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Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer’s disease mice J. Transl. Med. (IF 7.4) Pub Date : 2024-03-18 Nataraj Jagadeesan, G. Chuli Roules, Devaraj V. Chandrashekar, Joshua Yang, Sanjana Kolluru, Rachita K. Sumbria
Biologic TNF-α inhibitors (bTNFIs) can block cerebral TNF-α in Alzheimer’s disease (AD) if these macromolecules can cross the blood–brain barrier (BBB). Thus, a model bTNFI, the extracellular domain of type II TNF-α receptor (TNFR), which can bind to and sequester TNF-α, was fused with a mouse transferrin receptor antibody (TfRMAb) to enable brain delivery via BBB TfR-mediated transcytosis. Previously
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The role of DGAT1 and DGAT2 in regulating tumor cell growth and their potential clinical implications J. Transl. Med. (IF 7.4) Pub Date : 2024-03-18 Boer Deng, Weimin Kong, Xiaochang Shen, Chao Han, Ziyi Zhao, Shuning Chen, Chunxiao Zhou, Victoria Bae-Jump
Lipid metabolism is widely reprogrammed in tumor cells. Lipid droplet is a common organelle existing in most mammal cells, and its complex and dynamic functions in maintaining redox and metabolic balance, regulating endoplasmic reticulum stress, modulating chemoresistance, and providing essential biomolecules and ATP have been well established in tumor cells. The balance between lipid droplet formation
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Development and validation of predictive models for myopia onset and progression using extensive 15-year refractive data in children and adolescents J. Transl. Med. (IF 7.4) Pub Date : 2024-03-17 Jing Zhao, Yanze Yu, Yiming Li, Feng Li, Zhe Zhang, Weijun Jian, Zhi Chen, Yang Shen, Xiaoying Wang, Zhengqiang Ye, Chencui Huang, Xingtao Zhou
Global myopia prevalence poses a substantial public health burden with vision-threatening complications, necessitating effective prevention and control strategies. Precise prediction of spherical equivalent (SE), myopia, and high myopia onset is vital for proactive clinical interventions. We reviewed electronic medical records of pediatric and adolescent patients who underwent cycloplegic refraction
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Single-cell transcriptomic sequencing data reveal aberrant DNA methylation in SMAD3 promoter region in tumor-associated fibroblasts affecting molecular mechanism of radiosensitivity in non-small cell lung cancer J. Transl. Med. (IF 7.4) Pub Date : 2024-03-16 Fushi Han, Shuzhen Chen, Kangwei Zhang, Kunming Zhang, Meng Wang, Peijun Wang
Non-small cell lung cancer (NSCLC) often exhibits resistance to radiotherapy, posing significant treatment challenges. This study investigates the role of SMAD3 in NSCLC, focusing on its potential in influencing radiosensitivity via the ITGA6/PI3K/Akt pathway. The study utilized gene expression data from the GEO database to identify differentially expressed genes related to radiotherapy resistance
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Redox proteomics of PANC-1 cells reveals the significance of HIF-1 signaling protein oxidation in pancreatic ductal adenocarcinoma pathogenesis J. Transl. Med. (IF 7.4) Pub Date : 2024-03-16 Chaochao Tan, Lichun Chen, Xiaoyu Guan, Wenyi Huang, Yinhong Feng, Ziyi Li, Ling Wu, Xiangping Huang, Qianhui Ouyang, Sixiang Liu, Ying Huang, Jiliang Hu
Protein cysteine oxidation is substantially involved in various biological and pathogenic processes, but its implications in pancreatic cancer development remains poorly understood. In this study, we performed a global characterization of protein oxidation targets in PDAC cells through iodoTMT-based quantitative proteomics, which identified over 4300 oxidized cysteine sites in more than 2100 proteins
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Low-intensity pulsed ultrasound delays the progression of osteoarthritis by regulating the YAP–RIPK1–NF-κB axis and influencing autophagy J. Transl. Med. (IF 7.4) Pub Date : 2024-03-16 Chunran Pan, Fan Lu, Xiaoxia Hao, Xiaofeng Deng, Jiawei Liu, Kai Sun, Wenjie Hou, Xingru Shang, Ruimin Chi, Fengjing Guo, Tao Xu
Osteoarthritis (OA) is a degenerative disease characterized by chronic inflammation of the joint. As the disease progresses, patients will gradually develop symptoms such as pain, physical limitations and even disability. The risk factors for OA include genetics, gender, trauma, obesity, and age. Unfortunately, due to limited understanding of its pathological mechanism, there are currently no effective
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Lactate infusion elevates cardiac output through increased heart rate and decreased vascular resistance: a randomised, blinded, crossover trial in a healthy porcine model J. Transl. Med. (IF 7.4) Pub Date : 2024-03-16 Oskar Kjærgaard Hørsdal, Niels Moeslund, Kristoffer Berg-Hansen, Roni Nielsen, Niels Møller, Hans Eiskjær, Henrik Wiggers, Nigopan Gopalasingam
Lactate is traditionally recognized as a by-product of anaerobic metabolism. However, lactate is a preferred oxidative substrate for stressed myocardium. Exogenous lactate infusion increases cardiac output (CO). The exact mechanism underlying this mechanism has yet to be elucidated. The aim of this study was to investigate the cardiovascular mechanisms underlying the acute haemodynamic effects of exogenous
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Predictive biomarkers for anti-TNF alpha therapy in IBD patients J. Transl. Med. (IF 7.4) Pub Date : 2024-03-16 Manoj Kumar, Selvasankar Murugesan, Nazira Ibrahim, Mamoun Elawad, Souhaila Al Khodor
