Clinical and Translational Medicine最新文献

{"title":"Harnessing the power of ionising radiation to enhance cancer immunotherapy","authors":"Kai Pang, Zhongtao Zhang","doi":"10.1002/ctm2.70307","DOIUrl":"https://doi.org/10.1002/ctm2.70307","url":null,"abstract":"<p>In resectable rectal cancer, pre-operative chemoradiation therapy (CRT) significantly increases the amount of tumour-infiltrated CD8<sup>+</sup> T cell.<span><sup>1</sup></span> And evidences from colorectal cancer mouse models suggest that the extent of CD8<sup>+</sup> T-cell infiltration is increased by tumour-localised ionising radiation alone, without effect of chemotherapeutic agents.<span><sup>2</sup></span> These are all concordant with current evidences and consensuses supporting the immune-stimulating effect of radiotherapy. On the other hand, the extent of CD8<sup>+</sup> T-cell infiltration is a primary metric to distinguish between cold tumours and hot ones. And CD8<sup>+</sup> T cell are also the primary effector of immune checkpoint inhibitor (ICI). Hence, from a theoretical standpoint, radiotherapy primes the micro-environment of rectal cancer and lays a foundation for the efficacy of ICI.</p><p>In real-world clinical context, results of our POLARSTAR trial do show that combining ICI with radiotherapy leads to enhanced tumour regression for resectable rectal cancer,<span><sup>3</sup></span> and similar evidences are also acquired by other teams for resectable non-small-cell lung cancer (NSCLC).<span><sup>4</sup></span> Moreover, long-term results from the PACIFIC trial demonstrated that adding ICI sequentially after radiotherapy substantially increases 5-year disease-free survival and 5-year overall survival for NSCLC,<span><sup>5</sup></span> also confirming the synergism between radiation and ICI. Although results from mouse models point out a pan-cancer nature of the synergistic effect,<span><sup>6</sup></span> but several randomised controlled trials (RCTs) from other tumour types beyond rectal cancer and NSCLC failed to display improved efficacy for combining radiotherapy with ICI, mostly due to irrational sequence (i.e., starting ICI treatment before radiotherapy) and heavy interference from chemotherapy (i.e., chemoradiation plan containing heavy chemo content, with strong chemotherapy inhibiting circulating lymphocytes), highlighting the importance of pre-investigation and comprehensiveness when designing an RCT.</p><p>The POLARSTAR trial is part of our endeavor to explore the synergy between clinical radiotherapy and ICI in mismatch-repair proficient (pMMR) solid tumours. It enrolled resectable (i.e., non-metastatic) rectal cancer patients and treated them with standard-of-care CRT before surgery for all three groups (two experiment groups and a control group). Additionally, PD1 blockade was added to CRT in the two experiment groups, with PD1 blockade starting at different time points relative to CRT.<span><sup>3</sup></span> The CRT was composed of 50 Gy X-ray volumetric modulated arc therapy given in 25 fractions, accompanied by light dosage of oral chemo drug. We chose this pre-operative treatment modality for the trial among all modalities of rectal cancer for the fact that it is composed primarily of radiotherapy a","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 4","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865975","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}

{"title":"Ad-E6/7-HR vaccine improves the prophylactic and therapeutic efficacy in HPV-associated cancers","authors":"Yu Zhang,&nbsp;Ke Qiu,&nbsp;Jiayuan Ai,&nbsp;Maosen Xu,&nbsp;Binhan Wang,&nbsp;Aqu Alu,&nbsp;Chunjun Ye,&nbsp;Xiya Huang,&nbsp;Yu Zhang,&nbsp;Yingqiong Zhou,&nbsp;Zhiruo Song,&nbsp;Jie Shi,&nbsp;Yishan Lu,&nbsp;Yuquan Wei,&nbsp;Jianjun Ren,&nbsp;Yu Zhao,&nbsp;Ping Cheng,&nbsp;Xiawei Wei","doi":"10.1002/ctm2.70305","DOIUrl":"https://doi.org/10.1002/ctm2.70305","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>High-risk human papillomavirus (HPV), especially HPV16, is closely correlated with certain cancers. E6 and E7 proteins of HPV16 play critical roles in oncogenesis, making them optimal targets for treating HPV-associated cancers. Here, we engineered an innovative vaccine, Ad-E6/7-HR, designed to evoke immune responses through the incorporation of self-assembling heptad-repeat 1 (HR1) and