tbuckley/cabot-search huggingface dataset:
TMIC-25. MODIFICATION OF EXTRACELLULAR MATRIX ENHANCES ONCOLYTIC ADENOVIRUS IMMUNOTHERAPY IN GLIOBLASTOMA
Authors: Juri Kiyokawa, Yoichiro Kawamura, Robert Martuza, Samuel Rabkin, Khalid Shah, Hiroaki Wakimoto
Journal: Neuro-Oncology (2019)

Abstract Complex interplay between heterogeneous cells and extracellular matrix (ECM) in the tumor microenvironment drives the pathogenesis of glioblastoma (GBM). Glycosaminoglycan hyaluronic acid (HA) is a major component of GBM ECM, and is associated with tumor growth, invasion, and resistance to treatments. Delta24-RGD oncolytic adenovirus is a powerful cancer therapeutic and is currently under clinical evaluation for GBM. We hypothesized that degradation of HA would enhance oncolytic adenovirus immunotherapy of GBM by overcoming the immunosuppressive functions of GBM ECM. Intratumoral injections of ICOVIR17, a delta24-RGD oncolytic adenovirus carrying hyaluronidase PH20 cDNA, increased animal survival, in comparison to its parental virus ICOVIR15, in an orthotopic GBM model generated with murine 005 stem-like GBM cells in immunocompetent C57/Bl6 mice. ICOVIR17 promoted the degradation of HA, and induced an increase in tumor infiltrating CD8+ T cells and macrophages, compared with ICOVIR15. This led to the upregulation of immune checkpoint PD-L1 on GBM cells and macrophages, while it downregulated immune checkpoints TIM3 and CTLA-4 on CD8+ T cells. The combination therapy of ICOVIR17 and systemic administration of anti-PD-1 antibody significantly prolonged the survival of mice bearing intracerebral GBM compared to no treatment control group and monotherapy groups, and achieved long-term remission in 21% of treated animals. Flow cytometry analysis showed that the combination treatment significantly increased the ratio of effector/regulatory (CD8/Treg) T cells in the brain, compared with all the other three groups. Furthermore, antibody and clodronate-mediated in vivo depletion of immune subsets revealed that CD4+, CD8+ T cells and macrophages were all necessary for combination therapy to be effective as any of these depletions abrogated efficacy. Our findings reveal that ICOVIR17-mediated degradation of HA within GBM dramatically alters the immune landscape of the tumor microenvironment, and offer a mechanistically rationale combination immunotherapy with PD-L1/PD-1 blockade that results in superior anti-GBM efficacy.
Anti-Viral Prophylaxis for Hepatitis B Virus Is Associated with Improved Outcome in Patients with Diffuse Large B Cell Lymphoma in Taiwan - a Population-Based Study between 2011 and 2015
Authors: Huai-Hsuan Huang, Fei-Yuan Hsiao, Ho-Min Chen, Chen-Yu Wang, Hwei-Fang Tien, Bor-Sheng Ko
Journal: Blood (2019)
The Detection of Minor Clones with Somatic KIT D816V Mutations Using Droplet Digital PCR in Pediatric De Novo AML: AML-05 Trial from the Japanese Pediatric Leukemia/Lymphoma Study Group
Authors: Koji Sasaki, Yuri Uchiyama, Junji Ikeda, Masahiro Yoshitomi, Yuko Shimosato-Wada, Mayu Tokumasu, Hidemasa Matsuo, Kenichi Yoshida, Kentaro Oki, Genki Yamato, Yusuke Hara, Akitoshi Kinoshita, Daisuke Tomizawa, Takashi Taga, Souichi Adachi, Akio Tawa, Keizo Horibe, Naomichi Matsumoto, Shuichi Ito, Yasuhide Hayashi, Norio Shiba
Journal: Blood (2019)
Ptcy + ATG Vs Ptcy Alone As Gvhd Prophylaxis for Peripheral Blood Stem Cells Haplo-Transplants: Comparison of NK and T Cell Effector Reconstitution
Authors: Catherine Willem, Thierry Guillaume, Dhon Romeo Makanga, Nolwenn Legrand, Anne Cesbron, Katia Gagne, Pierre Peterlin, Alice Garnier, Amandine Le Bourgeois, Marie C Bene, Patrice Chevallier, Christelle Retière
Journal: Blood (2019)
Development and validation of an immune checkpoint-based signature to predict prognosis in nasopharyngeal carcinoma using computational pathology analysis
Authors: Ya-Qin Wang, Yu Zhang, Wei Jiang, Yu-Pei Chen, Shuo-Yu Xu, Na Liu, Yin Zhao, Li Li, Yuan Lei, Xiao-Hong Hong, Ye-Lin Liang, Jun-Yan Li, Lu-Lu Zhang, Jing-Ping Yun, Ying Sun, Ying-Qin Li, Jun Ma
