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Apigenin inhibits recurrent bladder cancer progression by targeting VEGF-β
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-04-02 DOI: 10.1016/j.canlet.2025.217676
Zhen-Duo Shi , Ying Liu , Zi-Qi Tao , Liu Chao , Zheng-Guo Zhang , Fang Sun , Fu-Kang Yuan , Qing-Fang Ma , Zong-Yun Li , Zhe-Sheng Chen , Shao-Yuan Wu , Cong-Hui Han
{"title":"Apigenin inhibits recurrent bladder cancer progression by targeting VEGF-β","authors":"Zhen-Duo Shi ,&nbsp;Ying Liu ,&nbsp;Zi-Qi Tao ,&nbsp;Liu Chao ,&nbsp;Zheng-Guo Zhang ,&nbsp;Fang Sun ,&nbsp;Fu-Kang Yuan ,&nbsp;Qing-Fang Ma ,&nbsp;Zong-Yun Li ,&nbsp;Zhe-Sheng Chen ,&nbsp;Shao-Yuan Wu ,&nbsp;Cong-Hui Han","doi":"10.1016/j.canlet.2025.217676","DOIUrl":"10.1016/j.canlet.2025.217676","url":null,"abstract":"<div><div>Bladder cancer is a major global health concern with high incidence and mortality rates. Both muscle-invasive bladder cancer (MIBC) and recurrent non-muscle-invasive bladder cancer (NMIBC) present significant challenges in treatment. Apigenin, a naturally occurring flavonoid, has shown promise in inhibiting the growth of bladder cancer cells, however, its therapeutic mechanism remains unclear. Single-cell RNA sequencing (scRNA-seq) data analysis and drug target screening were performed. Differentially expressed genes (DEGs) and potential therapeutic targets of apigenin were identified. Molecular docking was utilized to evaluate the binding affinity between apigenin and VEGF-β. <em>In vitro</em> assays were conducted to evaluate the association of VEGF-β and apigenin. Drug target screening identified 51 common targets between apigenin and bladder cancer, with VEGF-β emerging as a dominant gene. Molecular docking confirmed a high binding affinity between apigenin and VEGF-β. VEGF-β was significantly upregulated in fibroblasts from recurrent bladder cancer, correlating with increased tumor malignancy. Enhanced cell communication in VEGF-β-positive fibroblasts contributed to tumor progression. <em>In vitro</em> experiments demonstrated that VEGF-β promotes tumor cell proliferation, migration, and invasion. Apigenin significantly inhibits bladder cancer progression by targeting VEGF-β. The upregulation of VEGF-β in fibroblasts from recurrent bladder cancer highlights its potential as a diagnostic marker and therapeutic target. This study underscores the promise of apigenin as a chemopreventive and therapeutic agent for recurrent bladder cancer.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"620 ","pages":"Article 217676"},"PeriodicalIF":9.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787971","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
ADAM12 promotes temozolomide resistance in glioblastoma by activating the TNF-α - NF-κB pathway
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-04-01 DOI: 10.1016/j.canlet.2025.217684
Chunchao Cheng , Longtao Cui , Xiaoteng Cui , Qi Zhan , Jiasheng Ju , Biao Hong , Yanping Huang , Yaqing Ding , Hanyi Xu , Tian Qiu , Chunsheng Kang , Xiaomin Liu , Qixue Wang , Liang Zeng
{"title":"ADAM12 promotes temozolomide resistance in glioblastoma by activating the TNF-α - NF-κB pathway","authors":"Chunchao Cheng ,&nbsp;Longtao Cui ,&nbsp;Xiaoteng Cui ,&nbsp;Qi Zhan ,&nbsp;Jiasheng Ju ,&nbsp;Biao Hong ,&nbsp;Yanping Huang ,&nbsp;Yaqing Ding ,&nbsp;Hanyi Xu ,&nbsp;Tian Qiu ,&nbsp;Chunsheng Kang ,&nbsp;Xiaomin Liu ,&nbsp;Qixue Wang ,&nbsp;Liang Zeng","doi":"10.1016/j.canlet.2025.217684","DOIUrl":"10.1016/j.canlet.2025.217684","url":null,"abstract":"<div><div>Development of temozolomide (TMZ) resistance is a critical factor contributing to a poor prognosis in glioma patients. TMZ resistance is also closely associated with the phosphorylation level of NF-κB, yet targeted inhibition of NF-κB activity in glioma can be leveraged to overcome TMZ resistance. ADAM12, a protein significantly overexpressed in glioma cells, is implicated in the pathogenesis and progression of glioma, yet its role in the development of TMZ resistance is completely understood. We found that knockdown of ADAM12 was shown to arrest the glioma cell cycle, enhance apoptosis, inhibit DNA damage repair