Inflammatory bowel disease (IBD) is a chronic gastrointestinal condition characterized by severe gut inflammation, commonly presenting as Crohn’s disease, ulcerative colitis or categorized as IBD- unclassified. While various treatments have demonstrated efficacy in adult IBD patients, the advent of anti-TNF therapies has significantly revolutionized treatment outcomes and clinical management. These
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Hypoxia promotes metastasis by relieving miR-598-3p-restricted glycolysis in gastric cancer J. Transl. Med. (IF 7.4) Pub Date : 2024-03-15 Wei Zhou, Mengyuan Tang, Dan He, Yi Shen, Ziwei Huang, Wenxin Xia, Zhiyun Wu, Wenxiang Wei, Hui Zheng, Qi Wang, Weifeng Shi, Jingting Jiang
The activation of glycolysis, particularly in the context of reprogrammed energy metabolism, is increasingly recognized as a significant characteristic of cancer. However, the precise mechanisms by which glycolysis is promoted in metastatic gastric cancer cells under normal oxygen conditions remain poorly understood. MicroRNAs (miRNAs) play a crucial role in the development of malignant phenotypes
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OralExplorer: a web server for exploring the mechanisms of oral inflammatory diseases J. Transl. Med. (IF 7.4) Pub Date : 2024-03-15 Weiyin Lin, Hong Yang, Jiayu Lin, Xia Yang, Zhihao Liao, Yifan Zheng, Peng Luo, Chufeng Liu
Oral inflammatory diseases are localized infectious diseases primarily caused by oral pathogens with the potential for serious systemic complications. However, publicly available datasets for these diseases are underutilized. To address this issue, a web tool called OralExplorer was developed. This tool integrates the available data and provides comprehensive online bioinformatic analysis. Human oral
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Identification of therapeutic targets in osteoarthritis by combining heterogeneous transcriptional datasets, drug-induced expression profiles, and known drug-target interactions J. Transl. Med. (IF 7.4) Pub Date : 2024-03-15 Maria Claudia Costa, Claudia Angelini, Monica Franzese, Concetta Iside, Marco Salvatore, Luigi Laezza, Francesco Napolitano, Michele Ceccarelli
Osteoarthritis (OA) is a multifactorial, hypertrophic, and degenerative condition involving the whole joint and affecting a high percentage of middle-aged people. It is due to a combination of factors, although the pivotal mechanisms underlying the disease are still obscure. Moreover, current treatments are still poorly effective, and patients experience a painful and degenerative disease course. We
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Cancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoter J. Transl. Med. (IF 7.4) Pub Date : 2024-03-15 Songwei Feng, Bo Ding, Zhu Dai, Han Yin, Yue Ding, Sicong Liu, Ke Zhang, Hao Lin, Zhongdang Xiao, Yang Shen
Ovarian cancer (OC) is distinguished by its aggressive nature and the limited efficacy of current treatment strategies. Recent studies have emphasized the significant role of cancer-associated fibroblasts (CAFs) in OC development and progression. Employing sophisticated machine learning techniques on bulk transcriptomic datasets, we identified fibroblast growth factor 7 (FGF7), derived from CAFs, as
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The epitome of tailor-made short positively charged peptides against HCC via integrated pharmacology J. Transl. Med. (IF 7.4) Pub Date : 2024-03-15 Ki-Kwang Oh, Jung-A Eom, Kyeong Jin Lee, Goo-Hyun Kwon, Sang-Jun Yoon, Seol Hee Song, Jeong Ha Park, Jeong Su Kim, Dong Joon Kim, Ki-Tae Suk
Dear Editor, Recently, short positively charged peptides (SPCPs ≤ 500 Dalton) with positively charged residues (Arginine; R, Histidine; H, and Lysine; K) have been identified as alternative therapy with anti-cancer efficacy, which can penetrate plasma membrane to reach at target(s) [1]. The peptides are exposed to unfavorable pharmacokinetic properties such as hydrophilicity, high degradability, and
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CLPs-miR-103a-2-5p inhibits proliferation and promotes cell apoptosis in AML cells by targeting LILRB3 and Nrf2/HO-1 axis, regulating CD8 + T cell response J. Transl. Med. (IF 7.4) Pub Date : 2024-03-14 Qingyan Cen, Jianyu Chen, Jiaxin Guo, Mu Chen, Hao Wang, Suwan Wu, Honghao Zhang, Xiaoling Xie, Yuhua Li
LILRB3, a member of the leukocyte immunoglobulin-like receptor B (LILRB) family, has immunosuppressive functions and directly regulates cancer development, which indicates that LILRB3 is an attractive target for cancer diagnosis and therapy. Novel therapeutic treatments for acute myeloid leukemia (AML) are urgent and important, and RNA therapeutics including microRNAs (miRNAs) could be an effective
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Correction: Mesenchymal–epithelial transition in lymph node metastases of oral squamous cell carcinoma is accompanied by ZEB1 expression J. Transl. Med. (IF 7.4) Pub Date : 2024-03-14 Kai Horny, Christoph Sproll, Lukas Peiffer, Frauke Furtmann, Patricia Gerhardt, Jan Gravemeyer, Nikolas H. Stoecklein, Ivelina Spassova, Jürgen C. Becker
Correction: Journal of Translational Medicine (2023) 21:267 https://doi.org/10.1186/s12967-023-04102-w Following publication of the original article [1], we have been notified by the authors that the legends of supplementary material was not provided. Now legends are as follows: Additional file 1: Figure S1. Histology of OSCC primary and metastatic tumors. Additional file 2: Figure S2. Cell type identification
