tbuckley/cabot-search huggingface dataset:
Using Circ-ANAPC7 As a Novel Type of Biomarker in the Monitoring of Acute Myeloid Leukemia
Authors: Ying Shen, Yachun Jia, Ru Zhang, Hongli Chen, Yuandong Feng, Fang-Xia Wang, Wanhong Zhao, Jianli Wang, Aili He, Yun Yang, Yan Xu
Journal: Blood (2019)
EXTH-32. DEVELOPMENT OF EPHA3 DIRECTED CHIMERIC ANTIGEN RECEPTOR T CELL THERAPY FOR THE TREATMENT OF GLIOBLASTOMA MULTIFORME
Authors: Michael Ruff, Reona Sakemura, Michelle Cox, Mehrdad Hefazi Torghabeh, Paulina Roman Moreno, Kendall Schick, Jann Sarkaria, Saad Kenderian
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Efficacy of chimeric antigen receptor T cell (CART) therapy remains limited in solid tumors. Given the heterogeneity of surface receptor expression and immunosuppressive stromal microenvironment, strategies to target tumor neovasculature and tumor stromal cells are needed to help overcome CART inhibition by GBM. Eph receptors are the largest family of receptor tyrosine kinases and are integral to cell adhesion, migration, and axon guidance, during development and homeostasis. EphA3 is a receptor tyrosine kinase which is lowly expressed in adult tissues but is highly expressed in tumor neovasculature and tumor stromal cells in GBM and other solid tumors. EphA3 is over-expressed in up to 40% of GBM samples. We aimed to develop CART cells directed against EphA3 to use in targeting tumor neovasculature and tumor stromal cells in GBM. METHODS we developed a second generation CD28 co-stimulated CAR construct in a third generation lentivirus backbone to generate EphA3 CART cells using the single chain variable fragment of ifabotuzumab, a monoclonal antibody directed against EphA3. Patient derived GBM xenograft cell lines were used in these experiments. RESULTS EphA3 directed CART cells exhibited specific and potent antitumor activity against EphA3+ GBM cell lines with variable transcriptome EphA3 expression indicating its broader applicability in patients with GBM. Killing over 24-hour incubation was significant at low effector: target ratio: 52.5% killing at 1.25:1 against cell lines with 25.05% EphA3 expression and 37.1% killing at 1.25:1and 90% killing at 5:1 ratio against a cell line with 19.28% expression. Conversely, when co-cultured with UTD controls there was significantly lower killing, or growth of tumor cells. CONCLUSION We demonstrate for the first time that targeting EphA3 with CART cells is feasible, efficacious and represents a novel therapeutics strategy to target GBM. Data from in vivo and combinatorial CART experiments will be reported at the meeting.
PDCT-13. ENTRECTINIB IN CHILDREN AND ADOLESCENTS WITH RECURRENT OR REFRACTORY SOLID TUMORS INCLUDING PRIMARY CNS TUMORS
Authors: Giles Robinson, Ami Desai, Karen Gauvain, Ellen Basu, Kathleen Dorris, Luke Maese, Amit Sabnis, Jennifer Foster, Suzanne Shusterman, Janet Yoon, Brian Weiss, Mohamed Abdelbaki, Mufiza Farid-Kapadia, Georgina Meneses-Lorente, Alison Cardenas, Katherine Hutchinson, Guillaume Bergthold, Edna Chow Maneval, Elizabeth Fox, Amar Gajjar
Journal: Neuro-Oncology (2019)

Abstract The phase 1/2 STARTRK-NG trial is evaluating entrectinib, a CNS-penetrant oral inhibitor of TRK, ROS1 and ALK tyrosine kinases, in children with solid tumors, including primary CNS tumors. Eligible patients are ≤22y with recurrent/refractory solid tumors. The recommended dose was determined in all-comers, and then expansion cohorts of CNS and solid tumors with NTRK1/2/3, ROS1 or ALK gene fusions, and neuroblastomas (NBL) regardless of mutation spectrum, were enrolled. Investigator-assessed response was classified as complete (CR) or partial response (PR), stable (SD) or progressive disease using RANO (CNS), RECIST (solid tumors), or Curie score (NBL). By the clinical data cut-off, 01 April 2019, 32 patients were enrolled. As of 31 Oct 2018 (enrollment data cut-off), 29 patients were enrolled and included in the evaluable population. Median age was 7y (range 4.9m to 20y). Entrectinib was well tolerated; phase 1 dose-limiting toxicities were: elevated creatinine, dysgeusia, fatigue, and pulmonary edema. The recommended dose was 550mg/m2 daily; all responses occurred at doses ≥400mg/m2. In 6 patients with