Article
Multidisciplinary Sciences
Gail P. Risbridger, Ashlee K. Clark, Laura H. Porter, Roxanne Toivanen, Andrew Bakshi, Natalie L. Lister, David Pook, Carmel J. Pezaro, Shahneen Sandhu, Shivakumar Keerthikumar, Rosalia Quezada Urban, Melissa Papargiris, Jenna Kraska, Heather B. Madsen, Hong Wang, Michelle G. Richards, Birunthi Niranjan, Samantha O'Dea, Linda Teng, William Wheelahan, Zhuoer Li, Nicholas Choo, John F. Ouyang, Heather Thorne, Lisa Devereux, Rodney J. Hicks, Shomik Sengupta, Laurence Harewood, Mahesh Iddawala, Arun A. Azad, Jeremy Goad, Jeremy Grummet, John Kourambas, Edmond M. Kwan, Daniel Moon, Declan G. Murphy, John Pedersen, David Clouston, Sam Norden, Andrew Ryan, Luc Furic, David L. Goode, Mark Frydenberg, Mitchell G. Lawrence, Renea A. Taylor
Summary: The Melbourne Urological Research Alliance has established patient-derived xenografts of prostate cancer, used for organoids and single-cell RNA-seq, demonstrating the efficacy of PARP inhibitor combination treatments. This preclinical model is crucial for evaluating cancer therapeutics.
NATURE COMMUNICATIONS
(2021)
Review
Medicine, General & Internal
Elaine Butterly, Lili Wei, Amanda Adler, Saleh A. M. Almazam, Khalid Alsallumi, Luke A. K. Blackbourn, Sofia Dias, Peter Hanlon, Katherine Hughes, Jim Lewsey, Robert Lindsay, Stuart McGurnaghan, John Petrie, David Phillippo, Naveed Sattar, Laurie A. Tomlinson, Nicky Welton, Sarah Wild, David McAllister
Summary: This study aims to calibrate trial results to improve the applicability of randomised controlled trials by using a network meta-analysis approach. The study will calibrate trial results for sodium glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP1) receptor analogues, and dipeptidyl peptidase-4 (DPP4) inhibitors to the Scottish diabetes register.
Article
Medicine, Research & Experimental
Kristen L. Mueller, Anne Trolard, Vicki Moran, Joshua M. Landman, Randi Foraker
Summary: This study outlines the establishment and querying methods of a new regional database for patients with violent injuries at St. Louis level I trauma hospitals. Preliminary results show over 121,955 patient visits for violent injuries, including more than 18,000 visits for firearm injuries, between 2010 and 2019 among the four partner hospitals. The STL-HVIP-DR database aims to address the identification and outcomes of violently injured individuals, particularly those with non-lethal firearm injuries, and may serve as a model for developing similar repositories in other regions.
CONTEMPORARY CLINICAL TRIALS COMMUNICATIONS
(2021)
Article
Oncology
Kathrin Heinrich, Lisa Miller-Phillips, Frank Ziemann, Korbinian Hasselmann, Katharina Ruehlmann, Madeleine Flach, Dorottya Biro, Michael von Bergwelt-Baildon, Julian Holch, Tobias Herold, Louisa von Baumgarten, Philip A. Greif, Irmela Jeremias, Rachel Wuerstlein, Jozefina Casuscelli, Christine Spitzweg, Max Seidensticker, Bernhard Renz, Stefanie Corradini, Philipp Baumeister, Elisabetta Goni, Amanda Tufman, Andreas Jung, Joerg Kumbrink, Thomas Kirchner, Frederick Klauschen, Klaus H. Metzeler, Volker Heinemann, C. Benedikt Westphalen
Summary: This study retrospectively analyzed the first 1000 cases of the University of Munich Molecular Tumor Board (MTB) precision oncology program. The results showed that patients with breast and biliary tract cancers were more likely to have actionable genetic variants. However, only 17% of patients implemented the treatment recommendations from the tumor board, highlighting the importance of meticulous follow-up and broad access to innovative therapies for these patients.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Oncology
Florian Selt, Romain Sigaud, Gintvile Valinciute, Philipp Sievers, Julia Zaman, Clara Alco, Simone Schmid, Heike Peterziel, Jessica W. Tsai, Romain Guiho, Juan Pedro Martinez-Barbera, Stefan Pusch, Jing Deng, Yifan Zhai, Cornelis M. van Tilburg, Martin U. Schuhman, Ahmed E. L. Damaty, Pratiti Bandopadhayay, Christel Herold-Mende, Andreas von Deimling, Stefan M. Pfister, Joan Montero, David Capper, Ina Oehme, Felix Sahm, David T. W. Jones, Olaf Witt, Till Milde
Summary: Our study demonstrates that BCL-XL is critical for the survival of senescent PA tumor cells and provides evidence for the use of clinically available BCL-XL-dependent senolytic agents.