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Exosomal-miRNas expression and growth factors released by mononuclear cells of CLAD patients in response to extracorporeal photopheresis J. Transl. Med. (IF 7.4) Pub Date : 2024-03-14 Sara Bozzini, Eleonora Bozza, Cecilia Bagnera, Claudia Del Fante, Eugenio Barone, Simona De Vitis, Mara De Amici, Giorgia Testa, Stefania Croce, Chiara Valsecchi, Maria A Avanzini, Rosalia Cacciatore, Cristina Mortellaro, Gianluca Viarengo, Cesare Perotti, Federica Meloni
CLAD (Chronic Lung Allograft Dysfunction) remains a serious complication following lung transplantation. Some evidence shows that portions of Extracorporeal Photopheresis (ECP)-treated patients improve/stabilize their graft function. In spite of that, data concerning molecular mechanisms are still lacking. Aims of our study were to assess whether ECP effects are mediated by Mononuclear Cells (MNCs)
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Impact of myelofibrosis on patients with myelodysplastic syndromes following allogeneic hematopoietic stem cell transplantation J. Transl. Med. (IF 7.4) Pub Date : 2024-03-13 Panpan Zhu, Xiaoyu Lai, Lizhen Liu, Jimin Shi, Jian Yu, Yanmin Zhao, Luxin Yang, Tingting Yang, Weiyan Zheng, Jie Sun, Wenjun Wu, Yi Zhao, Zhen Cai, He Huang, Yi Luo
The prognostic significance of myelofibrosis (MF) grade in patients with myelodysplastic syndrome (MDS) following an allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains elusive. We retrospectively analyzed data from 153 patients with MDS who underwent allo-HSCT and divided the patients into the MF-0/1 (N = 119) and MF-2/3 (N = 34) cohorts to explore the impact of MF on outcomes of
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CD19/CD20 dual-targeted chimeric antigen receptor-engineered natural killer cells exhibit improved cytotoxicity against acute lymphoblastic leukemia J. Transl. Med. (IF 7.4) Pub Date : 2024-03-13 Na Yang, Caili Zhang, Yingchun Zhang, Yuting Fan, Jing Zhang, Xiaojin Lin, Ting Guo, Yangzuo Gu, Jieheng Wu, Jianmei Gao, Xing Zhao, Zhixu He
Chimeric antigen receptor natural killer (CAR-NK) cells represent a promising advancement in CAR cell therapy, addressing limitations observed in CAR-T cell therapy. However, our prior study revealed challenges in CAR-NK cells targeting CD19 antigens, as they failed to eliminate CD19+ Raji cells in NSG tumor-bearing mice, noting down-regulation or loss of CD19 antigen expression in some Raji cells
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CAR T cells and T cells phenotype and function are impacted by glucocorticoid exposure with different magnitude J. Transl. Med. (IF 7.4) Pub Date : 2024-03-12 Thomas Poiret, Sara Vikberg, Esther Schoutrop, Jonas Mattsson, Isabelle Magalhaes
Chimeric antigen receptor (CAR) T cell therapy is associated with high risk of adverse events. Glucocorticoids (GCs) are cornerstone in the management of high-grade cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Given the potentially deleterious effects of GCs on CAR T cells anti-tumor activity, increasing our understanding of GCs impact on CAR T
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HBV DNA polymerase upregulates the transcription of PD-L1 and suppresses T cell activity in hepatocellular carcinoma J. Transl. Med. (IF 7.4) Pub Date : 2024-03-12 Yan Jia, Jianing Zhao, Chunqing Wang, Jing Meng, Liqing Zhao, Hongwei Yang, Xiaoqing Zhao
In HBV-associated HCC, T cells often exhibit a state of functional exhaustion, which prevents the immune response from rejecting the tumor and allows HCC to progress. Moreover, polymerase-specific T cells exhibit more severe T-cell exhaustion compared to core-specific T cells. However, whether HBV DNA polymerase drives HBV-specific CD8+ T cell exhaustion in HBV-related HCC remains unclear. We constructed
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Investigation of the acute pathogenesis of spondyloarthritis/HLA-B27-associated anterior uveitis based on genome-wide association analysis and single-cell transcriptomics J. Transl. Med. (IF 7.4) Pub Date : 2024-03-12 Shuming Chen, Weidi Huang, Qiaoqian Wan, Zichun Tang, Xie Li, Fang Zeng, Shuyan Zheng, Zhuo Li, Xiao Liu
Patients with spondyloarthritis (SpA)/HLA-B27-associated acute anterior uveitis (AAU) experience recurring acute flares, which pose significant visual and financial challenges. Despite established links between SpA and HLA-B27-associated AAU, the exact mechanism involved remains unclear, and further understanding is needed for effective prevention and treatment. To investigate the acute pathogenesis
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Shifting the paradigm: engaging multicellular networks for cancer therapy J. Transl. Med. (IF 7.4) Pub Date : 2024-03-12 Joyce Hu, Paolo Ascierto, Alessandra Cesano, Volker Herrmann, Francesco M. Marincola
Most anti-cancer modalities are designed to directly kill cancer cells deploying mechanisms of action (MOAs) centered on the presence of a precise target on cancer cells. The efficacy of these approaches is limited because the rapidly evolving genetics of neoplasia swiftly circumvents the MOA generating therapy-resistant cancer cell clones. Other modalities engage endogenous anti-cancer mechanisms
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Bacterial DnaK reduces the activity of anti-cancer drugs cisplatin and 5FU J. Transl. Med. (IF 7.4) Pub Date : 2024-03-12 Francesca Benedetti, Emmanuel F. Mongodin, Jonathan H. Badger, Arshi Munawwar, Ashley Cellini, Weirong Yuan, Giovannino Silvestri, Carl N. Kraus, Simone Marini, Chozha V. Rathinam, Marco Salemi, Hervé Tettelin, Robert C. Gallo, Davide Zella