high-grade CNS tumors, all gene-fusion-positive, ORR was 100% (Investigator-assessed responses): 2 CR (ETV6-NTRK3, EML1-NTRK2); 4 PR (TPR-NTRK1, KANK1-NTRK2, EEF1G-ROS1, GOPC-ROS1). In extracranial solid tumors 6/8 had a fusion; of these, 2 achieved a confirmed CR (DCTN1-ALK, ETV6-NTRK3), and 4 achieved PR (ETV6-NTRK3, EML4-NTRK3, TFG1-ROS1, KIF5B-ALK). Central imaging review is being performed and will be provided. Duration of therapy ranged from 0.2 to 22.2 months for all 32 patients. In responding patients, time to response ranged from 1 to 8.3 months. In children with refractory CNS tumors harboring NTRK1/2/3 or ROS1 fusions, entrectinib produced striking, rapid, and durable responses. No responses were seen in tumors lacking target gene fusions. These results support the continued evaluation of entrectinib in solid tumors with target gene fusions, especially high-grade CNS neoplasms.
Portia: A Phase 1b Study Evaluating Safety and Efficacy of Tisagenlecleucel and Pembrolizumab in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Authors: Ulrich Jaeger, Nina Worel, Joseph P. McGuirk, Peter A. Riedell, Isabelle Fleury, Peter Borchmann, Jufen Chu, Ahmed M Abdelhady, Alessandra Forcina, Lida Bubuteishvili Pacaud, Edmund K. Waller
Journal: Blood (2019)
A CRISPR/Cas9-Generated Murine Model Reveals Cooperation between BCR Signaling and CDKN2A/2B and TP53 Disruption in Richter Syndrome
Authors: Supriya Chakraborty, Ilaria Fortunati, Claudio Martines, Brijesh Yadav, Marija Dimishkovska, Idanna Innocenti, Rosa Fazio, Giovanni D'Arena, Aleksandar Dimovski, Luca Laurenti, Dimitar G Efremov
Journal: Blood (2019)
Associations between Persistent Inflammation and Oxidative Stress with Neurocognitive Impairment in Long-Term Hodgkin Lymphoma Survivors and Community Controls
Authors: AnnaLynn M Williams, Daniel A. Mulrooney, Wei Liu, Matt J. Ehrhardt, Sedigheh Mirzaei Salehabadi, Angela Panoskaltsis-Mortari, Deokumar Srivastava, Yutaka Yasui, Melissa M. Hudson, Leslie L. Robison, Noah D Sabin, Kevin R. Krull
Journal: Blood (2019)
ATIM-13. MULTIMODAL IMMUNOTHERAPY WITH IO-VAC® FOR PATIENTS WITH GBM: A SINGLE INSTITUTION EXPERIENCE
Authors: Stefaan Van Gool, Jennifer Makalowski, Wilfried Stuecker
Journal: Neuro-Oncology (2019)

Abstract Multimodal immunotherapy (Newcastle Disease Virus (NDV) + modulated electrohyperthermia + IO-VAC® + immunomodulatory strategies) is an innovative treatment for primary GBM and might prolong overall survival (OS). IO-VAC® consists of DCs loaded with autologous tumor antigens and matured with cytokine cocktail and NDV. We retrospectively reviewed 132 cases of primary GBM. Multimodal immunotherapy was integrated as individualized treatment approach and following different scenario’s in combination with standard treatment in the first line treatment in 71 patients, used at time of first or subsequent relapse as treatment with or without chemotherapy in 61 cases. Median ages were resp. 55 and 53 y. Median KPI at start of immunotherapy was 90 and 80. Median OS for the patients treated with immunotherapy as part of first-line treatment was 20 months with 2-y OS of 40% (CI95%: -13,+13). Median OS for patients treated at time of relapse was 7 months with but still with 18-m OS of 16% (CI95%: -12,+9). Two resp. 1 patients were lost of follow up. A subgroup of 34 GBM patients (10 females) with median age 58y (20–67) was detected, who received NDV + modulated electrohyperthermia during Temozolomide maintenance cycles followed by two IO-VAC® DC vaccinations, and further NDV + modulated electrohyperthermia courses. Median KPI was 70 (60–100). MGMT status was methylated (12), unmethylated (13), unknown (9). Median OS for this subgroup was 23.4 months with 2-year OS of 48% (CI95%: -18,+20). Immunotherapy was feasible without immunotherapy-related side effects of grade III or more. The data suggest that multimodal immunotherapy with IO-VAC® already during and after maintenance chemotherapy, at time of achieved minimal residual disease with local therapy, might help in prolongation of OS. Prolongation of OS in a small group of patients at time of relapse was also demonstrated. IO-VAC® is an approved advanced therapy medicinal product (DE-NW-04-GMP-2015-0030).