HR2 originated from Severe acute respiratory syndrome coronavirus 2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Ad-E6/7-HR was constructed utilising a replication-defective human adenovirus serotype 5 vector and evaluated its immunogenicity and therapeutic efficacy in murine models. We verified the antitumour efficacy of the vaccine in TC-1 subcutaneous and pulmonary models. Flow cytometry, enzyme-linked immunospot assay, and immunofluorescence staining were used to assess the cellular immunogenicity of Ad-E6/7-HR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ad-E6/7-HR induced robust immune responses, significantly increasing antigen-specific CD8⁺ T cells. The vaccine also enhanced memory T-cell generation and induced potent cytokine secretion, as exemplified by interferon-γ and tumour necrosis factor-α. Ad-E6/7-HR conferred complete protection against tumour growth in the prophylactic model. In therapeutic settings, Ad-E6/7-HR significantly reduced tumour size and improved survival. Furthermore, Ad-E6/7-HR reshaped the tumour microenvironment by increased CD8⁺ T-cell recruitment and reduced immunosuppressive cells, like myeloid-derived suppressor cells and M2 macrophages, thereby enhancing antitumour immunity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>By targeting HPV16 E6 and E7 proteins and leveraging the self-assembling HR1 and HR2 sequences to enhance immune responses, Ad-E6/7-HR represented a promising candidate for preventing and treating HPV-associated cancers. Further clinical investigation is warranted to evaluate its potential in human trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 4","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70305","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865551","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}

{"title":"Response-adapted zanubrutinib and tislelizumab as a potential strategy to enhance CD19 CAR T-cell therapy in relapsed/refractory large B-cell lymphoma: A retrospective observational study","authors":"Rong Shen,&nbsp;Wei-Guo Cao,&nbsp;Li Wang,&nbsp;Ling-Shuang Sheng,&nbsp;Yi-Lun Zhang,&nbsp;Wen Wu,&nbsp;Peng-Peng Xu,&nbsp;Shu Cheng,&nbsp;Meng-Ke Liu,&nbsp;Yan Dong,&nbsp;Yue Wang,&nbsp;Xiang-Qin Weng,&nbsp;Xu-Feng Jiang,&nbsp;Qi Song,&nbsp;Hong-Mei Yi,&nbsp;Lei Li,&nbsp;Sheng Chen,&nbsp;Zi-Xun Yan,&nbsp;Wei-Li Zhao","doi":"10.1002/ctm2.70310","DOIUrl":"https://doi.org/10.1002/ctm2.70310","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;CD19 chimeric antigen receptor (CAR) T-cell therapy is a potential treatment for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). The combination of targeted therapeutic strategies, particularly bruton tyrosine kinase inhibitor zanubrutinib and programmed death-1 inhibitor tislelizumab, may improve clinical outcomes and modulate the tumour microenvironment (TME).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We studied patients with R/R LBCL who received response-adapted zanubrutinib plus tislelizumab upon CD19 CAR T-cell therapy between June 2021 and March 2023. Patients were treated with zanubrutinib daily from leukapheresis to day 28 post-infusion; those achieving complete response continued zanubrutinib monotherapy for 3 months, while partial responders received combined zanubrutinib for 3 months and tislelizumab for up to 2 years. We evaluated the overall response rate (ORR), complete response rate (CRR), progression-free survival (PFS), overall survival (OS), and safety. DNA sequencing and RNA sequencing were performed on available tumour samples to analyse genetic aberrations and TME characteristics.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A total of 54 patients with LBCL were included, with a median follow-up of 23.6 months. The ORR at day 28, month 3, and month 6 were 94% (CRR 66%), 87% (CRR 80%), and 80% (CRR 76%), respectively. The 2-year PFS and 2-year OS rates were 68% and 76%, respectively. Median PFS and median OS were not reached. Grade ≥ 3 cytokine release syndrome occurred in 9% of patients, with no grade ≥ 3 neurotoxicity observed. Genomic and transcriptomic data indicated that this regimen was effective across genetic subtypes and abrogated T-cell exhaustion within the TME. However, tumour-infiltrating M2 macrophages with dysregulated lipid metabolism were associated with poor clinical outcome.