Cancer gene therapy最新文献_第2页

Reversible downregulation of MYC in a spheroid model of metastatic epithelial ovarian cancer. 转移性上皮性卵巢癌球形模型中 MYC 的可逆下调。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-11-21 DOI: 10.1038/s41417-024-00850-z

Adrian Buensuceso, Matthew J Borrelli, Yudith Ramos Valdés, Trevor G Shepherd

{"title":"Reversible downregulation of MYC in a spheroid model of metastatic epithelial ovarian cancer.","authors":"Adrian Buensuceso, Matthew J Borrelli, Yudith Ramos Valdés, Trevor G Shepherd","doi":"10.1038/s41417-024-00850-z","DOIUrl":"https://doi.org/10.1038/s41417-024-00850-z","url":null,"abstract":"Upon detachment from the primary tumour, epithelial ovarian cancer cells can form multicellular aggregates, also referred to as spheroids, that have the capacity to establish metastases at distant sites. These structures exhibit numerous adaptations that may facilitate metastatic transit and promote tumorigenic potential. One such adaptation is the acquisition of dormancy, characterized by decreased proliferation and molecular features of quiescence. One of the most frequently dysregulated genes in cancer is MYC, which encodes a transcription factor that promotes cell proliferation. In this study, we demonstrate that MYC protein abundance and associated gene expression is significantly decreased in EOC spheroids compared to adherent cells. This downregulation occurs rapidly upon cell detachment and is proteasome-dependent. Moreover, MYC protein abundance and associated gene expression is restored upon spheroid reattachment to an adherent culture surface. Overall, our findings suggest that suppression of MYC activity is a common feature of EOC spheroids and may contribute to the reversible acquisition of dormancy.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686230","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

Oncolytic virus encoding 4-1BBL and IL15 enhances the efficacy of tumor-infiltrating lymphocyte adoptive therapy in HCC. 编码4-1BBL和IL15的肿瘤溶解病毒可提高肿瘤浸润淋巴细胞采纳疗法对HCC的疗效。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-11-20 DOI: 10.1038/s41417-024-00853-w

Kai Ye, Yongfeng Yan, Rui Su, Qinghai Dai, Kunyan Qiao, Yu Cao, Jian Xu, Lihua Yan, Zhixiao Huo, Wei Liu, Yue Hu, Yu Zhu, Liang Xu, Yuqiang Mi

{"title":"Oncolytic virus encoding 4-1BBL and IL15 enhances the efficacy of tumor-infiltrating lymphocyte adoptive therapy in HCC.","authors":"Kai Ye, Yongfeng Yan, Rui Su, Qinghai Dai, Kunyan Qiao, Yu Cao, Jian Xu, Lihua Yan, Zhixiao Huo, Wei Liu, Yue Hu, Yu Zhu, Liang Xu, Yuqiang Mi","doi":"10.1038/s41417-024-00853-w","DOIUrl":"https://doi.org/10.1038/s41417-024-00853-w","url":null,"abstract":"Previous studies have found that oncolytic virus (OVs) can improve the efficacy of TIL adoptive therapy in oral cancer, colon cancer, and pancreatic cancer. However, the curative effect in hepatocellular carcinoma (HCC) is still unclear. Therefore, this study aims to explore the therapeutic effect and mechanism of OVs encoding 4-1BBL and IL15 (OV-4-1BBL/IL15) combined with TIL adoptive therapy on HCC. In this study, the role and immunological mechanism of armed OVs combined with TILs were evaluated by flow cytometry and ELISA in patient-derived xenograft and syngeneic mouse tumor models. Co-culturing with TILs can up-regulate the expression of antigen-presenting cell (APC) markers on the surface of OV-infected primary HCC cells, and promote the specific activation ability and tumor-killing ability of TILs. OV-4-1BBL/IL15 combined with TIL adoptive therapy could induce tumor volume reduction and anti-tumor immune memory in patient-derived xenograft and syngeneic mouse tumor models. Furthermore, OV combined with TIL adoptive therapy can endow tumor cells with aAPC characteristics, activate T cells at the same time, and reprogram tumor macrophages into anti-tumor phenotype. OV-4-1BBL/IL15 can stimulate the anti-tumor potential of TIL therapy in HCC, and possess broad clinical application prospects.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680975","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