Review: In dyslipidemia or atherosclerotic CVD, alirocumab and evolocumab vs control each reduce MI and stroke
Authors: Donald A. Smith
Journal: Annals of Internal Medicine (2019)

Source Citation Guedeney P, Giustino G, Sorrentino S, et al. Efficacy and safety of alirocumab and evolocumab: a systematic review and meta-analysis of randomized controlled trials. Eur Heart J. 2019. [Epub ahead of print]. 31270529
Is Variance Ratio a Valid Indicator of Heterogeneous Treatment Effect?
Authors: Sunjae Bae
Journal: JAMA Psychiatry (2019)

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Real-World Effectiveness and Safety of Eltrombopag in Patients with Aplastic Anemia: A Chinese Nationwide Survey
Authors: Wenrui Yang, Bing Han, Hong Chang, Bingyi Wu, Fankai Meng, Dexiang Ji, Yingmei Li, Zhengjin Zheng, Yan Fei, Jianping Shen, Ping Hu, Jianxiang Wang, Fengkui Zhang
Journal: Blood (2019)
Inhibition of Fatty Acid Metabolism Re-Sensitizes Resistant Leukemia Stem Cells to Venetoclax with Azacitidine
Authors: Courtney L Jones, Brett M. Stevens, Rachel Culp-Hill, Angelo Dalessandro, Anna Krug, Madeline Goosman, Shanshan Pei, Daniel A Pollyea, Craig T Jordan
Journal: Blood (2019)
Combined Ibrutinib and Venetoclax Changes Myeloid Phenotype and Improves Immune Function in CLL Patients
Authors: Rebecka Svanberg, Sisse Rye Ostrowski, Jakob Thaning Bay, Lars Peter Ryder, Hanne Vibeke Vibeke Marquart, Arnon P Kater, Carsten Utoft Niemann
Journal: Blood (2019)
Symmetric dimethylarginine in dysfunctional high-density lipoprotein mediates endothelial glycocalyx breakdown in chronic kidney disease
Authors: Bettina Hesse, Alexandros Rovas, Konrad Buscher, Kristina Kusche-Vihrog, Marcus Brand, Giovana Seno Di Marco, Jan T. Kielstein, Hermann Pavenstädt, Wolfgang A. Linke, Jerzy-Roch Nofer, Philipp Kümpers, Alexander Lukasz
Journal: Kidney International (2019)
Equate, a Phase 1b/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of a Novel Targeted Anti-CD6 Therapy, Itolizumab, in Subjects with Newly Diagnosed Acute Graft Versus Host Disease
Authors: John Koreth, Saurabh Chhabra, Joseph Pidala, Thomas C. Shea, Madan Jagasia, Edmund K. Waller, Ryotaro Nakamura, Marco Mielcarek, George L. Chen, Gabrielle Meyers, Daanish Hoda, Betty K. Hamilton, Cherie Tracy Ng, Mark Sonnemann, Susan Light, Nuwan Nanayakkara, David Essayan, Joel Rothman, Stephen Connelly, Krishna Polu, Leslie Kean, Jerome Ritz, Robert J. Soiffer, Corey Cutler
Journal: Blood (2019)
Inter-Cell Networking Profiling Enables Comprehensive Characterization of Immune-Mediated Activity of Anti-CD38 Therapy through Ex-Vivo Analysis of Multiple Myeloma Patients
Authors: Alice Bettelli, Rita Ruggiano, Silvia Bocchi, Laura Rocchi, Andrea Faenza, Enrica Borsi, Carolina Terragna, Elena Zamagni, Marina Martello, Marco Bettelli, Laura Rambelli, Viviana Guadagnuolo, Nicola Pecorari, Luca Giulianelli, Matteo Pisani, Dario Biscarini, Michele Cavo, Roberto Guerrieri, Massimo Bocchi
Journal: Blood (2019)
