Translational Oncology最新文献

{"title":"m6A methyltransferase METTL3 promotes non-small-cell lung carcinoma progression by inhibiting the RIG-I-MAVS innate immune pathway","authors":"Tinghui Huang ,&nbsp;Xudong Ao ,&nbsp;Jie Liu ,&nbsp;Chuancheng Sun ,&nbsp;Yunfei Dong ,&nbsp;Xuechen Yin ,&nbsp;Yan Zhang ,&nbsp;Xinping Wang ,&nbsp;Wenying Li ,&nbsp;Jiujiu Cao ,&nbsp;Feiyan Pan ,&nbsp;Zhigang Hu ,&nbsp;Zhigang Guo ,&nbsp;Lingfeng He","doi":"10.1016/j.tranon.2024.102230","DOIUrl":"10.1016/j.tranon.2024.102230","url":null,"abstract":"<div><div>Our experimental study showed that METTL3 was highly expressed in NSCLC cells and promoted the growth of tumor cells. METTL3 takes N6-methyladenosine (m6A) as the main means of mRNA modification to control the expression and function of RIG-I-MAVS signalling pathway. RIG-I-MAVS constitute the first line frontier in the innate immune defense of human cells. Activation of RIG-I-MAVS signaling can inhibit tumor cell growth and activate the immune microenvironment. Our experimental data reveal that lung cancer cells utilize METTL3-mediated methylation modifications to inhibit the activation of RIG-I-MAVS signaling pathway and immune responses. Our work provides new ideas for biotherapy and immunotherapy.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102230"},"PeriodicalIF":5.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"4′-Demethylpodophyllotoxin functions as a mechanism-driven therapy by targeting the PI3K-AKT pathway in Colorectal cancer","authors":"Jun Liu ,&nbsp;Dandong Luo ,&nbsp;Xiaochuan Chen ,&nbsp;Jiaqi Liu ,&nbsp;Junxiong Chen ,&nbsp;Mengchen Shi ,&nbsp;Haiyan Dong ,&nbsp;Yucheng Xu ,&nbsp;Xinyou Wang ,&nbsp;Zhaoliang Yu ,&nbsp;Huanliang Liu ,&nbsp;Yanchun Feng","doi":"10.1016/j.tranon.2024.102199","DOIUrl":"10.1016/j.tranon.2024.102199","url":null,"abstract":"<div><div>The treatment of colorectal cancer (CRC) poses significant challenges in terms of drug resistance and poor prognosis, necessitating the exploration of effective therapeutic strategies. In this study, high-throughput drug screening was utilized to identify Chinese herbal medicines with notable therapeutic effects on CRC. Among the compounds identified, 4′-demethylpodophyllotoxin (DOP), a derivative of podophyllotoxin, emerged as a potent anti-cancer compound. DOP exhibited time- and dose-dependent growth inhibition on CRC cell lines and tumor organoids derived from patients. RNA-seq revealed that DOP activated the PI3K-AKT pathway, leading to tumor cell apoptosis and cell cycle arrest at the G2/M phase. Additionally, DOP induced DNA damage in CRC cells. To further validate its therapeutic efficacy in CRC, the DLD1-derived xenograft model demonstrated that DOP effectively suppressed CRC growth in vivo. In conclusion, these findings highlight the significant therapeutic potential of DOP as an anti-tumor drug for treating CRC, thereby opening new avenues for investigating Podophyllotoxin derivatives in this specific field.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102199"},"PeriodicalIF":5.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Exosomes in malignant pleural effusion from lung cancer patients impaired the cytotoxicity of double-negative T cells” [Translational Oncology 27 (2023) 1–9/101564]","authors":"Jingjing Wu ,&nbsp;Ranran Zhu ,&nbsp;Zhengxia Wang ,&nbsp;Xueqin Chen ,&nbsp;Tingting Xu ,&nbsp;Yanan Liu ,&nbsp;Meijuan Song ,&nbsp;Jingxian Jiang ,&nbsp;Qiyun Ma ,&nbsp;Zhongqi Chen ,&nbsp;Yuan Liu ,&nbsp;Xiaoyue Wang ,&nbsp;Mingshun Zhang ,&nbsp;Mao Huang ,&nbsp;Ningfei Ji","doi":"10.1016/j.tranon.2024.102205","DOIUrl":"10.1016/j.tranon.2024.102205","url":null,"abstract":"","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102205"},"PeriodicalIF":5.