tbuckley/cabot-search huggingface dataset:
Germline Variants Associated with Cancer Predisposition and Bone Marrow Failure Are Common in <i>KMT2A-</i>r Infant Acute Lymphoblastic Leukemia Patients
Authors: Sarah Mc Dermott, Midhat S. Farooqi, Azhar Saeed, Byunggil Yoo, Emily Farrow, Neil Miller, Patrick A. Brown, Erin Guest
Journal: Blood (2020)
Factors Associated with the Platelet Graft in Hematopoietic Precursor Cell Transplant Patients in a Third Level Hospital in Mexico
Authors: Cynthia Pelayo Mena, Luis Manuel Valero Saldaña, Brenda Lizeth Acosta-Maldonado, Dana Perez Camargo, Victor Itaí Urbalejo Ceniceros
Journal: Blood (2020)
Response-Adaptive Phase II Study of Daratumumab Combined with Carfilzomib, Lenalidomide and Dexamethasone in Newly Diagnosed Multiple Myeloma
Authors: Manisha Bhutani, Monika House, Jiaxian He, Shebli Atrash, David M Foureau, Barry Paul, Reed Friend, James T Symanowski, Sarah Norek, Xhevahire Begic, Donna Acampora, Katherine K Farmer, Carrie Ann Syfert, Mauricio Pineda-Roman, Peter Voorhees, Saad Z. Usmani
Journal: Blood (2020)
Correction: Social distancing to slow the US COVID-19 epidemic: Longitudinal pretest–posttest comparison group study
Authors: Mark J. Siedner, Guy Harling, Zahra Reynolds, Rebecca F. Gilbert, Sebastien Haneuse, Atheendar S. Venkataramani, Alexander C. Tsai
Journal: PLoS Medicine (2020)

[This corrects the article DOI: 10.1371/journal.pmed.1003244.].
Validation of the European Leukemianet 2017 Prognostic Classification for Patients with De Novo Acute Myeloid Leukemia Treated with a Risk-Adapted Protocol (CETLAM 2012)
Authors: Alex Bataller, Ana Garrido, Francesca Guijarro, Marina Diaz-Beyá, Guadalupe Oñate, Montserrat Hoyos, Montserrat Arnan, Mar Tormo, Susana Vives, Maria Paz Queipo De Llano, Olga Salamero, Rosa Coll, David Gallardo, Ferran Vall-Llovera, Lourdes Escoda, Antonia Sampol, Antonio Garcia-Guiñon, Brayan Merchan, Joan Bargay, Monica Lopez-Guerra, Marta Pratcorona, Lurdes Zamora, Salut Brunet, Josep F Nomdedeu, Jorge Sierra, Jordi Esteve
Journal: Blood (2020)
A probiotic yeast-based immunotherapy against <i>Clostridioides difficile</i> infection
Authors: Kevin Chen, Yixuan Zhu, Yongrong Zhang, Therwa Hamza, Hua Yu, Ashley Saint Fleur, James Galen, Zhiyong Yang, Hanping Feng
Journal: Science Translational Medicine (2020)

Antibiotic-resistant Clostridioides difficile is an anaerobic Gram-positive bacterium that colonizes the colon and is responsible for more than 29,000 deaths in the United States each year. Hence, C. difficile infection (CDI) poses an urgent threat to public health. Antibody-mediated neutralization of TcdA and TcdB toxins, the major virulence factors of CDI, represents an effective strategy to combat the disease without invoking antibiotic resistance. However, current antitoxin approaches are mostly based on parenteral infusion of monoclonal antibodies that are costly, narrow spectrum, and not optimized against the intestinal disease. Here, we engineered probiotic Saccharomyces boulardii to constitutively secrete a single tetra-specific antibody that potently and broadly neutralized both toxins and demonstrated protection against primary and recurrent CDI in both prophylactic and therapeutic mouse models of disease. This yeast immunotherapy is orally administered, can be used concurrently with antibiotics, and may have potential as a prophylactic against CDI risk and as a therapeutic for patients with CDI.