Chemotherapy is a primary treatment for cancer, but its efficacy is often limited by cancer-associated bacteria (CAB) that impair tumor suppressor functions. Our previous research found that Mycoplasma fermentans DnaK, a chaperone protein, impairs p53 activities, which are essential for most anti-cancer chemotherapeutic responses. To investigate the role of DnaK in chemotherapy, we treated cancer cell
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Systematic integration of molecular and clinical approaches in HCV-induced hepatocellular carcinoma J. Transl. Med. (IF 7.4) Pub Date : 2024-03-12 Ciniso Sylvester Shabangu, Wen-Hsiu Su, Chia-Yang Li, Ming-Lung Yu, Chia-Yen Dai, Jee-Fu Huang, Wan-Long Chuang, Shu-Chi Wang
MicroRNAs (miRNAs) play a crucial role in gene expression and regulation, with dysregulation of miRNA function linked to various diseases, including hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). There is still a gap in understanding the regulatory relationship between miRNAs and mRNAs in HCV-HCC. This study aimed to investigate the function and effects of persistent HCV-induced miRNA
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Kynurenine in IDO1high cancer cell-derived extracellular vesicles promotes angiogenesis by inducing endothelial mitophagy in ovarian cancer J. Transl. Med. (IF 7.4) Pub Date : 2024-03-11 Xiang Ying, Xiaocui Zheng, Xiaoqian Zhang, Yujia Yin, Xipeng Wang
Mitophagy, a prominent cellular homeostasis process, has been implicated in modulating endothelial cell function. Emerging evidence suggests that extracellular vesicles (EVs) participate in intercellular communication, which could modulate tumor angiogenesis, a hallmark of ovarian cancer (OC) progression. However, the underlying mechanisms through how EVs regulate endothelial mitophagy associated with
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Routine evaluation of HBV-specific T cell reactivity in chronic hepatitis B using a broad-spectrum T-cell epitope peptide library and ELISpot assay J. Transl. Med. (IF 7.4) Pub Date : 2024-03-11 Yandan Wu, Xiaotao Liu, Yuan Mao, Ruixue Ji, Lingzhi Xia, Zining Zhou, Yan Ding, Pinqing Li, Yu Zhao, Min Peng, Jie Qiu, Chuanlai Shen
The clinical routine test of HBV-specific T cell reactivity is still limited due to the high polymorphisms of human leukocyte antigens (HLA) in patient cohort and the lack of universal detection kit, thus the clinical implication remains disputed. A broad-spectrum peptide library, which consists of 103 functionally validated CD8+ T-cell epitopes spanning overall HBsAg, HBeAg, HBx and HBpol proteins
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Predicting long-term progression of Alzheimer’s disease using a multimodal deep learning model incorporating interaction effects J. Transl. Med. (IF 7.4) Pub Date : 2024-03-11 Yifan Wang, Ruitian Gao, Ting Wei, Luke Johnston, Xin Yuan, Yue Zhang, Zhangsheng Yu
Identifying individuals with mild cognitive impairment (MCI) at risk of progressing to Alzheimer’s disease (AD) provides a unique opportunity for early interventions. Therefore, accurate and long-term prediction of the conversion from MCI to AD is desired but, to date, remains challenging. Here, we developed an interpretable deep learning model featuring a novel design that incorporates interaction
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Exosomal circRNAs in the plasma serve as novel biomarkers for IPF diagnosis and progression prediction J. Transl. Med. (IF 7.4) Pub Date : 2024-03-10 Wenhua Gan, Wenwen Song, Yujuan Gao, Xuexue Zheng, Fengjuan Wang, Zirui Zhang, Ke Zen, Hongwei Liang, Xin Yan
Idiopathic Pulmonary Fibrosis (IPF) is a type of chronic interstitial pneumonia, often fatal, with elusive causes and a bleak prognosis. Its treatment options are limited and largely ineffective. Early detection and precise diagnosis are pivotal in managing the disease effectively and enhancing patient survival rates. Recently, the quest for trustworthy biomarkers for IPF has gained momentum. Notably
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ANGPTL3 is a novel HDL component that regulates HDL function J. Transl. Med. (IF 7.4) Pub Date : 2024-03-10 Longyan Yang, Yan Wang, Yongsong Xu, Kun Li, Ruili Yin, Lijie Zhang, Di Wang, Lingling Wei, Jianan Lang, Yanan Cheng, Lu Wang, Jing Ke, Dong Zhao
Angiopoietin-like protein 3 (ANGPTL3) is secreted by hepatocytes and inhibits lipoprotein lipase and endothelial lipase activity. Previous studies reported the correlation between plasma ANGPTL3 levels and high-density lipoprotein (HDL). Recently ANGPTL3 was found to preferentially bind to HDL in healthy human circulation. Here, we examined whether ANGPTL3, as a component of HDL, modulates HDL function
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A strategy to pioneer key agent(s) in Cephalotaxus alkaloids against pan-cancer via filtering methodology based on integrated pharmacology J. Transl. Med. (IF 7.4) Pub Date : 2024-03-10 Ki-Kwang Oh, Sang-Jun Yoon, Jung-A Eom, Kyeong Jin Lee, Goo-Hyun Kwon, Dong Joon Kim, Ki-Tae Suk
Dear Editor, Over the past few decades, Cephalotaxus alkaloids (CAs) have been considered as significant natural agents with their intriguing chemical structures and diverse bioactivities, in particular, as anti-cancer mediator. However, the investigation of its medicinal values has put in dilemma due to the limited reservoir from nature. Furthermore, the chemical synthesis of the CAs required great
