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Immune-mediated colitis after immune checkpoint inhibitor therapy. 免疫检查点抑制剂治疗后的免疫介导结肠炎。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-29 DOI: 10.1016/j.molmed.2024.09.009
Sophie Giesler, Roxane Riemer, Theresa Lowinus, Robert Zeiser
{"title":"Immune-mediated colitis after immune checkpoint inhibitor therapy.","authors":"Sophie Giesler, Roxane Riemer, Theresa Lowinus, Robert Zeiser","doi":"10.1016/j.molmed.2024.09.009","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.09.009","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have led to improved outcome in patients with various types of cancer. Due to inhibition of physiological anti-inflammatory mechanisms, patients treated with ICIs may develop autoimmune inflammation of the colon, associated with morbidity, decreased quality of life (QoL), and mortality. In this review, we summarize clinical and pathophysiological aspects of immune-mediated colitis (ImC), highlighting novel treatment options. In the colon, ICIs trigger resident and circulating T cell activation and infiltration of myeloid cells. In addition, the gut microbiota critically contribute to intestinal immune dysregulation and loss of barrier function, thereby propagating local and systemic inflammation. Currently available therapies for ImC include corticosteroids, antitumor necrosis factor-α (TNF-α)- and anti-integrin α<sub>4</sub>β<sub>7</sub> antibodies. Given that systemic immunosuppression might impair antitumor immune responses, novel therapeutic approaches are urgently needed.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clonal hematopoiesis of indeterminate potential: the root cause of, and fertile ground for, hematological malignancies. 具有不确定潜能的克隆造血：血液恶性肿瘤的根源和沃土。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-25 DOI: 10.1016/j.molmed.2024.10.005
Qiqi Zhuang, Shengjie Jin, Wei Wang, Yan Wang, Hongyan Tong, Zuyun Liu, Jie Sun
{"title":"Clonal hematopoiesis of indeterminate potential: the root cause of, and fertile ground for, hematological malignancies.","authors":"Qiqi Zhuang, Shengjie Jin, Wei Wang, Yan Wang, Hongyan Tong, Zuyun Liu, Jie Sun","doi":"10.1016/j.molmed.2024.10.005","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.10.005","url":null,"abstract":"<p><p>Clonal hematopoiesis (CH) of indeterminate potential (CHIP), characterized by propagation of blood cell clones carrying somatic mutations in specific driver genes, is increasingly recognized as a critical factor in the development of hematological malignancies. This phenomenon, which often emerges with age, underscores the complex interplay between genetic predisposition and environmental influences in cancer initiation and progression. Recent years have witnessed significant advances in our understanding of the link between CHIP and hematological diseases. In this review, we provide a comprehensive overview of the features of CHIP and explore its role in promoting tumorigenesis and influencing treatment outcomes for blood cancers. Finally, we summarize current available tools for risk stratification and discuss management strategies for patients with CHIP.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in Hodgkin lymphoma research. 霍奇金淋巴瘤研究进展。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-22 DOI: 10.1016/j.molmed.2024.10.004
Ralf Küppers
{"title":"Advances in Hodgkin lymphoma research.","authors":"Ralf Küppers","doi":"10.1016/j.molmed.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.10.004","url":null,"abstract":"<p><p>Hodgkin lymphoma (HL) has been and still is the most enigmatic lymphoid malignancy in humans. Since the first molecular analysis of isolated Hodgkin and Reed-Sternberg (HRS) tumor cells of classic HL 30 years ago, substantial advances in our understanding of HL have been made. This review describes the cellular origin of HL, summarizes the current knowledge about the genetic lesions in HRS cells, and highlights the role of Epstein-Barr virus (EBV) in HL pathogenesis. Moreover, the pathobiological roles of altered gene expression and deregulated signaling pathways are discussed and key aspects of the HL microenvironment are presented.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting monoamine oxidases in cancer: advances and opportunities. 以癌症中的单胺氧化酶为靶点：进展与机遇。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-21 DOI: 10.1016/j.molmed.2024.09.010
Jing Wei, Boyang Jason Wu