Article
Oncology
Clement Larrue, Sarah Mouche, Shan Lin, Federico Simonetta, Nastassja K. Scheidegger, Laury Poulain, Rudy Birsen, Jean-Emmanuel Sarry, Kimberly Stegmaier, Jerome Tamburini
Summary: Mitochondrial fusion is a critical dependency in acute myeloid leukemia (AML). Inhibition of mitochondrial fusion through genetic depletion or pharmacological inhibition showed significant anti-leukemic activity in patient-derived xenograft (PDX) models, without impacting normal hematopoietic cells. Mechanistically, disruption of mitochondrial fusion led to cell cycle arrest and impaired mitochondrial respiration and reactive oxygen species production. These findings suggest that inhibition of mitochondrial fusion holds promise as a therapeutic approach for AML.
Letter
Hematology
Esther Rheinbay, Meifang Qi, Juliette M. Bouyssou, Andrew J. Oler, Lauren Thumm, Michelle Makiya, Irina Maric, Amy D. Klion, Andrew A. Lane
Article
Hematology
J. Dufour, S. Choquet, K. Hoang-Xuan, A. Schmitt, G. Ahle, R. Houot, L. Taillandier, R. Gressin, O. Casasnovas, J. P. Marolleau, J. Tamburini, C. Serrier, E. Perez, J. Paillassa, E. Gyan, A. Chauchet, R. Ursu, A. Kas, C. Soussain, C. Houillier
Summary: This nationwide population-based study found rare extracerebral relapses of primary central nervous system lymphomas (PCNSL). The extracerebral relapses were mainly found in visceral organs (particularly testis and breast) and the peripheral nervous system. The prognosis was worse for mixed relapses. The study suggests the use of PET-CT in diagnosis and paired tumor analysis at diagnosis/relapse to better understand the underlying molecular mechanisms.
ANNALS OF HEMATOLOGY
(2023)
Article
Hematology
Bing Z. Carter, Po Yee Mak, Muharrem Muftuoglu, Wenjing Tao, Baozhen Ke, Jingqi Pei, Andrea D. Bedoy, Lauren B. Ostermann, Yuki Nishida, Sevinj Isgandarova, Mary Sobieski, Nghi Nguyen, Reid T. Powell, Margarita Martinez-Moczygemba, Clifford Stephan, Mahesh Basyal, Naveen Pemmaraju, Steffen Boettcher, Benjamin L. Ebert, Elizabeth J. Shpall, Barbara Wallner, Robert A. Morgan, Georgios I. Karras, Ute M. Moll, Michael Andreeff
Summary: This study suggests that targeting epichaperomes, formed by heat shock protein 90 (HSP90) and associated proteins, in TP53-mutant acute myeloid leukemia (AML) cells has therapeutic potential. Inhibiting epichaperomes with PU-H71 effectively suppresses AML cell growth, induces apoptosis, and prolongs survival in TP53-mutant AML models. The findings highlight the importance of epichaperome function in TP53-mutant AML and suggest that targeting epichaperomes could be a promising therapeutic strategy.