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Proteomic analysis of mitochondria associated membranes in renal ischemic reperfusion injury J. Transl. Med. (IF 7.4) Pub Date : 2024-03-10 Yi Li, Hua-bin Wang, Jin-long Cao, Wen-jun Zhang, Hai-long Wang, Chang-hong Xu, Kun-peng Li, Yi Liu, Ji-rong Wang, Hua-lan Ha, Sheng-jun Fu, Li Yang
The mitochondria and endoplasmic reticulum (ER) communicate via contact sites known as mitochondria associated membranes (MAMs). Many important cellular functions such as bioenergetics, mitophagy, apoptosis, and calcium signaling are regulated by MAMs, which are thought to be closely related to ischemic reperfusion injury (IRI). However, there exists a gap in systematic proteomic research addressing
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HERVs may perform as the initial trigger for acquired aplastic anemia J. Transl. Med. (IF 7.4) Pub Date : 2024-03-09 Ting Wang, Nianbin Li, Heng Wu, Rong Fu
Current evidence indicates that during the onset of acquired aplastic anemia (AA), the characteristic immune state features an increased number and hyperactivity of CD8+ T lymphocytes [1]. The reactivation of human endogenous retroviruses (HERVs) promotes the production of viral transcripts and induces the dysregulation of host gene expression and render host cells susceptible to immune attacks [2]
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Amino acid profile alteration in age-related atrial fibrillation J. Transl. Med. (IF 7.4) Pub Date : 2024-03-09 Yunying Huang, Qiuzhen Lin, Yong Zhou, Jiayi Zhu, Yingxu Ma, Keke Wu, Zuodong Ning, Zixi Zhang, Na Liu, Mohan Li, Yaozhong Liu, Tao Tu, Qiming Liu
Amino acids (AAs) are one of the primary metabolic substrates for cardiac work. The correlation between AAs and both atrial fibrillation (AF) and aging has been documented. However, the relationship between AAs and age-related AF remains unclear. Initially, the plasma AA levels of persistent AF patients and control subjects were assessed, and the correlations between AA levels, age, and other clinical
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Incorporating genetic similarity of auxiliary samples into eGene identification under the transfer learning framework J. Transl. Med. (IF 7.4) Pub Date : 2024-03-09 Shuo Zhang, Zhou Jiang, Ping Zeng
The term eGene has been applied to define a gene whose expression level is affected by at least one independent expression quantitative trait locus (eQTL). It is both theoretically and empirically important to identify eQTLs and eGenes in genomic studies. However, standard eGene detection methods generally focus on individual cis-variants and cannot efficiently leverage useful knowledge acquired from
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Characterizing neuroinflammation and identifying prenatal diagnostic markers for neural tube defects through integrated multi-omics analysis J. Transl. Med. (IF 7.4) Pub Date : 2024-03-09 Wenshuang Wang, Yanhong Ji, Zhexu Dong, Zheran Liu, Shuang Chen, Lei Dai, Xiaolan Su, Qingyuan Jiang, Hongxin Deng
Neural Tube Defects (NTDs) are congenital malformations of the central nervous system resulting from the incomplete closure of the neural tube during early embryonic development. Neuroinflammation refers to the inflammatory response in the nervous system, typically resulting from damage to neural tissue. Immune-related processes have been identified in NTDs, however, the detailed relationship and underlying
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Multi-omics analysis of the gut microbiome and metabolites associated with the psychoneurological symptom cluster in children with cancer receiving chemotherapy J. Transl. Med. (IF 7.4) Pub Date : 2024-03-09 Jinbing Bai, Ronald Eldridge, Madelyn Houser, Melissa Martin, Christie Powell, Kathryn S. Sutton, Hye In Noh, Yuhua Wu, Thomas Olson, Konstantinos T. Konstantinidis, Deborah W. Bruner
Children with cancer receiving chemotherapy commonly report a cluster of psychoneurological symptoms (PNS), including pain, fatigue, anxiety, depression, and cognitive dysfunction. The role of the gut microbiome and its functional metabolites in PNS is rarely studied among children with cancer. This study investigated the associations between the gut microbiome–metabolome pathways and PNS in children
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Identification and functional activity of Nik related kinase (NRK) in benign hyperplastic prostate J. Transl. Med. (IF 7.4) Pub Date : 2024-03-09 Weixiang He, Zelin Tian, Bingchen Dong, Yitong Cao, Wei Hu, Peng Wu, Lei Yu, Xinhua Zhang, Shanshan Guo
Benign prostatic hyperplasia (BPH) is common in elder men. The current study aims to identify differentially expressed genes (DEGs) in hyperplastic prostate and to explore the role of Nik related kinase (NRK) in BPH. Four datasets including three bulk and one single cell RNA-seq (scRNA-seq) were obtained to perform integrated bioinformatics. Cell clusters and specific metabolism pathways were analyzed
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PTEN deficiency potentiates HBV-associated liver cancer development through augmented GP73/GOLM1 J. Transl. Med. (IF 7.4) Pub Date : 2024-03-08 Fuqiang Huang, Jing Guo, Na Zhao, Mengjie Hou, Xiaochen Gai, Shuhui Yang, Pei Cai, Yanan Wang, Qian Ma, Qi Zhao, Li Li, Huayu Yang, Yanling Jing, Di Jin, Zhongdong Hu, Xiaojun Zha, Hongyang Wang, Yilei Mao, Fangming Liu, Hongbing Zhang
Although hepatitis B virus (HBV) infection is a major risk factor for hepatic cancer, the majority of HBV carriers do not develop this lethal disease. Additional molecular alterations are thus implicated in the process of liver tumorigenesis. Since phosphatase and tensin homolog (PTEN) is decreased in approximately half of liver cancers, we investigated the significance of PTEN deficiency in HBV-related
