作者机构:
[Liu, Qian-Wen; Yu, Hong; Liu, Xin-Yun; Yang, Qin-Xin] Department of Pathology, The Affiliated Taizhou People's Hospital of Nanjing Medical University,Taizhou,Jiangsu Province 225300,China;[Liu, Qian-Wen] General Surgery, Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine,Shanghai 200025,China;[Yang, Zhi-Wen] Department of Pharmacy, Changning Maternity and Infant Health Hospital, East China Normal University, Shanghai,Shanghai 200050,China;[Tang, Qing-Hai] Hunan Key Laboratory for Conservation and Utilization of Biological Resources in the Nanyue Mountainous Region and College of Life Sciences, Hengyang Normal University,Hengyang,Hunan Province 421008,China;[Wang, Wen -Er] General Surgery, the Fourth Hospital Of Changsha, Changsha Hospital Of Hunan Normal University,Changsha,Hunan Province 410006,China
摘要:
Synthetic lethality is a phenomenon wherein the simultaneous deficiency of two or more genes results in cell death, while the deficiency of any individual gene does not lead to cell death. In recent years, synthetic lethality has emerged as a significant topic in the field of targeted cancer therapy, with certain drugs based on this concept exhibiting promising outcomes in clinical trials. Nevertheless, the presence of tumor heterogeneity and the intricate DNA repair mechanisms pose challenges to the effective implementation of synthetic lethality. This review aims to explore the concepts, development, and ethical quandaries surrounding synthetic lethality. Additionally, it will provide an in-depth analysis of the clinical application and underlying mechanism of synthetic lethality.
期刊:
Journal of Advanced Research,2023年54:133-146 ISSN:2090-1232
通讯作者:
Liu, JB;Fu, D;Ma, YS
作者机构:
[Diao, Xun; Liu, Ji-Bin; Liu, JB; Li, Sha; Fan, Qi-Yu] Nantong Univ, Inst Oncol, Affiliated Tumor Hosp, Nantong 226631, Jiangsu, Peoples R China.;[Li, Sha] Cent South Univ, Hunan Canc Hosp, Dept Head & Neck Surg, Cent Lab, Changsha 410013, Hunan, Peoples R China.;[Li, Sha] Cent South Univ, Xiangya Sch Med, Affiliated Canc Hosp, Changsha 410013, Hunan, Peoples R China.;[Xue, Pei] Shanghai Jiao Tong Univ, Sch Med, Dept Gen Surg, Div Gastrointestinal & Colorectal Surg,Ruijin Hosp, Shanghai 200025, Peoples R China.;[Ye, Kun] Cent South Univ, Xiangya Hosp 2, Dept Urol, Changsha 410011, Hunan, Peoples R China.
通讯机构:
[Liu, JB ] N;[Fu, D ; Ma, YS ] S;Nantong Univ, Inst Oncol, Affiliated Tumor Hosp, Nantong 226631, Jiangsu, Peoples R China.;Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Gen Surg,Inst Pancreat Dis, Shanghai 200025, Peoples R China.;Shanghai Univ Tradit Chinese Med, Longhua Hosp, Canc Inst, Shanghai 200032, Peoples R China.
关键词:
LIHC;Tumor;Treatment;Biomarker;Therapy
摘要:
Background: Aberrations in MYC underlie a large proportion of liver hepatocellular carcinoma (LIHC) cases; however, MYC is difficult to target because of its undruggable structure. We aimed to uncover MYC-associated molecular targets to provide new strategies for LIHC treatment. Methods: LIHC transcriptome datasets and clinical information were obtained from The Cancer Genome Atlas. A series of bioinformatics analyses were performed for 370 patients who were stratified based on the median MYC expression level (high-MYC group and low-MYC group). Correlation analysis was performed to determine relationships between the expression of key MYC-associated genes and prognosis, DNA promotor methylation, and immune cell infiltration. Gene ontology and Kyoto Encyclopedia of Genes and Genomes Pathway enrichment analyses were performed to elucidate the functions of these genes in LIHC. Their expression and functions in LIHC were further verified using transgenic mice overexpressing c-Myc under control of the hepatocyte-specific promoter (Alb-Cre). Results: AURKB, CCNB2, and CDKN3 were overexpressed in LIHC patients with high MYC expression and were associated with poor prognosis. Upregulation of these 3 genes was significantly correlated with hypomethylated promoter status, advanced T stage, metastasis, and immune cell infiltration in LIHC patients. Functional enrichment analyses indicated that these genes participate in the "p53 signaling pathway" and "cell cycle". Furthermore, RT-PCR and IHC analysis revealed that their mRNA and protein expression levels were upregulated in an Alb-Cre;cMYClsl/- mouse model. Drugs that target these 3 MYCrelated genes were identified. Conclusion: Taken together, our results identify biomarkers of potential utility for managing liver cancer therapy owing to their significance in tumorigenesis, proliferation, and tumor immunity. (c) 2023 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article
期刊:
Annals of Medicine,2022年54(1):2785-2795 ISSN:0785-3890
通讯作者:
Fu, D.;Cao, Y.-F.;Ma, Y.-S.
