Article
Oncology
David Allard, Pavel Chrobak, Yacine Bareche, Bertrand Allard, Priscilla Tessier, Marjorie A. Bergeron, Nathalie A. Johnson, John Stagg
Summary: Our study identified CD73 as a pro-leukemic immune checkpoint in CLL and uncovered a previously unknown sex bias for the CD73-adenosine pathway. The therapeutic potential of targeting CD73 in CLL was investigated using genetically engineered mice, revealing a pro-leukemic role for CD73 in an autochthonous mouse model of CLL. Our findings suggest that targeting CD73 in CLL in combination with anti-PD-1/PD-L1 immunotherapies may be beneficial, with sex potentially contributing to responses to adenosine-targeting agents.
Article
Multidisciplinary Sciences
Melanie R. Walker, Hira Lal Goel, Dimpi Mukhopadhyay, Peter Chhoy, Emmet R. Karner, Jennifer L. Clark, Haibo Liu, Rui Li, Julie Lihua Zhu, Shuhui Chen, Lara K. Mahal, Barbara A. Bensing, Arthur M. Mercurio
Summary: Specific glycans can be used to distinguish breast cancer stem cells and influence their function. The expression of certain glycans plays a role in the enrichment and fate of breast cancer stem cells.
Article
Oncology
Nandini Karthik, Jane Jia Hui Lee, Joshua Ling Jun Soon, Hsin Yao Chiu, Amos Hong Pheng Loh, Derrick Sek Tong Ong, Wai Leong Tam, Reshma Taneja
Summary: This study reveals that histone variant H3.3 is overexpressed in alveolar rhabdomyosarcoma (ARMS), impacting the migration and invasion ability of tumor cells and correlating with metastasis and prognosis in ARMS. Mechanistically, melanoma cell adhesion molecule (MCAM) is identified as a direct downstream target of H3.3, and its overexpression rescues cell migration and invasion in H3F3A-depleted cells. Furthermore, G9a, an upstream regulator of H3F3A, is discovered. This study uncovers a novel H3.3-dependent axis and establishes the potential of MCAM as a therapeutic target for high-risk ARMS patients.
JOURNAL OF PATHOLOGY
(2023)
Review
Multidisciplinary Sciences
Tara E. Sutherland, Douglas P. Dyer, Judith E. Allen
Summary: For decades, immunologists have focused on studying circulating immune cells, but recently there is a growing appreciation for the role of immune cells within the tissue microenvironment. However, the understanding of the extracellular matrix (ECM) and its interaction with the immune system remains limited. This review aims to explore the potential for biological discovery at the intersection of immunology and matrix biology.
Article
Oncology
Marie Beck Enemark, Trine Engelbrecht Hybel, Charlotte Madsen, Kristina Lystlund Lauridsen, Bent Honore, Trine Lindhardt Plesner, Stephen Hamilton-Dutoit, Francesco d'Amore, Maja Ludvigsen
Summary: This study investigated the predictive value of hyaluronic acid receptors RHAMM and CD44 in patients with follicular lymphoma. Higher expression levels of RHAMM were associated with subsequent transformation and poorer outcome. The results suggest that high tumor tissue RHAMM expression predicts the risk of shorter transformation-free survival in patients with follicular lymphoma.
Article
Cell Biology
Yunfei He, Dongdong Cheng, Cheng Lian, Yingjie Liu, Wenqian Luo, Yuan Wang, Chengxin Ma, Qiuyao Wu, Pu Tian, Dasa He, Zhenchang Jia, Xianzhe Lv, Xue Zhang, Zhen Pan, Jinxi Lu, Yansen Xiao, Peiyuan Zhang, Yajun Liang, Qingcheng Yang, Guohong Hu
Summary: In the context of giant cell tumor of bone, the proteoglycan Serglycin secreted by neoplastic stromal cells plays a crucial role in the formation of multinucleated giant cells and tumorigenesis. Through interaction with CD44 on the surface of monocytes, SRGN promotes osteoclast differentiation. Targeting CD44 may provide a new therapeutic approach for GCTB.
