Cancer gene therapy最新文献_第8页

Correction: H3.3-G34W in giant cell tumor of bone functionally aligns with the exon choice repressor hnRNPA1L2 更正：骨巨细胞瘤中的 H3.3-G34W 与外显子选择抑制因子 hnRNPA1L2 在功能上一致。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-06-27 DOI: 10.1038/s41417-024-00803-6

Eunbi Lee, Yoon Jung Park, Anders M. Lindroth

引用次数: 0

Anti-angiogenesis and anti-immunosuppression gene therapy through targeting COUP-TFII in an in situ glioblastoma mouse model 在原位胶质母细胞瘤小鼠模型中通过靶向 COUP-TFII 抗血管生成和抗免疫抑制基因疗法。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-06-26 DOI: 10.1038/s41417-024-00799-z

Fei Wang, Shuo Zhang, Fengjiao Sun, Weiwei Chen, Cuilan Liu, Hongliang Dong, Bingjie Cui, Lingyu Li, Chunlong Sun, Wen Du, Bin Liu, Wanfeng Fan, Jiong Deng, Clemens A. Schmitt, Xiuwen Wang, Jing Du

{"title":"Anti-angiogenesis and anti-immunosuppression gene therapy through targeting COUP-TFII in an in situ glioblastoma mouse model","authors":"Fei Wang, Shuo Zhang, Fengjiao Sun, Weiwei Chen, Cuilan Liu, Hongliang Dong, Bingjie Cui, Lingyu Li, Chunlong Sun, Wen Du, Bin Liu, Wanfeng Fan, Jiong Deng, Clemens A. Schmitt, Xiuwen Wang, Jing Du","doi":"10.1038/s41417-024-00799-z","DOIUrl":"10.1038/s41417-024-00799-z","url":null,"abstract":"Glioblastoma (GBM) is the most common and aggressive primary brain cancer; angiogenesis and immunosuppression exacerbate GBM progression. COUP-TFII demonstrates pro-angiogenesis activity; however, its role in glioma progression remains unclear. This study revealed that COUP-TFII promotes angiogenesis in gliomas by inducing transdifferentiation of glioma cells into endothelial-like cells. Mechanistic investigation suggested that COUP-TFII as a transcription factor exerts its function via binding to the promoter of TXNIP. Interestingly, COUP-TFII knockdown attenuated tumorigenesis and tumor progression in an immunocompetent mouse model but promoted tumor progression in an immuno-deficient mouse model. As an explanation, repression of COUP-TFII induces cellular senescence and activates immune surveillance in glioma cells in vitro and in vivo. In addition, we used heparin–polyethyleneimine (HPEI) nanoparticles to deliver COUP-TFII shRNA, which regulated tumor angiogenesis and immunosuppression in an in situ GBM mouse model. This study provides a novel strategy and potential therapeutic targets to treat GBM.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 8","pages":"1135-1150"},"PeriodicalIF":4.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Correction: TRIM58 downregulation maintains stemness via MYH9-GRK3-YAP axis activation in triple-negative breast cancer stem cells 更正：在三阴性乳腺癌干细胞中，TRIM58下调可通过激活MYH9-GRK3-YAP轴维持干性。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-06-25 DOI: 10.1038/s41417-024-00798-0

Xujun Li, Jing Jiang, Qian Wu, Tianzi You, Fan Yang

引用次数: 0

Extracellular vesicles from type-2 macrophages increase the survival of chronic lymphocytic leukemia cells ex vivo 来自 2 型巨噬细胞的细胞外囊泡可提高慢性淋巴细胞白血病细胞的体内存活率。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-06-25 DOI: 10.1038/s41417-024-00802-7

Léa Ikhlef, Nina Ratti, Stéphanie Durand, Rémy Formento, Héloïse Daverat, Marie Boutaud, Clément Guillou, Natalya Dmytruk, Nathalie Gachard, Pascal Cosette, Marie-Odile Jauberteau, Paul-François Gallet