作者机构:
[Diao, Xun; Li, Sha; Yu, Xue-Chen; Fan, Qi-Yu; Liu, Ji-Bin] Nantong Univ, Affiliated Tumor Hosp, Inst Oncol, Nantong, Peoples R China.;[Yu, Xue-Chen] Macalester Coll, Dept Math Stat & Comp Sci, St Paul, MN USA.;[Tang, Qing-Hai] Hengyang Normal Univ, Hunan Key Lab Conservat & Utilizat Biol Resource, Hengyang, Peoples R China.;[Tang, Qing-Hai] Hengyang Normal Univ, Coll Life Sci & Environm, Hengyang, Peoples R China.;[Tang, Xiao-Mei; Fu, Da; Huang, Zhong-Yan] Shanghai Jiao Tong Univ, Ruijin Hosp, Gen Surg, Sch Med, Shanghai, Peoples R China.
通讯机构:
[Yong-Feng Cao] D;[Yu-Shui Ma] C;[Da Fu] G;Department of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, China<&wdkj&>Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China<&wdkj&>General Surgery, Ruijin Hospital & Institute of Pancreatic Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, China<&wdkj&>Central Laboratory for Medical Research, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
摘要:
Nitric oxide (NO), an essential biological messenger molecule, participates in various physiological and pathological processes. The sensitive and specific detection of NO is of great significance for understanding the biological function of NO. Here, we synthesized a fluorescent probe (Rho-NO) for highly selective detection of NO both in vitro and in vivo. The high selectivity of Rho-NO is attributed to the fact that NO is easily replaced by electron donor amino group to form N-nitrosation products, causing rhodamine spiro ring open and fluorescence emit. Rho-NO showed a good linear response to NO (0-100 mu M) with a low detection limit (0.06 mu M). Importantly, it exhibited excellent specificity for NO detection in human serum and was also applied for imaging NO in living cells and inflammatory model of zebrafish. This work proves the potential of Rho-NO in pathological research and disease diagnosis. (C) 2021 Elsevier B.V. All rights reserved.
摘要:
<jats:title>Abstract</jats:title><jats:p>In order to determine the effect of different oligosaccharides on growth performance, intestinal health, and antioxidant status of broilers, 240 1‐day‐old XiangHuang broilers were randomly distributed to 4 treatments with 6 replicates each. Birds were fed corn‐soybean‐based diets (CON), and birds in xylo‐oligosaccharides (XOS), fructo‐oligosaccharides (FOS), and iso‐maltooligosaccharide (IMO) groups were given the basal diet supplemented with 200 mg/kg XOS, FOS, and IMO, respectively. Result showed that average daily gain (ADG) during the whole 5weeks in FOS group was greater than that in control group (<jats:italic>p</jats:italic> < 0.05). Both breast and thigh muscle percentages were higher for birds fed XOS versus CON (<jats:italic>p</jats:italic> < 0.05). Oligosaccharides supplementation increased jejunal villus height compared with control group (<jats:italic>p <</jats:italic> 0.05). Malondialdehyde (MDA) concentration in breast muscle was lower for birds fed diet containing FOS versus CON (<jats:italic>p</jats:italic> < 0.05). Activities of total superoxide dismutase (T‐SOD) in serum and thigh muscle were higher in IMO than in control group (<jats:italic>p</jats:italic> < 0.05). Serum T‐SOD and breast muscle's glutathione peroxidase (GSH‐Px) activity was higher in XOS compared with control group (<jats:italic>p</jats:italic> < 0.05). Conclusion, dietary oligosaccharides such as XOS, FOS, and IMO could improve intestinal health and antioxidant ability of muscle without affect growth performance in broilers.</jats:p>
摘要:
本研究旨在对临床1份腹泻病料进行病原的分离培养并探究该病原编码的主要抗原蛋白的生物学特点。采用巢式PCR检测病料猪腺病毒3型(Porcine adenovirus type 3,PADV3)核酸并进行病毒分离培养,采用免疫过氧化物酶单层细胞染色法(IPMA)进行病毒血清学鉴定,PCR扩增fiber基因,将其ORF区克隆至pET-28a(+)载体并转化大肠杆菌BL21(DE3)感受态细胞,IPTG诱导重组fiber蛋白表达,采用SDS-PAGE和Western blotting鉴定重组蛋白,将纯化的重组蛋白免疫家兔,制备多克隆抗体并测定抗体免疫活性。结果表明,病料为PADV3核酸阳性,感染ST细胞产生典型的"葡萄串"细胞病变效应(CPE),P5~P11代次中的PADV3核酸稳定,分离的毒株P5代为PADV3型血清学阳性,fiber基因开放阅读框(ORF)为1 296 bp (GenBank登录号:MT774498),与PADV3毒株的核苷酸相似性最高(86.1%),与其他毒株相似性均低于40%;原核表达的重组fiber蛋白分子质量为45.2 ku,fiber蛋白多克隆抗体与PADV3感染的细胞呈特异性的细胞核染色。本试验成功分离得到1株PADV3毒株,命名为PADV3-HY1812,所制备的fiber蛋白多克隆抗体具有良好的免疫活性。