tbuckley/cabot-search huggingface dataset:
Phase I/II vaccine study targeting novel HLA-A2-restricted CTL epitopes in combination with poly-ICLC in patients with recurrent malignant glioma.
Authors: H. Okada, P. Kalinski, A. H. Mintz, J. A. Engh, L. H. Butterfield, R. H. Hamilton, D. M. Potter, A. M. Salazar, F. S. Lieberman
Journal: Journal of Clinical Oncology (2011)

2506 Background: We conducted a phase I/II trial to evaluate the safety and immunogenicity of a novel vaccination with α-type-1-polarized dendritic cells (αDC1) loaded with synthetic peptides for glioma associated antigen (GAA) epitopes and administration of poly-ICLC in HLA-A2+ patients with recurrent malignant gliomas. GAAs for these peptides are EphA2, IL-13Rα2, YKL-40 and gp100. Methods: The study enrolled twenty-two recurrent malignant glioma patients with glioblastoma (GBM) (n = 13), anaplastic astrocytoma (n = 5), anaplastic oligodendroglioma (n = 3), or anaplastic oligoastrocytoma (n = 1). Half the patients had 2nd relapse or greater. Two recurrent GBM patients had prior bevacizumab. Peptide-loaded αDC1 were injected intra/peri-nodally every two weeks for 4 injections with the possibility of boosters. 20 µg/kg poly-ICLC was administered intramuscularly two times per week for 8 weeks. Immunogenicity was assessed by ELISPOT, tetramer, and IL-12 assays. Efficacy was determined by MRI according to McDonald criteria. Results: The regimen was well-tolerated and demonstrated efficacy in heavily pre-treated patients. There were no grade 3 or greater toxicities and no dose limiting toxicities. Injection site reactions, transient fatigues and chills were the most common adverse events. Eighty-one percent (13/16) had ≥ 1 positive immunogenicity assay. Forty-six percent (6/13) of recurrent GBM and sixty-seven percent (6/9) of recurrent anaplastic glioma patients had tumor shrinkage or stable disease. One recurrent GBM patient sustained a complete response (CR) for greater than 14 months, and 2 patients achieved a partial response (PR). In recurrent GBM patients, the median overall survival (OS) was 12 months, 6 month OS was 80%, and 12 month OS was 46%. Conclusions: The novel αDC1-based vaccine in combination with poly-ICLC demonstrated safety, immune-reactivity as well as efficacy in patients with recurrent malignant glioma. Given these promising results, Phase II/III clinical studies are planned in recurrent GBM. Phase I/II trials are also underway with peptide emulsion in adult low-grade and pediatric malignant glioma.
Replacement Therapy for Minor Surgery and Invasive Procedures in Factor VII Deficiency: The STER Experience
Authors: Mariasanta Napolitano, Alberto Dolce, Jorgen Ingerslev, Muriel Giansily-Blaizot, Matteo ND Di Minno, Guenter K.H. Auerswald, Arlette Ruiz de Saez, Annarita Tagliaferri, Angelika Batorova, Teresa Maria Caimi, Ampaiwan Chuansumrit, Maria Fernanda Lopez Fernandez, Marie-Anne Bertrand, Elisabeth Verdy, Ezio Zanon, Lien Abecassis, Sophie Aronis, Sergio Siragusa, Assunta Orecchioni, Guglielmo Mariani
Journal: Blood (2011)
Deregulated Apoptotic Pathways Point to Effectiveness of IAP Inhibitor Therapy in Acute Myeloid Leukemia.
Authors: Sonja C Lück, Annika C Russ, Konstanze Döhner, Ursula Botzenhardt, Domagoj Vucic, Kurt Deshayes, Richard F Schlenk, Hartmut Döhner, Simone Fulda, Lars Bullinger
Journal: Blood (2009)
Stroke Caused by Atherosclerosis of the Major Intracranial Arteries
Authors: Chirantan Banerjee, Marc I. Chimowitz
Journal: Circulation Research (2017)