The antitumor peptide M1-20 induced the degradation of CDK1 through CUL4-DDB1-DCAF1-involved ubiquitination. 抗肿瘤肽 M1-20 通过 CUL4-DDB1-DCAF1 参与的泛素化作用诱导 CDK1 降解。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-11-20 DOI: 10.1038/s41417-024-00855-8

Huitong Bu, Chaozhu Pei, Min Ouyang, Yan Chen, Li Yu, Xiaoqin Huang, Yongjun Tan

引用次数: 0

Correction: SEMA7A-mediated juxtacrine stimulation of IGFBP-3 upregulates IL-17RB at pancreatic cancer invasive front. 更正：SEMA7A介导的IGFBP-3并体刺激可上调胰腺癌浸润前沿的IL-17RB。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-11-20 DOI: 10.1038/s41417-024-00857-6

Yi-Ing Chen, Sui-Chih Tien, Yi-Ling Ko, Chin-Chun Chang, Min-Fen Hsu, Hung Jen Chien, Hsuan-Yu Peng, Yung-Ming Jeng, Yun-Wen Tien, Yu-Ting Chang, Ming-Chu Chang, Chun-Mei Hu

引用次数: 0

CEACAM6 facilitates gastric cancer progression through upregulating SLC27A2. CEACAM6 通过上调 SLC27A2 促进胃癌进展。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-11-19 DOI: 10.1038/s41417-024-00846-9

Xiaqiong Mao, Tongtai Liu, Shunying Yu, Yuqi Wei, Chunli Zhou, Xiaoyi Kuai

引用次数: 0

Serum small extracellular vesicles-derived BST2 as a biomarker for papillary thyroid microcarcinoma promotes lymph node metastasis. 血清小细胞外囊泡衍生的BST2是甲状腺乳头状微癌促进淋巴结转移的生物标记物

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-11-18 DOI: 10.1038/s41417-024-00854-9

Zhen Cao, Yuanyang Wang, Jianqiang Wu, Xiaoyue Tang, Zhihong Qian, Zejian Zhang, Rui Liu, Peng Liu, Zepeng Li, Xiequn Xu, Ziwen Liu

{"title":"Serum small extracellular vesicles-derived BST2 as a biomarker for papillary thyroid microcarcinoma promotes lymph node metastasis.","authors":"Zhen Cao, Yuanyang Wang, Jianqiang Wu, Xiaoyue Tang, Zhihong Qian, Zejian Zhang, Rui Liu, Peng Liu, Zepeng Li, Xiequn Xu, Ziwen Liu","doi":"10.1038/s41417-024-00854-9","DOIUrl":"10.1038/s41417-024-00854-9","url":null,"abstract":"Papillary thyroid microcarcinoma (PTMC), although frequently indolent, could be aggressive in a few patients, leading to lymph node metastasis (LNM) and worsened prognosis. To explore the role of protein profiling of small extracellular vesicles (sEVs) in the auxiliary diagnosis and risk stratification of PTMC, proteins in serum sEVs isolated from PTMC patients with (N = 10) and without (N = 10) LNM and benign thyroid nodule (BN) patients (N = 9) were profiled via a bioinformatics-integrated data-independent acquisition proteomic technique. The performance of candidate proteins as diagnostic and prognostic biomarkers in PTMC was assessed via receiver operating characteristic analysis. We found that serum sEVs from PTMC patients promoted the proliferation and migration of human papillary thyroid cancer (PTC) cells and tube formation in human lymphatic endothelial cells (HLECs). SEV proteins from PTMC patients with and without LNM have differential expression profiles, with bone marrow stromal cell antigen 2 (BST2) being best associated with PTMC progression. Through knockdown and overexpression, we proved that the high expression of sEV-derived BST2 was bound up with higher proliferation and migration ability of PTC cells as well as stronger lymphangiogenesis in HLECs. This study brought insight into the differential sEV-protein profile with or without LNM in PTMC. The serum sEV-BST2 may contribute to PTMC progression and LNM and may have diagnostic, prognostic, and therapeutic implications.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667066","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

