Signal Transduction and Targeted Therapy最新文献_第2页

Metformin: decelerates biomarkers of aging clocks 二甲双胍：减慢生物标志物的衰老时钟

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-11-13 DOI: 10.1038/s41392-024-02046-1

Ram Abou Zaki, Assam El-Osta

引用次数: 0

Comparison of drug-eluting bead transarterial chemoembolization combined with apatinib versus drug-eluting bead transarterial chemoembolization for the treatment of unresectable hepatocellular carcinoma: a randomized, prospective, multicenter phase III trial 药物洗脱珠经动脉化疗栓塞联合阿帕替尼与药物洗脱珠经动脉化疗栓塞治疗不可切除肝细胞癌的比较：随机、前瞻性、多中心III期试验

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-11-13 DOI: 10.1038/s41392-024-02012-x

Xuhua Duan, Hao Li, Donglin Kuang, Pengfei Chen, Mengfan Zhang, Tengfei Li, Dechao Jiao, Yanliang Li, Xiang He, Cheng Xing, Haibo Wang, Yaoxian Liu, Limin Xie, Shixi Zhang, Qiang Zhang, Peixin Zhu, Yongchuang Chang, Jichen Xie, Jianzhuang Ren, Xinwei Han

{"title":"Comparison of drug-eluting bead transarterial chemoembolization combined with apatinib versus drug-eluting bead transarterial chemoembolization for the treatment of unresectable hepatocellular carcinoma: a randomized, prospective, multicenter phase III trial","authors":"Xuhua Duan, Hao Li, Donglin Kuang, Pengfei Chen, Mengfan Zhang, Tengfei Li, Dechao Jiao, Yanliang Li, Xiang He, Cheng Xing, Haibo Wang, Yaoxian Liu, Limin Xie, Shixi Zhang, Qiang Zhang, Peixin Zhu, Yongchuang Chang, Jichen Xie, Jianzhuang Ren, Xinwei Han","doi":"10.1038/s41392-024-02012-x","DOIUrl":"https://doi.org/10.1038/s41392-024-02012-x","url":null,"abstract":"This randomized, prospective, multicenter (12 centers in China) phase III trial (Chinese Clinical Trial Registry #ChiCTR2000041170) compared drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with apatinib and DEB-TACE monotherapy for patients with unresectable hepatocellular carcinoma (uHCC). Progression-free survival (PFS) was the primary endpoint. Overall survival (OS), mRECIST-based objective response rates (ORR) and disease control rates (DCR), and treatment-related adverse events (TRAEs) were secondary endpoints. Totally 243 cases were randomized, with 122 and 121 in the DEB-TACE + apatinib and DEB-TACE groups, respectively. Cases administered DEB-TACE + apatinib displayed markedly improved median PFS (7.1 months [95%CI 6.6–8.3] vs. 5.2 months [95%CI 5.0–5.9]) and OS (23.3 months [95%CI 20.7–29.6] vs. 18.9 months [95%CI 17.9–20.1] compared with those treated with DEB-TACE (both p < 0.001). Additionally, patients administered DEB-TACE + apatinib had elevated ORR (56.6% vs. 38.8%) and DCR (89.3% vs. 80.2%) versus the DEB-TACE group (both p < 0.001). Majority of TRAEs were mild and manageable. Regarding DEB-TACE-related TRAEs, the rates of hepatic artery thinning and spasms were elevated during the second DEB-TACE in cases administered DEB-TACE + apatinib vs. DEB-TACE. The commonest apatinib-related TRAEs in the DEB-TACE + apatinib group included hypertension, hand-foot syndrome, fatigue, and diarrhea. In conclusion, DEB-TACE plus apatinib demonstrates superior PFS versus DEB-TACE monotherapy in uHCC cases, maintaining a favorable safety profile with similar occurrences of AEs.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"19 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601148","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

Overexpression of STX11 alleviates pulmonary fibrosis by inhibiting fibroblast activation via the PI3K/AKT/mTOR pathway 过表达 STX11 可通过 PI3K/AKT/mTOR 通路抑制成纤维细胞的活化，从而减轻肺纤维化程度

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-11-11 DOI: 10.1038/s41392-024-02011-y

Guichuan Huang, Xiangsheng Yang, Qingyang Yu, Qun Luo, Chunrong Ju, Bangyan Zhang, Yijing Chen, Zihan Liang, Shu Xia, Xiaohua Wang, Dong Xiang, Nanshan Zhong, Xiao Xiao Tang