Our goal in this review is to discuss the pathophysiology, diagnosis, and treatment of stroke caused by atherosclerosis of the major intracranial arteries. References for the review were identified by searching PubMed for related studies published from 1955 to June 2016 using search terms intracranial stenosis and intracranial atherosclerosis. Reference sections of published randomized clinical trials and previously published reviews were searched for additional references. Intracranial atherosclerotic disease is a highly prevalent cause of stroke that is associated with a high risk of recurrent stroke. It is more prevalent among blacks, Hispanics, and Asians compared with whites. Diabetes mellitus, hypertension, metabolic syndrome, smoking, hyperlipidemia, and a sedentary lifestyle are the major modifiable risk factors associated with intracranial atherosclerotic disease. Randomized clinical trials comparing aggressive management (dual antiplatelet treatment for 90 days followed by aspirin monotherapy and intensive management of vascular risk factors) with intracranial stenting plus aggressive medical management have shown medical management alone to be safer and more effective for preventing stroke. As such, aggressive medical management has become the standard of care for symptomatic patients with intracranial atherosclerotic disease. Nevertheless, there are subgroups of patients who are still at high risk of stroke despite being treated with aggressive medical management. Future research should aim to establish clinical, serological, and imaging biomarkers to identify high-risk patients, and clinical trials evaluating novel therapies should be focused on these patients.
A Phase II Study of Elacytarabine/Idarubicin As Second Course Remission-Induction in Patients with Acute Myeloid Leukemia Who Failed Cytarabine/Anthracycline
Authors: David A. Rizzieri, Norbert Vey, Xavier Thomas, Françoise Huguet, Richard F Schlenk, Jürgen Krauter, Thomas Kindler, Bjorn Gjertsen, Igor W. Blau, Malin Johansen, Trygve Bergeland, Athos Gianella-Borradori, Tove Flem Jacobsen, Jianyu Rao, Utz Krug
Journal: Blood (2012)
DNA Methylation–Based Biomarkers
Authors: Leandro Cerchietti, Ari Melnick
Journal: Journal of Clinical Oncology (2017)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES CpG Methylation Signature Predicts Recurrence in Early-Stage Hepatocellular Carcinoma: Results From a Multicenter Study. January 09, 2017 Monitoring of Serum DNA Methylation as an Early Independent Marker of Response and Survival in Metastatic Breast Cancer: TBCRC 005 Prospective Biomarker Study. November 21, 2016 ARTICLE CITATION DOI: 10.1200/JCO.2016.71.0616 Journal of Clinical Oncology - published online before print January 23, 2017 PMID: 28113009 DNA Methylation–Based Biomarkers Leandro CerchiettixLeandro CerchiettiSearch for articles by this author and Ari MelnickxAri MelnickSearch for articles by this author Show More Leandro Cerchietti and Ari Melnick, Weill Cornell Medicine, New York, NY https://doi.org/10.1200/JCO.2016.71.0616 First Page Full Text PDF Figures and Tables © 2017 by American Society of Clinical Oncology Companion CpG Methylation Signature Predicts Recurrence in Early-Stage Hepatocellular Carcinoma: Results From a Multicenter Study Monitoring of Serum DNA Methylation as an Early Independent Marker of Response and Survival in Metastatic Breast Cancer: TBCRC 005 Prospective Biomarker Study
Targeting the adenosine 2A receptor enhances chimeric antigen receptor T cell efficacy
Authors: Paul A. Beavis, Melissa A. Henderson, Lauren Giuffrida, Jane K. Mills, Kevin Sek, Ryan S. Cross, Alexander J. Davenport, Liza B. John, Sherly Mardiana, Clare Y. Slaney, Ricky W. Johnstone, Joseph A. Trapani, John Stagg, Sherene Loi, Lev Kats, David Gyorki, Michael H. Kershaw, Phillip K. Darcy
Journal: Journal of Clinical Investigation (2017)