{"title":"Extracellular vesicles from type-2 macrophages increase the survival of chronic lymphocytic leukemia cells ex vivo","authors":"Léa Ikhlef, Nina Ratti, Stéphanie Durand, Rémy Formento, Héloïse Daverat, Marie Boutaud, Clément Guillou, Natalya Dmytruk, Nathalie Gachard, Pascal Cosette, Marie-Odile Jauberteau, Paul-François Gallet","doi":"10.1038/s41417-024-00802-7","DOIUrl":"10.1038/s41417-024-00802-7","url":null,"abstract":"The resistance of Chronic Lymphocytic Leukemia (CLL) B-cells to cell death is mainly attributed to interactions within their microenvironment, where they interact with various types of cells. Within this microenvironment, CLL-B-cells produce and bind cytokines, growth factors, and extracellular vesicles (EVs). In the present study, EVs purified from nurse-like cells and M2-polarized THP1 cell (M2-THP1) cultures were added to CLL-B-cells cultures. EVs were rapidly internalized by B-cells, leading to a decrease in apoptosis (P = 0.0162 and 0.0469, respectively) and an increased proliferation (P = 0.0335 and 0.0109). Additionally, they induced an increase in the resistance of CLL-B-cells to Ibrutinib, the Bruton kinase inhibitor in vitro (P = 0.0344). A transcriptomic analysis showed an increase in the expression of anti-apoptotic gene BCL-2 (P = 0.0286) but not MCL-1 and an increase in the expression of proliferation-inducing gene APRIL (P = 0.0286) following treatment with EVs. Meanwhile, an analysis of apoptotic protein markers revealed increased amounts of IGFBP-2 (P = 0.0338), CD40 (P = 0.0338), p53 (P = 0.0219) and BCL-2 (P = 0.0338). Finally, exploration of EVs protein content by mass spectrometry revealed they carry various proteins involved in known oncogenic pathways and the RNAseq analysis of CLL-B-cells treated or not with NLCs EVs show various differentially expressed genes.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 8","pages":"1164-1176"},"PeriodicalIF":4.8,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00802-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Gut microbiota-mediated activation of GSDMD ignites colorectal tumorigenesis 肠道微生物群介导的 GSDMD 激活引发结直肠肿瘤发生。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-06-19 DOI: 10.1038/s41417-024-00796-2

Ju Chen, Neha Singh, Xiaoyang Ye, Eileen Victoria Theune, Kepeng Wang

{"title":"Gut microbiota-mediated activation of GSDMD ignites colorectal tumorigenesis","authors":"Ju Chen, Neha Singh, Xiaoyang Ye, Eileen Victoria Theune, Kepeng Wang","doi":"10.1038/s41417-024-00796-2","DOIUrl":"10.1038/s41417-024-00796-2","url":null,"abstract":"Activation of Gasdermin D (GSDMD) results in its cleavage, oligomerization, and subsequent formation of plasma membrane pores, leading to a form of inflammatory cell death denoted as pyroptosis. The roles of GSDMD in inflammation and immune responses to infection are well documented. However, whether GSDMD also plays a role in sporadic cancer development, especially that in the gut epithelium, remains unknown. Here, we show that GSDMD is activated in colorectal tumors of both human and mouse origins. Ablation of GSDMD in a mouse model of sporadic colorectal cancer resulted in reduced tumor formation in the colon and rectum, suggesting a tumor-promoting role of the protein in the gut. Both antibiotic-mediated depletion of gut microbiota and pharmacological inhibition of NLRP3 inflammasome reduced the activation of GSDMD. Loss of GSDMD resulted in reduced infiltration of immature myeloid cells, and increased numbers of macrophages in colorectal tumors. Activation of GSDMD is also accompanied by the aggregation of the endosomal sorting complex required for transport (ESCRT) membrane repair proteins on the membrane of colorectal tumor cells, suggesting that active membrane repairment may prevent pyroptosis induced by the formation of GSDMD pore in tumor cells. Our results show that gut microbiota/NLRP3-mediated activation of GSDMD promotes the development of colorectal tumors, and supports the use of NLRP3 inhibitors to treat colon cancer.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 7","pages":"1007-1017"},"PeriodicalIF":4.8,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00796-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Deciphering the role of post-translational modifications in fanconi anemia proteins and their influence on tumorigenesis 破解范可尼贫血症蛋白翻译后修饰的作用及其对肿瘤发生的影响。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-06-15 DOI: 10.1038/s41417-024-00797-1