Associations of Clinical Outcomes after Allogeneic Hematopoietic Cell Transplantation with Number of Predicted Class II Restricted mHA
Authors: Othmane Jadi, Hancong Tang, Junke Wang, Dante Bortone, Steven Vensko, Loreall Pooler, Xin Sheng, Christopher A. Haiman, David Van Den Berg, Stephen R. Spellman, Marcelo C. Pasquini, Theresa E. Hahn, Paul M. Armistead, Benjamin G. Vincent, Lara E. Sucheston-Campbell
Journal: Blood (2020)
American Radium Society Appropriate Use Criteria: Radiation Therapy for Limited-Stage SCLC 2020
Authors: Stephen G. Chun, Charles B. Simone, Arya Amini, Indrin J. Chetty, Jessica Donington, Martin J. Edelman, Kristin A. Higgins, Larry L. Kestin, Benjamin Movsas, George B. Rodrigues, Kenneth E. Rosenzweig, Ben J. Slotman, Igor I. Rybkin, Andrea Wolf, Joe Y. Chang
Journal: Journal of Thoracic Oncology (2020)

IntroductionCombined modality therapy with concurrent chemotherapy and radiation has long been the standard of care for limited-stage SCLC (LS-SCLC). However, there is controversy over best combined modality practices for LS-SCLC. To address these controversies, the American Radium Society (ARS) Thoracic Appropriate Use Criteria (AUC) Committee have developed updated consensus guidelines for the treatment of LS-SCLC.MethodsThe ARS AUC are evidence-based guidelines for specific clinical conditions that are reviewed by a multidisciplinary expert panel. The guidelines include a review and analysis of current evidence with application of consensus methodology (modified Delphi) to rate the appropriateness of treatments recommended by the panel for LS-SCLC. Agreement or consensus was defined as less than or equal to 3 rating points from the panel median. The consensus ratings and recommendations were then vetted by the ARS Executive Committee and subject to public comment before finalization.ResultsThe ARS Thoracic AUC committee developed multiple consensus recommendations for LS-SCLC. There was strong consensus that patients with unresectable LS-SCLC should receive concurrent chemotherapy with radiation delivered either once or twice daily. For medically inoperable T1-T2N0 LS-SCLC, either concurrent chemoradiation or stereotactic body radiation followed by adjuvant chemotherapy is a reasonable treatment option. The panel continues to recommend whole-brain prophylactic cranial irradiation after response to chemoradiation for LS-SCLC. There was panel agreement that prophylactic cranial irradiation with hippocampal avoidance and programmed cell death protein-1/programmed death-ligand 1–directed immune therapy should not be routinely administered outside the context of clinical trials at this time.ConclusionsThe ARS Thoracic AUC Committee provide consensus recommendations for LS-SCLC that aim to provide a groundwork for multidisciplinary care and clinical trials.
