tbuckley/cabot-search huggingface dataset:
Post-Treatment FDG-Avid Splenic Lesions in DLBCL: Clinical and Radiographic Characteristics for Risk Assessment
Authors: Boaz Nachmias, Geremy Godefroy, Chezi Ganzel, Neta Goldschmidt, Eyal Rozenbach, Rachel Bar-Shalom, Diana Libster, Vladimir Vainstein
Journal: Blood (2019)
Rapid Response to Treatment of Autoimmune Hepatitis Associated With Remission at 6 and 12 Months
Authors: Simon Pape, Tom J.G. Gevers, Jan Maarten Vrolijk, Bart van Hoek, Gerd Bouma, Carin M.J. van Nieuwkerk, Richard Taubert, Elmar Jaeckel, Michael P. Manns, Maria Papp, Nora Sipeki, Felix Stickel, Cumali Efe, Ersan Ozaslan, Tugrul Purnak, Frederik Nevens, Dominik J.N. Kessener, Alisan Kahraman, Heiner Wedemeyer, Johannes Hartl, Christoph Schramm, Ansgar W. Lohse, Joost P.H. Drenth, Michael A. Heneghan
Journal: Clinical Gastroenterology and Hepatology (2019)
“Self-Deposition” of Matrix Proteins from Platelet α-Granules Enable Extended Adhesion and Spreading on Micron/Submicron-Scale Fibrinogen and Collagen Substrates.
Authors: Yumiko Sakurai, Jennifer L Fitch-Tewfik, Yongzhi Qiu, David R Myers, Byungwook Ahn, Robert Flaumenhaft, Wilbur A Lam
Journal: Blood (2014)
Type H blood vessels in bone modeling and remodeling
Authors: Yi Peng, Song Wu, Yusheng Li, Janet L. Crane
Journal: Theranostics (2019)

In the mammalian skeletal system, osteogenesis and angiogenesis are intimately linked during bone growth and regeneration in bone modeling and during bone homeostasis in bone remodeling. Recent studies have expanded our knowledge about the molecular and cellular mechanisms responsible for coupling angiogenesis and bone formation. Type H vessels, termed such because of high expression of Endomucin (Emcn) and CD31, have recently been identified and have the ability to induce bone formation. Factors including platelet-derived growth factor type BB (PDGF-BB), slit guidance ligand 3 (SLIT3), hypoxia-inducible factor 1-alpha (HIF-1α), Notch, and vascular endothelial growth factor (VEGF) are involved in the coupling of angiogenesis and osteogenesis. This review summarizes the current understanding of signaling pathways that regulate type H vessels and how type H vessels modulate osteogenesis. Further studies dissecting the regulation and function of type H vessels will provide new insights into the role of bone vasculature in the metabolism of the skeleton. We also discuss considerations for therapeutic approaches targeting type H vessels to promote fracture healing, prevent pathological bone loss, osteonecrosis, osteoarthritis, and bone metastases.
US Food and Drug Administration Recommendations on the Use of Surrogate Measures as End Points in New Anti-infective Drug Approvals
Authors: Spencer Phillips Hey, Aaron S. Kesselheim, Pranav Patel, Preeti Mehrotra, John H. Powers
Journal: JAMA Internal Medicine (2019)

Regulatory and scientific guidelines stipulate that indirect, surrogate measures of patient benefit, such as a change in microbial culture status, should be used as primary end points only in pivotal trials of chronic conditions that are serious or life threatening and when the experimental therapy is expected to offer substantial benefit compared with available therapy. However, many recent US Food and Drug Administration (FDA) anti-infective drug approvals for acute and/or non-life-threatening diseases have been based on pivotal trials using surrogate measures as primary end points rather than clinical outcomes, such as symptom resolution or survival.To review FDA recommendations for primary end points in pivotal trials of new anti-infective drugs and assess the concordance of those recommendations with the regulatory and scientific conditions for the appropriate use of surrogate measures as primary trial outcomes.All guidance documents for antimicrobial drug development hosted on the FDA website were searched in November 2017; the search was updated in June 2018. For each document, 2 reviewers independently extracted data on the recommended primary end points for a pivotal or phase 3 trial.Twenty-two FDA guidance documents met the inclusion criteria, which included recommendations for primary end points in pivotal clinical trials in 27 infectious disease indications. Twenty-one of 27 indications recommended surrogate outcomes as either the sole primary end point or as components of composite end points. None of the recommendations for the use of surrogate measures matched the regulatory and scientific conditions favoring indirect outcomes in place of clinical outcomes.The FDA guidance documents for developing new anti-infective agents frequently recommend indirect measures of patient benefit, rather than direct measures of patient benefit, as sole primary end points or components of primary end points. Existing guidance documents should be updated and revised to recommend appropriate clinical outcomes consistent with general scientific and regulatory parameters.