mechanisms, and sensitize glioma cells to TMZ. Targeting ADAM12 <em>in vivo</em> was found to increase the sensitivity of glioma cells to TMZ. Survival analysis indicated that ADAM12 serves as a prognostic marker for TMZ treatment. Using ELISA and protein interaction predictions via docking simulation, we identified the TNF-α shedding function of ADAM12 as a critical regulator of glioma progression. Furthermore, in glioma cell lines with unmethylated MGMT, the knockdown of ADAM12 enhanced sensitivity to TMZ by inhibiting the TNF-α/NF-κB pathway and reducing MGMT expression. In all, these results demonstrated that ADAM12 aids in shedding of membrane-bound TNF-a to drive TMZ resistance in glioma.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"620 ","pages":"Article 217684"},"PeriodicalIF":9.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779248","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
CAR T-Cell therapy in chronic myeloid leukemia patients with lymphoid blast crisis: A multicenter clinical analysis
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-04-01 DOI: 10.1016/j.canlet.2025.217688
Yujie Liu , Yuqing Tu , Zhiling Yan , Jinyan Xiao , Biqi Zhou , Tianhui Liu , Lijuan Qi , Depei Wu , Yongxian Hu , Yang Cao , Yang Xu
{"title":"CAR T-Cell therapy in chronic myeloid leukemia patients with lymphoid blast crisis: A multicenter clinical analysis","authors":"Yujie Liu ,&nbsp;Yuqing Tu ,&nbsp;Zhiling Yan ,&nbsp;Jinyan Xiao ,&nbsp;Biqi Zhou ,&nbsp;Tianhui Liu ,&nbsp;Lijuan Qi ,&nbsp;Depei Wu ,&nbsp;Yongxian Hu ,&nbsp;Yang Cao ,&nbsp;Yang Xu","doi":"10.1016/j.canlet.2025.217688","DOIUrl":"10.1016/j.canlet.2025.217688","url":null,"abstract":"","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"621 ","pages":"Article 217688"},"PeriodicalIF":9.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779249","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
The colorectal cancer microenvironment governs clinical behaviors and chemotherapy response
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-04-01 DOI: 10.1016/j.canlet.2025.217687
André Holdfeldt , Simona Salerno , Anders Ståhlberg , Elinor Bexe Lindskog , Göran Landberg
{"title":"The colorectal cancer microenvironment governs clinical behaviors and chemotherapy response","authors":"André Holdfeldt ,&nbsp;Simona Salerno ,&nbsp;Anders Ståhlberg ,&nbsp;Elinor Bexe Lindskog ,&nbsp;Göran Landberg","doi":"10.1016/j.canlet.2025.217687","DOIUrl":"10.1016/j.canlet.2025.217687","url":null,"abstract":"","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"621 ","pages":"Article 217687"},"PeriodicalIF":9.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779250","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
A High-Affinity Antibody-Drug Conjugates Actuximab-MMAE for Potent and Selective Targeting of CEACAM5-Positive Tumors
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-03-29 DOI: 10.1016/j.canlet.2025.217685
Yuqi Hu , Xin Du , Jiayu Yuan , Xizhao Gong , Yue Zhu , Hongde Li , Xiaorong Lin , Fang Zheng , Yuliang Ran , Zhenkun Na , Hai Hu
{"title":"A High-Affinity Antibody-Drug Conjugates Actuximab-MMAE for Potent and Selective Targeting of CEACAM5-Positive Tumors","authors":"Yuqi Hu ,&nbsp;Xin Du ,&nbsp;Jiayu Yuan ,&nbsp;Xizhao Gong ,&nbsp;Yue Zhu ,&nbsp;Hongde Li ,&nbsp;Xiaorong Lin ,&nbsp;Fang Zheng ,&nbsp;Yuliang Ran ,&nbsp;Zhenkun Na ,&nbsp;Hai Hu","doi":"10.1016/j.canlet.2025.217685","DOIUrl":"10.1016/j.canlet.2025.217685","url":null,"abstract":"<div><div>Antibody-drug conjugates (ADCs) represent a promising class of anti-cancer therapy with an increasingly critical role in treating various tumors. They broaden the range of therapeutic targets, enabling the consideration of tumor-associated proteins that are overexpressed but lack well-defined mechanisms. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a clinically relevant screening marker due to its tumor-specific overexpression, making it an attractive target for ADC development. However, the therapeutic potential of earlier anti-CEACAM5 ADCs has been limited by side effects and suboptimal drug-to-antibody ratios (DARs), restricting their clinical utility. In this study, we developed a novel anti-CEACAM5 ADC (named Actuximab-MMAE), characterized by high affinity, an optimized DAR, and potent tumor-selective cytotoxicity. Actuximab-MMAE demonstrated rapid and effective elimination of CEACAM5-positive tumors <em>in vivo</em> at low doses, while maintaining a favorable safety profile. These findings highlight Actuximab-MMAE as a promising therapeutic option for CEACAM5-overexpressing tumors, offering a new therapeutic method for targeted cancer therapy.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"620 ","pages":"Article 217685"},"PeriodicalIF":9.1,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750107","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
The arginine metabolism and its deprivation in cancer therapy 精氨酸代谢及其在癌症治疗中的应用。
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-03-27 DOI: 10.1016/j.canlet.2025.217680
Tiejun Feng , Fuda Xie , Yang Lyu , Peiyao Yu , Bonan Chen , Jun Yu , Ge Zhang , Ka Fai To , Chi Man Tsang , Wei Kang
{"title":"The arginine metabolism and its deprivation in cancer therapy","authors":"Tiejun Feng ,&nbsp;Fuda Xie ,&nbsp;Yang Lyu ,&nbsp;Peiyao Yu ,&nbsp;Bonan Chen ,&nbsp;Jun Yu ,&nbsp;Ge Zhang ,&nbsp;Ka Fai To ,&nbsp;Chi Man Tsang ,&nbsp;Wei Kang","doi":"10.1016/j.canlet.2025.217680","DOIUrl":"10.1016/j.canlet.2025.217680","url":null,"abstract":"<div><div>Arginine deprivation has emerged as a promising therapeutic strategy in cancer treatment due to the auxotrophy of certain tumors. Many cancers, such as pancreatic, colorectal, and hepatocellular carcinoma, exhibit downregulated argininosuccinate synthetase, making them reliant on external arginine sources. This dependency allows targeted therapies that deplete arginine, inhibiting tumor growth while sparing normal cells. Arginine is crucial for various cellular processes, including protein synthesis and immune function. Its deprivation affects both tumor metabolism and immune responses, potentially enhancing cancer therapy. Studies have explored using enzymes like arginine deiminase and arginase, often modified for increased stability and reduced immunogenicity, to effectively lower arginine levels in the tumor microenvironment. These approaches show promise, particularly in tumors with low argininosuccinate synthetase expression. However, the impact on immune cells and the potential for resistance highlight the need for further research. Combining arginine deprivation with other treatments might improve outcomes, offering a novel approach to combat arginine-dependent cancers.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"620 ","pages":"Article 217680"},"PeriodicalIF":9.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742528","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
Glycosaminoglycan modification of NRP1 exon 4-skipping variant drives colorectal cancer metastasis via endosomal-exosomal trafficking
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-03-27 DOI: 10.1016/j.canlet.2025.217683
Yiwei Gu , Qing Ye , Xiuping Huang , Yanan Cao , Luksana Chaiswing , Qing-Bai She
{"title":"Glycosaminoglycan modification of NRP1 exon 4-skipping variant drives colorectal cancer metastasis via endosomal-exosomal trafficking","authors":"Yiwei Gu ,&nbsp;Qing Ye ,&nbsp;Xiuping Huang ,&nbsp;Yanan Cao ,&nbsp;Luksana Chaiswing ,&nbsp;Qing-Bai She","doi":"10.1016/j.canlet.2025.217683","DOIUrl":"10.1016/j.canlet.2025.217683","url":null,"abstract":"<div><div>Neuropilin-1 (NRP1) is a transmembrane glycoprotein that functions as a co-receptor with various cellular functions. Our previous studies identified the NRP1 exon 4-skipping (NRP1-ΔE4) splice variant as an aggressive metastasis driver by activating endosomal signals. Here, we demonstrate the critical role of glycosaminoglycan (GAG) modification in regulating NRP1-ΔE4’s cellular trafficking and oncogenic activity. NRP1-ΔE4 undergoes constitutive internalization into endosomes and subsequent exosomal release from colorectal cancer (CRC) cells. Exosomal NRP1-ΔE4 enhances the migration and invasion of both donor and recipient CRC cells. Genetic or pharmacological inhibition of exosome secretion, or immunodepletion of exosomal NRP1-ΔE4, markedly reduces its metastatic potential. Notably, GAG modification at the O-glycosylation site Ser612 is essential for NRP1-ΔE4’s endosomal trafficking and exosomal release. This modification also promotes the formation of a trimeric complex with Met and β1-integrin, leading to their co-internalization and accumulation in endosomes, which activates FAK signaling and drives CRC metastasis. These findings reveal GAG modification as a key regulatory process that governs the endosomal-exosomal trafficking of NRP1-ΔE4 to facilitate CRC cell dissemination.