Chimeric antigen receptor (CAR) T cells have been highly successful in treating hematological malignancies, including acute and chronic lymphoblastic leukemia. However, treatment of solid tumors using CAR T cells has been largely unsuccessful to date, partly because of tumor-induced immunosuppressive mechanisms, including adenosine production. Previous studies have shown that adenosine generated by tumor cells potently inhibits endogenous antitumor T cell responses through activation of adenosine 2A receptors (A2ARs). Herein, we have observed that CAR activation resulted in increased A2AR expression and suppression of both murine and human CAR T cells. This was reversible using either A2AR antagonists or genetic targeting of A2AR using shRNA. In 2 syngeneic HER2+ self-antigen tumor models, we found that either genetic or pharmacological targeting of the A2AR profoundly increased CAR T cell efficacy, particularly when combined with PD-1 blockade. Mechanistically, this was associated with increased cytokine production of CD8+ CAR T cells and increased activation of both CD8+ and CD4+ CAR T cells. Given the known clinical relevance of the CD73/adenosine pathway in several solid tumor types, and the initiation of phase I trials for A2AR antagonists in oncology, this approach has high translational potential to enhance CAR T cell efficacy in several cancer types.
Improved Prediction of Kidney Disease by Estimating Renal Function: Use in Multiple Myeloma Patients Treated with Standard Versus High-Dose Chemotherapy Followed by Autologous Peripheral Blood Stem Cell Transplantation.
Authors: Martina Kleber, Truc Ngo, Gabriele Ihorst, Bernd Koch, Monika Engelhardt
Journal: Blood (2006)
Genetic alterations of m6A regulators predict poorer survival in acute myeloid leukemia
Authors: Chau-To Kwok, Amy D. Marshall, John E. J. Rasko, Justin J. L. Wong
Journal: Journal of Hematology & Oncology (2017)

Methylation of N6 adenosine (m6A) is known to be important for diverse biological processes including gene expression control, translation of protein, and messenger RNA (mRNA) splicing. However, its role in the development of human cancers is poorly understood. By analyzing datasets from the Cancer Genome Atlas Research Network (TCGA) acute myeloid leukemia (AML) study, we discover that mutations and/or copy number variations of m6A regulatory genes are strongly associated with the presence of TP53 mutations in AML patients. Further, our analyses reveal that alterations in m6A regulatory genes confer a worse survival in AML. Our work indicates that genetic alterations of m6A regulatory genes may cooperate with TP53 and/or its regulator/downstream targets in the pathogenesis and/or maintenance of AML.
MacArthur Winner Adapts High-Tech Medicine to Third World
Authors: Jeff Lyon
Journal: JAMA (2017)

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Magnetic Resonance Imaging quantification of breast density in BRCA carriers following gonadotropin releasing hormone agonist (GnRHA)-based hormonal chemoprevention
Authors: C. Klifa, S. Sand, L. Vora, M. Press, A. Orisamolu, M. Pike, D. Spicer, A. Daniels, K. Blazer, J. Weitzel
Journal: Journal of Clinical Oncology (2009)