{"title":"Overexpression of STX11 alleviates pulmonary fibrosis by inhibiting fibroblast activation via the PI3K/AKT/mTOR pathway","authors":"Guichuan Huang, Xiangsheng Yang, Qingyang Yu, Qun Luo, Chunrong Ju, Bangyan Zhang, Yijing Chen, Zihan Liang, Shu Xia, Xiaohua Wang, Dong Xiang, Nanshan Zhong, Xiao Xiao Tang","doi":"10.1038/s41392-024-02011-y","DOIUrl":"https://doi.org/10.1038/s41392-024-02011-y","url":null,"abstract":"Fibroblast activation plays an important role in the occurrence and development of idiopathic pulmonary fibrosis (IPF), which is a progressive, incurable, and fibrotic lung disease. However, the underlying mechanism of fibroblast activation in IPF remains elusive. Here, we showed that the expression levels of STX11 and SNAP25 were downregulated in the lung tissues from patients with IPF and mice with bleomycin (BLM)-induced lung fibrosis as well as in the activated fibroblasts. Upregulation of STX11 or SNAP25 suppressed TGF-β1-induced activation of human lung fibroblasts (HLFs) via promoting autophagy. However, they failed to suppress fibroblast actviation when autophagy was blocked with the use of chloroquine (CQ). In addition, STX11 or SNAP25 could inhibit TGF-β1-induced fibroblast proliferation and migration. In vivo, overexpression of STX11 exerted its protective role in the mice with BLM-induced lung fibrosis. STX11 and SNAP25 mutually promoted expression of each other. Co-IP assay indicated that STX11 has an interaction with SNAP25. Mechanistically, STX11-SNAP25 interaction activated fibroblast autophagy and further inhibited fibroblast activation via blocking the PI3K/AKT/mTOR pathway. Overall, the results suggested that STX11-SNAP25 interaction significantly inhibited lung fibrosis by promoting fibroblast autophagy and suppressing fibroblast activation via blocking the PI3K/ATK/mTOR signaling pathway. Therefore, STX11 serves as a promising therapeutic target in IPF.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"30 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598025","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

Post-fast refeeding: rise of intestinal stemness and mutagen-induced cancer risk through polyamine metabolism 禁食后再喂养：通过多胺代谢提高肠道干性和诱变致癌风险

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-11-11 DOI: 10.1038/s41392-024-02038-1

Sarah Brunner, Klaus-Peter Janssen, Josef Ecker

引用次数: 0

Comprehensive snapshots of natural killer cells functions, signaling, molecular mechanisms and clinical utilization 自然杀伤细胞功能、信号传导、分子机制和临床应用的综合快照

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-11-08 DOI: 10.1038/s41392-024-02005-w

Sumei Chen, Haitao Zhu, Youssef Jounaidi

{"title":"Comprehensive snapshots of natural killer cells functions, signaling, molecular mechanisms and clinical utilization","authors":"Sumei Chen, Haitao Zhu, Youssef Jounaidi","doi":"10.1038/s41392-024-02005-w","DOIUrl":"https://doi.org/10.1038/s41392-024-02005-w","url":null,"abstract":"Natural killer (NK) cells, initially identified for their rapid virus-infected and leukemia cell killing and tumor destruction, are pivotal in immunity. They exhibit multifaceted roles in cancer, viral infections, autoimmunity, pregnancy, wound healing, and more. Derived from a common lymphoid progenitor, they lack CD3, B-cell, or T-cell receptors but wield high cytotoxicity via perforin and granzymes. NK cells orchestrate immune responses, secreting inflammatory IFNγ or immunosuppressive TGFβ and IL-10. CD56dim and CD56bright NK cells execute cytotoxicity, while CD56bright cells also regulate immunity. However, beyond the CD56 dichotomy, detailed phenotypic diversity reveals many functional subsets that may not be optimal for cancer immunotherapy. In this review, we provide comprehensive and detailed snapshots of NK cells’ functions and states of activation and inhibitions in cancer, autoimmunity, angiogenesis, wound healing, pregnancy and fertility, aging, and senescence mediated by complex signaling and ligand-receptor interactions, including the impact of the environment. As the use of engineered NK cells for cancer immunotherapy accelerates, often in the footsteps of T-cell-derived engineering, we examine the interactions of NK cells with other immune effectors and relevant signaling and the limitations in the tumor microenvironment, intending to understand how to enhance their cytolytic activities specifically for cancer immunotherapy.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"36 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597072","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