CELL DEATH & DISEASE
(2021)
Article
Hematology
Delphine Tardivon, Mateusz Antoszewski, Nadine Zangger, Marianne Nkosi, Jessica Sordet-Dessimoz, Rudi Hendriks, Ute Koch, Freddy Radtke
Summary: NOTCH1 gain-of-function mutations are common in B-cell chronic lymphocytic leukemia, and play a role in disease progression and chemotherapy resistance. In an in vivo mouse model of CLL, activation of Notch signaling facilitated disease initiation and promoted CLL cell proliferation and disease progression, while inhibition of Notch signaling delayed disease induction.
Article
Biochemistry & Molecular Biology
Kelie Chen, Xiaoyu Yuan, Shengchao Wang, Fang Zheng, Zhiqin Fu, Zhangjin Shen, Xiaodong Cheng, Yuwei Wang, Song Tang, Heng Ni, Fang Wang, Guang Lu, Yihua Wu, Dajing Xia, Weiguo Lu
Summary: Peritoneal metastasis is a key feature of advanced ovarian cancer. The protein MAP4K4 was found to be highly expressed in metastatic sites and its increased expression was associated with poorer survival and more advanced stage. Down regulation of MAP4K4 inhibited cancer cell adhesion, migration, and invasion. MAP4K4 was also found to stabilize N-cadherin by suppressing its cleavage, leading to N-cadherin stabilization and promoting ovarian cancer metastasis. Targeting MAP4K4 may be a potential therapeutic approach for ovarian cancer patients.
Article
Pediatrics
Laszlo Markasz, Rashmin C. Savani, Anders Jonzon, Richard Sindelar
Summary: The study identified a linear correlation between CD44 and RHAMM expression during the late saccular phase of lung development, with postnatal influences affecting CD44 and RHAMM expression in preterm infants. The interplay between CD44 and RHAMM receptors may depend on the lung developmental stage at birth.
PEDIATRIC RESEARCH
(2021)
Article
Multidisciplinary Sciences
Luca Di Leo, Valerie Bodemeyer, Francesca M. Bosisio, Giuseppina Claps, Marco Carretta, Salvatore Rizza, Fiorella Faienza, Alex Frias, Shawez Khan, Matteo Bordi, Maria P. Pacheco, Julie Di Martino, Jose J. Bravo-Cordero, Colin J. Daniel, Rosalie C. Sears, Marco Donia, Daniel H. Madsen, Per Guldberg, Giuseppe Filomeni, Thomas Sauter, Caroline Robert, Daniela De Zio, Francesco Cecconi
Summary: AMBRA1 deficiency accelerates melanoma growth and increases metastasis through FAK1 hyperactivation in mouse models of melanoma, suggesting FAK1 inhibition as a therapeutic strategy for melanoma with low AMBRA1 expression.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Zachary A. Hing, Janek S. Walker, Ethan C. Whipp, Lindsey Brinton, Matthew Cannon, Pu Zhang, Steven Sher, Casey B. Cempre, Fiona Brown, Porsha L. Smith, Claudio Agostinelli, Stefano A. Pileri, Jordan N. Skinner, Katie Williams, Hannah Phillips, Jami Shaffer, Larry P. Beaver, Alexander Pan, Kyle Shin, Charles T. Gregory, Gulcin H. Ozer, Selen A. Yilmaz, Bonnie K. Harrington, Amy M. Lehman, Lianbo Yu, Vincenzo Coppola, Pearlly Yan, Peggy Scherle, Min Wang, Philip Pitis, Chaoyi Xu, Kris Vaddi, Selina Chen-Kiang, Jennifer Woyach, James S. Blachly, Lapo Alinari, Yiping Yang, John C. Byrd, Robert A. Baiocchi, Bradley W. Blaser, Rosa Lapalombella
Summary: PRMT5 plays an important role in the progression of CLL to Richter transformation, and the PRMT5 inhibitor PRT382 shows potential therapeutic value.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Natasha Malik, Jodie Hay, Hassan N. B. Almuhanna, Karen M. Dunn, Jamie Lees, Jennifer Cassels, Jiatian Li, Rinako Nakagawa, Owen J. Sansom, Alison M. Michie
Summary: This study reveals the essential role of mTORC1 in the initiation/maintenance of leukemia in a CLL model and identifies the inactivation of eEF2 activity as a novel therapeutic target for blocking CLL progression.
