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JOURNAL ARTICLE
Franco Locatelli, Peter Lang, Donna Wall, Roland Meisel, Selim Corbacioglu, Amanda M Li, Josu de la Fuente, Ami J Shah, Ben Carpenter, Janet L Kwiatkowski, Markus Mapara, Robert I Liem, Maria Domenica Cappellini, Mattia Algeri, Antonis Kattamis, Sujit Sheth, Stephan Grupp, Rupert Handgretinger, Puja Kohli, Daoyuan Shi, Leorah Ross, Yael Bobruff, Christopher Simard, Lanju Zhang, Phuong Khanh Morrow, William E Hobbs, Haydar Frangoul
BACKGROUND: Exagamglogene autotemcel (exa-cel) is a nonviral cell therapy designed to reactivate fetal hemoglobin synthesis through ex vivo clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 gene editing of the erythroid-specific enhancer region of BCL11A in autologous CD34+ hematopoietic stem and progenitor cells (HSPCs). METHODS: We conducted an open-label, single-group, phase 3 study of exa-cel in patients 12 to 35 years of age with transfusion-dependent β-thalassemia and a β0 /β0 , β0 /β0 -like, or non-β0 /β0 -like genotype...
April 24, 2024: New England Journal of Medicine
#2
JOURNAL ARTICLE
Yongxian Hu, Mingming Zhang, Tingting Yang, Zhuomao Mo, Guoqing Wei, Ruirui Jing, Houli Zhao, Rongrong Chen, Cheng Zu, Tianning Gu, Pingnan Xiao, Ruimin Hong, Jingjing Feng, Shan Fu, Delin Kong, Huijun Xu, Jiazhen Cui, Simao Huang, Bin Liang, Xiaolin Yuan, Qu Cui, Hongshan Guo, Yunxian Yu, Youqin Feng, Chunxiang Jin, Jiangtao Ren, Alex H Chang, Dongrui Wang, He Huang
BACKGROUND: Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects. Whether the integration of CAR T-cell therapy and allogeneic HSCT can preserve CAR T-cell function and improve tumor control is unclear...
April 25, 2024: New England Journal of Medicine
#3
JOURNAL ARTICLE
Joseph Markowitz, Michael Shamblott, Andrew S Brohl, Amod A Sarnaik, Zeynep Eroglu, Nikhil I Khushalani, Christopher W Dukes, Alejandra Chamizo, Marina Bastawrous, Edward T Garcia, Ashraf Delhawi, Pei-Ling Chen, Deanryan B De Aquino, Vernon K Sondak, Ahmad A Tarhini, Youngchul Kim, Patricia Lawman, Shari Pilon-Thomas
IFx-Hu2.0 was designed to encode part of the Emm55 protein contained within a plasmid in a formulation intended for transfection into mammalian cells. IFx-Hu2.0 promotes both adaptive and innate immune responses in animal studies. Furthermore, previous studies have demonstrated safety/efficacy in equine, canine, and murine species. We present the first-in-human study of IFx-Hu2.0, administered by intralesional injection into melanoma tumors of seven patients with stage III/IV unresectable melanoma. No dose-limiting toxicities attributable to IFx-Hu2...
April 24, 2024: Molecular Cancer Therapeutics
#4
JOURNAL ARTICLE
Abdulnaser Nourallah, Abdulrahman Alshehri, Ayman Alhejazi, Binyam Usman, Ghada ElGohary, Hafiz Malhan, Ibraheem Motabi, Khalil Al Farsi, Mohammed Alshuaibi, Mustaqeem Siddiqui, Rasha Ghonema, Ruba Yasin Taha, Tarek Abouzeid, Wesam Ahmed, Mohanad Diab, Ahmad Alhuraiji, Magdy Rabea, Mohamed Zahir Chouikrat
BACKGROUND: Multiple myeloma (MM) is the second-most common cancer among hematological malignancies. Patients with active disease may experience several comorbidities, including renal insufficiency and asthma, which may lead to treatment failure. The treatment of relapsed or refractory MM (RRMM) has been associated with multiple factors, causing a decline in progression-free survival as well as overall survival with subsequent lines of therapy. Data about the characteristics of this group of patients in the Greater Gulf region are lacking...