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Integrated mRNA- and miRNA-sequencing analyses unveil the underlying mechanism of tobacco pollutant-induced developmental toxicity in zebrafish embryos J. Transl. Med. (IF 7.4) Pub Date : 2024-03-08 Jiasheng Chen, Yuxin Lin, Deyi Gen, Wanxian Chen, Rui Han, Hao Li, Shijie Tang, Shukai Zheng, Xiaoping Zhong
Tobacco pollutants are prevalent in the environment, leading to inadvertent exposure of pregnant females. Studies of these pollutants' toxic effects on embryonic development have not fully elucidated the potential underlying mechanisms. Therefore, in this study, we aimed to investigate the developmental toxicity induced by cigarette smoke extract (CSE) at concentrations of 0.25, 1, and 2.5% using a
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Association of domain-specific physical activity with albuminuria among prediabetes and diabetes: a large cross-sectional study J. Transl. Med. (IF 7.4) Pub Date : 2024-03-08 Bingquan Xiong, Yufan Wang, Juan He, Lisha Wang, Rui He, Min Zhu, Jiaxing Wang, Yingrui Li, Bin Liu, Kaihu Xiao, Qiang She
Albuminuria, the presence of excess of protein in urine, is a well-known risk factor for early kidney damage among diabetic/prediabetic patients. There is a complex interaction between physical activity (PA) and albuminuria. However, the relationship of specific-domain PA and albuminuria remained obscure. Albuminuria was defined as urinary albumin/creatinine ratio (ACR) > 30 mg/g. PA was self-reported
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CircGLIS3 promotes gastric cancer progression by regulating the miR-1343-3p/PGK1 pathway and inhibiting vimentin phosphorylation J. Transl. Med. (IF 7.4) Pub Date : 2024-03-08 Yongxin Zhang, Xiaofeng Wang, Wenwei Liu, Tianxiang Lei, Tang Qiao, Wei Feng, Wu Song
Circular RNAs (circRNAs) have been proved to play crucial roles in the development of various cancers. However, the molecular mechanism of circGLIS3 involved in gastric cancer (GC) tumorigenesis has not been elucidated. The higher expression level of circGLIS3 was identified in GC through RNA sequencing and subsequent tissue verification using Quantitative real-time PCR (qRT-PCR). A series of functional
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Inducing expression of ICOS-L by oncolytic adenovirus to enhance tumor-specific bi-specific antibody efficacy J. Transl. Med. (IF 7.4) Pub Date : 2024-03-07 Neshat Saffarzadeh, Emelie Foord, Eoghan O’Leary, Rand Mahmoun, Thomas Birkballe Hansen, Victor Levitsky, Thomas Poiret, Michael Uhlin
Intratumoral injection of oncolytic viruses (OVs) shows promise in immunotherapy: ONCOS-102, a genetically engineered OV that encodes Granulocyte–Macrophage Colony-Stimulating Factor (GM-CSF) demonstrated efficacy in early clinical trials, enhancing T cell infiltration in tumors. This suggests OVs may boost various forms of immunotherapy, including tumor-specific bi-specific antibodies (BsAbs). Our
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PLA2G4A and ACHE modulate lipid profiles via glycerophospholipid metabolism in platinum-resistant gastric cancer J. Transl. Med. (IF 7.4) Pub Date : 2024-03-07 Menglin Chen, Cancan Zhang, Huaizhi Li, Shanshan Zheng, Yaqi Li, Mengyun Yuan, Yuxuan Chen, Jian Wu, Qingmin Sun
Bioactive lipids involved in the progression of various diseases. Nevertheless, there is still a lack of biomarkers and relative regulatory targets. The lipidomic analysis of the samples from platinum-resistant in gastric cancer patients is expected to help us further improve our understanding of it. We employed LC–MS based untargeted lipidomic analysis to search for potential candidate biomarkers
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Inhibition of OGFOD1 by FG4592 confers neuroprotection by activating unfolded protein response and autophagy after ischemic stroke J. Transl. Med. (IF 7.4) Pub Date : 2024-03-07 Jian Xie, Yuan Zhang, Bin Li, Wen Xi, Yu Wang, Lu Li, Chenchen Liu, Ling Shen, Bing Han, Yan Kong, HongHong Yao, Zhijun Zhang
Acute ischemic stroke is a common neurological disease with a significant financial burden but lacks effective drugs. Hypoxia-inducible factor (HIF) and prolyl hydroxylases (PHDs) participate in the pathophysiological process of ischemia. However, whether FG4592, the first clinically approved PHDs inhibitor, can alleviate ischemic brain injury remains unclear. The infarct volumes and behaviour tests
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Characterization of the proteome of stable and unstable carotid atherosclerotic plaques using data-independent acquisition mass spectrometry J. Transl. Med. (IF 7.4) Pub Date : 2024-03-07 Zhichao Lai, Chaonan Wang, Xiaoyan Liu, Haidan Sun, Zhengguang Guo, Jiang Shao, Kang Li, Junye Chen, Jiaxian Wang, Xiangling Lei, Keqiang Shu, Yuyao Feng, Deqiang Kong, Wei Sun, Bao Liu
Currently, noninvasive imaging techniques and circulating biomarkers are still insufficient to accurately assess carotid plaque stability, and an in-depth understanding of the molecular mechanisms that contribute to plaque instability is still lacking. We established a clinical study cohort containing 182 patients with carotid artery stenosis. After screening, 39 stable and 49 unstable plaques were
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Impaired balance between neutrophil extracellular trap formation and degradation by DNases in COVID-19 disease J. Transl. Med. (IF 7.4) Pub Date : 2024-03-07 Geoffrey Garcia, Sylvie Labrouche-Colomer, Alexandre Duvignaud, Etienne Clequin, Charles Dussiau, David-Alexandre Trégouët, Denis Malvy, Renaud Prevel, Atika Zouine, Isabelle Pellegrin, Julien Goret, Maria Mamani-Matsuda, Antoine Dewitte, Chloe James