Ammonia death: a novel potential strategy to augment immunotherapy in cancer 氨死亡：增强癌症免疫疗法的潜在新策略。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-11-11 DOI: 10.1038/s41417-024-00851-y

Zhi Li, Junyi Lin, Peihao Yin

引用次数: 0

Overexpression of Pin1 regulated by TOP2A, which subsequently stabilizes Pyk2 to promote bortezomib resistance in multiple myeloma. 受TOP2A调控的Pin1过表达，随后稳定Pyk2，从而促进多发性骨髓瘤的硼替佐米耐药性。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-11-07 DOI: 10.1038/s41417-024-00845-w

Honghao Zhang, Jianyu Chen, Yabo Meng, Qingyan Cen, Hao Wang, Xiangyang Ding, Kexin Ai, Yulu Yang, Yang Gao, Yingqi Qiu, Yuxing Hu, Meifang Li, Yanjie He, Yuhua Li

{"title":"Overexpression of Pin1 regulated by TOP2A, which subsequently stabilizes Pyk2 to promote bortezomib resistance in multiple myeloma.","authors":"Honghao Zhang, Jianyu Chen, Yabo Meng, Qingyan Cen, Hao Wang, Xiangyang Ding, Kexin Ai, Yulu Yang, Yang Gao, Yingqi Qiu, Yuxing Hu, Meifang Li, Yanjie He, Yuhua Li","doi":"10.1038/s41417-024-00845-w","DOIUrl":"https://doi.org/10.1038/s41417-024-00845-w","url":null,"abstract":"Multiple myeloma (MM), a hematological malignancy of plasma cells, has remained largely incurable owing to drug resistance and disease relapse, which requires novel therapeutic targets and treatment approaches. Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) acts as an oncoprotein linked to the development of various tumors. However, the functional consequence of Pin1 overexpression in modulating MM biology has not been established. In the present study, we show that Pin1 expression is highly variable in myeloma cell lines and primary MMs and that high Pin1 expression is associated with poor survival of MM patients. Next, TOP2A is identified to be a Pin1 promoter-binding protein and CK2 activates TOP2A to promote the expression level of Pin1. Additionally, we demonstrate that Pin1 positively modulates the stability and function of Pyk2 to enhance bortezomib resistance in MM. Pin1 recognizes three phosphorylated Ser/Thr-Pro motifs in Pyk2 via its WW domain and increases the cellular levels of Pyk2 in an isomerase activity-dependent manner by inhibiting the ubiquitination and proteasomal degradation of Pyk2. Moreover, Pin1 inhibition combined with Pyk2 inhibition decreases myeloma burden both in vitro and in vivo. Altogether, our findings reveal the tumor-promoting role of Pin1 in MM and provide evidence that targeting Pin1 could be a therapeutic strategy for MM.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603103","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

Novel pharmacologic inhibition of lysine-specific demethylase 1 as a potential therapeutic for glioblastoma 新型赖氨酸特异性去甲基化酶 1 药物抑制剂作为胶质母细胞瘤的一种潜在疗法。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-11-05 DOI: 10.1038/s41417-024-00847-8

Keiko Shinjo, Takashi Umehara, Hideaki Niwa, Shin Sato, Keisuke Katsushima, Shinya Sato, Xingxing Wang, Yoshiteru Murofushi, Miho M. Suzuki, Hiroo Koyama, Yutaka Kondo