April 24, 2024: JMIR Research Protocols
#5
JOURNAL ARTICLE
Francesco Di Mauro, Giuseppina Arbore
Chemotherapeutics, radiation, targeted therapeutics and immunotherapeutics each demonstrate clinical benefits for a small subset of patients with solid malignancies. Immune cells infiltrating the tumor and the surrounding stroma play a critical role in shaping cancer progression and modulating therapy response. They do this by interacting with the other cellular and molecular components of the tumor microenvironment (TME). Spatial multi-OMICs technologies are rapidly evolving. Currently, such technologies allow high-throughput RNA and protein profiling and retain geographical information about the TME cellular architecture and the functional phenotype of tumor, immune and stromal cells...
April 24, 2024: Cancer Immunology Research
#6
COMPARATIVE STUDY
Florian Lamblin, Jeroen Kerstens, Sergio Muñiz-Castrillo, Alberto Vogrig, David Goncalves, Veronique Rogemond, Geraldine Picard, Marine Villard, Anne-Laurie Pinto, Marleen H Van Coevorden-Hameete, Marienke A De Bruijn, Juna M De Vries, Marco Schreurs, Louise Tyvaert, Lucie Hopes, Jerome Aupy, Cecile Marchal, Dimitri Psimaras, Laurent Kremer, Veronique Bourg, Jean-Christophe G Antoine, Adrien Wang, Philippe Kahane, Sophie Demeret, Guido Ahle, Vicente Peris Sempere, Noemie Timestit, Mikail Nourredine, Aurelien Maureille, Marie Benaiteau, Bastien Joubert, Emmanuel Mignot, Maarten J Titulaer, Jerome Honnorat
BACKGROUND AND OBJECTIVES: While patients with paraneoplastic autoimmune encephalitis (AE) with gamma-aminobutyric-acid B receptor antibodies (GABAB R-AE) have poor functional outcomes and high mortality, the prognosis of nonparaneoplastic cases has not been well studied. METHODS: Patients with GABAB R-AE from the French and the Dutch Paraneoplastic Neurologic Syndromes Reference Centers databases were retrospectively included and their data collected; the neurologic outcomes of paraneoplastic and nonparaneoplastic cases were compared...
May 2024: Neurology® Neuroimmunology & Neuroinflammation
#7
JOURNAL ARTICLE
Elizabeth A Sloss, Jordan P McPherson, Anna C Beck, Jia-Wen Guo, Carolyn H Scheese, Naomi R Flake, George Chalkidis, Catherine J Staes
PURPOSE: Use of artificial intelligence (AI) in cancer care is increasing. What remains unclear is how best to design patient-facing systems that communicate AI output. With oncologist input, we designed an interface that presents patient-specific, machine learning-based 6-month survival prognosis information designed to aid oncology providers in preparing for and discussing prognosis with patients with advanced solid tumors and their caregivers. The primary purpose of this study was to assess patient and caregiver perceptions and identify enhancements of the interface for communicating 6-month survival and other prognosis information when making treatment decisions concerning anticancer and supportive therapy...