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"620 ","pages":"Article 217683"},"PeriodicalIF":9.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742526","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
Comparable Survival Outcomes in HLA-Matched and Haploidentical Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia Patients Aged 40-50: A CBMTR Registry-Based Propensity Score Matching Analysis Over the Last Decade. 40-50 岁重型再生障碍性贫血患者接受 HLA 匹配和同种异体造血干细胞移植的生存结果相当:过去十年基于 CBMTR 注册的倾向得分匹配分析。
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-03-27 DOI: 10.1016/j.canlet.2025.217594
Zheng-Li Xu, Yu-Ping Zhang, Bao-Dong Ye, Xin Zhao, Ming Zhou, Pei-Hua Lu, Zi-Min Sun, Xin Li, Er-Lie Jiang, Dai-Hong Liu, Ya-Jing Xu, Fang Zhou, Li Liu, Xi Zhang, Xian-Min Song, Jian-Ping Zhang, Hai Yi, Xue-Jun Zhang, Xue-Hong Ran, Guo-Hong Su, Yan-Ming Zhang, Jie-Ping Chen, Jin-Xiong Huang, Chun Wang, Hai-Ping Yang, Peng-Cheng He, Nan Su, Zi-Wen Guo, Tong Wu, Guan-Chen Bai, Sheng-Jin Fan, Xiao-Jun Huang, Shun-Qing Wang, Lan-Ping Xu
{"title":"Comparable Survival Outcomes in HLA-Matched and Haploidentical Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia Patients Aged 40-50: A CBMTR Registry-Based Propensity Score Matching Analysis Over the Last Decade.","authors":"Zheng-Li Xu, Yu-Ping Zhang, Bao-Dong Ye, Xin Zhao, Ming Zhou, Pei-Hua Lu, Zi-Min Sun, Xin Li, Er-Lie Jiang, Dai-Hong Liu, Ya-Jing Xu, Fang Zhou, Li Liu, Xi Zhang, Xian-Min Song, Jian-Ping Zhang, Hai Yi, Xue-Jun Zhang, Xue-Hong Ran, Guo-Hong Su, Yan-Ming Zhang, Jie-Ping Chen, Jin-Xiong Huang, Chun Wang, Hai-Ping Yang, Peng-Cheng He, Nan Su, Zi-Wen Guo, Tong Wu, Guan-Chen Bai, Sheng-Jin Fan, Xiao-Jun Huang, Shun-Qing Wang, Lan-Ping Xu","doi":"10.1016/j.canlet.2025.217594","DOIUrl":"https://doi.org/10.1016/j.canlet.2025.217594","url":null,"abstract":"<p><p>Our study includes 278 patients aged between 40 and 50 years from 29 centers who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) from matched sibling donors (MSDs) (n=106) and haploidentical donors (HIDs) (n=172) over the last decade. Univariate analysis revealed that HID recipients was associated with more serious disease severity, a delayed allo-HSCT after diagnosis, a higher pretransplant transfusion burden and poor performance status pre-transplant than MSD recipients in clinical settings. After these pretransplant clinical factors were well balanced following propensity score-matching (PSM), 80 matched pairs were selected for further analysis. Following PSM, the cumulative incidences of neutrophil were comparable between two matched groups (P = 0.14), while the 100-day engraftment rates of platelet were significant lower in HID-HCT (P < 0.001); The HID cohort showed higher cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) compared with MSD group (P = 0.04). In contrast, the incidence of severe (grade III-IV) acute GVHD and chronic GVHD were not statistically significant (severe acute GVHD P = 0.10; chronic GVHD P = 0.28). Our study observed comparable overall survival (OS) (P = 0.14); failure free survival (FFS) (P = 0.23); GVHD-free/relapse-free survival (GRFS) (P = 0.26) between matched HID and MSD recipients. In conclusion, our data indicates that allo-HSCT from an HID could be considered for SAA patients between 40-50 years old who do not have an MSD.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217594"},"PeriodicalIF":9.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742525","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
