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Shikonin is a novel antagonist of prostaglandin E2 receptor 4 that targets myeloid-derived suppressor cells Shikonin 是一种新型前列腺素 E2 受体 4 拮抗剂,可靶向髓源性抑制细胞
IF 6.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-20 DOI: 10.1016/j.gendis.2024.101356
Yang Wang, Naijipu Abuduaini, Wenjuan Liu, Yuanjun Song, Zunping Ke, Xilong Wang, Wei Jiao, Si Chen, Xianhua Lin, Weiwei Yu, Weiqiang Lu, Bo Feng, Jiacheng He
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引用次数: 0
Targeting MUC1 with fisetin in oral squamous cell carcinoma 用菲赛汀靶向治疗口腔鳞状细胞癌中的 MUC1
IF 6.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-20 DOI: 10.1016/j.gendis.2024.101357
Qian Wang, Hongyan Zhang, Shuzhen Xiang, Lan Zhang, Jiajia Fan, Zengyan Xu, Fengfei Zhao, Minda Liu, Yanshu Li, Wei Dai
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引用次数: 0
GATA6 in pancreatic cancer initiation and progression GATA6 在胰腺癌发生和发展过程中的作用
IF 6.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-17 DOI: 10.1016/j.gendis.2024.101353
Muyuan Ma, Jianhong An, Tingting Jiang, Keping Xie
Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy characterized by insidious onset and lack of effective therapy. The molecular pathogenesis of PDA remains to be understood fully. Transcriptional factor GATA6 is an important transcriptional regulator in normal pancreas development, particularly in the initial specification and differentiation of the pancreas. Recent studies have linked pancreatic malignancy closely to GATA6. Increased levels of GATA6 expression enhance pancreatic cancer cell growth. GATA6 emerges as a lineage-specific oncogenic factor in PDA, augmenting the oncogenic phenotypes of PDA cells upon its overexpression. However, elevated GATA6 levels are correlated with well-differentiated tumors and a more favorable patient prognosis. Experimental evidence in genetic mouse models has revealed a tumor-suppressive role for GATA6. The circumstantial roles of GATA6 in pancreatic tumorigenesis remain to be defined. This review aims to elucidate recent advances in comprehending GATA6, emphasizing its crucial roles in both pancreas physiology and pathology. Special attention will be given to its involvement in PDA pathogenesis, exploring its potential as a novel biomarker and a promising therapeutic target for PDA.
胰腺导管腺癌(PDA)是一种致命的恶性肿瘤,其特点是起病隐匿且缺乏有效治疗。PDA 的分子发病机制仍有待全面了解。转录因子 GATA6 是胰腺正常发育过程中的一个重要转录调节因子,尤其是在胰腺的初始规格化和分化过程中。最近的研究表明,胰腺恶性肿瘤与 GATA6 密切相关。GATA6 表达水平的升高会促进胰腺癌细胞的生长。在胰腺癌中,GATA6 是一种细胞系特异性致癌因子,其过量表达会增强胰腺癌细胞的致癌表型。然而,GATA6 水平的升高与肿瘤分化良好和患者预后较好有关。遗传小鼠模型的实验证据表明,GATA6 具有抑制肿瘤的作用。GATA6 在胰腺肿瘤发生中的间接作用仍有待明确。本综述旨在阐明在理解 GATA6 方面的最新进展,强调其在胰腺生理和病理中的关键作用。本综述将特别关注 GATA6 在胰腺肿瘤发病机制中的作用,探讨其作为新型生物标志物和有希望成为胰腺肿瘤治疗靶点的潜力。
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引用次数: 0
HER3: Unmasking a twist in the tale of a previously unsuccessful therapeutic pursuit targeting a key cancer survival pathway HER3:揭开以前针对关键癌症生存途径的不成功疗法的曲折故事
IF 6.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-17 DOI: 10.1016/j.gendis.2024.101354
Omkar Desai, Moeez Rathore, Christina S. Boutros, Michel'le Wright, Elizabeth Bryson, Kimberly Curry, Rui Wang
HER3, formally referred to as ERB-B2 receptor tyrosine kinase 3, is a member of the ErbB receptor tyrosine kinases (also known as EGFR) family. HER3 plays a significant pro-cancer role in various types of cancer due to its overexpression and abnormal activation, which initiates downstream signaling pathways crucial in cancer cell survival and progression. As a result, numerous monoclonal antibodies have been developed to block HER3 activation and subsequent signaling pathways. While pre-clinical investigations have effectively showcased significant anti-cancer effects of HER3-targeted therapies, these therapies have had little impact on cancer patient outcomes in the clinic, except for patients with rare fusion mutations. This review offers a comprehensive description of the oncogenic functions of HER3, encompassing its structure and mediating signaling pathways. More importantly, it provides an in-depth exploration of past and ongoing clinical trials investigating HER3-targeted therapies for distinct types of cancer and discusses the tumor microenvironment and other critical determinants that may contribute to the observed suboptimal outcomes in most clinical studies using HER3-targeted therapies. Lastly, we suggest alternative approaches and the exploration of novel strategies to potentially improve the efficacy of targeting the pivotal oncogenic HER3 signaling pathway in future translational investigations.