{"title":"Targeting monoamine oxidases in cancer: advances and opportunities.","authors":"Jing Wei, Boyang Jason Wu","doi":"10.1016/j.molmed.2024.09.010","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.09.010","url":null,"abstract":"<p><p>Monoamine oxidases (MAOs) are a crucial pair of isoenzymes responsible for degrading monoamine neurotransmitters and dietary amines. In addition to extensive studies of their roles in the context of brain functions and disorders over decades, emerging evidence indicates that MAOs are also often dysregulated and associated with clinical outcomes in diverse cancers, with the ability to differentially regulate cancer growth, invasion, metastasis, progression, and therapy response depending on the cancer type. In this review, we summarize recent advances in understanding the clinical relevance, functional importance, and mechanisms of MAOs in a broad range of cancers, and discuss the application and therapeutic benefit of MAO inhibitors (MAOIs) for cancer treatment, highlighting the roles of MAOs as novel regulators, prognostic biomarkers, and therapeutic targets in cancer.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Assessment of the therapeutic potential of salubrinal for ME/CFS and long-COVID. 评估柳氮磺吡啶对 ME/CFS 和长期 COVID 的治疗潜力。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-21 DOI: 10.1016/j.molmed.2024.10.001
Aseel Warrayat, Ayah Ali, Joulin Waked, Darcy Tocci, Robert C Speth
{"title":"Assessment of the therapeutic potential of salubrinal for ME/CFS and long-COVID.","authors":"Aseel Warrayat, Ayah Ali, Joulin Waked, Darcy Tocci, Robert C Speth","doi":"10.1016/j.molmed.2024.10.001","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.10.001","url":null,"abstract":"<p><p>Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating condition with no cure that shares commonality with long-COVID. This review examines current understanding of long-COVID symptoms, characteristics of the affected population, the connection with ME/CFS, and the potential for salubrinal, an agent known for its influence on cellular stress pathways, to mitigate these disorders It also describes the historical development and mechanism of action of salubrinal, to mitigate endoplasmic reticulum (ER)/cellular stress responses, that could potentially contribute to symptom improvement in both ME/CFS and long-COVID patients. Further research and clinical trials are warranted to advance our understanding of the potential role of salubrinal in improving the quality of life for individuals with long-COVID-related ME/CFS symptoms as well as ME/CFS patients.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bone-brain crosstalk in osteoarthritis: pathophysiology and interventions. 骨关节炎中的骨脑串扰：病理生理学和干预措施。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-21 DOI: 10.1016/j.molmed.2024.09.006
Yilan Tang, Zhiyan Wang, Jin Cao, Yiheng Tu
{"title":"Bone-brain crosstalk in osteoarthritis: pathophysiology and interventions.","authors":"Yilan Tang, Zhiyan Wang, Jin Cao, Yiheng Tu","doi":"10.1016/j.molmed.2024.09.006","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.09.006","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a prevalent articular disorder characterized by joint degeneration and persistent pain; it imposes a significant burden on both individuals and society. While OA has traditionally been viewed as a localized peripheral disorder, recent preclinical and clinical studies have revealed the crucial interconnections between the bone and the brain, highlighting the systemic nature of OA. The neuronal pathway, molecular signaling, circadian rhythms, and genetic underpinnings within the bone-brain axis play vital roles in the complex interplay that contributes to OA initiation and progression. This review explores emerging evidence of the crosstalk between the bone and brain in OA progression, and discusses the potential contributions of the bone-brain axis to the development of effective interventions for managing OA.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular evolution of central nervous system metastasis and therapeutic implications. 中枢神经系统转移的分子演化及治疗意义。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-17 DOI: 10.1016/j.molmed.2024.09.008
David Gritsch, Priscilla K Brastianos
{"title":"Molecular evolution of central nervous system metastasis and therapeutic implications.","authors":"David Gritsch, Priscilla K Brastianos","doi":"10.1016/j.molmed.2024.09.008","DOIUrl":"10.1016/j.molmed.2024.09.008","url":null,"abstract":"<p><p>The increasing prevalence and poor prognosis of central nervous system (CNS) metastases pose a significant challenge in oncology, necessitating improved therapeutic strategies. Recent research has shed light on the complex genomic landscape of brain metastases, identifying unique and potentially actionable genetic alterations. These insights offer new avenues for targeted therapy, highlighting the potential of precision medicine approaches in treating CNS metastases. However, translating these discoveries into clinical practice requires overcoming challenges such as availability of tissue for characterization, access to molecular testing, drug delivery across the blood-brain barrier (BBB) and addressing intra- and intertumoral genetic heterogeneity. This review explores novel insights into the evolution of CNS metastases, the molecular mechanisms underlying their development, and implications for therapeutic interventions.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pig models for translational Duchenne muscular dystrophy research. 用于杜兴氏肌肉萎缩症转化研究的猪模型。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-01 Epub Date: 2024-05-14 DOI: 10.1016/j.molmed.2024.04.013