April 2024: JCO Clinical Cancer Informatics
#8
JOURNAL ARTICLE
Niklas Klümper, Ngoc Khanh Tran, Stefanie Zschäbitz, Oliver Hahn, Thomas Büttner, Florian Roghmann, Christian Bolenz, Friedemann Zengerling, Constantin Schwab, Dora Nagy, Marieta Toma, Glen Kristiansen, Hendrik Heers, Philipp Ivanyi, Günter Niegisch, Camilla Marisa Grunewald, Christopher Darr, Arian Farid, Katrin Schlack, Mahmoud Abbas, Can Aydogdu, Jozefina Casuscelli, Theresa Mokry, Michael Mayr, Dora Niedersüß-Beke, Steffen Rausch, Dimo Dietrich, Jonas Saal, Jörg Ellinger, Manuel Ritter, Abdullah Alajati, Christoph Kuppe, Joshua Meeks, Francisco E Vera Badillo, J Alberto Nakauma-González, Joost Boormans, Kerstin Junker, Arndt Hartmann, Viktor Grünwald, Michael Hölzel, Markus Eckstein
PURPOSE: The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit is only achieved in a small, yet uncharacterized patient subset. NECTIN4 is located on chromosome 1q23.3, and 1q23.3 gains represent frequent copy number variations (CNVs) in urothelial cancer. Here, we aimed to evaluate NECTIN4 amplifications as a genomic biomarker to predict EV response in patients with mUC. MATERIALS AND METHODS: We established a NECTIN4 -specific fluorescence in situ hybridization (FISH) assay to assess the predictive value of NECTIN4 CNVs in a multicenter EV-treated mUC patient cohort (mUC-EV, n = 108)...
April 24, 2024: Journal of Clinical Oncology
#9
JOURNAL ARTICLE
S Velázquez-Rodríguez, M A Clara-Altamirano, D Y García-Ortega, A R Lizcano-Suárez, H Martínez-Said, V Villavicencio-Valencia, M Cuellar-Hubbe
INTRODUCTION: reconstruction of large bone defects using modular knee arthroplasty (MKA) presents a significant challenge in terms of functionality. The objective of the present work was to identify the different prognostic factors associated with failure of MKA in cancer patients. MATERIAL AND METHODS: a retrospective cohort study was conducted, including patients with a diagnosis of musculoskeletal tumor in the distal femur or proximal tibia, who underwent MKA between January 1, 2010, and December 31, 2021...
2024: Acta Ortopédica Mexicana
#10
JOURNAL ARTICLE
Anqi Fu, Vicki T Taasti, Masoud Zarepisheh
BACKGROUND: Reducing proton treatment time improves patient comfort and decreases the risk of error from intrafractional motion, but must be balanced against clinical goals and treatment plan quality. PURPOSE: To improve the delivery efficiency of spot scanning proton therapy by simultaneously reducing the number of spots and energy layers using the reweighted <mml:math xmlns:mml="https://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:msub><mml:mi>l</mml:mi> <mml:mn>1</mml:mn></mml:msub> <mml:annotation>$l_1$</mml:annotation></mml:semantics> </mml:math> regularization method...
April 24, 2024: Medical Physics
#11
JOURNAL ARTICLE
Jie Xia, Lixing Zhang, Xilei Peng, Juchuanli Tu, Siqin Li, Xueyan He, Fengkai Li, Jiankun Qiang, Haonan Dong, Qiaodan Deng, Cuicui Liu, Jiahui Xu, Rui Zhang, Quentin Liu, Guohong Hu, Chong Liu, Yi-Zhou Jiang, Zhi-Ming Shao, Ceshi Chen, Suling Liu
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options. Interleukin-1 receptor type 2 (IL1R2) promotes breast tumor-initiating cell (BTIC) self-renewal and tumor growth in TNBC, indicating that targeting it could improve patient treatment. Here, we observed that IL1R2 blockade strongly attenuated macrophage recruitment and the polarization of tumor-associated macrophages (TAMs) to inhibit BTIC self-renewal and CD8+ T cell exhaustion, which resulted in reduced tumor burden and prolonged survival in TNBC mouse models...
April 24, 2024: Cancer Research
#12
JOURNAL ARTICLE
Sheng Yang, Dongsheng Zhang, Qingyang Sun, Hongxu Nie, Yue Zhang, Xiaowei Wang, Yuanjian Huang, Yueming Sun
Colorectal cancer (CRC) is one of the most common malignant tumors in humans, with liver metastasis being the primary cause of mortality. The epithelial-mesenchymal transition (EMT) process endows cancer cells with enhanced metastatic potential. To elucidate the cellular mechanisms driving EMT in CRC, we analyzed single-cell RNA-sequencing (scRNA-seq) data from 11 non-metastatic primary tumors (TnM) and 11 metastatic primary tumors (TM) from CRC patients. Compared to TnM group, the TM samples showed elevated numbers of malignant epithelial cell and cancer-associated fibroblast (CAF) subsets that displayed enrichments of EMT, angiogenesis, and TGF-β signaling pathways...