Total Diffusion Volume Estimated By Whole-Body Diffusion Magnetic Resonance Imaging for the Assessment of Tumor Burden in Multiple Myeloma
Authors: Kentaro Narita, Youichi Machida, Ayumi Kuzume, Toshiki Terao, Rikako Tabata, Takafumi Tsushima, Daisuke Miura, Masami Takeuchi, Kosei Matsue
Journal: Blood (2020)
Generation of Natural Killer Cells with Enhanced Function from a CRISPR/Cas12a-Edited Induced Pluripotent Stem Cell Line
Authors: Jung-Il Moon, Melissa S Chin, Andrew T Burden, Steven Sexton, Kevin Wasko, Jared M Nasser, Lincy P Antony, Karrie K Wong, Christopher M Borges, Richard A. Morgan, G. Grant Welstead
Journal: Blood (2020)
Tumor-mesoporous silica nanoparticle interactions following intraperitoneal delivery for targeting peritoneal metastasis
Authors: Derek Hargrove, Brian Liang, Raana Kashfi-Sadabad, Gaurav N. Joshi, Laura Gonzalez-Fajardo, Sterling Glass, Michael Jay, Andrew Salner, Xiuling Lu
Journal: Journal of Controlled Release (2020)
Safety and Efficacy of Anti-Bcma CAR-T Cells for Relapsed/Refractory Multiple Myeloma: A Systematic Review of Literature
Authors: Israr Khan, Abdul Rafae, Anum Javaid, Zahoor Ahmed, Haifza Abeera Qadeer, Sana Irfan Khan, Abdul Jabbar Dar, Qasim Khurshid, Ali Jaan, Farhan Khalid, Zobia Aijaz, Mydah Sajid Hashmi, Mustafa Nadeem Malik, Faiz Anwer
Journal: Blood (2020)
First Results of the Acsé Pembrolizumab Phase II in the Primary CNS Lymphoma (PCNSL) Cohort
Authors: Khe Hoang-Xuan, Roch Houot, Carole Soussain, Marie Blonski, Anna Schmitt, Vincent Delwail, Gandhi Laurent Damaj, Herve Ghesquieres, Frédéric Peyrade, Adrian Tempescul, Julie Abraham, Philippe Agape, Guido Ahle, Nathalie Baize, Pierre Bories, Chantal Campello, Emmanuel Gyan, Fabrice Jardin, Philippe Rey, Sylvain Choquet, Caroline Houillier, Nathalie Cassoux, Valerie Touitou, Nadine Martin-Duverneuil, Frederic Legrand, Assia Lamrani-Ghaouti, Ophelie Querel, Natalie Hoog Labouret, Clotilde Simon, Sylvie Chevret, Christophe Massard
Journal: Blood (2020)
Lower Apache II Score and Exchange Transfusions Predict Better Outcomes in the Intensive Care Unit for Patients with Sickle Cell Disease
Authors: Renee Cheng, Andrew Srisuwananukorn, Jin Han, Michel Gowhari, Franklin Njoku, Faiz Ahmed Hussain, Robert E. Molokie, Victor R. Gordeuk, Santosh L. Saraf
Journal: Blood (2020)
FGF/FGFR Axis-Blockade Leads to Anti-Tumor Activity in Waldenstrom's Macroglobulinemia By Silencing MYD88
Authors: Antonio Sacco, Cinzia Federico, Arianna Giacomini, Cinzia Caprio, Federica Maccarinelli, Katia Todoerti, Vanessa Favasuli, Antonella Anastasia, Marina Motta, Giuseppe Rossi, Nicole Bozza, Riccardo Castelli, Antonino Neri, Roberto Ronca, Chiara Cattaneo, Alessandra Tucci, Marco Mor, Marco Presta, Aldo M. Roccaro
Journal: Blood (2020)
Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set
Authors: Ajai Chari, Mehmet Kemal Samur, Joaquin Martinez-Lopez, Gordon Cook, Noa Biran, Kwee Yong, Vania Hungria, Monika Engelhardt, Francesca Gay, Ana García Feria, Stefania Oliva, Rimke Oostvogels, Alessandro Gozzetti, Cara Rosenbaum, Shaji Kumar, Edward A. Stadtmauer, Hermann Einsele, Meral Beksac, Katja Weisel, Kenneth C. Anderson, María-Victoria Mateos, Philippe Moreau, Jesus San-Miguel, Nikhil C. Munshi, Hervé Avet-Loiseau
Journal: Blood (2020)
<i>The Prevalence of Reactive Thrombocytosis and Thromboembolic Events in Arab Population with Iron Deficiency Anemia (a retrospective study)</i>
Authors: Rita Wafik Ahmad, Ashraf Tawfiq Soliman, Vincenzo Desanctis, Lina A Okar, Mustafa A Al-Tikrity, Mona M Babikir, Arwa E Alsaud, Mahmoud S Eisa, Majd M Aldwairi, Mohammad N Kloub, Shaima Ahmed, Ruoa Alhashimy, Mohamed A Yassin
Journal: Blood (2020)