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Immunotherapy, especially immune checkpoint inhibition, has provided powerful tools against cancer. We aimed to detect the expression of common immune checkpoints and evaluate their prognostic values in nasopharyngeal carcinoma (NPC). <h3>Methods</h3> The expression of 9 immune checkpoints consistent with 13 features was detected in the training cohort (<i>n</i> = 208) by immunohistochemistry and quantified by computational pathology. Then, the LASSO cox regression model was used to construct an immune checkpoint-based signature (ICS), which was validated in a validation cohort containing 125 patients. <h3>Results</h3> High positive expression of PD-L1 and B7-H4 was observed in tumour cells (TCs), whereas PD-L1, B7-H3, B7-H4, IDO-1, VISTA, ICOS and OX40 were highly expressed in tumour-associated immune cells (TAICs). Eight of the 13 immune features were associated with patient overall survival, and an ICS classifier consisting of 5 features (B7-H3TAIC, IDO-1TAIC, VISTATAIC, ICOSTAIC, and LAG3TAIC) was established. Patients with high-risk scores in the training cohort had shorter overall (<i>P</i> &lt; 0.001), disease-free (<i>P</i> = 0.002), and distant metastasis-free survival (<i>P</i> = 0.004), which were confirmed in the validation cohort. Multivariate analysis revealed that the ICS classifier was an independent prognostic factor. A combination of the ICS classifier and TNM stage had better prognostic value than the TNM stage alone. In addition, the ICS classifier was significantly associated with survivals in patients with high EBV-DNA load. <h3>Conclusions</h3> We determined the expression status of nine immune checkpoints consistent with 13 features in NPC and further constructed an ICS prognostic model, which might add prognostic value to the TNM staging system.
Prognostic Impact of Pre-Transplant Serum C-Reactive Protein in Patients Receiving a Single-Unit Unrelated Cord Blood Transplantation
Authors: Akiko Negoro, Heiwa Kanamori, Jun Aoki, Satoshi Koyama, Takayoshi Tachibana, Masatsugu Tanaka, Hideaki Nakajima
Journal: Blood (2016)
CRISPR-Cas9 Genome Editing of γ-Globin Promoters in Human Hematopoietic Stem Cells to Induce Erythrocyte Fetal Hemoglobin for Treatment of β-Hemoglobinopathies
Authors: Jean-Yves Metais, Phillip A Doerfler, Thiyagaraj Mayuranathan, Daniel E. Bauer, Stephanie Fowler, Matthew Hsieh, Varun Katta, Sagar Keriwala, Cicera Lazzarotto, Kevin Luk, Michael Neel, Scott Perry, Shaina Porter, Byoung Y. Ryu, Akshay Sharma, Devlin Shea, Samuel Peters, John F. Tisdale, Scot A. Wolfe, Kaitly Jensen Woodard, Naoya Uchida, Yuxuan Wu, Yu Yao, Jing Zeng, Shondra M. Pruett-Miller, Shengdar Q. Tsai, Mitchell J. Weiss
Journal: Blood (2019)
TMOD-07. IN SITU MICROSCOPY OF DRUG AND IMMUNE CELL INTERACTIONS AGAINST BIOFABRICATED TUMOR MODELS
Authors: Eric McGhee, Juan Uruena, Padraic Levings, Kylie van Meter, Ryan Smolchek, Derek Hood, Catherine Flores, Duane Mitchell, W Gregory Sawyer
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND &amp; SIGNIFICANCE Cancer is a disease in 3-dimensions and there is a desperate need for infrastructure and models to study immuno-oncology treatment strategies in 3D. A new culture system for long-duration maturation of patient derived microtumors has been developed. This system enables in situconfocal imaging and movies of T-cells and tumor model interactions, including measurements of T-cell migration, infiltration, and killing. HYPOTHESIS: Biofabrication of 3D microtumors using bioprinting in transparent soft granular gel media can facilitate the precise arrangement and stability of extra-cellular matrix components, tumor, and immune cells while maintaining continuous liquid perfusion. METHODS The design, development, and validation of a modular negative pressure perfusion system controls the transport of liquid growth medium, drugs, antibodies, growth factors, and metabolic waste management in 3D. In situ confocal fluorescent microscopy