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting response to PD-1 inhibitors in head and neck squamous cell carcinomas using peripheral blood inflammatory markers","authors":"Ruihua Fang ,&nbsp;Yi Chen ,&nbsp;Bixue Huang ,&nbsp;Zhangfeng Wang ,&nbsp;Xiaolin Zhu ,&nbsp;Dawei Liu ,&nbsp;Wei Sun ,&nbsp;Lin Chen ,&nbsp;Minjuan Zhang ,&nbsp;Kexing Lyu ,&nbsp;Wenbin Lei","doi":"10.1016/j.tranon.2024.102222","DOIUrl":"10.1016/j.tranon.2024.102222","url":null,"abstract":"<div><div>Immune checkpoint inhibitor (ICI) treatment has the potential to induce durable disease remission. However, the current combined positive score (CPS) is insufficient accurate for predicting which patients will benefit from it. In the present study, a real-world retrospective study was conducted on 56 patients of HNSCC who received ICI treatment. Then the treatment that patient received and levels of pre-treatment blood inflammatory markers (NLR, MLR and PLR) were identified to develop a model for predicting immunotherapy response. Notably, the model achieved an area under the curve (AUC) of 0.877 (95 % CI 0.769–0.985) , providing a larger net benefit than the CPS marker (AUC=0.614, 95 % CI 0.466–0.762). Furthermore, the internal validation of the prediction model showed a C-index of 0.835. Patients with high score of the model would get improved PFS than those with low score. Therefore, the prediction model for patients with local advanced or R/M HNSCC receiving ICI treatment, which represented an better efficient prediction of immunotherapy response than CPS marker.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102222"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-derived tumor organoids: A preclinical platform for personalized cancer therapy","authors":"Sebastien Taurin,&nbsp;Reem Alzahrani,&nbsp;Sahar Aloraibi,&nbsp;Layal Ashi,&nbsp;Rawan Alharmi,&nbsp;Noora Hassani","doi":"10.1016/j.tranon.2024.102226","DOIUrl":"10.1016/j.tranon.2024.102226","url":null,"abstract":"<div><div>Patient-derived tumor organoids (PDTOs) represent a significant advancement in cancer research and personalized medicine. These organoids, derived from various cancer types, have shown the ability to retain the genetic and molecular characteristics of the original tumors, allowing for the detailed study of tumor biology and drug responses on an individual basis. The success rates of establishing PDTOs vary widely and are influenced by factors such as cancer type, tissue quality, and media composition. Furthermore, the dynamic nature of organoid cultures may also lead to unique molecular characteristics that deviate from the original tumors, affecting their interpretation in clinical settings without the implementation of rigorous validation and establishment of standardized protocols. Recent studies have supported the correlation between PDTOs and the corresponding patient response. Although these studies involved a small number of patients, they promoted the integration of PDTOs in observational and interventional clinical trials to advance translational cancer therapies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102226"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular profiling of head and neck squamous cell carcinomas in North-eastern Italy identifies possible tumour cell vulnerabilities","authors":"Monica Schiappacassi ,&nbsp;Riccardo Spizzo ,&nbsp;Jerry Polesel ,&nbsp;Lorena Musco ,&nbsp;Roberto Doliana ,&nbsp;Luca Pellizzari ,&nbsp;Valentina Lupato ,&nbsp;Giuseppe Fanetti ,&nbsp;Emanuela Vaccher ,&nbsp;Diego Serraino ,&nbsp;Luigi Barzan ,&nbsp;Sandro Sulfaro ,&nbsp;Vittorio Giacomarra ,&nbsp;Giovanni Franchin ,&nbsp;Gustavo Baldassarre","doi":"10.1016/j.tranon.2024.102221","DOIUrl":"10.1016/j.tranon.2024.102221","url":null,"abstract":"<div><h3>Background and Purpose</h3><div>Head and Neck Squamous Cell Cancer (HNSCC) originates from the oral cavity, oropharynx, hypopharynx and larynx, and it ranks sixth among global cancers. Despite modest 5-year survival gains, the integration of molecular personalization lags behind and there is an urgent need to develop novel therapies and biomarkers.</div></div><div><h3>Material and Methods</h3><div>This study outlined the somatic mutational profile of 15 HNSCC-enriched genes in a case series from North-eastern Italy, the region with the highest national HNSCC incidence. We conducted a comparative analysis with prior case studies and assessed the prognostic implications of the mutations that we found in these genes.</div></div><div><h3>Results</h3><div>Consistent with previous studies, oral cavity tumours showed a lower gene mutation frequency. We highlighted a significant enrichment of somatic <em>AJUBA</em> mutations in the hypopharyngeal region, linked to a poorer prognosis. Moreover, <em>KMT2C</em> mutations co-occurring with <em>CDKN2A</em> or <em>NOTCH1</em> mutations were associated with a worse prognosis. At the same time, only 7 % of the cases exhibited mutations that are predictive biomarker in HNSCC according to compelling clinical evidence but that need further investigation in a clinical trial setting.