Tumor Microenvironment Differs between Germinal Centre B-Cell and Non-Germinal Centre B-Cell like Diffuse Large B-Cell Lymphomas and Has Subtype-Specific Prognostic Impact on Survival
Authors: Matias Autio, Suvi-Katri Leivonen, Marja-Liisa Karjalainen-Lindsberg, Teijo Pellinen, Sirpa Leppa
Journal: Blood (2019)
IMMU-50. SYSTEMIC ADOPTIVE TRANSFER IMMUNOTHERAPY WITH TCR-TRANSDUCED T-CELLS TARGETING NY-ESO-1 FOR MENINGIOMA
Authors: Matthew Sun, Joey Orpilla, Erick Contreras, Janet Treger, Donna Molaie, Jonathan Tsang, Joseph Antonios, Anthony Wang, Linda Liau, Robert Prins, Richard Everson
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION The lack of immunotherapeutic antigen targets selectively expressed on meningiomas have historically hindered its immunotherapy development. However, recent literature showed that in meningiomas, NY-ESO-1 is the most frequently expressed Cancer-Testis(CT)-antigen, which is a group of proteins silent in somatic cells but reactivated in cancers. NY-ESO-1 also has higher expression in higher-grade meningiomas. Decitabine is known to upregulate CT-antigens and augment immunotherapy. To evaluate systemic adoptive transfer for meningiomas, we tested the efficacy of NY-ESO-1 T-cell-receptor(TCR)-transduced T-cells in vitro and in vivo, and the role of decitabine in meningioma immunotherapy. METHODS NY-ESO-1 TCR-Transduced T-cells were generated by double-transfection with supernatants from PG-13 retroviral packaging cell line encoding HLA-A*0201–restricted NY-ESO-1(157 – 165)-specific TCR. In vitro cytolysis was measured using the xCelligence Real-Time Cell Analyzer System. We utilized human meningioma cells SF1335(Grade I, HLA-A2.1 positive) and CH157(Grade III, HLA-A2.1 negative) in vitro and in vivo. RESULTS CH157 and SF1335 have high and low NY-ESO-1 expression, respectively. Decitabine upregulated NY-ESO-1 mRNA expression in SF1335 by 6-fold after 2 days and by 100-fold after 9 days, with similar effect on protein expression. Co-culturing CH157, CH157-HLA-A2.1(CH157 transduced with HLA-A2.1 vector), SF1335, and decitabine-pretreated-SF1335 cells individually with NY-ESO-1 TCR transduced T-cells at a ratio of 1:1 resulted in 0%, 65%, 20% and 40% cytolysis at 10hours, respectively. Systemic(intravenous) adoptive transfer of TCR-transduced T-cells significantly increased overall survival in NSG mice with intracranial xenografts of CH157-HLA-A2.1 (p=0.04) and SF1335(not treated with decitabine) (p=0.06). CONCLUSIONS NY-ESO-1 TCR-transduced T-cells induce NY-ESO-1 and HLA-A2.1-specific cytolysis in meningioma in vitro, and systemic adoptive transfer confers a statistically significant survival benefit in vivo for meningiomas with high NY-ESO-1 expression. Decitabine upregulates NY-ESO-1 expression and increases tumor cytolysis by TCR-transduced T-cells in meningiomas. Targeting NY-ESO-1 may be a clinically feasible immunotherapeutic strategy to treat aggressive meningiomas.