April 24, 2024: Cancer Research
#13
REVIEW
Roxana Florentina Chivu, Florin Bobirca, Ionut Melesteu, Traian Patrascu
Helicobacter pylori (H. pylori), classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC), is linked to gastric cancer. The progression from atrophy to metaplasia, dysplasia, and carcinoma constitutes the pathway for intestinal-type gastric carcinoma development. H. pylori infection significantly increases gastric cancer risk, particularly in individuals with atrophic gastritis. Virulence factors like CagA and VacA disrupt host signaling pathways, contributing to chronic inflammation and carcinogenesis...
April 2024: Chirurgia
#14
JOURNAL ARTICLE
Betul Budak, Kazim Yalcin Arga
Tumor mutation burden (TMB) has profound implications for personalized cancer therapy, particularly immunotherapy. However, the size of the panel and the cutoff values for an accurate determination of TMB are still controversial. In this study, a pan-cancer analysis was performed on 22 cancer types from The Cancer Genome Atlas. The efficiency of gene panels of different sizes and the effect of cutoff values in accurate TMB determination was assessed on a large cohort using Whole Exome Sequencing data ( n = 9929 patients) as the gold standard...
April 2024: Omics: a Journal of Integrative Biology
#15
JOURNAL ARTICLE
Jorg Dietrich, Michael W Parsons, Emiliano Santarnecchi
Many cancer patients are at risk of developing cognitive symptoms that often become evident during or after cancer-directed therapy and may involve difficulties with attention, concentration, multitasking, executive function, and memory. Despite recent advances in identifying potential molecular and cellular mechanisms underlying cancer and chemotherapy-related cognitive impairment, there is generally a lack of effective treatment strategies, and the development of novel therapeutic interventions represents a major unmet medical need in clinical practice...
April 24, 2024: Cancer Research
#16
JOURNAL ARTICLE
Min Fu, Qian Gao, Mian Xiao, Rui-Feng Li, Xin-Yi Sun, Sheng-Lin Li, Xin Peng, Xi-Yuan Ge
Adenoid cystic carcinoma (ACC) is a rare malignant epithelial neoplasm that arises in secretory glands and commonly metastasizes to the lungs. MYBL1 is frequently overexpressed in ACC and has been suggested to be a driver of the disease. Here, we identified a circRNA derived from MYBL1 pre-mRNA that accompanied overexpression of MYBL1 in ACC. Overexpression of circMYBL1 was correlated with increased lung metastasis and poor overall survival in ACC patients. Ectopic circMYBL1 overexpression promoted malignant phenotypes and lung metastasis of ACC cells...