</div></div><div><h3>Conclusion</h3><div>Our findings underlined novel differences in somatic gene mutations among the four anatomic sites. However, at present, the identified mutations cannot yet be considered predictive biomarkers either for the lack of supporting clinical findings or for the lack of approved targeted therapies in HNSCC. This underscores the imperative for continued investigation into the biology of HNSCC to unveil novel vulnerabilities that can be leveraged to enhance patient treatment strategies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102221"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"O-GlcNAcylation in ovarian tumorigenesis and its therapeutic implications","authors":"Lu Xia,&nbsp;Jie Mei,&nbsp;Min Huang,&nbsp;Dandan Bao,&nbsp;Zhiwei Wang,&nbsp;Yizhe Chen","doi":"10.1016/j.tranon.2024.102220","DOIUrl":"10.1016/j.tranon.2024.102220","url":null,"abstract":"<div><div>Ovarian cancer is a prevalent malignancy among women, often associated with a poor prognosis. Post-translational modifications (PTMs), particularly O-GlcNAcylation, have been implicated in the progression of ovarian cancer. Emerging evidence indicates that dysregulation of O-GlcNAcylation contributes to the initiation and malignant progression of ovarian cancer. This review discusses the potential role of O-GlcNAcylation in ovarian tumorigenesis, with a focus on its regulation of various cellular signaling pathways, including p53, RhoA/ROCK/MLC, Ezrin/Radixin/Moesin (ERM), and β-catenin. This review also emphasizes the O-GlcNAcylation of critical proteins in ovarian cancer, such as SNAP-23, SNAP-29, E-cadherin, and calreticulin. Additionally, the potential of O-GlcNAcylation to enhance immunotherapy for ovarian cancer patients is explored. Several compounds targeting OGT and OGA in ovarian cancer are also highlighted. Targeting the dynamic and versatile nature of O-GlcNAcylation could undoubtedly contribute to more effective treatments and improved outcomes for ovarian cancer patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102220"},"PeriodicalIF":5.0,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT5 inhibits glycolysis and nasal type extranodal NK/T cell lymphoma cell proliferation by catalyzing the desuccinylation of glucose-6-phosphate isomerase","authors":"Tiansheng Wang ,&nbsp;Guolin Tan ,&nbsp;Ming Jiang ,&nbsp;Guohui Liu ,&nbsp;Wei Li ,&nbsp;Xiang Qing","doi":"10.1016/j.tranon.2024.102215","DOIUrl":"10.1016/j.tranon.2024.102215","url":null,"abstract":"<div><h3>Background</h3><div>Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is a malignant tumor harboring a poor prognosis and unsatisfactory treatment outcomes. This study was performed to explore the pathogenesis and exact etiology of ENKTL. <strong>Methods</strong> Bioinformatic analysis was conducted to investigate the expression of SIRT5 and glucose-6-phosphate isomerase (GPI), as well their correlation with ENKTL overall survival. Cell proliferation ability and cell apoptosis were determined by CCK8, soft-agar colony formation and Tunel assays. Pyruvic acid and lactate production, GPI activity and F6P levels were detected to indicate glycolysis process. Succinylation modification in GPI protein was quantified by 4D label-free succinylation modification quantitative proteome. ENKTL mouse model was established by the injection of SNK6 cells.</div></div><div><h3>Results</h3><div>SIRT5 suppressed the NKTL cell proliferation through the desuccinylation effect, while it was down-regulated in the ENKTL. SIRT5 catalyzed the desuccinylation of glycolytic enzyme GPI in ENKTL cells, which accelerated GPI protein degradation through the autophagy-lysosome system. SIRT5 inhibited glycolysis via mediating the desuccinylation of GPI, thereby suppressing ENKTL cell proliferation. The antitumor role of SIRT5 was also certified in ENKTL mouse model by targeting GPI.</div></div><div><h3>Conclusion</h3><div>SIRT5 inhibits glycolysis via catalyzed the desuccinylation of glycolytic enzyme GPI, thereby repressing ENKTL cells proliferation and tumor growth. As SIRT5 serves as a tumor suppressor in ENKTL, it may be a promising molecular target in therapy strategy.