{"title":"Novel pharmacologic inhibition of lysine-specific demethylase 1 as a potential therapeutic for glioblastoma","authors":"Keiko Shinjo, Takashi Umehara, Hideaki Niwa, Shin Sato, Keisuke Katsushima, Shinya Sato, Xingxing Wang, Yoshiteru Murofushi, Miho M. Suzuki, Hiroo Koyama, Yutaka Kondo","doi":"10.1038/s41417-024-00847-8","DOIUrl":"10.1038/s41417-024-00847-8","url":null,"abstract":"Lysine-specific demethylase 1 (LSD1/KDM1A) is a pivotal epigenetic enzyme that contributes to several malignancies including malignant glioma. LSD1 is a flavin adenine dinucleotide dependent histone demethylase that specifically targets histone H3 lysine (K) 4 mono- (me1) and di-methylation (me2) and H3K9me1/2 for demethylation. Herein we report the development of an LSD inhibitor, S2172, which efficiently penetrates the blood-brain barrier. S2172 effectively suppresses LSD1 enzymatic activity, resulting in the depletion of cell growth both in vitro in glioma stem cells (GSCs) (mean half-maximal inhibitory concentration (IC50) of 13.8 μM) and in vivo in a GSC orthotopic xenograft mouse model. Treatment with S2172 robustly reduced the expression of the stemness-related genes MYC and Nestin in GSC cells. Consistent with this, chromatin immunoprecipitation-sequencing revealed a significant S2172-dependent alteration in H3K4me2/H3K4me3 status. Furthermore, we identified 284 newly acquired H3K4me2 peak regions after S2172 treatment, which were encompassed within super-enhancer regions. The altered H3K4me2/H3K4me3 status induced by S2172 treatment affected the expression of genes related to tumorigenesis. Our data suggest that targeting LSD1 with S2172 could provide a promising treatment option for glioblastomas, particularly due to targeting of GSC populations.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 12","pages":"1884-1894"},"PeriodicalIF":4.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00847-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581945","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

Role of non-coding RNA in lineage plasticity of prostate cancer. 非编码 RNA 在前列腺癌血统可塑性中的作用

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-11-04 DOI: 10.1038/s41417-024-00834-z

Wenhui Tan, Changkai Xiao, Min Ma, Youhan Cao, Zhenguo Huang, Xiaolan Wang, Ran Kang, Zhenfa Li, Ermao Li

{"title":"Role of non-coding RNA in lineage plasticity of prostate cancer.","authors":"Wenhui Tan, Changkai Xiao, Min Ma, Youhan Cao, Zhenguo Huang, Xiaolan Wang, Ran Kang, Zhenfa Li, Ermao Li","doi":"10.1038/s41417-024-00834-z","DOIUrl":"10.1038/s41417-024-00834-z","url":null,"abstract":"The treatment of prostate cancer (PCa) has made great progress in recent years, but treatment resistance always develops and can even lead to fatal disease. Exploring the mechanism of drug resistance is of great significance for improving treatment outcomes and developing biomarkers with predictive value. It is increasingly recognized that mechanism of drug resistance in advanced PCa is related to lineage plasticity and tissue differentiation. Specifically, one of the mechanisms by which castration-resistant prostate cancer (CRPC) cells acquire drug resistance and transform into neuroendocrine prostate cancer (NEPC) cells is lineage plasticity. NEPC is a subtype of PCa that is highly aggressive and lethal, with a median survival of only 7 months. With the development of high-throughput RNA sequencing technology, more and more non-coding RNAs have been identified, which play important roles in different diseases through different mechanisms. Several ncRNAs have shown great potential in PCa lineage plasticity and as biomarkers. In the review, the role of ncRNA in PCa lineage plasticity and its use as biomarkers were reviewed.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575078","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