Frontline Bendamustine and Rituximab in Extranodal Marginal Zone Lymphoma: An International Analysis
Authors: Juan Pablo Alderuccio, Anne W. Beaven, Geoffrey Shouse, Narendranath Epperla, Alexandra Stefanovic, Pallawi Torka, Jorge J. Castillo, Lisa Argnani, Timothy J Voorhees, Ash B Alpert, Sayan Chowdhury, Isildinha M. Reis, Wei Zhao, Dali Edwards, Peter Martin, Manali Kamdar, Alex F. Herrera, Jonathan W. Friedberg, Pier Luigi Zinzani, Izidore S. Lossos
Journal: Blood (2020)
Detection of M-Protein in Acetonitrile Precipitates of Serum Using MALDI-TOF Mass Spectrometry: A Novel Methodology
Authors: Nikita Mehra, Gopal Gopisetty, Jayavelu S, Arivazhagan Rajamanickam, Shirley Sundersingh, Jayachandran PK, Parathan Karunakaran, Krishnarathinam Kannan, Venkatraman Radhakrishnan, Tenali Gnana Sagar, Thangarajan Rajkumar
Journal: Blood (2020)
The CLL-1100 Project: Towards Complete Genomic Characterization and Improved Prognostics for CLL
Authors: Binyamin A. Knisbacher, Ziao Lin, Cynthia K. Hahn, Ferran Nadeu, Martí Duran-Ferrer, Kristen E. Stevenson, Eugen Tausch, Alex Barbera-Mourelle, Andrew Dunford, Shankara Anand, Julio Delgado, Julian M. Hess, Amaro Taylor-Weiner, Helene Kretzmer, Pablo Bousquets Muñoz, Conner J. Shaughnessy, Stacey M. Fernandes, Mariela Sivina, Laura Z. Rassenti, Alexander Meissner, Adrian Wiestner, Jan A. Burger, Thomas J. Kipps, Jennifer R Brown, Michael Hallek, François Aguet, Donna S. Neuberg, Xose S Puente, Chip Stewart, José I. Martín-Subero, Stephan Stilgenbauer, Catherine J. Wu, Elías Campo, Gad Getz
Journal: Blood (2020)
Impedance planimetry values for predicting clinical response following peroral endoscopic myotomy
Authors: Robert A. Moran, Olaya I. Brewer Gutierrez, Burkhard Rahden, Kenneth Chang, Michael Ujiki, In Kyung Yoo, Shraddha Gulati, John Romanelli, Mohammed Al-Nasser, Toshitaka Shimizu, Mason H. Hedberg, Joo Young Cho, Bu Hayee, David Desilets, Jörg Filser, Kyle Fortinsky, Amyn Haji, Lea Fayad, Omid Sanaei, Mohamad Dbouk, Vivek Kumbhari, Bethany J. Wolf, B. Joseph Elmunzer, Mouen A. Khashab
Journal: Endoscopy (2020)

Abstract Background There is growing interest in developing impedance planimetry as a tool to enhance the clinical outcomes for endoscopic and surgical management of achalasia. The primary aim of this study was to determine whether impedance planimetry measurements can predict clinical response and reflux following peroral endoscopic myotomy (POEM). Methods A multicenter cohort study of patients with achalasia undergoing POEM was established from prospective databases and retrospective chart reviews. Patients who underwent impedance planimetry before and after POEM were included. Clinical response was defined as an Eckardt score of ≤ 3. Tenfold cross-validated area under curve (AUC) values were established for the different impedance planimetry measurements associated with clinical response and reflux development. Results Of the 290 patients included, 91.7 % (266/290) had a clinical response and 39.4 % (108/274) developed reflux following POEM. The most predictive impedance planimetry measurements for a clinical response were: percent change in cross-sectional area (%ΔCSA) and percent change in distensibility index (%ΔDI), with AUCs of 0.75 and 0.73, respectively. Optimal cutoff values for %ΔCSA and %ΔDI to determine a clinical response were a change of 360 % and 272 %, respectively. Impedance planimetry values were much poorer at predicting post-POEM reflux, with AUCs ranging from 0.40 to 0.62. Conclusion Percent change in CSA and distensibility index were the most predictive measures of a clinical response, with a moderate predictive ability. Impedance planimetry values for predicting reflux following POEM showed weak predictive capacity.