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102215"},"PeriodicalIF":5.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the tumor-suppressive role of miRNA-200c in head and neck squamous cell carcinoma: Potential and mechanisms of exosome-mediated delivery for therapeutic applications","authors":"Mohamed S. Kishta ,&nbsp;Aya Khamis ,&nbsp;Hafez AM ,&nbsp;Abdelrahman H. Elshaar ,&nbsp;Désirée Gül","doi":"10.1016/j.tranon.2024.102216","DOIUrl":"10.1016/j.tranon.2024.102216","url":null,"abstract":"<div><div>Head and neck squamous cell carcinoma (HNSCC) remains a challenging malignancy due to its high rates of recurrence, metastasis, and resistance to conventional therapies. microRNA-200c (miRNA-200c) has emerged as a critical tumor suppressor in HNSCC, with the potential to inhibit epithelial-mesenchymal transition (EMT), which is considered as a key process in cancer metastasis and progression. Interestingly, there are also controversial findings in HNSCC characterizing miRNA-200c as oncogenic factor. This review article provides a comprehensive overview of the current understanding of miRNA-200c's general role in cancer, and particularly in HNSCC, highlighting its mechanisms of action, including the regulation of EMT and other oncogenic pathways.</div><div>Additionally, the review explores the innovative approach of exosome-mediated delivery of miRNA-200c as a therapeutic strategy. Exosomes, as natural nanocarriers, offer a promising vehicle for the targeted delivery of miRNA-200c to tumor cells, potentially overcoming the limitations of traditional delivery methods and enhancing therapeutic efficacy. The review also discusses the challenges and future directions in the clinical application of miRNA-200c, particularly focusing on its potential to improve outcomes for HNSCC patients. This article seeks to provide valuable insights for researchers and clinicians working towards innovative treatments for this aggressive cancer type.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102216"},"PeriodicalIF":5.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FLASH radiotherapy combined with immunotherapy: From biological mechanisms to blockbuster therapeutics","authors":"Yu Wang ,&nbsp;Shu-Nan Qi ,&nbsp;Nan Bi ,&nbsp;Ye-Xiong Li","doi":"10.1016/j.tranon.2024.102183","DOIUrl":"10.1016/j.tranon.2024.102183","url":null,"abstract":"<div><div>FLASH ultra-high dose rate radiotherapy (RT) can effectively exert the protective effect on normal tissue and reduce the risk of treatment-related toxicity, without compromising the killing effect on tumor tissue, resulting in a significant differential biological effect between tumor control and normal tissue damage, namely the FLASH effect. To date, the precise biological details of the FLASH effect remain uncertain. The currently mainstream mechanisms proposed by the academic community include the transient oxygen depletion hypothesis, free radical hypothesis, immune protection hypothesis, and DNA integrity hypothesis, which have attracted increasing attention in recent years. Based on these theoretical principles and numerous investigations on the FLASH effect in vivo and in vitro, the combined application of FLASH and immune checkpoint inhibitors (ICIs) has been considered synergistic and potentially practical. The primary underlying basis is that FLASH might actively preserve the number and function of circulating immune cells, thereby enhancing the efficacy of immune cell-mediated immunotherapy. Meanwhile, FLASH RT could activate the tumor immune microenvironment and transform \"cold'' tumors into ''hot'' ones, consequently boosting local and systemic anti-tumor immunity and expanding the therapeutic benefits of ICIs. Moreover, FLASH might attenuate immunoinflammatory responses and minimize the incidence of radiation-related adverse events, allowing for the potentially safer and promising clinical application of combing FLASH RT with ICI therapy. Nevertheless, data on this treatment modality is currently lacking, and several barriers remain to be addressed, including the logistical bottlenecks, technical hurdles, limited availability, and unclear biological mechanisms. Further research is warranted in the future.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102183"},"PeriodicalIF":5.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}