Blood signatures for early liver cancer detection in patients with chronic hepatitis B.
Authors: Choong-Chin Liew, Haniza Omar, Chun Ren Lim, Chin Wei Bong, Edie Jian Jiek Ooi, Michelle Mei Lin Lee, Choon Geok Yu, Soek Siam Tan, Muhammad Radzi Abu Hassan, Jarayam Menon, Raman Muthukaruppan, Mandeep Singh, Nik Azim Nik Abdullah, Boon Phoe Ooi, Robert Phooi Huat Ding, Eng Joo Low, Francis Tan, Samuel Chao, Hengxuan Yang, Ismail Merican
Journal: Journal of Clinical Oncology (2012)

4106 Background: Some 20-30% of patients with chronic hepatitis B (CHB) eventually develop hepatocellular carcinoma (HCC), a disease with poor prognosis and high mortality unless detected early. Ultrasound and/or alpha-fetoprotein (AFP) are widely used for HCC surveillance. However these technologies are operator-dependent, have low sensitivity and are considered inadequate for screening. This study describes a blood-based gene-expression signature prognostic for HCC in CHB patients. Methods: PaxGene was used to extract RNA from whole blood samples taken from more than 1,000 Malaysian patients (matched HCC, CHB, healthy controls). Complementary DNA was generated from isolated RNA via reverse transcription and analyzed using Affymetrix U133Plus 2.0 with MAS 5.0 normalization. To minimize bias we developed a novel algorithm based on SentinelPair regression analysis to identify biomarker panels. A Monte Carlo search identified pair combinations that could differentiate between cancer and controls. Twelve genes were selected for qRT-PCR Cohort 1 verification (n=139). Six genes were then short-listed for qRT-PCR Cohort 2 verification using independent samples (n=150). Results: Multivariate quantitative microarray analysis of 147 samples (HCC=47; CHB=50; controls=50) identified 12 probe sets differentially expressed between HCC patients and controls and CHB (ROC AUC=0.90). These genes were evaluated using qRT-PCR on the same cohort (ROC AUC=0.86). Six genes were subsequently short listed for qRT-PCR Cohort 2 verification. The AUC of the 6-gene-combination of Cohort 2 (HCC=50; CHB=50; controls=50) was 0.80. Importantly, of the thirteen HCC with low AFP (&lt;15ng/ml), 9 were predicted as “positive.” Conclusions: Blood RNA biomarkers identified in this study may form the basis of a test that can be used in patients with CHB for detection of early HCC, potentially improving prognosis for this cancer. This blood-based test would represent a significant clinical alternative to ultrasound and/or AFP.
Filgrastim Administered after Early Assessment Bone Marrow Biopsy during 7+3 Induction Therapy for Acute Myeloid Leukemia Reduces Length of Hospital Stay
Authors: Jiasheng Wang, Kirsten M Boughan, Paolo F Caimi, Brenda Cooper, Marcos de Lima, Molly M Gallogly, Ehsan Malek, Leland Metheny, Folashade Otegbeye, Shufen Cao, Pingfu Fu, Benjamin Tomlinson
Journal: Blood (2019)
Methodology for the Start-up of a Pediatric Hematopoietic Stem Cell Transplant Unit (pHSCTU) in Middle-Income Countries (MICs): An Exportable Model?
