cfDNA. cfDNA is representative of tumor DNA and may be used for the prospective selection of cancer patients for treatment with targeted therapeutics. No significant financial relationships to disclose.
t(8;21) Positive AML with Favorable Clinical Characteristics, in a Child with Ependymoma after Combined Treatment with Neuroaxis Irradiation and Topoisomerase II Inhibitors.
Authors: Vassilios Papadakis, Stefanos Papadhimitriou, Anna Paisiou, Agapi Parcharidou, Natalia Tourkantoni, George Paterakis, Chrysoula Belesi, Constantina Sambani, Sophia Polychronopoulou
Journal: Blood (2006)
Phase II Trial of Lenalidomide - Rituximab +/− Dexamethasone in Relapsed or Refractory Indolent B-Cell or Mantle Cell Lymphomas Resistant to Rituximab
Authors: Tahamtan Ahmadi, Elise A. Chong, Amanda Gordon, Nicole A. Aqui, YinYan Xu, Jakub Svoboda, Sunita D. Nasta, Stephen J. Schuster
Journal: Blood (2011)
NIMG-58PRELIMINARY TRENDS IN ADVANCED IMAGING RELATIVE TO STANDARD IMAGING IN SUBJECTS TREATED WITH OPTUNE
Authors: Melissa Prah, Jennifer Connelly, Kathleen Schmainda
Journal: Neuro-Oncology (2015)

BACKGROUND: Optune has recently received FDA approval for antimitotic treatment of subjects with recurrent glioblastoma. Response to Optune treatment is generally delayed (5.2 months) with the response duration highly correlated with OS. Recently, it was shown that 44% of responders developed initial tumor growth based on standard imaging. The aim of this preliminary analysis is to determine if there is a potential role for advanced imaging to distinguish responders from non-responders based on the directional change in MRI-derived perfusion and diffusion metrics. METHODS: Advanced MRI was examined in 7 recurrent high-grade glioma subjects (WHO IV = 4/WHO III = 3; 3M/4F) treated with Optune. When available, FLAIR (FV) and enhancing tumor volumes (ETV) were examined with diffusion (ADC) and DSC perfusion (rCBV and rCBF). Mean parameter values were obtained within FV and ETV prior to and following Optune treatment and trends in perfusion and diffusion are reported, relative to standard imaging. RESULTS: All but one subject had increased FV. In cases where FV increased, 3/4 cases had a decrease in perfusion and 2/5 cases had an increase in ADC indicating response. Half of subjects had increased ETV. In cases where ETV decreased, 2/2 subjects had an increase in perfusion and 1/3 cases had a decrease in ADC. In cases where ETV increased, 1/3 cases had a decrease in perfusion and 2/3 cases had an increase in ADC. CONCLUSIONS: Advanced imaging may potentially provide additional information beyond standard imaging, with potential to help identify early responders to Optune treatment. Additional information may be obtained through the use of advanced imaging as decreases in perfusion or increases in diffusion did not trend well with decreases in FV (≥50% case differences) or ETV (≥66% case differences). Further analysis in a larger cohort is underway, where future goals include correlation of advanced imaging to survival and device compliance.
BTK inhibitor PCI-32765 targets endogenous and microenvironment-mediated B-cell receptor signaling to suppress lymphoma cell growth and is highly synergistic with Bortezmib against non-Hodgkin B-cell lymphomas
Authors: Bing Xia, Xiaowu Li, Le Zhang, Qing Guo, Xin Jin, Shanqi Guo, Eduardo M. Sotomayor, Yizhuo Zhang
Journal: Blood (2012)
First Results of the GRAAPH-2005 Study in younger Adult Patients with De Novo Philadelphia Positive Acute Lymphoblastic Leukemia
Authors: Yves Chalandon, Xavier Thomas, Sandrine Hayette, Jean-Michel Cayuela, Claire Abbal, Martine Escoffre-Barbe, Sebastien Maury, Stephane Lepretre, Francis Witz, Lofti Benboubker, Jean-Valère Malfuson, Thibaut Leguay, Agnes Buzyn, Veronique Lheritier, Marie-Christine Bene, Marina Lafage, Norbert Ifrah, Herve Dombret
Journal: Blood (2008)
An in Vitro and in Vivo Evidence That Human Rhabdomyosarcomas (RMS) Express Functional CXCR7 Receptor: Overlapping and Distinct Role of CXCR4-SDF-1 and CXCR7-SDF-1/ITAC Axes in Regulating Metastatic Behavior of RMS Cells
Authors: Kasia Grymula, Maciek Tarnowski, Radoslaw Maksym, Magdalena Kucia, Janina Ratajczak, Mariusz Z Ratajczak
Journal: Blood (2008)
Homozygous Mutations in PHRF1 and PPARG in a Patient with Congenital Neutropenia and Profound Monocytosis: Understanding the Pathway Beyond Monocyte Versus Granulocyte Cell-Fate Choice
Authors: Houra Loghmani-khouzani, Maksim Klimiankou, Siarhei Kandabarau, Cornelia Zeidler, Karl Welte, Julia Skokowa
Journal: Blood (2015)
The influence of regional radiation oncologist and urologist capacities on treatment choice for prostate cancer management.
Authors: James B. Yu, Sanjay Aneja, Danil V. Makarov, Kenneth B Roberts, Cary P. Gross
Journal: Journal of Clinical Oncology (2012)