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Response-adapted zanubrutinib and tislelizumab potentially enhances the efficacy of CAR T-cell therapy with a favourable safety profile in R/R LBCL, effectively counteracting T-cell exhaustion. Future studies should focus on targeting M2 macrophages by reprogramming lipid metabolism to further attenuate the immunosuppressive TME.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;\u0000 &lt;p&gt;Response-adapted zanubrutinib plus tislelizumab potentially e","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 4","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70310","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865976","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}

{"title":"Skeletal muscle effects of antisense oligonucleotides targeting glycogen synthase 1 in a mouse model of Pompe disease","authors":"Lan Weiss,&nbsp;Michele Carrer,&nbsp;Alyaa Shmara,&nbsp;Angela Martin,&nbsp;Hong Yin,&nbsp;Pallabi Pal,&nbsp;Cheng Cheng,&nbsp;Lac Ta,&nbsp;Victoria Boock,&nbsp;Yasamin Fazeli,&nbsp;Mindy Chang,&nbsp;Marvin Paguio,&nbsp;Jonathan Lee,&nbsp;Howard Yu,&nbsp;John Weiss,&nbsp;Tamar R Grossman,&nbsp;Nina Raben,&nbsp;Paymaan Jafar-Nejad,&nbsp;Virginia Kimonis","doi":"10.1002/ctm2.70314","DOIUrl":"https://doi.org/10.1002/ctm2.70314","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Pompe disease (PD) is a progressive myopathy caused by the aberrant accumulation of glycogen in skeletal and cardiac muscle resulting from the deficiency of the enzyme acid alpha-glucosidase (GAA). Administration of recombinant human GAA as enzyme replacement therapy (ERT) works well in alleviating the cardiac manifestations of PD but loses sustained benefit in ameliorating the skeletal muscle pathology. The limited efficacy of ERT in skeletal muscle is partially attributable to its inability to curb the accumulation of new glycogen produced by the muscle enzyme glycogen synthase 1 (GYS1). Substrate reduction therapies aimed at knocking down GYS1 expression represent a promising avenue to improve Pompe myopathy. However, finding specific inhibitors for GYS1 is challenging given the presence of the highly homologous GYS2 in the liver. Antisense oligonucleotides (ASOs) are chemically modified oligomers that hybridise to their complementary target RNA to induce their degradation with exquisite specificity. In the present study, we show that ASO-mediated <i>Gys1</i> knockdown in the <i>Gaa^−/−</i> mouse model of PD led to a robust reduction in glycogen accumulation in skeletal muscle. In addition, combining <i>Gys1</i> ASO with ERT slightly further reduced glycogen content in muscle, eliminated autophagic buildup and lysosomal dysfunction, and improved motor function in <i>Gaa^−/−</i> mice. Our results provide a strong foundation for validation of the use of <i>Gys1</i> ASO, alone or in combination with ERT, as a therapy for PD. We propose that early administration of <i>Gys1</i> ASO in combination with ERT may be the key to preventative treatment options in PD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key points</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>\u0000 <p>Antisense oligonucleotide (ASO) treatment in a mouse model of Pompe disease achieves robust knockdown of glycogen synthase (GYS1).</p>\u0000 </li>\u0000 \u0000 <li>\u0000 <p>ASO treatment reduces glycogen content in skeletal muscle.</p>\u0000 </li>\u0000 \u0000 <li>\u0000 <p>Combination of ASO and enzyme replacement therapy (ERT) further improves motor performance compared to ASO alone in a mouse model of Pompe disease.</p>\u0000 </li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 4","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70314","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865550","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}