Authors: Marta Verna, Attilio Rovelli, Valentino Conter, Marta Canesi, Ignazio Majolino, Dosti Othman, Vian Faeq, Jabibi Noguera, Maria Liz Benitez, Othman Dastan, Andrea Biondi
Journal: Blood (2019)
Late Effects in Survivors of Infant Acute Lymphoblastic Leukemia from the 3 Consecutive Japanese Nationwide Clinical Trials
Authors: Yuki Aoki, Akira Hayakawa, Kazutoshi Koike, Hisamichi Tauchi, Eiichi Ishii, Katsuyoshi Koh, Takako Miyamura, Yasushi Ishida, Akiko Kada, Akiko M Saito, Atsushi Manabe, Keizo Horibe, Shuki Mizutani, Miho Maeda, Daisuke Tomizawa
Journal: Blood (2019)
DRES-05. PREDICTORS OF SENSITIVITY TO COMBINED TEMOZOLOMIDE AND PARP INHIBITOR IN GLIOMA
Authors: Hiroaki Nagashima, Fumi Higuchi, Christine Lee, Seamus Rafferty, Julie Miller, Hiroaki Wakimoto, Daniel Cahill
Journal: Neuro-Oncology (2019)

Abstract Agents targeting the PARP enzyme family are under active development for the treatment of gliomas. PARP inhibitors (PARPi) can enhance the effect of temozolomide (TMZ) in IDH wild-type glioblastomas, and in addition recent studies have shown that PARP inhibitors can be selectively lethal in IDH1 mutant cancers. Here, we sought to identify predictors of sensitivity and resistance to PARP inhibition in gliomas. We treated 4 IDH1 mutant and 8 IDH wild-type glioma lines, as well as IDH1 mutant fibrosarcoma line HT1080, with TMZ, the PARPi olaparib, or the combination, and assessed cellular growth and survival. In dose response assessments, 7 out of 13 lines were sensitive to olaparib monotherapy (3 IDH1 mutant and 4 IDH wild-type). Combination with TMZ resulted in 6 of 13 lines responding to dual therapy, with an additive effect seen in 5 PARPi monotherapy sensitive gliomas. Notably, 5 of the 6 lines responsive to the combination harbored CDKN2A deletion, compared to none of the non-responsive lines (p=.0021). Treatment with CDK inhibitor palbociclib partially reversed sensitivity to TMZ+PARPi in HT1080, supporting a mechanistic basis for this association. PARPi sensitivity in glioma lines can be augmented by the addition of TMZ. CDKN2A deletion may serve as a potential biomarker identifying tumors sensitive to this combination therapy.
The DNA Helicase Hells Is a New Unconventional Player in ALK- Anaplastic Large Cell Lymphoma Biology
Authors: Valentina Fragliasso, Annalisa Tameni, Akanksha Verma, Rohan Bareja, Tayla Heavican, Javeed Iqbal, Gloria Manzotti, Danilo Fiore, Valentina Mularoni, Wing C. Chan, Francesco Merli, Olivier Elemento, Alessia Ciarrocchi, Giorgio Inghirami
Journal: Blood (2019)
P2.02 Second-line Afatinib vs Erlotinib for Advanced Lung Squamous Cell Carcinoma: Final Analysis of the Phase 3 LUX-Lung 8 Trial
Authors: G.D. Goss, M. Cobo, S. Lu, K. Syrigos, K.H. Lee, E. Göker, V. Georgoulias, W. Li, D. Isla, A. Morabito, Y.J. Min, A. Ardizzoni, H. Jian, Y. Yu, S. Bender, A. Cseh, E. Felip
Journal: Journal of Thoracic Oncology (2019)
The Patient I Didn’t Like
Authors: Marinos G. Sotiropoulos
Journal: JAMA Neurology (2019)

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QOLP-39. UNRAVELING THE TRUE COST OF CARE THROUGH ANALYSIS OF THE SOCIOECONOMIC IMPACT OF GLIOMA SURVIVORSHIP
Authors: Sameah Haider, Karam Asmaro, Steven Kalkanis, Ian Lee, Michael Bazydlo, Sam Nerenz, Ramzi Salloum, James Snyder, Tobias Walbert