HOUT-18. TREATMENT STRATEGIES FOR GLIOBLASTOMA IN OLDER PATIENTS: AGE IS JUST A NUMBER
Authors: Michael Youssef, Ethan Ludmir, Jacob Mandel, Akash Patel, Ali Jalali, Jeffrey Treiber, Jimin Wu, Mary McAleer, John DeGroot
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Optimal care for elderly patients with glioblastoma (GBM) remains in question due to their exclusion from and underrepresentation in clinical trials (including EORTC 22981) as well as their historically-poor overall survival. METHODS Retrospective chart review was conducted at a single high-volume cancer center for newly-diagnosed elderly (65 years old or older) GBM patients diagnosed from 2011 through 2017. RESULTS A total of 158 newly-diagnosed GBM patients aged 65 years and older were identified. 144 patients (91.1%) underwent radiation therapy. One-hundred thirty patient (90.3%) received concurrent temozolomide with radiotherapy. A minority of patients (23%) discontinued temozolomide during concurrent or adjuvant treatment due to side effects or complications of chemotherapy. Sixty-one patients (38.6%) completed concurrent chemoradiation and 6 cycles of adjuvant temodar. The median overall survival (OS) time for our cohort was 18.6 months, with estimated OS rates of 74.8%, 35.9%, and 9.5% at 1, 2, and 5 years, respectively. On multivariable analysis, higher KPS (p=0.002, HR 0.46; 95% CI: 0.63–0.82), completing planned course of radiation (p=0.01, HR 0.29; 95% CI: 0.11–0.75), and completing 6 cycles of adjuvant temozolomide (p=0.01, HR 2.62; 95% CI: 1.67–4.12) were associated with improved OS. CONCLUSIONS Our cohort of elderly GBM patients were predominately treated with a standard of care based on EORTC 22981. Despite their age, these patients tolerated treatment well and had a favorable overall survival compared to outcomes reported for patients treated on EORTC 22981. Using age alone as the reason to de-escalate treatment or as an exclusionary criteria in clinical trials should be discouraged.
Frontline Treatment with Ibrutinib Plus Rituximab (IR) Followed By Short Course R-Hypercvad/MTX Is Extremely Potent and Safe in Patients (age ≤ 65 years) with Mantle Cell Lymphoma (MCL) - Results of Phase-II Window-1 Clinical Trial
Authors: Michael L. Wang, Preetesh Jain, Hun Ju Lee, F. B. Hagemeister, Felipe Samaniego, Jason R. Westin, Loretta J. Nastoupil, Wendy Chen, Krystle Nomie, Shaojun Zhang, Omar Moghrabi, Shuangtao Zhao, Rashmi Kanagal-Shamanna, Chi Young Ok, Onyeka Oriabure, Graciela M. Nogueras González, Dayoung Jung, Lucy Navsaria, Ann Uy, Archie Pedersen, Liang Zhang, Changying Jiang, Feng Lei, Yixin Yao, Guofang Xu, Nicolaus Wagner-Bartak, Selvi Thirumurthi, David Santos, Guilin Tang, Keyur Patel, C. Cameron Yin, Michelle Avellaneda, Maria Badillo, Luis Fayad, Sattva S Neelapu, Nathan H. Fowler, Jorge Enrique Romaguera, Linghua Wang
Journal: Blood (2019)
Clinical Implications of Abnormal Cytogenetics at Diagnosis of Aplastic Anemia.