{"title":"Angiogenesis and targeted therapy in the tumour microenvironment: From basic to clinical practice","authors":"Shuaixi Yang,&nbsp;Yingshuai Fang,&nbsp;Yangcheng Ma,&nbsp;Fuqi Wang,&nbsp;Yuhang Wang,&nbsp;Jiachi Jia,&nbsp;Yabing Yang,&nbsp;Weipeng Sun,&nbsp;Quanbo Zhou,&nbsp;Zhen Li","doi":"10.1002/ctm2.70313","DOIUrl":"https://doi.org/10.1002/ctm2.70313","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Angiogenesis, as a core marker of cancer survival and growth, is integral to the processes of tumour growth, invasion and metastasis. In recent years, targeted angiogenesis treatment strategies have gradually become an important direction in cancer treatment. Single-cell sequencing technology can provide new insights into targeted angiogenesis by providing a deeper understanding of the heterogeneity of tumour endothelial cells and exploring the interactions between endothelial cells and surrounding cells in the tumour microenvironment. Here, we systematically review the research progress in endothelial cell pathophysiology and its endothelial‒mesenchymal transition and illustrate the heterogeneity of endothelial cells from a single-cell perspective. Finally, we examine the contributions of different cell types within the tumour microenvironment in relation to tumour angiogenesis, as well as the latest progress and strategies in targeted angiogenesis therapy, hoping to provide useful insights into the clinical application of antiangiogenic treatment. Furthermore, a summary of the present progress in the development of potential angiogenesis inhibitors and the ongoing clinical trials for combination therapies is provided.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key points</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Angiogenesis plays a key role in tumour progression, invasion and metastasis, so strategies targeting angiogenesis are gradually becoming an important direction in cancer therapy.</li>\u0000 \u0000 <li>Interactions between endothelial cells and stromal cells and immune cells in the tumour microenvironment are significant in angiogenesis.</li>\u0000 \u0000 <li>The application of antiangiogenic immunotherapy and nanotechnology in antiangiogenic therapy provides a vital strategy for prolonging the survival of cancer patients.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 4","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70313","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865549","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}

{"title":"EEPD1 regulates inflammation and endothelial apoptosis in atherosclerosis through KLF4-EEPD1-ERK axis","authors":"Kaiwen Yu,&nbsp;Xiang Li,&nbsp;Xin Shi,&nbsp;Ruogu Li,&nbsp;Min Zhang","doi":"10.1002/ctm2.70311","DOIUrl":"https://doi.org/10.1002/ctm2.70311","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inflammation and endothelial apoptosis are implicated in the advancement of atherosclerosis. EEPD1 holds a pivotal position in the repair of DNA damage and contributes to the progression of multiple cancers. However, the role of <i>EEPD1</i> in cardiovascular diseases needs to be explored further, especially in atherosclerosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We constructed <i>EEPD1</i> and ApoE (apolipoprotein E)-deficient mice to assess how EEPD1 influences endothelial inflammation and apoptosis within atherosclerotic plaques. High-throughput RNA sequencing of human aortic endothelial cell groups treated with siCon+TNFα and si<i>EEPD1</i>+TNFα identified notable disparities in the MAPK pathway between groups. Chromatin immunoprecipitation and luciferase reporter assay confirmed that KLF4 directly regulates EEPD1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Further examination of gene expression data revealed elevated EEPD1 concentrations in atherosclerotic plaques of patients, which findings were corroborated in the aortas of ApoE^−/− mice. Present study demonstrated that adhesion molecule expression, endothelial apoptosis, aortic root plaques and macrophage accumulation were markedly ameliorated in <i>EEPD1</i>^−/−<i>ApoE</i>^−/− mice compared to WT <i>ApoE</i>^−/− mice. Functional analysis revealed that increase in <i>EEPD1</i> promotes <i>ERK</i> phosphorylation and significantly increases endothelial apoptosis and inflammation in atherosclerosis, which was abrogated by inhibition of <i>ERK</i> phosphorylation. We found <i>KLF4</i> to be the transcription repressor of <i>EEPD1</i> through luciferase assay and chromatin immunoprecipitation, and <i>KLF4</i> inhibition abrogated the amelioration of endothelial apoptosis and inflammation caused by <i>EEPD1</i> deletion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Collectively, this study revealed that EEPD1 deletion can lead to amelioration of atherosclerosis through the KLF4-EEPD1-ERK axis. Hence, targeting EEPD1 could be a promising therapeutic strategy for patients with atherosclerosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 4","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865593","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}