1506 Background: Breast tissue density limits the usefulness of mammography as a surveillance tool in young women. Breast Magnetic Resonance Imaging (MRI) provides high tissue contrast and three-dimensional structural information not impaired by high breast density. We developed a volumetric “MR density” measure of breast structural composition that may be complementary to mammographic breast density. We tested this MR density measure in unaffected women with known high risk of breast cancer due to a BRCA gene mutation (or empiric risk &gt; 30% lifetime), who were recruited in a phase II trial to study the effects of a hormonal chemoprevention regimen. Methods: Nine premenopausal high-risk women age 21 to 48 were treated with intranasal GnRHA (deslorelin), low-dose estradiol, and testosterone daily for 10 months. All patients underwent one contrast-enhanced breast MRI exam before and after treatment. We measured MR density as the ratio of fibroglandular tissue volume to total volume of the breast, at both time points. Our technique involved the semi-automated delineation of the breast and the automated segmentation of fibroglandular from adipose tissue. An “MR index” was also defined to quantify partial voluming effects due to the presence of adipose/fibroglandular edges in the MR data. Results: Eight out of nine patients showed a reduction in MR density (p = 0.026) with treatment. Three patients had less than 5% MR density at baseline, making it difficult to quantitate a change with treatment. All of the remaining six patients had reduced MR density after treatment (mean reduction 35.5%; p = 0.035). Conclusions: We have demonstrated the use of breast MR density as a robust volumetric quantitative measure of breast tissue composition. Our findings suggest that MR could be used to measure hormonal chemoprevention effects in BRCA carriers. [Table: see text]
Cancer stem cell niche models and contribution by mesenchymal stroma/stem cells
Authors: Catharina Melzer, Juliane von der Ohe, Hendrik Lehnert, Hendrik Ungefroren, Ralf Hass
Journal: Molecular Cancer (2017)

The initiation and progression of malignant tumors is driven by distinct subsets of tumor-initiating or cancer stem-like cells (CSCs) which develop therapy/apoptosis resistance and self-renewal capacity. In order to be able to eradicate these CSCs with novel classes of anti-cancer therapeutics, a better understanding of their biology and clinically-relevant traits is mandatory. Several requirements and functions of a CSC niche physiology are combined with current concepts for CSC generation such as development in a hierarchical tumor model, by stochastic processes, or via a retrodifferentiation program. Moreover, progressive adaptation of endothelial cells and recruited immune and stromal cells to the tumor site substantially contribute to generate a tumor growth-permissive environment resembling a CSC niche. Particular emphasis is put on the pivotal role of multipotent mesenchymal stroma/stem cells (MSCs) in supporting CSC development by various kinds of interaction and cell fusion to form hybrid tumor cells. A better knowledge of CSC niche physiology may increase the chances that cancer stemness-depleting interventions ultimately result in arrest of tumor growth and metastasis.
Improved Therapy for PSA Recurrence after Prostatectomy
Authors: Ian M. Thompson
Journal: New England Journal of Medicine (2017)

In developed countries around the world, prostate cancer is the most common solid neoplastic disease. In the United States, approximately half the men with localized prostate cancer undergo radical prostatectomy.1 Prostate-specific antigen (PSA) levels should be undetectable after surgery; a detectable PSA level usually indicates disease recurrence. Almost uniformly, patients who have progression to metastatic disease and subsequently die from prostate cancer present with a detectable PSA level as the first evidence of cancer recurrence.In many patients, residual or recurrent disease is limited to the prostatic bed or pelvis, a phenomenon that has been confirmed by observations that adjuvant . . .
Single liver enzyme test in statin patients cuts full testing by a quarter, study finds
Authors: Susan Mayor
Journal: BMJ (2017)

Using a test for only one liver enzyme and providing clearer guidance on when to test can reduce GP requests for full liver function testing in patients taking statins by a quarter, an observational study in UK general practice has shown.1

“Current liver function testing for statin monitoring is largely unnecessary and costly,” said the study authors, led by John Robson, of the Centre for Primary Care and Public Health at Queen Mary University of London.

They found that patients taking statins undergo routine testing because of longstanding concerns about possible hepatotoxicity, although clinical practice has shown only a transient elevation of …
MONITORING FIELD HOCKEY INJURIES: THE FIRST STEP FOR PREVENTION
Authors: Saulo Delfino Barboza, Willem van Mechelen, Evert Verhagen
Journal: British Journal of Sports Medicine (2017)