Article
Biochemistry & Molecular Biology
Nannan Pang, Xierenguli Alimu, Rong Chen, Maliya Muhashi, Jiajia Ma, Gang Chen, Fang Zhao, Lei Wang, Jianhua Qu, Jianbing Ding
Summary: This study revealed that Tim-3 was overexpressed in CLL patients, along with elevated levels of Galectin-9/Tim-3 signaling pathway, which were associated with disease progression. By negatively regulating CD4(+) T cells, the activated Galectin-9/Tim-3 pathway suppressed Th1 effector function and promoted Treg cells to participate in immune escape of CLL. These findings suggest that this pathway could be a potential target for immunotherapy in CLL patients.
Article
Oncology
Mehdi Chaib, Laura M. M. Sipe, Johnathan R. R. Yarbro, Margaret S. S. Bohm, Brittany R. R. Counts, Ubaid Tanveer, Ajeeth K. K. Pingili, Deidre Daria, Tony N. N. Marion, James A. A. Carson, Paul G. G. Thomas, Liza Makowski
Summary: This study investigates the effect of PKC agonists on MDSC expansion, differentiation, and recruitment to the tumor microenvironment. The results demonstrate that PKC agonists decrease MDSC expansion and induce their differentiation to an APC-like phenotype. Additionally, PKC agonists enhance MDSC cross-priming capacity and reduce their suppressive activity. Furthermore, the combination of PKC agonists with CD40 agonist leads to reduced tumor growth and increased activated CD8(+) T cells in a breast cancer mouse model.
Article
Multidisciplinary Sciences
Sara Garcia-Garcia, Maria Rodrigo-Faus, Noelia Fonseca, Sara Manzano, Balazs Gyorffy, Alberto Ocana, Paloma Bragado, Almudena Porras, Alvaro Gutierrez-Uzquiza
Summary: The study identifies MAP4K4 as a key gene in prostate cancer metastasis, with its deletion or inhibition blocking cell migration and clonogenic properties, suggesting a potential role of MAP4K4 in promoting tumor dissemination and growth. Moreover, the upregulation of HGK correlates with poor prognosis in prostate cancer, indicating its potential use as a prognostic biomarker for predicting aggressive phenotype and metastasis appearance.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Florian Huemer, Stefan Hecht, Bernhard Scharinger, Verena Schlintl, Gabriel Rinnerthaler, Konstantin Schlick, Ronald Heregger, Thomas Melchardt, Angela Wimmer, Iris Muehlbacher, Oliver Owen Koch, Daniel Neureiter, Eckhard Klieser, Sara Seyedinia, Mohsen Beheshti, Richard Greil, Lukas Weiss
Summary: This study investigated the impact of body composition parameters and dynamics on clinical outcomes in gastric/GEJ cancer patients undergoing perioperative FLOT chemotherapy. The study found that the skeletal muscle index (SMI) was the only body composition parameter that significantly decreased during pre-operative FLOT. Pre-FLOT BMI and SMI were significantly associated with progression-free survival (PFS) in multivariable analysis.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Hematology
Olga Oleshko, Sonja Werwitzke, Annika Klingberg, Torsten Witte, Hermann Eichler, Robert Klamroth, Katharina Holstein, Christina Hart, Christian Pfrepper, Paul Knoebl, Richard Greil, Peter Neumeister, Birgit M. Reipert, Andreas Tiede
Summary: The root cause of autoantibody formation against FVIII in AHA is unclear. A diverse pattern of autoantibodies is associated with AHA, suggesting a more general breakdown of immune tolerance might be involved in its pathology.