{"title":"Clinical marine biomedicine: An emerging area in clinical and translational medicine","authors":"Xiaojun Yan,&nbsp;Wanxin Duan,&nbsp;Xiangdong Wang","doi":"10.1002/ctm2.70303","DOIUrl":"https://doi.org/10.1002/ctm2.70303","url":null,"abstract":"<p>Marine biomedicine is an important field in oceanology and bio-ecosystem and has evolved significantly alongside advances in biotechnology and growing understanding of marine life. In this perspective, we propose a refined concept of clinical marine biomedicine, with a clear mission to establish an emerging discipline that bridges marine biomedicine and clinical practice. The exploration of marine-origin sources should be emphasised, with a strong focus on the identification, validation and development of human disease-specific diagnostics and target-oriented pharmaceutics. The perspective headlines some of critical components, including marine-oriented human evolution and development, humanised marine-based models, biomarker innovation and validation, marine microbiomes and metabolites, and target nutrition and therapy. We envision that clinical marine biomedicine will become a crucial pillar clinical molecular medicine, contributing to the improvement of human health and the prognosis of patient.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 4","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70303","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853031","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}

{"title":"MS-based multi-dimensional metabolomics reveals protective effect of Polygalae Radix against metabolic disturbances in Alzheimer's disease mice","authors":"Yanwen Chen,&nbsp;Lisha Zhao,&nbsp;Shuo Cai,&nbsp;Yuchen Zou,&nbsp;Weiwei Tang,&nbsp;Bin Li","doi":"10.1002/ctm2.70292","DOIUrl":"https://doi.org/10.1002/ctm2.70292","url":null,"abstract":"&lt;p&gt;Dear Editor&lt;/p&gt;&lt;p&gt;The system-wide metabolic dysregulation is a central hallmark of Alzheimer's disease (AD).&lt;span&gt;&lt;sup&gt;1-3&lt;/sup&gt;&lt;/span&gt; Growing evidence indicated that Polygalae Radix (PR) has ameliorative effects on memory deficits of AD.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; However, the anti-AD effect of PR extract (PRE) via regulating metabolic disturbance is seldom investigated from the perspective of a system-wide level. In this study, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI–MSI)-based spatial metabolomics and liquid chromatography-mass spectrometry (LC–MS)-based metabolomics were applied to explore the anti-AD effect of PRE via improving the system-wide metabolic disorders in APPswe/PSEN1dE9 (APP/PS1) double transgenic AD model mice.&lt;/p&gt;&lt;p&gt;The chemical composition of PRE was first characterised by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) (Figure S1 and Table S1). The results of behavioural and pharmacological experiments indicated that PRE treatment remarkably ameliorated the impairment of learning and memory in AD model mice, and significantly reduced the levels of amyloid-β (Aβ) plaques (Figure S2) and Aβ&lt;sub&gt;1–42&lt;/sub&gt; monomers, and increased the levels of acetylcholine and brain-derived neurotrophic factor in the cerebral cortex (Ccx) and hippocampus (Hp) of AD mice (Figure S3) (see the Supporting Information for details). Subsequently, MALDI–MSI was utilised to investigate the ameliorative effect of PRE against regional metabolic disturbances in AD mouse brains. Principal component analysis (PCA) and partial least squares discrimination analysis (PLS-DA) showed that the metabolic profiles in Ccx, Hp, corpus callosum (Cc), thalamus (Th) and hypothalamus (Hth) of PRE-treated mice were remarkably distinguished from AD, indicating that notable spatial metabolic disturbances could be changed by PRE (Figures 1A and S4). Tissue-specific differential metabolites between PRE-treated and AD model mice were identified in five brain regions. In Ccx, 59 differential metabolites were observed, and the levels of 27 out of 59 returned to control (CON) after PRE treatments (Figure 1B-1C and Table S2). The spatial distribution and level changes of representative metabolites in CCx before and after PRE treatment are shown in Figure 1C. Similarly, a total of 75, 59, 56 and 53 differential metabolites between the PRE-treated and AD model groups were identified in Hp, Th, Hth and Cc regions, respectively (Figure S5 and Tables S3–S6). Among them, the levels of 39 differential metabolites in Hp, 23 in Th, 23 in Hth and 19 in Cc had been reversed after PRE treatments (Figures S6 and S7). Therefore, MALDI–MSI results revealed that PRE treatment could regulate the drastic brain metabolic disturbances with a critical spatial metabolic heterogeneity (Figure 1D). According to KEGG reference pathways, PRE treatment regulated the imbalance of multiple metabolism pathways at different levels in five b","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 4","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70292","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836030","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}

{"title":"Fruquintinib as first-line or second-line treatment in unresectable or metastatic soft-tissue sarcoma: A prospective, single-arm phase II study","authors":"Xiaowei Zhang,&nbsp;Ting Zhao,&nbsp;Biqiang Zheng,&nbsp;Wangjun Yan,&nbsp;Yong Chen,&nbsp;Yu Xu,&nbsp;Chunmeng Wang,&nbsp;Junhua Zhang,&nbsp;Jian Wang,&nbsp;Lin Yu,&nbsp;Xin Liu,&nbsp;Zhiguo Luo","doi":"10.1002/ctm2.70308","DOIUrl":"https://doi.org/10.1002/ctm2.70308","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;We conducted the first prospective, single-arm phase II study and confirmed that fruquintinib is an effective and well-tolerated chemo-free regimen for the first-line or second-line therapy of patients with unresectable or metastatic soft-tissue sarcoma (STS), particularly for those with the histopathologic subtype of angiosarcoma (AS).&lt;/p&gt;&lt;p&gt;STS are rare tumours that comprise over 50 distinct histologic subtypes, accounting for 1% of all adult malignancies.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; For individuals with unresectable or metastatic STS, the median overall survival (OS) varies between 12 and 16 months, while the 5-year OS rate is 60%–80%.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Over the past decade, anti-angiogenic therapy has been utilised to treat advanced STS.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Pazopanib was the first tyrosine kinase inhibitor approved for advanced STS,&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; followed by regorafenib and anlotinib, both of which have shown excellent performance in the treatment of advanced STS.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Fruquintinib, a multi-target inhibitor of VEGF receptors 1, 2 and 3, has shown overall response rate (ORR) of 13.1% and 17.7% in two retrospective studies&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; underscoring its promise as a chemo-free treatment for advanced STS. However, due to the inherent limitations of retrospective studies, further investigation is necessary to assess the efficacy and safety of fruquintinib in unresectable or metastatic STS.&lt;/p&gt;&lt;p&gt;In our study, a total of 31 individuals were evaluated for eligibility and assigned to receive fruquintinib monotherapy (Figure 1A). Details of the study design and statistical analysis are described in Supporting Information. All patients were aged between 19 and 78 years. Among them, there were 15 (48.4%) males and 16 (51.6%) females. In the total population, 22 (71.0%) participants had distant metastases at first diagnosis, while another nine (29.0%) were categorised as unresectable STS without metastases. Among the 22 metastatic STSs, 15 (68.2%) had metastatic lesions in two or more organs. The most common primary lesions were trunk and extremity (36.7%), followed by lung (20.0%), brain (16.7%), head (13.3%), spleen (10.0%) and breast (3.3%). During metastasis, most cases spread to lungs (63.6%), followed by other sites including bones (50.0%), lymph nodes (36.4%), liver (27.3%), pleura (13.6%) and muscle (9.1%). Of them, 18 (58.1%) underwent prior surgery, 12 (38.7%) received prior first-line therapy and four (12.9%) received prior radiotherapy (Table S1).&lt;/p&gt;&lt;p&gt;As of the data cutoff on 26 November 2024, patients received between 1 and 35 treatment cycles, with a median of eight cycles. The median follow-up duration was 19.2 months (95% confidence interval [CI]: 16.3‒34.0). Among them, 18 patients (58.1%) experienced progression-free survival (PFS) events, and 12 patients (38.7%) died. ORR was 25.8% (95% CI: 10.4‒41.2), and the disease control rate (DCR) was 90.3% (95% ","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 4","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70308","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836029","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}