Single-cell transcriptomic analysis identifies tissue-specific fibroblasts as the main modulators of myeloid cells in peritoneal metastasis of different origin 单细胞转录组分析发现,组织特异性成纤维细胞是不同来源腹膜转移中髓系细胞的主要调节因子。
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-03-26 DOI: 10.1016/j.canlet.2025.217678
Vasileios Gerakopoulos , Cristiano Ramos , Catharina Müller , Natalie Walterskirchen , Stefania Vintila , Chiara Zotter , Mathias Ilg , Anna Pap , Stefan Riss , Michael Bergmann , Lukas W. Unger , Anne B. Vogt , Rudolf Oehler , Samuel W. Lukowski
{"title":"Single-cell transcriptomic analysis identifies tissue-specific fibroblasts as the main modulators of myeloid cells in peritoneal metastasis of different origin","authors":"Vasileios Gerakopoulos ,&nbsp;Cristiano Ramos ,&nbsp;Catharina Müller ,&nbsp;Natalie Walterskirchen ,&nbsp;Stefania Vintila ,&nbsp;Chiara Zotter ,&nbsp;Mathias Ilg ,&nbsp;Anna Pap ,&nbsp;Stefan Riss ,&nbsp;Michael Bergmann ,&nbsp;Lukas W. Unger ,&nbsp;Anne B. Vogt ,&nbsp;Rudolf Oehler ,&nbsp;Samuel W. Lukowski","doi":"10.1016/j.canlet.2025.217678","DOIUrl":"10.1016/j.canlet.2025.217678","url":null,"abstract":"<div><div>Colorectal cancer (CRC) peritoneal metastasis (CPM) is related to limited therapy options and poor prognosis. Although stromal cells heavily infiltrate most CPMs, interactions between different cell types in their microenvironment remain unclear. Here, we investigated tumor and distant normal tissue from CPM and CRC patients using single-cell RNA sequencing. Investigating the incoming and outgoing signals between cells revealed that fibroblasts dominate the CPM signaling landscape with myeloid cells as their strongest interaction partner. Using immunohistochemistry, we confirmed that fibroblasts co-localize with macrophages in the CPM microenvironment. A fibroblast sub-population detected only in CPM and normal peritoneum demonstrated immunoregulatory properties in co-culture experiments, and was further detected in additional peritoneal malignancies derived from ovarian and gastric origin. This novel fibroblast type and its communication with macrophages could be attractive targets for therapeutic interventions in CPM and potentially peritoneal surface malignancies in general.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"620 ","pages":"Article 217678"},"PeriodicalIF":9.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742527","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
Anticancer therapy-induced peripheral neuropathy in solid tumors: diagnosis, mechanisms, and treatment strategies 实体瘤抗癌治疗诱发的周围神经病变:诊断、机制和治疗策略。
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-03-26 DOI: 10.1016/j.canlet.2025.217679
Jiahong Jiang , Luying Zhan , Boyang Jiang , Jingyi Pan , Chaojin Hong , Zheling Chen , Liu Yang
{"title":"Anticancer therapy-induced peripheral neuropathy in solid tumors: diagnosis, mechanisms, and treatment strategies","authors":"Jiahong Jiang ,&nbsp;Luying Zhan ,&nbsp;Boyang Jiang ,&nbsp;Jingyi Pan ,&nbsp;Chaojin Hong ,&nbsp;Zheling Chen ,&nbsp;Liu Yang","doi":"10.1016/j.canlet.2025.217679","DOIUrl":"10.1016/j.canlet.2025.217679","url":null,"abstract":"<div><div>Anticancer therapy-induced peripheral neuropathy (PN) is a common adverse event during the diagnosis and treatment of solid tumors. The drug class, cumulative dose, and individual susceptibility affect the incidence and severity of PN. Owing to the lack of specific biomarkers and imaging tests, the diagnostic criteria for PN remain unclear. Moreover, the available and effective clinical treatment strategies are very limited, and most of the current drugs focus on symptom management rather than fundamental reversal of the disease course. The morbidity mechanisms of PN are diverse, including direct neurotoxicity, mitochondrial dysfunction, and disruption of axonal transport. Here, we summarize the diagnosis, mechanisms, and neuroprotective strategies of PN and discuss potential intervention treatments.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"620 ","pages":"Article 217679"},"PeriodicalIF":9.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742524","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
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