HER3,正式名称为 ERB-B2 受体酪氨酸激酶 3,是 ErbB 受体酪氨酸激酶(又称表皮生长因子受体)家族的成员。HER3 在各种癌症中发挥着重要的促癌作用,因为它的过度表达和异常激活会启动对癌细胞存活和发展至关重要的下游信号通路。因此,人们开发了许多单克隆抗体来阻断 HER3 的活化和后续信号通路。虽然临床前研究有效地展示了 HER3 靶向疗法的显著抗癌效果,但这些疗法在临床上对癌症患者的治疗效果影响甚微,只有罕见的融合突变患者除外。本综述全面描述了 HER3 的致癌功能,包括其结构和介导信号通路。更重要的是,它深入探讨了过去和正在进行的针对不同类型癌症的 HER3 靶向疗法临床试验,并讨论了肿瘤微环境和其他可能导致大多数使用 HER3 靶向疗法的临床研究结果不理想的关键因素。最后,我们建议在未来的转化研究中采用其他方法和探索新策略,以提高靶向关键致癌因子 HER3 信号通路的疗效。
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引用次数: 0
Corrigendum to “N6-methyladenosine modified LINC00901 promotes pancreatic cancer progression through IGF2BP2/MYC axis” [Genes & Diseases 10 (2023) 554–567] 更正件
IF 6.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-15 DOI: 10.1016/j.gendis.2024.101352
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引用次数: 0
Alternative splicing of immune-related genes identifies breast cancer subtypes with differential immune cell infiltration 免疫相关基因的交替剪接确定了具有不同免疫细胞浸润的乳腺癌亚型
IF 6.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-14 DOI: 10.1016/j.gendis.2024.101349
Zhangxiang Zhao , Yuquan Wang , Zixin Jin , Huiming Han , Bo Chen , Mingyue Liu , Kaidong Liu , Shuping Zhuang , Haihai Liang , Yunyan Gu
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引用次数: 0
Gene expression analysis in subcutaneous adipose tissue reveals a predominant influence of lncRNAs during growth 皮下脂肪组织的基因表达分析揭示了生长过程中 lncRNA 的主要影响因素
IF 6.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-14 DOI: 10.1016/j.gendis.2024.101351
Federica Rey , Letizia Messa , Clarissa Berardo , Alessia Mauri , Gianvincenzo Zuccotti , Cristina Cereda , Stephana Carelli
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引用次数: 0
Anoikis-related gene signature associates with the immune infiltration and predicts the prognosis of glioma patients 免疫相关基因特征与免疫浸润有关,可预测胶质瘤患者的预后
IF 6.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-04 DOI: 10.1016/j.gendis.2024.101346
Jianghua Lin , Junbao Wang , Junmiao Zhao , Xinyi Wu , Leiyu Hao , Xiao Tan , Lixue Yang , Lei-Lei Wu , Yuyang Xia , Xiaoling Zhang , Kaijun Zhao , Yu'e Liu
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引用次数: 0
Mutational single nucleotide polymorphism rs198389 and demethylation promoted natriuretic peptide B gene transcription in heart failure caused by dilated cardiomyopathy 突变单核苷酸多态性 rs198389 和去甲基化促进扩张型心肌病所致心力衰竭中钠尿肽 B 基因的转录
IF 6.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-05-31 DOI: 10.1016/j.gendis.2024.101345
Yulong Li , Mingzhi Shen , Ting Yang , Shui Yu , Jianyuan Yin , Leiming Luo , Yali Zhao , Ping Ping , Shihui Fu