Authors: Sung-Yong Kim, Jong-Wook Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Hee-Je Kim, Seok-Goo Cho, Dong-Wook Kim, Woo-Sung Min, Chun-Choo Kim
Journal: Blood (2006)
EPID-03. HISTOLOGY-SPECIFIC BRAIN TUMOR INCIDENCE AND SURVIVAL VARIES BY SEX
Authors: Michelle Dong, Gino Cioffi, Carol Kruchko, Quinn Ostrom, Justin Lathia, Joshua Rubin, Michael Berens, James Connor, Jill Barnholtz-Sloan
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Significant sex differences exist in cancer, and males have higher incidence and lower survival compared to females for most cancers. No large-scale studies have systematically examined sex differences in incidence and survival across all primary brain histologies. We performed a comprehensive investigation of the differences in incidence and survival in patients diagnosed with primary malignant brain and other CNS tumors by specific histologies. METHODS Age-adjusted incidence rate ratios (IRR) and 95% confidence intervals (945% CI) were generated from the United States Cancer Statistics (USCS) Public Use Database. Data from the Surveillance, Epidemiology, and End-Results (SEER) program were used to calculate overall survival. Data was restricted to patients with histologically or radiologically confirmed, primary malignant tumors diagnosed between 2001 and 2015. Histological groupings were categorized based on the Central Brain Tumor Registry of the United States (CBTRUS). Cox proportional hazards models were used to calculate hazard ratios (HR) adjusted for age for males as compared to females. RESULTS Males exhibited higher incidence than females in all brain histologies except meningioma (IRR=0.83; 95% CI 0.73–0.93) and other neuroepithelial tumors (i.e. polar spongioblastomas and astroblastomas) (IRR=0.48; 95% CI 0.26–0.88). Males experienced better overall survival in germ cell tumors, cysts and heterotopias (HR=0.68; 95% CI 0.49–0.94) compared to females, but were observed to have lower survival in all other histologies. Survival was lowest for males among patients with nerve sheath tumors (HR=2.32; 95% CI 1.31–4.12) and other neoplasms related to the meninges (e.g. chondrosarcomas and chordomas) (HR=2.23; 95% CI 1.24–3.99). Survival in meningioma patients was significantly higher in females (HR=1.49; 95% CI 1.25–1.77). Patients with glioblastomas, had a slightly worse survival outcome in males (HR=1.02, 95% CI 1.00–1.05). CONCLUSION Understanding the role of sex differences is critical for addressing sex based inequalities and needs to be taken into account in clinical paradigms.
Composite Copy Number Variation in CDK4, CDKN2A and RB1 Predisposes Mantle Cell Lymphoma to Expansion of PD1+ Tumor Cells and Resistance to CDK4/6 Inhibitor Therapy as Revealed by Integrative Longitudinal scRNA-seq
Authors: Maurizio Di Liberto, Yang Hu, Xiangao Huang, Christina Y. Lee, Kevin Wang, Nancy L. Bartlett, LeAnn Ridling, Kristie A. Blum, Kami J. Maddocks, Steven I Park, Jia Ruan, Kenneth Eng, Lorenzo Galluzzi, John P. Leonard, Peter Martin, Olivier Elemento, Selina Chen-Kiang
Journal: Blood (2019)
Mapping microglia states in the human brain through the integration of high-dimensional techniques
Authors: Roman Sankowski, Chotima Böttcher, Takahiro Masuda, Laufey Geirsdottir, None Sagar, Elena Sindram, Tamara Seredenina, Andreas Muhs, Christian Scheiwe, Mukesch Johannes Shah, Dieter Henrik Heiland, Oliver Schnell, Dominic Grün, Josef Priller, Marco Prinz
Journal: Nature Neuroscience (2019)
Genomic and epidemiological evidence of bacterial transmission from probiotic capsule to blood in ICU patients