Michael Stirm, Nikolai Klymiuk, Hiroshi Nagashima, Christian Kupatt, Eckhard Wolf
{"title":"Pig models for translational Duchenne muscular dystrophy research.","authors":"Michael Stirm, Nikolai Klymiuk, Hiroshi Nagashima, Christian Kupatt, Eckhard Wolf","doi":"10.1016/j.molmed.2024.04.013","DOIUrl":"10.1016/j.molmed.2024.04.013","url":null,"abstract":"<p><p>Duchenne muscular dystrophy (DMD) is caused by mutations in the X-linked DMD gene, resulting in the absence of dystrophin, progressive muscle degeneration, and heart failure. Genetically tailored pig models resembling human DMD mutations recapitulate the biochemical, clinical, and pathological hallmarks of DMD with an accelerated disease progression compared to human patients. DMD pigs have been used to evaluate therapeutic concepts such as gene editing to reframe a disrupted DMD reading frame or the delivery of artificial chromosome vectors carrying the complete DMD gene. Moreover, DMD pigs have been instrumental in validating new diagnostic modalities such as multispectral optoacoustic tomography (MSOT) for non-invasive monitoring of disease progression. DMD pigs may thus help to bridge the gap between proof-of-concept studies in cellular or rodent models and clinical studies in patients.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"950-964"},"PeriodicalIF":12.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Does glial lipid dysregulation alter sleep in Alzheimer's and Parkinson's disease? 神经胶质脂质失调会改变阿尔茨海默氏症和帕金森氏症患者的睡眠吗？
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-01 Epub Date: 2024-05-15 DOI: 10.1016/j.molmed.2024.04.010
Lindsey D Goodman, Matthew J Moulton, Guang Lin, Hugo J Bellen
{"title":"Does glial lipid dysregulation alter sleep in Alzheimer's and Parkinson's disease?","authors":"Lindsey D Goodman, Matthew J Moulton, Guang Lin, Hugo J Bellen","doi":"10.1016/j.molmed.2024.04.010","DOIUrl":"10.1016/j.molmed.2024.04.010","url":null,"abstract":"<p><p>In this opinion article, we discuss potential connections between sleep disturbances observed in Alzheimer's disease (AD) and Parkinson's disease (PD) and the dysregulation of lipids in the brain. Research using Drosophila has highlighted the role of glial-mediated lipid metabolism in sleep and diurnal rhythms. Relevant to AD, the formation of lipid droplets in glia, which occurs in response to elevated neuronal reactive oxygen species (ROS), is required for sleep. In disease models, this process is disrupted, arguing a connection to sleep dysregulation. Relevant to PD, the degradation of neuronally synthesized glucosylceramides by glia requires glucocerebrosidase (GBA, a PD-associated risk factor) and this regulates sleep. Loss of GBA in glia causes an accumulation of glucosylceramides and neurodegeneration. Overall, research primarily using Drosophila has highlighted how dysregulation of glial lipid metabolism may underlie sleep disturbances in neurodegenerative diseases.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"913-923"},"PeriodicalIF":12.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
LRRK2 in Parkinson's disease: upstream regulation and therapeutic targeting. 帕金森病中的 LRRK2：上游调控和靶向治疗。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-01 Epub Date: 2024-08-16 DOI: 10.1016/j.molmed.2024.07.003
Yulan Xiong, Jianzhong Yu
{"title":"LRRK2 in Parkinson's disease: upstream regulation and therapeutic targeting.","authors":"Yulan Xiong, Jianzhong Yu","doi":"10.1016/j.molmed.2024.07.003","DOIUrl":"10.1016/j.molmed.2024.07.003","url":null,"abstract":"<p><p>Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common causes of Parkinson's disease (PD) to date. Dysfunction in LRRK2 enzymatic activities and elevated protein levels are associated with the disease. How is LRRK2 activated, and what downstream molecular and cellular processes does LRRK2 regulate? Addressing these questions is crucial to decipher the disease mechanisms. In this review we focus on the upstream regulations and briefly discuss downstream substrates of LRRK2 as well as the cellular consequences caused by these regulations. Building on these basic findings, we discuss therapeutic strategies targeting LRRK2 and highlight the challenges in clinical trials. We further highlight the important questions that remains to be answered in the LRRK2 field.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"982-996"},"PeriodicalIF":12.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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