108 Background: Our study investigates the influence of regional variations of radiation oncology and urology services on the treatment modality chosen for prostate cancer (PCa) management. Methods: PCa treatment choice and patient data from 2004-2007 were obtained from the NCI Surveillance, Epidemiology, and End Results (SEER) database and combined with the health system data from the Area Resource File. The health system characteristics analyzed were radiation oncologist (RO) density, urologist (U) density, primary care provider (PCP) density, IMRT equipped hospital density, general radiation therapy (RT) equipped hospital density, and median household income. Patient factors analyzed included race, marital status, and age. Separate logistic regression models were built to test the association between health system characteristics and whether patients received any form of RT (EBRT, brachytherapy, or a combination) or just surgical treatment. Results: Overall of the 108,612 patients in our sample, 43.7% received some form of RT. Patients residing in Health Service Areas (HSAs) with increased RO densities were more likely to receive some form of radiation to treat PCa (OR 1.07 [SE 0.02, p&lt;.001]). Conversely increased U density was associated decreased use of RT (OR .95 [SE .01, p&lt;.001]). Presence of IMRT equipped and general RT equipped hospitals were both associated with increased use of radiation therapy (OR 1.53 [SE .05, p&lt;.001] and OR 1.13 [SE .03, p&lt;.001] respectively). Alternatively, 39.3% of patients in our sample received just surgical interventions. Patients residing in HSAs with increased RO densities were less likely to receive only surgical treatment for PCa (OR .91 [SE .01, p&lt;.001]). Increased U density was associated with increased likelihood of only surgical treatment for PCa (OR 1.09 [SE 0.01, p&lt;.001]). Presence of IMRT equipped and general RT hospitals were both associated with decreased use of only surgical treatment for PCa (OR .82 [SE .03, p&lt;.001] and OR .82 [SE .02, p&lt;.001] respectively). Conclusions: Radiation oncologist and urologist capacities influence the regional variations in the treatment choice for prostate cancer.
Lung Cancer Screening With Low-Dose Computed Tomography in the United States—2010 to 2015
Authors: Ahmedin Jemal, Stacey A. Fedewa
Journal: JAMA Oncology (2017)

Lung cancer is the most preventable and leading cause of cancer deaths in the United States, with about 155 870 deaths each year. 1 In December 2013, the United States Preventive Services Task Force (USPSTF) recommended annual screening for lung cancer with low-dose computed tomography (LDCT) for asymptomatic persons aged 55 to 80 years who have a 30 pack or more per year smoking history and currently smoke or have quit within the past 15 years. 2 According to the 2010 National Health Interview Survey (NHIS), only 2% to 4% of high-risk smokers received LDCT for lung cancer screening in the prev i o u s ye a r. 3 I n t h i s s t u d y, we ex a m i n e d w h e t h e r LDCT screening has increased following the USPSTF recommendation.Methods | We used the and 2015 NHIS, which included 2347 respondents who met the USPSTF criteria for LDCT.