measures cell positions, velocities, and viability during experiments. Steady perfusion velocities are controlled through negative pressure, and velocities from 1–100 nm/s can be achieved. RESULTS Cell motility, adhesion, and dynamic rearrangement of fibroblasts and endothelial cells within a 3D co-culture of microtumors evolved dramatically over the first 72 hours. Tracking of activated CD8+ T-cells revealed super-diffusive motion in the presence of 3D tumors with a range of 250 µm. Activated T-cell migration speeds have been measured to be between 1.3–2.0 um/min in the 3D media, and preliminary estimates of T cell migration forces are on the order of 1 nN. Arrival of CD8+ T-cells to the tumors within the first 30 minutes revealed cell killing which continued for over 3-hours and resulted in a 2-fold reduction in tumor cell numbers. CONCLUSIONS This integrated system of 3D bioprinting, perfusion culture plates, and confocal microscopy enables in situ3D studies of cancer biology, immunotherapy, and drug treatment regimens and provides unique insights and measurements of immune cell invasion dynamics in 3D microtumors.
Differences in the Clinicopathological Feature, Prognostic Features and Treatment Outcomes between Molecular Subtypes Among Indian Cohort with Diffuse Large B-Cell Lymphoma - a Single Center Experience
Authors: Ashok K Vaid, Suman S Karanth, Aseem Khurana, Nitin Sood, Ashok Sen, Gautam Dheeraj, Bhuvan Chugh, Saurabh Mishra
Journal: Blood (2019)
Long-Term Follow-up Confirms Durability of Single-Agent Brentuximab Vedotin As Pre-Transplant Salvage for Classical Hodgkin Lymphoma
Authors: Alison J. Moskowitz, Heiko Schoder, Jisun Lee, Theresa Davey, Helen Hancock, Paul A. Hamlin, Steven M. Horwitz, Anita Kumar, Matthew J Matasar, Ariela Noy, M. Lia Palomba, Gunjan L. Shah, Miguel-Angel Perales, Craig S. Sauter, David J. Straus, Anas Younes, Andrew D. Zelenetz, Joachim Yahalom, Craig H. Moskowitz
Journal: Blood (2019)
ACTR-16. MATRix REGIMEN FOR NEWLY DIAGNOSED PRIMARY DIFFUSE B-CELL LYMPHOMA OF THE CENTRAL NERVOUS SYSTEM: PRELIMINARY RESULTS
Authors: Richard Green, Colleen Thornton
Journal: Neuro-Oncology (2019)

Abstract We report our preliminary experience treating 9 patients with newly diagnosed primary diffuse B-cell lymphoma of the central nervous system with the MATRix regimen as reported by Ferreri, et al in 2016. The median age was 63 y; 5 patients were men and 4 were women. Seven had cerebral mass lesions, 1 a paraspinal mass, and 1 leptomeningeal disease. Five patients underwent biopsy; 2 imaging total resection; 1 subtotal resection; and in 1 the extent of resection was indeterminate. Treatment consisted of 4 cycles of rituximab 375 mg/sq m (Days 1, 6); methotrexate 4 g/sq m (Day 2); cytarabine 2 g/sq m every 12 h (Days 3, 4); and thiotepa 30 mg/sq m (Day 5). Patients without disease progression received carmustine 400 mg/sq m and thiotepa 5 mg/kg followed by autologous bone marrow transplantation. Two patients were switched to MATRix after 6 cycles of methotrexate and rituximab and received 2 additional cycles that included cytarabine and thiotepa. Overall, 7 patients completed initial chemotherapy, with 5 complete responses and 2 partial responses. Six of these 7 went on to transplantation and remain alive without disease progression after a median follow-up of 470 days. One patient with initial PR progressed and did not proceed to transplantation. Two patients died after 1 cycle; they were both over 70 y (76 and 84) and succumbed to sepsis with neutropenic fever. No serious acute toxicity occurred in the 6 patients who completed the entire regimen including transplantation; 1 patient has experienced symptomatic leukoencephalopathy. Overall progression free survival was 394 days. These preliminary data suggest that the MATRix regimen in safe and highly effective in the newly diagnosed setting. However, the high early mortality in patients over 70 years in this group suggests that the regimen may be too toxic for very elderly individuals.