First-line benmelstobart plus anlotinib and chemotherapy in advanced or metastatic/recurrent esophageal squamous cell carcinoma: a multi-center phase 2 study 晚期或转移性/复发性食管鳞状细胞癌一线治疗本迈斯托巴特+安罗替尼和化疗：一项多中心2期研究

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-11-08 DOI: 10.1038/s41392-024-02008-7

Ning Li, Jin Xia, Xiaohui Gao, Jianwei Zhou, Yonggui Hong, Donghai Cui, Xuesong Zhao, Tao Wu, Yanzhen Guo, Junsheng Wang, Suxia Luo

{"title":"First-line benmelstobart plus anlotinib and chemotherapy in advanced or metastatic/recurrent esophageal squamous cell carcinoma: a multi-center phase 2 study","authors":"Ning Li, Jin Xia, Xiaohui Gao, Jianwei Zhou, Yonggui Hong, Donghai Cui, Xuesong Zhao, Tao Wu, Yanzhen Guo, Junsheng Wang, Suxia Luo","doi":"10.1038/s41392-024-02008-7","DOIUrl":"https://doi.org/10.1038/s41392-024-02008-7","url":null,"abstract":"Although first-line immunochemotherapy has improved prognosis for patients with advanced esophageal squamous cell carcinoma (ESCC), more effective strategies still require further investigation. This multi-center, phase II study (ClinicalTrials.gov NCT05013697) assessed the feasibility of benmelstobart (a novel PD-L1 inhibitor) plus anlotinib (multitargeted TKI) and chemotherapy in advanced or metastatic/recurrent ESCC. Eligible patients received 4–6 cycles (21-day) of benmelstobart (1200 mg), anlotinib (10 mg) plus paclitaxel (135 mg/m2)/cisplatin (60–75 mg/m2), then maintained with benmelstobart and anlotinib. Primary endpoint was progression-free survival (PFS) assessed according to RECIST v1.1. Secondary endpoints were tumor response, overall survival (OS), and safety assessed by adverse events (AEs). From September 2021 to November 2023, 50 patients were enrolled and received study treatment. With median follow-up of 23.7 months as of April 1, 2024, median PFS was 14.9 months (95% CI, 11.4-not estimable [NE]) and the 1-year PFS was 58.5% (95% CI, 41.9%–71.9%). Among 50 patients, confirmed objective response rate was 72.0% and disease control rate was 84.0%. Median duration of response of 36 responders was 16.2 months (95% CI, 10.2-NE). At the cutoff date, 31 patients remained alive; median OS was not reached (95% CI, 13.2 months-NE) with 1-year OS of 74.8% (95% CI, 59.8%–84.8%). Forty-six (92.0%) patients reported treatment-related AEs, with 37 (74.0%) were grade ≥3. Overall, benmelstobart plus anlotinib and chemotherapy showed promising efficacy and acceptable toxicity in advanced or metastatic/recurrent ESCC.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"24 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597115","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}

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Multiplexed RNAs in lipid nanoparticles: potential therapeutic vaccine for chronic hepatitis B 脂质纳米颗粒中的多重 RNA：慢性乙型肝炎的潜在治疗疫苗

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-11-07 DOI: 10.1038/s41392-024-02026-5

Hari Krishnareddy Rachamala, Srujan Marepally

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Moving towards precision psychiatry: the hard nut of depression 迈向精准精神病学：抑郁症这块硬骨头

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-11-07 DOI: 10.1038/s41392-024-02023-8

Juergen Dukart, Leon D. Lotter, Simon B. Eickhoff

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Mef2d: a novel transcription factor in type 2 allergic lung inflammation Mef2d：2型过敏性肺部炎症中的新型转录因子

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-11-07 DOI: 10.1038/s41392-024-02022-9

Laura Surace, Christoph Wilhelm, Christian Bode

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Early intermittent cholesterol exposure accelerates atherosclerosis: an oscillating amplifier calling for preemptive control 早期间歇性接触胆固醇会加速动脉粥样硬化：振荡放大器需要预先控制

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-11-07 DOI: 10.1038/s41392-024-02032-7

Maria Kral, Yvonne Döring, Christian Weber

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