Article
Oncology
Kevin J. Harrington, Barbara Burtness, Richard Greil, Denis Soulieres, Makoto Tahara, Gilberto de Castro Jr, Amanda Psyrri, Irene Brana, Neus Baste, Prakash Neupane, Ase Bratland, Thorsten Fuereder, Brett G. M. Hughes, Ricard Mesia, Nuttapong Ngamphaiboon, Tamara Rordorf, Wan Zamaniah Wan Ishak, Jianxin Lin, Burak Gumuscu, Ramona F. Swaby, Danny Rischin
Summary: The study presents a post hoc analysis of the long-term efficacy and progression-free survival in recurrent/metastatic head and neck squamous cell carcinoma patients treated with pembrolizumab and pembrolizumab-chemotherapy as next-line therapy. The results demonstrate favorable clinical efficacy and progression-free survival with pembrolizumab and pembrolizumab-chemotherapy in patients with programmed death ligand 1 (PD-L1) combined positive score (CPS) >= 20, CPS >= 1, and total populations. Subsequent treatments after pembrolizumab-based therapy also showed good efficacy.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
S. P. Gampenrieder, V. Dezentje, M. Lambertini, A. de Nonneville, M. Marhold, F. Le Du, A. Cortes Salgado, D. Alpuim Costa, M. Vaz Batista, N. Chic Ruche, C. Tinchon, A. Petzer, E. Blondeaux, L. Del Mastro, G. Targato, F. Bertucci, A. Goncalves, F. Viret, R. Bartsch, C. Mannsbart, A. Deleuze, L. Robert, C. Saavedra Serrano, M. Gion Cortes, M. Sampaio-Alves, M. Vitorino, L. Pecen, C. Singer, N. Harbeck, G. Rinnerthaler, R. Greil
Summary: Based on a large international dataset of metastatic TNBC, the frequency of HER2-low was 32.0%, but it showed no significant impact on overall survival (OS).
Review
Oncology
T. Melchardt, A. Egle, R. Greil
Article
Oncology
Georg Hopfinger, Bernhard Rupp, Richard Greil
Summary: Chimeric antigen receptor (CAR) T cell therapies have the potential to be an effective treatment option for B cell malignancies, particularly relapsed or refractory diffuse large B cell lymphoma (DLBCL). However, despite being available in wealthy Western countries, patient access to CAR-T therapy can be limited due to systemic barriers. In Austria, a significant percentage of eligible DLBCL patients did not receive CAR-T therapy in 2021, raising concerns about accessibility. This report identifies barriers to access and provides recommendations for systemic solutions to improve CAR-T access in Austria.
MEMO-MAGAZINE OF EUROPEAN MEDICAL ONCOLOGY
(2023)
Article
Hematology
Grzegorz S. Nowakowski, Dok Hyun Yoon, Patrizia Mondello, Erel Joffe, Anthea Peters, Isabelle Fleury, Richard Greil, Matthew Ku, Reinhard Marks, Kibum Kim, Pier Luigi Zinzani, Judith Trotman, Lorenzo Sabatelli, Eva E. Waltl, Mark Winderlich, Andrea Sporchia, Nuwan C. Kurukulasuriya, Raul Cordoba, Georg Hess, Gilles Salles
Summary: The RE-MIND2 study compared the patient outcomes of tafasitamab+lenalidomide with other therapies for relapsed/refractory DLBCL. The data showed that tafasitamab+lenalidomide had better overall survival rates compared to polatuzumab vedotin+bendamustine+rituximab and rituximab+lenalidomide.
ANNALS OF HEMATOLOGY
(2023)
Article
Oncology
Sandro. M. Wagner, Teresa Magnes, Thomas Melchardt, Dominik Kiem, Lukas Weiss, Daniel Neureiter, Christina Wagner, Marie-Bernadette Aretin, Stefan Nemec, Gabriele Gamerith, Georg Pall, Richard Greil, Thorsten Fuereder
Summary: This study evaluated the efficacy and safety of immune checkpoint inhibitor therapy in unselected patients with SCCHN. The results showed that CPI therapy alone or in combination with chemotherapy is an effective treatment for SCCHN patients, consistent with previous studies.
ANTICANCER RESEARCH
(2023)
Article
Biochemical Research Methods
Marc Vaisband, Maria Schubert, Franz Josef Gassner, Roland Geisberger, Richard Greil, Nadja Zaborsky, Jan Hasenauer
Summary: Accurate somatic variant calling from next-generation sequencing data is crucial for personalised cancer therapy. A machine learning approach using a Convolutional Neural Network can improve the validation of genetic variants, incorporating contextual data from sequencing tracks. This model performs on par with trained researchers and enhances reproducibility and scalability.