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引用次数: 0
GAPDH suppresses adenovirus-induced oxidative stress and enables a superfast production of recombinant adenovirus GAPDH 可抑制腺病毒诱导的氧化应激,实现重组腺病毒的超快速生产
IF 6.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-05-31 DOI: 10.1016/j.gendis.2024.101344

Recombinant adenovirus (rAdV) is a commonly used vector system for gene transfer. Efficient initial packaging and subsequent production of rAdV remains time-consuming and labor-intensive, possibly attributable to rAdV infection-associated oxidative stress and reactive oxygen species (ROS) production. Here, we show that exogenous GAPDH expression mitigates adenovirus-induced ROS-associated apoptosis in HEK293 cells, and expedites adenovirus production. By stably overexpressing GAPDH in HEK293 (293G) and 293pTP (293GP) cells, respectively, we demonstrated that rAdV-induced ROS production and cell apoptosis were significantly suppressed in 293G and 293GP cells. Transfection of 293G cells with adenoviral plasmid pAd-G2Luc yielded much higher titers of Ad-G2Luc at day 7 than that in HEK293 cells. Similarly, Ad-G2Luc was amplified more efficiently in 293G than in HEK293 cells. We further showed that transfection of 293GP cells with pAd-G2Luc produced much higher titers of Ad-G2Luc at day 5 than that of 293pTP cells. 293GP cells amplified the Ad-G2Luc much more efficiently than 293pTP cells, indicating that exogenous GAPDH can further augment pTP-enhanced adenovirus production. These results demonstrate that exogenous GAPDH can effectively suppress adenovirus-induced ROS and thus accelerate adenovirus production. Therefore, the engineered 293GP cells represent a superfast rAdV production system for adenovirus-based gene transfer and gene therapy.

重组腺病毒(rAdV)是一种常用的基因转移载体系统。高效的 rAdV 初始包装和后续生产仍然耗时耗力,这可能归因于 rAdV 感染引起的氧化应激和活性氧(ROS)的产生。在这里,我们发现外源 GAPDH 的表达可减轻 HEK293 细胞中腺病毒诱导的 ROS 相关凋亡,并加快腺病毒的生产。通过分别在 HEK293(293G)和 293pTP(293GP)细胞中稳定地过表达 GAPDH,我们证明 rAdV 诱导的 ROS 产生和细胞凋亡在 293G 和 293GP 细胞中受到显著抑制。用腺病毒质粒 pAd-G2Luc 转染 293G 细胞,在第 7 天获得的 Ad-G2Luc 滴度远高于 HEK293 细胞。同样,Ad-G2Luc 在 293G 细胞中的扩增效率也高于 HEK293 细胞。我们进一步发现,用 pAd-G2Luc 转染 293GP 细胞,在第 5 天产生的 Ad-G2Luc 滴度远高于 293pTP 细胞。与 293pTP 细胞相比,293GP 细胞扩增 Ad-G2Luc 的效率更高,这表明外源 GAPDH 可进一步增强 pTP 增强的腺病毒生产。这些结果表明,外源 GAPDH 能有效抑制腺病毒诱导的 ROS,从而加速腺病毒的产生。因此,工程化的 293GP 细胞是基于腺病毒的基因转移和基因治疗的超快速 rAdV 生产系统。
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引用次数: 0
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