Significance of Marker Chromosome on the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for AML
Authors: Kyoko Fuse, Masayoshi Masuko, Shohei Mizuno, Kaito Harada, Naoyuki Uchida, Noriko Doki, Takahiro Fukuda, Masatsugu Tanaka, Yukiyasu Ozawa, Kazuhiro Ikegame, Tetsuya Eto, Yoshinobu Kanda, Tatsuo Ichinohe, Yoshiko Atsuta, Masamitsu Yanada
Journal: Blood (2020)
Clinical Benefit of Crenolanib, with or without Salvage Chemotherapy, in Multiply Relapsed, FLT3 Mutant AML Patients after Prior Treatment with Gilteritinib
Authors: Aaron D Goldberg, Mark B. Geyer, Jonathan Kell, Eros Di Bona, Timothy S. Pardee, Rupali Bhave, Michael R. Grunwald, Giovanni Marconi, Yijia Wang, Asif Pathan, Boo Messahel
Journal: Blood (2020)
Minimal Residual Disease in Autografts and Bone Marrow of Patients with Multiple Myeloma: 8-Color Multiparameter Flow Cytometry (EuroFlow-NGF) <i>Vs</i>. Next-Generation Sequencing
Authors: Hiroyuki Takamatsu, Naoki Takezako, Takeshi Yoroidaka, Takeshi Yamashita, Ryoichi Murata, Atsuko Yamazaki, Masahiro Takeuchi, Naoya Mimura, Chiaki Nakaseko, Emiko Sakaida, Masahiro Onoda, Yoshikazu Utsu, Motoharu Fukazawa, Kosei Matsue, Shinji Nakao
Journal: Blood (2020)
Comparing Nasopharyngeal and BAL SARS-CoV-2 Assays in Respiratory Failure
Authors: Catherine A. Gao, Michael J. Cuttica, Elizabeth S. Malsin, A. Christine Argento, Richard G. Wunderink, Sean B. Smith, A. Christine Argento, Ajay A. Wagh, Alexandra C. McQuattie-Pimentel, Alexis Rose Wolfe, Ankit Bharat, Anne R. Levenson, Anthony M. Joudi, Arjun Sinha, Ashley N. Budd, Benjamin D. Singer, Betty Tran, Catherine A. Gao, Chiagozie O. Pickens, Chitaru Kurihara, Christopher J. Soriano, Clara J. Schroedl, Daniel Meza, David Alexander Kidd, David W. Kamp, Elizabeth S. Malsin, Emily M. Leibenguth, Eric P. Cantey, Gabrielle Y. Liu, Giang T. Quach, G. R. Scott Budinger, Jacqueline M. Kruser, James M. Walter, Jane E. Dematte, Jason A. Bonomo, John M. Coleman, Joseph Isaac Bailey, Joseph S. Deters, Joseph Sun, Justin A. Fiala, Kaitlyn Vitale, Kara M. Joseph, Katharine Secunda, Khalilah L. Gates, Kristy Todd, Lindsey D. Gradone, Lindsey N. Textor, Lisa F. Wolfe, Luisa Morales-Nebreda, Madeline L. Rosenbaum, Manu Jain, Marc A. Sala, Mark Saine, Marysa V. Leya, Michael J. Alexander, Michael J. Cuttica, Michelle Hinsch Prickett, Natalie Jensema, Paul A. Reyfman, Peter H. S. Sporn, Rachel B. Kadar, Rachel M. Kaplan, Rade Tomic, Radhika Patel, Rafael Garza-Castillon, Ravi Kalhan, Richard G. Wunderink, Romy Lawrence, Ruben J. Mylvaganam, Samuel S. Kim, Sanket Thakkar, Sean B. Smith, SeungHye Han, Sharon R. Rosenberg, Susan R. Russell, Sydney M. Hyder, Taylor A. Poor, Theresa A. Lombardo
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Combining IMGN632, a Novel CD123-Targeting Antibody Drug Conjugate with Azacitidine and Venetoclax Facilitates Apoptosis <i>in Vitro</i> and Prolongs Survival <i>In Vivo</i> in AML Models
Authors: Vinitha Mary Kuruvilla, Qi Zhang, Naval Daver, Krystal Watkins, Callum M Sloss, Patrick A Zweidler-McKay, Angela Romanelli, Marina Konopleva
Journal: Blood (2020)
<scp>European Society of Cardiology Working Group</scp> on Adult Congenital Heart Disease and <scp>Study Group for Adult Congenital Heart Care in Central and South Eastern European Countries</scp> consensus paper: current status, provision gaps and investment required