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND There is a paucity of data describing the socioeconomic impact and long-term implications of glioma survivorship. Objective: To characterize the socioeconomic impact of glioma survivorship using the standardized Medical Expenditure Panel Survey – Household Component (MEPS-HC). METHODS 89 of 107 eligible adult glioma survivors that were post-treatment with stable disease were enrolled. The MEPS-HC was utilized to assess the socioeconomic hardship referable to the patient’s tumor. Comparisons between groups were evaluated using a Fisher’s exact test. RESULTS 89 patients responded to the survey (response rate = 85%, female =52%). Median follow-up from diagnosis was 6.0 years (4.3, 9.2). Pathology at diagnosis was high-grade (40%) and low-grade (60. The majority of glioma survivors were insured (91%), employed (79%), and reported annual household incomes slightly above national average. Nearly a quarter incurred debt because of their tumor (24%), 53% required extended unpaid time off, and 46% retired or were no longer working. While 85% had a Karnofsky Performance Score of &gt; 90, the majority of respondents reported lost productivity and decreased ability to perform cognitive and physical tasks (69%). Financial burden and workforce morbidity were insensitive to tumor location, laterality, and annual household income. Patients with a gross-total resection (GTR) at initial surgery were less likely to report ongoing limitations in daily activities (45% v. 83%, p=0.004). CONCLUSIONS Despite the skewed population of high-functioning glioma survivors, financial burden and workforce morbidity was ubiquitous across all tumor subtypes, treatment paradigms, and income levels. Those with GTR were less likely to report ongoing limitations. There was a trend towards greater financial burden among those with frontal and temporal lesions.
Plasma gene conversions after one cycle (C) abiraterone acetate (AA) for metastatic castration-resistant prostate cancer (mCRPC): A biomarker analysis of a multi-centre, international trial
Authors: A.K. Jayaram, D. Shen, A. Wingate, D. Wetterskog, C. Sternberg, R. Jones, A. Berruti, F. Lefresne, M. Lahaye, S. Thomas, S. Joshi, M. Gormley, B. Tombal, A. Merseburger, D. Ricci, G. Attard
Journal: Annals of Oncology (2019)
Prognostic Significance of Hospitalization Status at Second Cycle of Hypomethylating Agent Induction Therapy in Acute Myeloid Leukemia Patients Ineligible for Intensive Chemotherapy
Authors: Douglas Tremblay, Rafael Madero-Marroquin, Guido Lancman, Alexander Coltoff, Jonathan Feld, Jessica Caro, Nicole Zubizarreta, Marina Kremyanskaya, Alla Keyzner, Michal Bar-Natan, Shyamala C. Navada, Lewis R. Silverman, Janice L. Gabrilove, John Mascarenhas
Journal: Blood (2019)
Validity of HbA1c in Diagnosing Diabetes Among People with Sickle Cell Trait in Tanzania
Authors: Belinda Kweka, Eric Lyimo, Jeremiah Kidola, Suzanne Filteau, Henrik Friis, Alphaxard Manjurano, Daniel Faurholt Jepsen, George PrayGod, Heimburger Douglas C
Journal: Blood (2019)
TMIC-41. PROSTATE SPECIFIC MEMBRANE ANTIGEN EXPRESSION IN PRIMARY AND RECURRENT GLIOBLASTOMA
Authors: Mathew Lozinski, Michael Fay, Nikola Bowden, Moira Graves, Paul Tooney
Journal: Neuro-Oncology (2019)