{"title":"An important step to translate single-cell measurement into clinical practice: Stereoscopic cells","authors":"Xiangdong Wang,&nbsp;Wanxin Duan,&nbsp;Xuanqi Liu,&nbsp;Jia Fan","doi":"10.1002/ctm2.70304","DOIUrl":"https://doi.org/10.1002/ctm2.70304","url":null,"abstract":"&lt;p&gt;Clinical single-cell measurements are gaining increasing attention of clinicians and researchers to conventional parameters in clinical biochemistry of haematology. However, significant challenges need to be overcome before these technologies can be fully integrated into clinical practice.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; With the rapid development of biotechnology and methodology, single-cell multi-omics and trans-omics analyses have become increasingly feasible, stable and reproducible. The comprehensive profiles generated at the single-cell level provide novel insights into molecular phenomes, functional states, microenvironmental configurations, disease mechanisms and potential therapeutic targets. This emerging field—termed &lt;i&gt;clinical single-cell biomedicine&lt;/i&gt;—is opening new frontiers in precision medicine.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; In particular, spatial transcriptome furthermore enables the spatiotemporal cellular and molecular mapping, which brings the development of functional histopathology, by defining the precise locations and interactions of target cells, and integrating clinical image phenomes.&lt;span&gt;&lt;sup&gt;3, 4&lt;/sup&gt;&lt;/span&gt; A spatial enhanced resolution omics-sequencing, Stereo-Seq (Figure 1B), utilises DNA nanoball-patterned arrays for high-resolution in situ RNA capture to demonstrate tissue/organ spatiotemporal transcriptomes at a single-cell level.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; This technology enables multi-dimensional, single-cell–level visualisation of transcriptomic data across tissues and organs. By integrating continuous transcriptomic images, stereoscopic molecular maps of cells can be reconstructed, providing detailed insights into cellular heterogeneity, lineage trajectories and functional states.&lt;span&gt;&lt;sup&gt;5, 6&lt;/sup&gt;&lt;/span&gt; Such stereoscopic and temporal resolution of transcriptomics enables the identification of spatiotemporal variations, classifications, architectonics and functional communications of cells, all of which can be translated into clinical strategies. The application of single-cell multi-omics, combined with multi-dimensional genomic data, to human pathology has been proposed as a transformative milestone in stereoscopic diagnosis and therapeutic strategies.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Stereo-Cell is a breakthrough spatially enhanced-resolution single-cell sequencing technology utilising high-density DNA nanoball-patterned arrays (Figure 1A). It enables the capture of intact individual cells or microstructures, and facilitates the profiling of stereoscopic, spatiotemporal multi-omics at true single-cell resolution.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; Unlike Stereo-Seq (Figure 1B), Stereo-Cell is designed to acquire stereoscopic multi-omic information from entire, structurally preserved cells, including complete morphological characteristics, surface protein profiles and intracellular molecular landscapes (Figure 1A). In contrast to conventional instrument-based cell separation methods, the DNA nanoball-oriented chips used ","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 4","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70304","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827027","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}