Background Field hockey is a team sport with a high amount of running, stepping manoeuvres and player/material contact. Consequently, it can be expected that injury risk is high. Yet, little is know about injuries in this sport. Objective To measure the prevalence of injury during a field hockey season. Design Prospective cohort. Setting A field hockey season of the Dutch elite division. Participants 83 field hockey players (54 women and 29 men) of 5 different teams selected by convenience. Four players dropped out the study (1 woman and 3 men). Independent variables Hours of sport exposure (specific training [i.e., on the field], additional training [e.g, fitness training], and competition). Main Outcome Measurements Prevalence of injury. Results In total, field hockey players spent 9,063 hours in hockey specific training, 3,378 in additional training and 2,412 in competition. The total hours of sport exposure was 14,853. A total of 143 injuries were recorded (63% overuse and 37% traumatic). This corresponds to a rate of 9.6 injuries per 1,000 hours of sport exposure. The average prevalence of injury was 26.7% (ranging from 9.6% to 49.1% per two weeks). Lower limbs were the most reported injury location (58.4%), followed by lumbar and thoracic spine/thorax (20.2%), upper limbs (17.8%) and head/neck (3.6%). Conclusions This study establishes the extent and pattern of injuries in Dutch field hockey elite players. The next step, according to van Mechelen's sequence of prevention (1992), is to investigate the aetiology and mechanism of such injuries in order to develop and introduce preventive measures.
Treatment Effect of First Line Rituximab, Fludarabine and Cyclosphosphamide in a Chronic Lymphocytic Leukemia Patient Cohort: An Evaluation of Prognostic Factors, Estimated Life Expectancy and Economic Outcomes
Authors: Emma Carr, Susan Lerner, Rick Aultman, Ute Weisgerber-Kriegl, Michael Keating
Journal: Blood (2008)
Philadelphia-Positive Acute Lymphoblastic Leukemia Patients Already Harbor Bcr-Abl Kinase Domain Mutations at Low Levels at the Time of Diagnosis - a Report by the GIMEMA ALL Working Party
Authors: Simona Soverini, Giovanni Martinelli, Antonella Vitale, Alessandra Gnani, Sabrina Colarossi, Stefania Paolini, Ilaria Iacobucci, Cristina Papayannidis, Marco Vignetti, Annalisa Lonetti, Loredana Elia, Giuseppe Leone, Mario Lazzarino, Giuseppe Torelli, Renato Fanin, Giuseppe Cimino, Giovanna Meloni, Anna Guarini, Franco Mandelli, Michele Baccarani, Robin Foà
Journal: Blood (2008)
Role of Host miRNA Hsa-miR-139-3p in HPV-16–Induced Carcinomas
Authors: M.K. Sannigrahi, Rajni Sharma, Varinder Singh, Naresh K. Panda, Vidya Rattan, Madhu Khullar
Journal: Clinical Cancer Research (2017)