Abstract Patients with glioblastoma almost always suffer a recurrence of an aggressive treatment resistant tumour and succumb within months highlighting the need to develop treatment options for recurrent glioblastoma. One potential target is prostate specific membrane antigen (PSMA) expressed on the new vessels in primary glioblastoma tumours. This study compared the expression of PSMA in primary and recurrent glioblastoma tumours. Formalin-fixed paraffin-embedded sections of primary and matched recurrent tumours from 13 patients with glioblastoma were processed for PSMA immunohistochemical labelling. PSMA expression was scored from digitally scanned sections using a categorical system (Total PSMA expression = PSMA label intensity (0–3) x percent PSMA-positive blood vessels). Little PSMA labelling was observed in any adjacent ‘unaffected’ brain tissue. PSMA was localised to blood vessels including those displaying microvascular proliferation in 12/13 primary and 9/13 recurrent glioblastoma tumours. Total PSMA expression scores ranged from 0 – 230 (maximum score = 300) and was divided into low and high expression based on a median split (median = 57) of PSMA expression across all tumours. Regression analysis showed a significant difference in PSMA expression between primary and recurrent glioblastoma (p = 0.04) with PSMA being highly expressed in ~70% of primary and only 31% of recurrent glioblastoma. Three cases displayed high expression in both primary and recurrent glioblastoma and one case had no PSMA expression at all. In conclusion, whilst higher expression of PSMA was detected in more primary tumours, 70%+ of all primary and recurrent tumours expressed PSMA to some extent adding evidence that this may be a useful target for treatment of glioblastoma. Larger cohorts and other techniques for detecting PSMA are needed to provide further evidence for PSMA’s utility as a target and to further define which glioblastoma patients are most likely to benefit from this approach.
Comparison of Lost Productivity Due to Eculizumab and Ravulizumab Treatments for Paroxysmal Nocturnal Hemoglobinuria in France, Germany, Italy, Russia, Spain, the United Kingdom, and the United States
Authors: Adrian R Levy, Laura Dysart, Yogesh Patel, Andrew Briggs, John Schneider, Karl-Johan Myren, Ioannis Tomazos
Journal: Blood (2019)
Cpit (Check Point Inhibitor Trial) 002: Phase I Study of Single-Agent and Combined Checkpoint Inhibition (CI) after Allogenic Hematopoietic Stem Cell Transplantation (alloHCT) in Patients at High Risk for Post-Transplant Recurrence
Authors: Jamie Koprivnikar, James K McCloskey, Rena Feinman, Robert Korngold, Michele L. Donato, Scott D. Rowley, Themba Nyirenda, Andrew L. Pecora
Journal: Blood (2019)
Imaging-Guided Therapies for Pericardial Diseases
Authors: Michael Chetrit, Bo Xu, Deborah H. Kwon, Jay Ramchand, Rene E. Rodriguez, Carmela D. Tan, Christine L. Jellis, Douglas R. Johnston, Rahul D. Renapurkar, Paul C. Cremer, Allan L. Klein
Journal: JACC. Cardiovascular imaging (2019)
Clinical Significance of Uptake Value on F18-FDG PET/CT and Histological Grade in 164 Patients with Follicular Lymphoma Including Transformation - a Single Center Retrospective Study
Authors: Mitsuhiro Yuasa, Daisuke Kaji, Kosei Kageyama, Yuki Taya, Shinsuke Takagi, Hisashi Yamamoto, Yuki Asano-Mori, Akiko Yoneyama, Shigeyoshi Makino, Naoyuki Uchida, Shuichi Taniguchi, Go Yamamoto
Journal: Blood (2019)
A Machine Learning Approach Identifies a 30-Gene Model That Predicts Sensitivity to Selinexor in Multiple Myeloma
Authors: Alessandro Lagana, Sherry Bhalla, Adolfo Aleman, Anna Huo-Chang Mei, Violetta Leshchenko, Yosef Landesman, David Melnekoff, Itai Beno, Deepu Madduri, Joshua R Richter, Ajai Chari, Hearn Jay Cho, Sundar Jagannath, Joel Dudley, Samir Parekh
Journal: Blood (2019)