Authors: Margarita Brida, Iveta Šimkova, Ljiljana Jovović, Katja Prokšelj, Petra Antonová, Hajnalka Olga Balint, Lina Gumbiene, Ihor H. Lebid, Monika Komar, Pencho Kratunkov, Tamara Kovačević Preradović, Raili Ermel, Agnese Strenge, Ioan Mircea Coman, Vladislav Vukomanović, Michael A. Gatzoulis, Jolien W. Roos‐Hesselink, Gerhard‐Paul Diller
Journal: European Journal of Heart Failure (2020)
Exportin-1 (XPO1) Inhibition Sequesters p53 from MDM2 and MDM4 and Is Highly Synergistic with MDM2 Inhibition in Inducing Apoptosis in Wild-Type p53 Acute Myeloid Leukemias
Authors: Yuki Nishida, Jo Ishizawa, Edward Ayoub, Rafael Heinz Montoya, Vivian Ruvolo, Kensuke Kojima, Naval Daver, Arnaud Lesegretain, Sharon Shacham, Michael Andreeff
Journal: Blood (2020)
CAR-T Therapy for Lymphoma with Prophylactic Tocilizumab: Decreased Rates of Severe Cytokine Release Syndrome without Excessive Neurologic Toxicity
Authors: Paolo F Caimi, Ashish Sharma, Patricio Rojas, Seema Patel, Jane Reese, Folashade Otegbeye, Andrew Worden, Michael Kadan, Michael Maschan, Rimas J Orentas, Boro Dropulic, Rafick Sekaly, Marcos de Lima
Journal: Blood (2020)
Radiomic Detection of EGFR Mutations in NSCLC
Authors: Giovanni Rossi, Emanuele Barabino, Alessandro Fedeli, Gianluca Ficarra, Simona Coco, Alessandro Russo, Vincenzo Adamo, Francesco Buemi, Lodovica Zullo, Mariella Dono, Giuseppa De Luca, Luca Longo, Maria Giovanna Dal Bello, Marco Tagliamento, Angela Alama, Giuseppe Cittadini, Paolo Pronzato, Carlo Genova
Journal: Cancer Research (2020)

Radiomics is defined as the use of automated or semi-automated post-processing and analysis of multiple features derived from imaging exams. Extracted features might generate models able to predict the molecular profile of solid tumors. The aim of this study was to develop a predictive algorithm to define the mutational status of EGFR in treatment-naïve patients with advanced non-small cell lung cancer (NSCLC). CT scans from 109 treatment-naïve patients with NSCLC (21 EGFR-mutant and 88 EGFR-wild type) underwent radiomics analysis to develop a machine learning model able to recognize EGFR-mutant from EGFR-WT patients via CT scans. A "test-retest" approach was used to identify stable radiomics features. The accuracy of the model was tested on an external validation set from another institution and on a dataset from the Cancer Imaging Archive (TCIA). The machine learning model that considered both radiomic and clinical features (gender and smoking status) reached a diagnostic accuracy of 88.1% in our dataset with an AUC at the ROC curve of 0.85, whereas the accuracy values in the datasets from TCIA and the external institution were 76.6% and 83.3%, respectively. Furthermore, 17 distinct radiomics features detected at baseline CT scan were associated with subsequent development of T790M during treatment with an EGFR inhibitor. In conclusion, our machine learning model was able to identify EGFR-mutant patients in multiple validation sets with globally good accuracy, especially after data optimization. More comprehensive training sets might result in further improvement of radiomics-based algorithms. SIGNIFICANCE: These findings demonstrate that data normalization and "test-retest" methods might improve the performance of machine learning models on radiomics images and increase their reliability when used on external validation datasets.