Ibrutinib Therapy Downregulates Toso, the Fcr for IgM, Expression in CLL Patients
Authors: Mariela Sivina, Gordon Duncan, Takashi Sakamoto, Ekaterina Kim, Alicia Vaca, Elena Maria Hartmann, Michael J Keating, Alessandra Ferrajoli, William G. Wierda, Tak Mak, Andreas Rosenwald, Jan A. Burger
Journal: Blood (2019)
Dual checkpoint inhibitor-associated eosinophilic enteritis
Authors: J. Yang, S. M. Lagana, Y. M. Saenger, R. D. Carvajal
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Eosinophilia has been reported as a rare, new biological effect of immune checkpoint inhibition that may be associated with improved treatment response and the development of immune-related adverse events. <h3>Case presentation</h3> We report a case of dual checkpoint inhibitor-associated hypereosinophilia and eosinophilic enteritis in a patient with advanced cutaneous melanoma. Rapid resolution of peripheral eosinophilia and associated symptoms was achieved with steroids alone. <h3>Conclusions</h3> Immune checkpoint inhibition can trigger inflammation in virtually any organ in the body, leading to diverse clinical manifestations. To our knowledge, this is the first case report of eosinophilic enteritis due to ipilimumab plus nivolumab.
Prognostic Value of Total Metabolic Tumor Volume and Total Lesion Glycolysis Measured By 18F-FDG PET-CT in Patients with T-Cell Lymphoblastic Lymphoma
Authors: Xiaoyan Feng, Xin Wen, Ling Li, Xin Li, Sun Zhenchang, Lei Zhang, Lugui Qiu, Mingzhi Zhang
Journal: Blood (2019)
Efficacy and Safety of Carfilzomib-Lenalidomide-Dexamethasone (KRd) in Newly Diagnosed Multiple Myeloma: Pooled Analysis of 4 Single-Arm Studies
Authors: Ola Landgren, Michel Attal, Dickran Kazandjian, Murielle Roussel, Jagoda K. Jasielec, Dominik Dytfeld, Aparna Anderson, Tara Kervin, Karim Iskander, Khalid Mezzi, Tim Welliver, Akeem Yusuf, Andrzej Jakubowiak
Journal: Blood (2019)
Transplantation-Associated Microangiopathy (TAM) in Recipients of HLA-Haploidentical Hematopoietic Stem Cell Transplants Using Ptcy, CNI and MMF for GvHD Prophylaxis
Authors: Alessia Fraccaroli, Dusan Prevalsek, Sarah Haebe, Veit Bücklein, Heidrun Drolle, Ulf Schoenermarck, Wolfgang Hiddemann, Michael von Bergwelt, Johanna Tischer
Journal: Blood (2019)
Coagulation FXIII-a Protein Expression Defines Three Novel Sub-Populations in Pediatric B-Cell Progenitor Acute Lymphoblastic Leukemia Characterized By Distinct Gene Expression Signatures
Authors: Katalin Gyurina, Bettina Kárai, Anikó Ujfalusi, Zsuzsanna Hevessy, Gábor Barna, Pál Jáksó, Gyönygi Pálfi-Mészáros, Szilárd Páliska, Beáta Scholtz, János Kappelmayer, Gábor Zahuczky, Csongor Kiss
Journal: Blood (2019)
DNA Cytosine-Demethylating Agent 5-Aza-2'-Deoxycytidine Targets Leukemia Cells through Reducing DNA N6-Methyladenine
Authors: Xiaochang Liu, Jiuxia Pang, Christopher Seiler, Ryan Kempen, Hao Liu, Aref Al-Kali, Y. Natalia Tretyakova, Mark Litzow, Shujun Liu
Journal: Blood (2019)
Tropomyosin receptor kinase (TRK) biology and the role of NTRK gene fusions in cancer
Authors: A. Amatu, A. Sartore-Bianchi, K. Bencardino, E.G. Pizzutilo, F. Tosi, S. Siena
Journal: Annals of Oncology (2019)

The tropomyosin receptor kinase (TRK) family of receptor tyrosine kinases are encoded by NTRK genes and have a role in the development and normal functioning of the nervous system. Since the discovery of an oncogenic NTRK gene fusion in colorectal cancer in 1986, over 80 different fusion partner genes have been identified in a wide array of adult and paediatric tumours, providing actionable targets for targeted therapy. This review describes the normal function and physiology of TRK receptors and the biology behind NTRK gene fusions and how they act as oncogenic drivers in cancer. Finally, an overview of the incidence and prevalence of NTRK gene fusions in various types of cancers is discussed.