Thrombo-inflammation and neutrophil extracellular traps (NETs) are exacerbated in severe cases of COVID-19, potentially contributing to disease exacerbation. However, the mechanisms underpinning this dysregulation remain elusive. We hypothesised that lower DNase activity may be associated with higher NETosis and clinical worsening in patients with COVID-19. Biological samples were obtained from hospitalized
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WNT-inhibitory factor 1-mediated glycolysis protects photoreceptor cells in diabetic retinopathy J. Transl. Med. (IF 7.4) Pub Date : 2024-03-06 Bolin Chen, Jing Zou, Lihui Xie, Yinjun Cai, Bowen Li, Wei Tan, Jinhaohao Huang, Fangling Li, Huizhuo Xu
In diabetic retinopathy (DR), hypoxia-inducible factor (HIF-1α) induces oxidative stress by upregulating glycolysis. This process leads to neurodegeneration, particularly photoreceptor cell damage, which further contributes to retinal microvascular deterioration. Further, the regulation of Wnt-inhibitory factor 1 (WIF1), a secreted Wnt signaling antagonist, has not been fully characterized in neurodegenerative
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Prediction model for EBV infection following HLA haploidentical matched hematopoietic stem cell transplantation J. Transl. Med. (IF 7.4) Pub Date : 2024-03-06 Xun-Hong Cao, Ze-Ying Fan, Ying-Jun Chang, Lan-Ping Xu, Xiao-Hui Zhang, Xiao-Jun Huang, Xiang-Yu Zhao
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for hematological malignancies. However, viral infections, particularly EBV infection, frequently occur following allo-HSCT and can result in multi-tissue and organ damage. Due to the lack of effective antiviral drugs, these infections can even progress to post-transplant lymphoproliferative disorders (PTLD), thereby
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Integrative analysis of chromatin accessibility and transcriptome landscapes in the induction of peritoneal fibrosis by high glucose J. Transl. Med. (IF 7.4) Pub Date : 2024-03-05 Qiong Song, Pengbo Wang, Huan Wang, Meijing Pan, Xiujuan Li, Zhuan’e Yao, Wei Wang, Guangbo Tang, Sen Zhou
Peritoneal fibrosis is the prevailing complication induced by prolonged exposure to high glucose in patients undergoing peritoneal dialysis. To elucidate the molecular mechanisms underlying this process, we conducted an integrated analysis of the transcriptome and chromatin accessibility profiles of human peritoneal mesothelial cells (HMrSV5) during high-glucose treatment. Our study identified 2775
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Sex-related differences in serum biomarker levels predict the activity and efficacy of immune checkpoint inhibitors in advanced melanoma and non-small cell lung cancer patients J. Transl. Med. (IF 7.4) Pub Date : 2024-03-05 Giulia Pasello, Aline S. C. Fabricio, Paola Del Bianco, Valentina Salizzato, Adolfo Favaretto, Luisa Piccin, Fable Zustovich, Alessio Fabozzi, Costanza De Rossi, Jacopo Pigozzo, Mattia De Nuzzo, Elia Cappelletto, Laura Bonanno, Dario Palleschi, Gian Luca De Salvo, Valentina Guarneri, Massimo Gion, Vanna Chiarion-Sileni
Immune Checkpoint Inhibitors (ICIs) lead to durable response and a significant increase in long-term survival in patients with advanced malignant melanoma (MM) and Non-Small Cell Lung Cancer (NSCLC). The identification of serum cytokines that can predict their activity and efficacy, and their sex interaction, could improve treatment personalization. In this prospective study, we enrolled immunotherapy-naïve
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Comparing anti-tumor and anti-self immunity in a patient with melanoma receiving immune checkpoint blockade J. Transl. Med. (IF 7.4) Pub Date : 2024-03-05 Shuming Chen, Tracee L. McMiller, Abha Soni, Farah Succaria, John-William Sidhom, Laura C. Cappelli, Livia A. Casciola-Rosen, Isaac R. Morales, Preethi Sankaran, Alan E. Berger, Julie Stein Deutsch, Qingfeng C. Zhu, Robert A. Anders, Jody E. Hooper, Drew M. Pardoll, Evan J. Lipson, Janis M. Taube, Suzanne L. Topalian
Tumor regression following immune checkpoint blockade (ICB) is often associated with immune-related adverse events (irAEs), marked by inflammation in non-cancerous tissues. This study was undertaken to investigate the functional relationship between anti-tumor and anti-self immunity, to facilitate irAE management while promoting anti-tumor immunity. Multiple biopsies from tumor and inflamed tissues
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MORN2 regulates the morphology and energy metabolism of mitochondria and is required for male fertility in mice J. Transl. Med. (IF 7.4) Pub Date : 2024-03-05 Yining Liu, Tongtong Li, Mingze Shi, Yanling Wan, Hanzhen Li, Mingyu Zhang, Ziqi Wang, Shiyu Wang, Yue Lv, Gang Lu, Hongbin Liu, Haobo Zhang, Tao Huang
Mitochondria produce adenosine triphosphate through respiratory activities to power sperm differentiation and motility, and decreased mitochondrial respiratory activity can result in poor sperm motility and asthenospermia. The mitochondrial sheath is a component of the mid-piece of the sperm flagellum, and dysfunction of the sheath can reduce sperm motility and cause male infertility. The membrane
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Spatial insights into immunotherapy response in non-small cell lung cancer (NSCLC) by multiplexed tissue imaging J. Transl. Med. (IF 7.4) Pub Date : 2024-03-04 James Monkman, Afshin Moradi, Joseph Yunis, Geoff Ivison, Aaron Mayer, Rahul Ladwa, Ken O’Byrne, Arutha Kulasinghe