Purpose: Human papillomavirus 16 (HPV-16) is an important risk factor in head and neck cancer (HNC). Studies suggest that miRNAs play an important role in cancer; however, their role in HPV-mediated oncogenesis remains largely unknown. We investigated the role of miRNAs with HPV-16 as putative target in HPV-16-mediated cancers.Experimental Design: Using in silico tools, we identified miRNAs with putative binding sequences on HPV-16 miRNAs. Hsa-miR-139-3p was identified as best candidate miRNA by luciferase reporter assay and was found to be significantly downregulated in HPV-16-positive tissues and cell lines. Overexpression/inhibition studies were performed to determine the role of miRNA in regulating oncogenic pathways.Results: Hsa-miR-139-3p was found to target high-risk HPV-16 oncogenic proteins and revive major tumor suppressor proteins (p53, p21, and p16). This resulted in inhibition of cell proliferation and cell migration, cell-cycle arrest at G2-M phase and increased cell death of HPV-16-positive cells. Analysis of The Cancer Genome Atlas (TCGA) data showed decreased expression of Hsa-miR-139-3p in HPV-16-positive HNC and cervical cancer cases, and its higher expression correlated with better survival outcome in both cases. Increased DNA methylation of Hsa-miR-139-3p harboring gene PDE2A at its promoter/CpG islands was observed in HPV-16-positive tissues and cell lines, which further correlated with Hsa-miR-139-3p expression, suggesting its role in regulating Hsa-miR-139-3p expression. Furthermore, we observed an increased sensitization of Hsa-miR-139-3p overexpressed HPV-16-positive cells to chemotherapeutic drugs (cisplatin and 5-fluorouracil).Conclusions: HPV-16-mediated downregulation of Hsa-miR-139-3p may promote oncogenesis in HNC and cervical cancer. Clin Cancer Res; 23(14); 3884-95. ©2017 AACR.
Tolerability and Anti-Leukemic Activity of Ara-C, Topotecan, and Gemtuzumab Ozogamicin [ATGO] in Advanced MDS and AML: Interim Analysis of Phase I/II Data.
Authors: Sujatha Murali, Elliott F. Winton, Stephanie McMillan, Sagar Lonial, Ned Waller, Leonard Heffner, Christopher Flowers, Jonathan L. Kaufman, Mary Jo Lechowicz, H. Jean Khoury, Amelia Langston
Journal: Blood (2006)
Outcome of Patients with Primary Refractory Acute Myeloid Leukemia (AML) Undergoing Myeloablative Allogeneic Stem-Cell Transplantation (alloSCT) from HLA-Identical Sibling: Favorable Outcome in a Subset of Patients.
Authors: Jordi Esteve, Myriam Labopin, Gerhard Ehninger, Athanasios Fassas, Jurgen Finke, Miguel A. Sanz, Paolo Alessandrino, Axel Arthur Fauser, Vanderson Rocha
Journal: Blood (2006)
Mutational Spectrum Of Adult T-ALL
Authors: Martin Neumann, Sandra Heesch, Sebastian Vosberg, Cornelia Schlee, Stefan Schwartz, Nicola Gökbuget, Dieter Hoelzer, Alexander Graf, Stefan Krebs, Helmut Blum, Monika Brüggemann, Jochen Hecht, Stefan K. Bohlander, Philipp A. Greif, Claudia D. Baldus
Journal: Blood (2013)
Lower Incidence of Esophagitis in the Elderly Undergoing Definitive Radiation Therapy for Lung Cancer
Authors: Payal D. Soni, Philip S. Boonstra, Matthew J. Schipper, Latifa Bazzi, Robert T. Dess, Martha M. Matuszak, Feng-Ming Kong, James A. Hayman, Randall K. Ten Haken, Theodore S. Lawrence, Gregory P. Kalemkerian, Shruti Jolly
Journal: Journal of Thoracic Oncology (2017)
Gene Expression Profiles in Acute Myeloid Leukemia (AML): From Diagnosis to Prognosis.
Authors: Sanggyu Lee, Jianjun Chen, Goulin Zhou, Run Shi, Masha Kocherginsky, Theodore G. Karrison, Yeong Cheol Kim, Xijin Ge, Nimanthi Jayathilaka, Mary Beth Neilly, Gerard Bouffard, Alice Young, Steven Kornblau, Clara Bloomfield, Stefan Bohlander, Pu Paul Liu, Miao Sun, San Ming Wang, Janet D. Rowley
Journal: Blood (2005)
Effect of Adding Rituximab (R) to Induction Treatment and High Dose Chemotherapy (HDC) Prior to Autologous Stem Cell Transplantation (ASCT) as First Line Therapy in Stage III-IV Diffuse Large B-Cell Lymphoma (B-DLCL) at Poor Prognosis.
Authors: Umberto Vitolo, Giuseppe Rossi, Maria Giuseppina Cabras, Anna Marina Liberati, Annalisa Chiappella, Alessandro Levis, Enzo Pavone, Emanuele Angelucci, Barbara Botto, Manuela Ceccarelli, Roberto Freilone, Gianluca Gaidano, Domenico Novero, Lorella Orsucci, Isabella Palumbo, Enrico Pogliani, Delia Rota Scalabrini, Flavia Salvi, Anna Tonso, Alessandra Tucci, Eugenio Gallo
Journal: Blood (2005)