Rui Ma, Xinlin Xu

{"title":"Deciphering the role of post-translational modifications in fanconi anemia proteins and their influence on tumorigenesis","authors":"Rui Ma, Xinlin Xu","doi":"10.1038/s41417-024-00797-1","DOIUrl":"10.1038/s41417-024-00797-1","url":null,"abstract":"Fanconi anemia (FA) is an autosomal or X-linked human disease, characterized by bone marrow failure, cancer susceptibility and various developmental abnormalities. So far, at least 22 FA genes (FANCA-W) have been identified. Germline inactivation of any one of these FA genes causes FA symptoms. Proteins encoded by FA genes are involved in the Fanconi anemia pathway, which is known for its roles in DNA inter-strand crosslinks (ICLs) repair. Besides, its roles in genome maintenance upon replication stress has also been reported. Post-translational modifications (PTMs) of FA proteins, particularly phosphorylation and ubiquitination, emerge as critical determinants in the activation of the FA pathway during ICL repair or replication stress response. Consequent inactivation of the FA pathway engenders heightened chromosomal instability, thereby constituting a genetic susceptibility conducive to cancer predisposition and the exacerbation of tumorigenesis. In this review, we have combined recent structural analysis of FA proteins and summarized knowledge on the functions of different PTMs in regulating FA pathways, and discuss potential contributions stemming from mutations at PTMs to the genesis and progression of tumorigenesis.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 8","pages":"1113-1123"},"PeriodicalIF":4.8,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

ScRNA-seq revealed the tumor microenvironment heterogeneity related to the occurrence and metastasis in upper urinary tract urothelial carcinoma ScRNA-seq揭示了与上尿路尿路上皮癌发生和转移相关的肿瘤微环境异质性。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-06-14 DOI: 10.1038/s41417-024-00779-3

Shiyong Xin, Yanwei Zhang, Zhenhua Zhang, Ziyao Li, Xianchao Sun, Xiang Liu, Liang Jin, Weiyi Li, Chaozhi Tang, Wangli Mei, Qiong Cao, Haojie Wang, Zhihao Wei, Zhen Zhou, Rongbing Li, Xiaofei Wen, Guosheng Yang, Weihua Chen, Junhua Zheng, Lin Ye

{"title":"ScRNA-seq revealed the tumor microenvironment heterogeneity related to the occurrence and metastasis in upper urinary tract urothelial carcinoma","authors":"Shiyong Xin, Yanwei Zhang, Zhenhua Zhang, Ziyao Li, Xianchao Sun, Xiang Liu, Liang Jin, Weiyi Li, Chaozhi Tang, Wangli Mei, Qiong Cao, Haojie Wang, Zhihao Wei, Zhen Zhou, Rongbing Li, Xiaofei Wen, Guosheng Yang, Weihua Chen, Junhua Zheng, Lin Ye","doi":"10.1038/s41417-024-00779-3","DOIUrl":"10.1038/s41417-024-00779-3","url":null,"abstract":"Metastasis is the greatest clinical challenge for UTUCs, which may have distinct molecular and cellular characteristics from earlier cancers. Herein, we provide single-cell transcriptome profiles of UTUC para cancer normal tissue, primary tumor lesions, and lymphatic metastases to explore possible mechanisms associated with UTUC occurrence and metastasis. From 28,315 cells obtained from normal and tumor tissues of 3 high-grade UTUC patients, we revealed the origin of UTUC tumor cells and the homology between metastatic and primary tumor cells. Unlike the immunomicroenvironment suppression of other tumors, we found no immunosuppression in the tumor microenvironment of UTUC. Moreover, it is imperative to note that stromal cells are pivotal in the advancement of UTUC. This comprehensive single-cell exploration enhances our comprehension of the molecular and cellular dynamics of metastatic UTUCs and discloses promising diagnostic and therapeutic targets in cancer-microenvironment interactions.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 8","pages":"1201-1220"},"PeriodicalIF":4.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Lower ratio of IMPDH1 to IMPDH2 sensitizes gliomas to chemotherapy 较低的 IMPDH1 与 IMPDH2 比率会使胶质瘤对化疗敏感。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-06-13 DOI: 10.1038/s41417-024-00793-5