Article
Hematology
A. Marouf, N. Molinari, D. Sibon, A. S. Cottereau, S. Kanoun, C. Antoine, P. E. Debureaux, D. Cavalieri, L. M. Fornecker, R. O. Casasnovas, C. Herbaux, S. Amorim, C. Rossi, D. Bouscary, P. Brice, H. Ghesquieres, J. Tamburini, B. Deau
Summary: Autologous hematopoietic stem cell transplant (ASCT) is the standard curative treatment for high-risk relapsed/refractory Hodgkin lymphoma (R/R HL) patients. Maintenance therapy with Brentuximab Vedotin (BV) after ASCT has been shown to improve survival in BV-naive patients. In this study, BV maintenance was compared to tandem transplant strategies and was found to be associated with better survival outcomes in patients with high-risk R/R HL.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Esra D. Gumuser, Art Schuermans, So Mi Jemma Cho, Zachary A. Sporn, Md Mesbah Uddin, Kaavya Paruchuri, Tetsushi Nakao, Zhi Yu, Sara Haidermota, Whitney Hornsby, Lachelle D. Weeks, Abhishek Niroula, Siddhartha Jaiswal, Peter Libby, Benjamin L. Ebert, Alexander G. Bick, Pradeep Natarajan, Michael C. Honigberg
Summary: This study examined the prognostic value of clonal hematopoiesis of indeterminate potential (CHIP) in individuals with established atherosclerotic cardiovascular disease (ASCVD). The results showed that any CHIP and large CHIP were associated with adverse outcomes, with TET2 and spliceosome CHIP having the strongest associations.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2023)
Letter
Cardiac & Cardiovascular Systems
Tetsushi Nakao, Zhi Yu, Caitlyn Vlasschaert, Md Mesbah Uddin, Mark E. Lindsay, Patrick T. Ellinor, Benjamin L. Ebert, Alexander G. Bick, James P. Pirruccello, Pradeep Natarajan
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2023)
Article
Oncology
Marie Sabatier, Rudy Birsen, Laura Lauture, Sarah Mouche, Paolo Angelino, Jonas Dehairs, Ismael Boussaid, Mael Heiblig, Emeline Boet, Ambrine Sahal, Estelle Saland, Juliana C. Santos, Marc Armengol, Miranda Fernandez-Serrano, Thomas Farge, Guillaume Cognet, Federico Simonetta, Corentin Pignon, Antoine Graffeuil, Celine Mazzotti, Herve Avet-Loiseau, Oceane Delos, Justine Bertrand-Michel, Amelie Chedru, Vilma Dembitz, Paolo Gallipoli, Natasha S. Anstee, Sun Loo, Andrew H. Wei, Martin Carroll, Armelle Goubard, Remy Castellano, Yves Collette, Francois Vergez, Veronique Mansat-De Mas, Sarah Bertoli, Suzanne Tavitian, Muriel Picard, Christian Recher, Nathalie Bourges-Abella, Fanny Granat, Olivier Kosmider, Pierre Sujobert, Benoit Colsch, Carine Joffre, Lucille Stuani, Johannes V. Swinnen, Herve Guillou, Gael Roue, Nawad Hakim, Anne S. Dejean, Petros Tsantoulis, Clement Larrue, Didier Bouscary, Jerome Tamburini, Jean-Emmanuel Sarry
Summary: Although the role of CCAAT-enhancer binding protein α (C/EBPα) in cancer cell and metabolic homeostasis is largely unknown, this study reveals its coordination with FLT3 in lipid anabolism and its regulation of fatty acid biosynthesis and desaturation. Furthermore, FLT3 or C/EBPα inactivation decreases monounsaturated fatty acid incorporation and renders FLT3-mutant AML cells vulnerable to ferroptosis. This finding suggests a promising therapeutic potential for targeting FLT3-mutant AML cells.
Article
Multidisciplinary Sciences
Charles Zou, Hojong Yoon, Paul M. C. Park, J. J. Patten, Jesse Pellman, Jeannie Carreiro, Jonathan M. Tasi, Yen-Der Li, Shourya S. Roy Burman, Katherine A. Donovan, Jessica Gasser, Adam S. Sperling, Radoslaw P. Nowak, Eric S. Fischer, Robert A. Davey, Benjamin L. Ebert, Mikolaj Slabicki
Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes multiple human proteins during infection and replication. Researchers have discovered that the human E3 ubiquitin ligase RNF185 plays a role in regulating the stability of the SARS-CoV-2 envelope protein. This interaction occurs at the endoplasmic reticulum (ER) and depletion of RNF185 leads to an increase in SARS-CoV-2 viral titer. This finding suggests that modulating this interaction could be a potential strategy for developing antiviral therapies.