The spatial localisation of immune cells within tumours are key to understand the intercellular communications that can dictate clinical outcomes. Here, we demonstrate an analysis pipeline for highly multiplexed CODEX data to phenotype and profile spatial features and interactions in NSCLC patients that subsequently received PD1 axis immunotherapy. We found that regulatory T cells (Tregs) are enriched
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Mitochondrial metabolism in neural stem cells and implications for neurodevelopmental and neurodegenerative diseases J. Transl. Med. (IF 7.4) Pub Date : 2024-03-04 C. Garone, F. De Giorgio, S. Carli
Mitochondria are cytoplasmic organelles having a fundamental role in the regulation of neural stem cell (NSC) fate during neural development and maintenance. During embryonic and adult neurogenesis, NSCs undergo a metabolic switch from glycolytic to oxidative phosphorylation with a rise in mitochondrial DNA (mtDNA) content, changes in mitochondria shape and size, and a physiological augmentation of
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The interaction between intratumoral bacteria and metabolic distortion in hepatocellular carcinoma J. Transl. Med. (IF 7.4) Pub Date : 2024-03-04 Chen Xue, Xinyu Gu, Qingmiao Shi, Xiao Ma, Junjun Jia, Yuanshuai Su, Zhengyi Bao, Juan Lu, Lanjuan Li
Intratumoral bacteria might play essential roles in tumorigenesis in different cancer types. However, its features and potential roles in hepatocellular carcinoma (HCC) are largely unknown. In this study, we assessed bacterial RNA by 16S rRNA fluorescence in situ hybridization and detected bacterial lipopolysaccharide (LPS) via immunohistochemistry. Hepa1-6 cells were used to establish orthotopic HCC
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Development and validation of a machine learning-based predictive model for assessing the 90-day prognostic outcome of patients with spontaneous intracerebral hemorrhage J. Transl. Med. (IF 7.4) Pub Date : 2024-03-04 Zhi Geng, Chaoyi Yang, Ziye Zhao, Yibing Yan, Tao Guo, Chaofan Liu, Aimei Wu, Xingqi Wu, Ling Wei, Yanghua Tian, Panpan Hu, Kai Wang
Spontaneous intracerebral hemorrhage (sICH) is associated with significant mortality and morbidity. Predicting the prognosis of patients with sICH remains an important issue, which significantly affects treatment decisions. Utilizing readily available clinical parameters to anticipate the unfavorable prognosis of sICH patients holds notable clinical significance. This study employs five machine learning
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Keratinocyte-derived circulating microRNAs in extracellular vesicles: a novel biomarker of psoriasis severity and potential therapeutic target J. Transl. Med. (IF 7.4) Pub Date : 2024-03-04 Young Joon Park, Dong Chan Kim, Soo-Jin Lee, Han Seul Kim, Ji Young Pak, Junho Kim, Jae Youn Cheong, Eun-So Lee
Psoriasis is a chronic inflammatory disorder characterized by pathogenic hyperproliferation of keratinocytes and immune dysregulation. Currently, objective evaluation tools reflecting the severity of psoriasis are insufficient. MicroRNAs in extracellular vesicles (EV miRNAs) have been shown to be potential biomarkers for various inflammatory diseases. Our objective was to investigate the possibility
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CRISPR/Cas9-edited ROS1 + non-small cell lung cancer cell lines highlight differential drug sensitivity in 2D vs 3D cultures while reflecting established resistance profiles J. Transl. Med. (IF 7.4) Pub Date : 2024-03-03 Marc Terrones, Christophe Deben, Felicia Rodrigues-Fortes, Anne Schepers, Ken Op de Beeck, Guy Van Camp, Geert Vandeweyer
The study of resistance-causing mutations in oncogene-driven tumors is fundamental to guide clinical decisions. Several point mutations affecting the ROS1 kinase domain have been identified in the clinical setting, but their impact requires further exploration, particularly in improved pre-clinical models. Given the scarcity of solid pre-clinical models to approach rare cancer subtypes like ROS1 + NSCLC
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CDSKNNXMBD: a novel clustering framework for large-scale single-cell data based on a stable graph structure J. Transl. Med. (IF 7.4) Pub Date : 2024-03-03 Jun Ren, Xuejing Lyu, Jintao Guo, Xiaodong Shi, Ying Zhou, Qiyuan Li
Accurate and efficient cell grouping is essential for analyzing single-cell transcriptome sequencing (scRNA-seq) data. However, the existing clustering techniques often struggle to provide timely and accurate cell type groupings when dealing with datasets with large-scale or imbalanced cell types. Therefore, there is a need for improved methods that can handle the increasing size of scRNA-seq datasets
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Validation of the Meet-URO score in metastatic clear cell renal cell carcinoma patients receiving second or third-line tyrosine kinase inhibitors-immune checkpoint inhibitors combination therapy J. Transl. Med. (IF 7.4) Pub Date : 2024-03-03 Sike He, Haoyang Liu, Junru Chen, Hao Zeng
In recent years, the combinations of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have become the standard treatments for metastatic renal cell carcinoma (mRCC) irrespective of the International Metastatic RCC Database Consortium (IMDC) prognostic groups [1]. Despite their overall efficacy, not all patients achieve satisfactory response and long-term survival benefits [2]