Dreamm-5 Platform Trial: Belantamab Mafodotin (Belamaf) in Combination with Four Different Novel Agents in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)
Authors: Paul G. Richardson, Ajay Nooka, Hang Quach, Suzanne Trudel, David Routledge, Kevin Song, Hareth Nahi, Sofia Paul, Josephine Khan, Maria Brouch, Geraldine Ferron-Brady, Anne Yeakey, Chris Shelton, Rocio Montes de Oca, L. Mary Smith, Ellie Im, Christoph M Ahlers, Elaine M Paul, Beata Holkova, Ira Gupta, Brandon E. Kremer, Paula Rodriguez-Otero
Journal: Blood (2020)
The ATP synthase inhibition induces an AMPK-dependent glycolytic switch of mesenchymal stem cells that enhances their immunotherapeutic potential
Authors: Rafael Contreras-Lopez, Roberto Elizondo-Vega, Noymar Luque-Campos, María José Torres, Carolina Pradenas, Gautier Tejedor, María José Paredes-Martínez, Ana María Vega-Letter, Mauricio Campos-Mora, Yandi Rigual-Gonzalez, Karina Oyarce, Magdiel Salgado, Christian Jorgensen, Maroun Khoury, María de los Ángeles Garcia-Robles, Claudia Altamirano, Farida Djouad, Patricia Luz-Crawford
Journal: Theranostics (2020)

Objectives: Mesenchymal Stem/Stromal Cells (MSC) are promising therapeutic tools for inflammatory diseases due to their potent immunoregulatory capacities. Their suppressive activity mainly depends on inflammatory cues that have been recently associated with changes in MSC bioenergetic status towards a glycolytic metabolism. However, the molecular mechanisms behind this metabolic reprogramming and its impact on MSC therapeutic properties have not been investigated. Methods: Human and murine-derived MSC were metabolically reprogramed using pro-inflammatory cytokines, an inhibitor of ATP synthase (oligomycin), or 2-deoxy-D-glucose (2DG). The immunosuppressive activity of these cells was tested in vitro using co-culture experiments with pro-inflammatory T cells and in vivo with the Delayed-Type Hypersensitivity (DTH) and the Graph versus Host Disease (GVHD) murine models. Results: We found that the oligomycin-mediated pro-glycolytic switch of MSC significantly enhanced their immunosuppressive properties in vitro. Conversely, glycolysis inhibition using 2DG significantly reduced MSC immunoregulatory effects. Moreover, in vivo, MSC glycolytic reprogramming significantly increased their therapeutic benefit in the DTH and GVHD mouse models. Finally, we demonstrated that the MSC glycolytic switch effect partly depends on the activation of the AMPK signaling pathway. Conclusion: Altogether, our findings show that AMPK-dependent glycolytic reprogramming of MSC using an ATP synthase inhibitor contributes to their immunosuppressive and therapeutic functions, and suggest that pro-glycolytic drugs might be used to improve MSC-based therapy.
BCX9930, a Potent, Selective, Oral Factor D Inhibitor, Demonstrates Proof-of-Concept As Monotherapy in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)
Authors: Austin Kulasekararaj, Jacques Le Roux Malherbe, Andrew McDonald, Melanie Cornpropst, Phil Collis, Matthew Davidson, Xilin Chen, Kristin Tower, Diane Gesty-Palmer, William P. Sheridan, Antonio Risitano
Journal: Blood (2020)