Authors: Idan Yelin, Kelly B. Flett, Christina Merakou, Preeti Mehrotra, Jason Stam, Erik Snesrud, Mary Hinkle, Emil Lesho, Patrick McGann, Alexander J. McAdam, Thomas J. Sandora, Roy Kishony, Gregory P. Priebe
Journal: Nature Medicine (2019)
Next-Generation RNA Sequencing-Based Analysis Identifies a Novel Set of Prognostic Micrornas (miRs) in Cytogenetically Normal Acute Myeloid Leukemia (CN-AML)
Authors: Dimitrios Papaioannou, Deedra Nicolet, Kellie J Archer, Allison Walker, Krzysztof Mrózek, Andrew J. Carroll, Jessica Kohlschmidt, Ann-Kathrin Eisfeld, Marius Bill, Christopher J. Walker, Geoffrey L. Uy, Bayard L Powell, Jonathan E. Kolitz, Richard Stone, John C. Byrd, Ramiro Garzon, Clara D. Bloomfield
Journal: Blood (2019)
Phase 2 Results of APR-246 and Azacitidine (AZA) in Patients with TP53 mutant Myelodysplastic Syndromes (MDS) and Oligoblastic Acute Myeloid Leukemia (AML)
Authors: David A Sallman, Amy E. DeZern, Guillermo Garcia-Manero, David P. Steensma, Gail J. Roboz, Mikkael A. Sekeres, Thomas Cluzeau, Kendra L. Sweet, Amy F McLemore, Kathy McGraw, John Puskas, Ling Zhang, Jiqiang Yao, Qianxing Mo, Lisa Nardelli, Najla Al Ali, Eric Padron, Greg Korbel, Eyal C. Attar, Hagop M. Kantarjian, Jeffrey E. Lancet, Pierre Fenaux, Alan F. List, Rami S. Komrokji
Journal: Blood (2019)
The Combination of CUDC-907 and Gilteritinib Shows Promising Antileukemic Activity in Vitro and In Vivo in Preclinical Models of FLT3-ITD AML
Authors: Tristan Knight, Xinan Qiao, Jun Ma, Holly Edwards, Lisa Polin, Juiwanna Kushner, Sijana H Dzinic, Kathryn White, Hai Lin, Yue Wang, Jeffrey W. Taub, Yubin Ge
Journal: Blood (2019)
SCIDOT-07. ULTRASOUND DELIVERED ALBUMIN BOUND PACLITAXEL EXTENDS SURVIVAL IN MALIGNANT GLIOMA MODELS AND OUTPERFORMS ULTRASOUND DELIVERED CREMOPHOR PACLITAXEL IN BIO-DISTRIBUTION AND SAFETY
Authors: Adam Sonabend, Crismita Dmello, Li Chen, Victor A Arrieta, Edgar Gonzalez, J Robert Kane, Lisa Magnusson, Aneta H Braun, C David James, Craig Horbinski, Michael Canney, Alexandre Carpentier, Frédéric Sottilini, Carole Desseaux, Miguel Muzzio, Roger Stupp
Journal: Neuro-Oncology (2019)

Abstract Paclitaxel is anti-neoplastic agent shown to be extremely potent against glioblastoma in-vitro; however, it has yet to demonstrate antitumor activity in the clinic due to its inadequate brain penetration. Ultrasound-mediated drug delivery is an emerging new technology that transiently disrupts the blood-brain barrier to allow the passage of larger molecules that under physiological conditions would not reach the brain tissue. In this preclinical study, we investigated the ability of low intensity pulsed ultrasound (LIPU), delivered with the SonoCloud System (CarThera), to increase brain paclitaxel concentrations in a murine model. LIPU increased paclitaxel concentrations in the brain 300–500% after systemic administration of two different commercially available formulations of paclitaxel; paclitaxel dissolved in Cremophor (Taxol®) and albumin-bound paclitaxel (Abraxane®). The two formulations differed in their toxicity and biodistribution profiles with albumin-bound paclitaxel exhibiting increased tolerability and brain penetration. After sonication, albumin-bound paclitaxel increased survival in an orthotropic glioma model, whereas cremophor-paclitaxel induced central nervous system toxicity. Our experiments suggest that increased paclitaxel drug delivery by opening the BBB is feasible, and an effective anti-glioma treatment. Albumin-bound paclitaxel is the preferred formulation for further investigation with the SonoCloud system in the clinical setting.