April 24, 2024: Cancer Research
#17
JOURNAL ARTICLE
Yuta Ito, Amira Marouf, Yasunori Kogure, Junji Koya, Raphaël Liévin, Julie Bruneau, Mariko Tabata, Yuki Saito, Sumito Shingaki, Mitsuhiro Yuasa, Kentaro Yamaguchi, Koichi Murakami, Robert Weil, Manon Vavasseur, Guillaume P Andrieu, Mehdi Latiri, Layla Veleanu, Michaël Dussiot, Isabelle André, Akshay Joshi, Chantal Lagresle-Peyrou, Aude Magerus, Sammara Chaubard, David Lavergne, Emmanuel Bachy, Erika Brunet, Virginie Fataccioli, Chantal Brouzes, Camille Laurent, Laurence De Leval, Alexandra Traverse-Glehen, Céline Bossard, Marie-Cécile Parrens, Véronique Meignin, Laure Philippe, Julien Rossignol, Felipe Suarez, Jean-Marie Michot, Olivier Tournilhac, Gandhi Damaj, François Lemonnier, Christine Bôle-Feysot, Patrick Nitschké, Bruno Tesson, Cécile Laurent, Thierry Molina, Vahid Asnafi, Yosaku Watatani, Kenichi Chiba, Ai Okada, Yuichi Shiraishi, Sachiko Tsukita, Koji Izutsu, Hiroaki Miyoshi, Koichi Ohshima, Seiji Sakata, Akito Dobashi, Kengo Takeuchi, Masashi Sanada, Philippe Gaulard, Arnaud Jaccard, Seishi Ogawa, Olivier Hermine, Keisuke Kataoka, Lucile Couronné
Extranodal NK/T-cell lymphoma (ENKTCL) is an Epstein-Barr virus (EBV)-related neoplasm with male dominance and a poor prognosis. A better understanding of the genetic alterations and their functional roles in ENKTCL could help improve patient stratification and treatments. Here, we performed comprehensive genetic analysis of 177 ENKTCL cases to delineate the landscape of mutations, copy number alterations (CNAs), and structural variations, identifying 34 driver genes including six previously unappreciated ones, namely HLA-B, HLA-C, ROBO1, CD58, POT1, and MAP2K1...
April 24, 2024: Cancer Research
#18
JOURNAL ARTICLE
Nancy Gillis, Brittney L Dickey, Christelle Colin-Leitzinger, Yi-Han Tang, Ryan M Putney, Tania E Mesa, Sean J Yoder, Gita Suneja, Adam M Spivak, Ami B Patel, Martine Extermann, Anna R Giuliano, Mingxiang Teng, Jacob Kresovich, Anders Berglund, Anna E Coghill
BACKGROUND: Cancer-related deaths for people living with HIV (PWH) are increasing due to longer life expectancies and disparately poor cancer-related outcomes. We hypothesize that advanced biological aging contributes to cancer-related morbidity and mortality for PWH and cancer. We sought to determine the impact of clonal hematopoiesis (CH) on cancer disparities in PWH. METHODS: We conducted a retrospective study to compare the prevalence and clinical outcomes of CH in PWH and people without HIV (PWoH) and cancer...
April 24, 2024: Journal of Infectious Diseases
#19
JOURNAL ARTICLE
Yani Liu, Xueao Wang, Zheng Li, Liping Chen, Xinyi Cai, Zhigang Sun, Wei Cheng, Xiangjie Luo, Hai-Liang Zhu, Yong Qian
Hydrogen sulfide (H2 S), a critical gas signaling molecule, and N -acetyltransferase 2 (NAT2), a key enzyme in drug metabolism, are both known active biomarkers for liver function. However, the interactions and effects of H2 S and NAT2 in living cells or lesion sites remain unknown due to the lack of imaging tools to achieve simultaneous detection of these two substances, making it challenging to implement real-time imaging and precise tracking. Herein, we report an activity-based two-photon fluorescent probe, TPSP-1 , for the cascade detection of H2 S and NAT2 in living liver cells...
April 24, 2024: Analytical Chemistry
#20
JOURNAL ARTICLE
David J Sherman, Lei Liu, Jennifer L Mamrosh, Jiansong Xie, John Ferbas, Brett Lomenick, Mark S Ladinsky, Rati Verma, Ingrid C Rulifson, Raymond J Deshaies
Nonalcoholic fatty liver disease, recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is a progressive metabolic disorder that begins with aberrant triglyceride accumulation in the liver and can lead to cirrhosis and cancer. A common variant in the gene PNPLA3 , encoding the protein PNPLA3-I148M, is the strongest known genetic risk factor for MASLD. Despite its discovery 20 y ago, the function of PNPLA3, and now the role of PNPLA3-I148M, remain unclear. In this study, we sought to dissect the biogenesis of PNPLA3 and PNPLA3-I148M and characterize changes induced by endogenous expression of the disease-causing variant...
April 30, 2024: Proceedings of the National Academy of Sciences of the United States of America
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