Article
Oncology
Ricardo de Matos Simoes, Ryosuke Shirasaki, Sondra L. Downey-Kopyscinski, Geoffrey M. Matthews, Benjamin G. Barwick, Vikas A. Gupta, Daphne Dupere-Richer, Shizuka Yamano, Yiguo Hu, Michal Sheffer, Eugen Dhimolea, Olga Dashevsky, Sara Gandolfi, Kazuya Ishiguro, Robin M. Meyers, Jordan G. Bryan, Neekesh V. Dharia, Paul J. Hengeveld, Johanna B. Bruggenthies, Huihui Tang, Andrew J. Aguirre, Quinlan L. Sievers, Benjamin L. Ebert, Brian J. Glassner, Christopher J. Ott, James E. Bradner, Nicholas P. Kwiatkowski, Daniel Auclair, Joan Levy, Jonathan J. Keats, Richard W. J. Groen, Nathanael S. Gray, Aedin C. Culhane, James M. McFarland, Joshua M. Dempster, Jonathan D. Licht, Lawrence H. Boise, William C. Hahn, Francisca Vazquez, Aviad Tsherniak, Constantine S. Mitsiades
Summary: Clinical progress in multiple myeloma has been limited due to the lack of therapies targeting specific oncogenic mutations. However, a study using CRISPR technology identified 116 genes that significantly affect the fitness of MM cells compared to other malignancies. These genes encode various factors critical for MM cell biology and provide new therapeutic targets not easily identifiable by standard genomic analysis.
Editorial Material
Hematology
Christopher R. Reilly, Andrew A. Lane
Summary: In this study, Cheloor Kovilakam et al conducted a comprehensive population-level analysis of >450,000 adults in the UK Biobank to assess the epidemiological characteristics, clinical features, and malignancy risk associated with germ line pathogenic variants in the DEAD box RNA helicase 41 gene (DDX41-GPV).
Article
Medicine, Research & Experimental
Santhosh Kumar Pasupuleti, Baskar Ramdas, Sarah S. Burns, Lakshmi Reddy Palam, Rahul Kanumuri, Ramesh Kumar, Taruni Reddy Pandhiri, Utpal P. Dave, Nanda Kumar Yellapu, Xinyu Zhou, Chi Zhang, George E. Sandusky, Zhi Yu, Michael C. Honigberg, Alexander G. Bick, Gabriel K. Griffin, Abhishek Niroula, Benjamin L. Ebert, Sophie Paczesny, Pradeep Natarajan, Reuben Kapur
Summary: Characterized by the accumulation of somatic mutations in blood cell lineages, clonal hematopoiesis of indeterminate potential (CHIP) is associated with obesity and could potentially be treated using targeted drugs.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Medicine, Research & Experimental
Zhi Yu, Trevor P. Fidler, Yunfeng Ruan, Caitlyn Vlasschaert, Tetsushi Nakao, Md Mesbah Uddin, Taralynn Mack, Abhishek Niroula, J. Brett Heimlich, Seyedeh M. Zekavat, Christopher J. Gibson, Gabriel K. Griffin, Yuxuan Wang, Gina M. Peloso, Nancy Heard-Costa, Daniel Levy, Ramachandran S. Vasan, Francois Aguet, Kristin G. Ardlie, Kent D. Taylor, Stephen S. Rich, Jerome I. Rotter, Peter Libby, Siddhartha Jaiswal, Benjamin L. Ebert, Alexander G. Bick, Alan R. Tall, Pradeep Natarajan
Summary: This study investigated the role of inflammatory gene modifiers in CHIP-associated CVD risk and found IL1RAP and AIM2 as key molecules in modulating this risk. The study also supported gene-specific strategies for addressing CHIP-associated CVD risk.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