BRAFV600E Inhibitor Radiosensitizes Thyroid Cancer—Letter
Authors: Eva-Leonne Göttgens, Katrin Rabold, Paul N. Span
Journal: Clinical Cancer Research (2019)

We read with great interest the article by Robb and colleagues ([1][1]), wherein they explored the mechanisms of radiosensitizing BRAF V600E–mutated thyroid cancers using the tyrosine kinase inhibitor vemurafenib. The authors describe a mechanism for the increased radioresistance of V600E-mutated
Impact of Novel Agents on Outcomes of Patients with Classical Hodgkin Lymphoma and Primary Treatment Failure
Authors: Narendranath Epperla, Luciano J. Costa, John L Vaughn, Walter Hanel, Saba Raya, Amanda F Cashen, Rehan Sarmad, Talha Badar, Mehdi Hamadani, Yang Liu, Stefan K. Barta, Paolo Caimi, Tarsheen K. Sethi, Nishitha Reddy, Madelyn Burkart, Reem Karmali, Celeste Bello, Julio C. Chavez, Shalin K. Kothari, Francisco J. Hernandez-Ilizaliturri, Hatcher J. Ballard, Jakub Svoboda, Lukas Emery, Frederick Lansigan, Martha Glenn, Michael C. Churnetski, Jonathon B. Cohen, Caryn Sorge, Ana C. Xavier
Journal: Blood (2019)
How to Read Articles That Use Machine Learning
Authors: Yun Liu, Po-Hsuan Cameron Chen, Jonathan Krause, Lily Peng
Journal: JAMA (2019)

In recent years, many new clinical diagnostic tools have been developed using complicated machine learning methods. Irrespective of how a diagnostic tool is derived, it must be evaluated using a 3-step process of deriving, validating, and establishing the clinical effectiveness of the tool. Machine learning–based tools should also be assessed for the type of machine learning model used and its appropriateness for the input data type and data set size. Machine learning models also generally have additional prespecified settings called hyperparameters, which must be tuned on a data set independent of the validation set. On the validation set, the outcome against which the model is evaluated is termed the reference standard. The rigor of the reference standard must be assessed, such as against a universally accepted gold standard or expert grading.
Surgical primary treatment of stage IVA cervical cancer: A multicenter retrospective study.