BMC BIOINFORMATICS
(2023)
Article
Oncology
G. Stocker, S. Lorenzen, T. Ettrich, A. -l. Herz, F. Longo, A. Kiani, M. Venerito, J. Trojan, R. Mahlberg, N. Moosmann, B. Chibaudel, S. Kubicka, R. Greil, S. Daum, M. Geissler, J. Larcher-Senn, G. Keller, F. Lordick, G. M. Haag
Summary: S-1 maintenance therapy following platinum-based induction therapy leads to non-inferior survival outcomes compared with the continuation of platinum-based combination chemotherapy. It also has fewer adverse effects and supports the use of a fluoropyrimidine maintenance strategy. These findings challenge the practice of continuing platinum combination chemotherapy after 3 months of induction therapy in patients with advanced HER2-negative esophagogastric adenocarcinoma.
Review
Pharmacology & Pharmacy
Noemie Mercier, Drifa Belhadi, Aline DeChanet, Christelle Delmas, Juliette Saillard, Marina Dumousseaux, Soizic Le Mestre, Claire Fougerou-Leurent, Assia Ferrane, Charles Burdet, Helene Esperou, Florence Ader, Maya Hites, Nathan Peiffer-Smadja, Julien Poissy, Claire Andrejak, Jose Artur Paiva, Evelina Tacconelli, Therese Staub, Richard Greil, Dominique Costagliola, France Mentre, Yazdan Yazdanpanah, Alpha Diallo
Summary: This article presents the challenges faced by an academic Safety Department in managing the safety of a European trial during the COVID-19 pandemic. The trial involved repurposed and investigational drugs for hospitalized COVID-19 patients. The high number of Serious Adverse Events (SAEs) made it difficult to evaluate and identify potential safety signals.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2023)
Correction
Hematology
Grzegorz S. Nowakowski, Dok Hyun Yoon, Patrizia Mondello, Erel Joffe, Anthea Peters, Isabelle Fleury, Richard Greil, Matthew Ku, Reinhard Marks, Kibum Kim, Pier Luigi Zinzani, Judith Trotman, Lorenzo Sabatelli, Eva E. Waltl, Mark Winderlich, Andrea Sporchia, Nuwan C. Kurukulasuriya, Raul Cordoba, Georg Hess, Gilles Salles
ANNALS OF HEMATOLOGY
(2023)
Meeting Abstract
Oncology
F. Huemer, C. Dunkl, G. Rinnerthaler, K. Schlick, R. Heregger, K. Emmanuel, D. Neureiter, E. Klieser, M. Deutschmann, F. Roeder, R. Greil, L. Weiss
ANNALS OF ONCOLOGY
(2023)
Article
Oncology
Florian Huemer, Celine Dunkl, Gabriel Rinnerthaler, Konstantin Schlick, Ronald Heregger, Klaus Emmanuel, Daniel Neureiter, Eckhard Klieser, Michael Deutschmann, Falk Roeder, Richard Greil, Lukas Weiss
Summary: This retrospective analysis characterized elderly patients (70 years and older) with metastatic colorectal cancer (mCRC) undergoing systemic therapy. The median overall survival (OS) was 25.6 months. First-line anti-EGFR-based therapy showed a trend towards longer OS compared to anti-VEGF-based therapy or chemotherapy alone in left-sided mCRC. Metastasectomy and/or local ablative treatment with curative intent were associated with improved OS.
FRONTIERS IN ONCOLOGY
(2023)
Meeting Abstract
Oncology
Simon P. Gampenrieder, Gabriel Rinnerthaler, Christoph Tinchon, Andreas Petzer, Marija Balic, Sonja Heibl, Margit Sandholzer, August F. Zabernigg, Daniel Egle, Christopher Hager, Petra Pichler, Florian Roitner, Johannes Andel, Kathrin Strasser-Weippl, Michael Knauer, Michael Hubalek, Christian F. Singer, Richard Greil