Xiaoyu Ruan, Yundong Xiong, Xiaoman Li, Ence Yang, Jiadong Wang

引用次数: 0

Human adipose-derived stem cells genetically programmed to induce necroptosis for cancer immunotherapy 通过基因编程诱导坏死的人类脂肪源性干细胞用于癌症免疫疗法。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-06-10 DOI: 10.1038/s41417-024-00794-4

Soyeon Bak, Kyoung Sub Kim, Kun Na

{"title":"Human adipose-derived stem cells genetically programmed to induce necroptosis for cancer immunotherapy","authors":"Soyeon Bak, Kyoung Sub Kim, Kun Na","doi":"10.1038/s41417-024-00794-4","DOIUrl":"10.1038/s41417-024-00794-4","url":null,"abstract":"Herein, we present human adipose-derived stem cells (ADSCs) inserted with the receptor-interacting protein kinase-3 (RIP3) gene (RP@ADSCs), which induces cell necroptosis, for tumor immunotherapy. Necroptosis has characteristics of both apoptosis, such as programmed cell death, and necrosis, such as swelling and plasma membrane rupture, during which damage-related molecular patterns are released, triggering an immune response. Therefore, necroptosis has the potential to be used as an effective anticancer immunotherapy. RP@ADSCs were programmed to necroptosis after a particular time after being injected in vivo, and various pro-inflammatory cytokines secreted during the stem cell death process stimulated the immune system, showing local and sustained anticancer effects. It was confirmed that RIP3 protein expression increased in ADSCs after RP transfection. RP@ADSCs continued to induce ADSCs death for 7 days, and various pro-inflammatory cytokines were secreted through ADSCs death. The efficacy of RP@ADSCs-mediated immunotherapy was evaluated in mouse models bearing GL-26 (glioblastoma) and K1735 (melanoma), and it was found that RP resulted in an increase in the population of long-term cytotoxic T cells and a decrease in the population of regulatory T cells. This shows that RP@ADSCs have potential and applicability as an excellent anticancer immunotherapy agent in clinical practice.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 7","pages":"995-1006"},"PeriodicalIF":4.8,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

RhoJ: an emerging biomarker and target in cancer research and treatment RhoJ：癌症研究和治疗中的新兴生物标志物和靶点。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-06-10 DOI: 10.1038/s41417-024-00792-6

Jinze Shen, Xinming Su, Shana Wang, Zehua Wang, Chenming Zhong, Yi Huang, Shiwei Duan

{"title":"RhoJ: an emerging biomarker and target in cancer research and treatment","authors":"Jinze Shen, Xinming Su, Shana Wang, Zehua Wang, Chenming Zhong, Yi Huang, Shiwei Duan","doi":"10.1038/s41417-024-00792-6","DOIUrl":"10.1038/s41417-024-00792-6","url":null,"abstract":"RhoJ is a Rho GTPase that belongs to the Cdc42 subfamily and has a molecular weight of approximately 21 kDa. It can activate the p21-activated kinase family either directly or indirectly, influencing the activity of various downstream effectors and playing a role in regulating the cytoskeleton, cell movement, and cell cycle. RhoJ’s expression and activity are controlled by multiple upstream factors at different levels, including expression, subcellular localization, and activation. High RhoJ expression is generally associated with a poor prognosis for cancer patients and is mainly due to an increased number of tumor blood vessels and abnormal expression in malignant cells. RhoJ promotes tumor progression through several pathways, particularly in tumor angiogenesis and drug resistance. Clinical data also indicates that high RhoJ expression is closely linked to the pathological features of tumor malignancy. There are various cancer treatment methods that target RhoJ signaling, such as direct binding to inhibit the RhoJ effector pocket, inhibiting RhoJ expression, blocking RhoJ upstream and downstream signals, and indirectly inhibiting RhoJ’s effect. RhoJ is an emerging cancer biomarker and a significant target for future cancer clinical research and drug development.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 10","pages":"1454-1464"},"PeriodicalIF":4.8,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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