Authors: Patrizio Damiani, Francesco Plotti, Marzio Angelo Zullo, Carlo De Cicco Nardone, Roberto Montera, Ester Valentina Cafà , Federica Guzzo, Roberto Ricciardi, Alessia Aloisi, Eva Montone, Entela Hyseni, Daniela Luvero, Stella Capriglione, Salvatore Lopez, Giuseppe Scaletta, Andrea Miranda, Pierluigi Benedetti Panici, Roberto Angioli
Journal: Journal of Clinical Oncology (2012)

e15551 Background: The aim of the present study is to describe feasibility, surgical technique, perioperative data, early and late complications of anterior and total pelvic exenteration after neoadjuvant chemotherapy as primary treatment for stage IVa cervical cancer. Methods: It is a retrospective study which included 73 consecutive patients affected by stage IVa cervical cancer who required anterior or total pelvic exenteration referred to 3 international gynaecologic oncology centres. The steps of this extirpative surgical procedure were: 1) staging laparotomy; 2) frozen section biopsy of the paraaortic lymph nodes; 3) systematic lymphadenectomy, radical hysterectomy with adnexectomy and total or anterior pelvic exenteration; 4) continent urinary diversions and low colorectal anastomosis if it was possible. Results: The treatment of patients affected by FIGO stage IVA cervical cancer remains one of the most complex procedures gynecologic oncologists are faced with. Our study focused on clinical and operative data , in terms of overall survival (OS) and disease free survival (DFS) at 5 years. 5-year OS of our series was 43%. Conclusions: The surgical treatment of stage IVA cervical cancer appears therefore a suitable and valid alternative. Stage IVA cervical cancer patients in good general condition, with a disease resectable with clear surgical margins, should be considered for primary exenteration in referral centers where the surgical experience to perform this procedure is available.
CSIG-25. MTAP LOSS COMPROMISES DNA DAMAGE RESPONSE IN GBM CELLS
Authors: Changzheng Du, Landon Hansen, Simranjit Singh, Kristen Roso, Paula Greer, Yiping He
Journal: Neuro-Oncology (2019)

Abstract Homozygous deletion of methylthioadenosine phosphorylase (MTAP) is one of the most frequent genetic alterations in glioblastomas (GBMs), occurring in about half of all patients. Here, we demonstrated that MTAP loss compromises the proteostasis of genomic stability guardian, H2AX, via disrupting a signaling cascade of PRMT5-RNF168-SMURF2. We showed that PRMT5 sustains the expression of RNF168, an E3 ubiquitin ligase essential for cellular response to DNA damage. Suppression of PRMT5 function, as occurring in MTAP-null GBM cells, attenuates the expression of RNF168, which consequently leads to degradation of H2AX protein by a HECT-type E3 ubiquitin ligase, SMURF2. We revealed that RNF168 and SMURF2, serving as a stabilizer and destabilizer of H2AX respectively, functionally oppose each other via their dynamic interactions with H2AX. In supporting the important role of this PRMT5-RNF168-SMURF2 signaling cascade in controlling H2AX homeostasis, MTAP-null GBM cells display a compromised DNA damage response, highlighted by higher levels of DNA damage spontaneously or in response to genotoxic agents. Collectively, these results identify a novel signaling cascade that is essential to the DNA damage response, reveal the profound impact of MTAP loss on GBM cells, and suggest novel therapeutic opportunities.
Moral Distress, Anxiety, and Others Physical Symptoms Related to Hematopoietic Stem Cell Donation
Authors: Cesar Homero Gutierrez-Aguirre, Olga Graciela Cantu Rodriguez, Fernando De la Garza-Salazar, Rosario Salazar Riojas, Andres Gomez De Leon, Perla R. Colunga Pedraza, Geraldina Guerrero-González, Jose Carlos Jaime, Guillermo J. Ruiz-Arguelles, David Gomez-Almaguer, Oscar Gonzalez Llano, Consuelo Mancias
Journal: Blood (2019)
Training Pediatric Hematologists / Oncologists for Capacity Building in Ethiopia
Authors: Daniel Hailu, Haileyesus Adamu, Diriba Fufa, Doreen Karimi, Thomas Alexander, Catherine Habashy, Amit Dotan, Rabia M Wali, Prasanna N Kumar, Miguel Bonilla, Wondwessen Bekele, Sheila Weitzman, Julie Broas, David N Korones, Aziza T Shad
Journal: Blood (2019)
Preclinical Development of an Actinium-225-Labeled Antibody Radio-Conjugate Directed Against CD45 for Targeted Conditioning and Radioimmunotherapy
Authors: Dale Ludwig, Ruth Bryan, Wojciech Dawicki, Eileen M Geoghegan, Qing Liang, Sandesh Seth, Mamata Gokhale, Mark S. Berger, Vijay Reddy, Ravendra Garg, Kevin Allen, Ekaterina Dadachova
Journal: Blood (2019)