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《医学前沿(英文)》 2014年 第8卷 第2期 页码 227-235 doi: 10.1007/s11684-014-0327-1
Accelerated senescence is important because this process is involved in tumor suppression and has been induced by many chemotherapeutic agents. The platinum-based chemotherapeutic agent cisplatin displays a wide range of antitumor activities. However, the molecular mechanism of cisplatin-induced accelerated senescence in hepatocellular carcinoma (HCC) remains unclear. In the present study, the growth inhibitory effect of cisplatin on HepG2 and SMMC-7721 cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cellular senescence was then assessed by β-galactosidase assay. Senescence-related factors, including p53, p21, and p16, were evaluated by quantitative reverse transcription-polymerase chain reaction. Reactive oxygen species (ROS) was analyzed by flow cytometry. Our results revealed that cisplatin reduced the proliferation of HepG2 and SMMC-7721 cells in a dose- and time-dependent manner. Senescent phenotype observed in cisplatin-treated hepatoma cells was dependent on p53 and p21 activation but not on p16 activation. Furthermore, cisplatin-induced accelerated senescence depended on intracellular ROS generation. The ROS scavenger N-acetyl-L-cysteine also significantly suppressed the cisplatin-induced senescence of HepG2 and SMMC-7721 cells. In conclusion, our results revealed a functional link between intracellular ROS generation and cisplatin-induced accelerated senescence, and this link may be used as a potential target of HCC.
关键词: reactive oxygen species senescence cisplatin hepatocellular carcinoma
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《医学前沿(英文)》 2014年 第8卷 第1期 页码 106-112 doi: 10.1007/s11684-014-0307-5
Cervical carcinoma is associated with high propensity for local invasion and lymph node metastasis. However, the molecular alterations that drive progression and metastasis of cervical cancer remain unclear. Cellular senescence has been proposed as the mechanism that protects an organism against cancer progression and metastasis. In addition, Twist, a basic helix-loop-helix transcription factor, has been suggested as an oncogene because it is overexpressed in many types of human cancer. This gene also exhibits a positive function in regulating invasion and metastasis. In this study, Twist was strongly and positively expressed in normal tissue, squamous cell carcinoma (SCC) IA--IIA, and SCC IIB--IIIB (4.3%, 44%, and 88.9%, respectively). The strong positive expressions of the senescence marker CBX3 were 39.1%, 32%, and 15.6%, respectively. The strong positive expressions of Twist in the SCC groups with or without lymph node metastasis were 80.8% and 50%. For CBX3, such expressions were 7.7% and 29.5%, respectively. Results also showed that the expression of Twist was inversely correlated with that of CBX3. Moreover, the knockdown of Twist with target siRNA in SiHa triggered the induction of the chromatin marker of the cellular senescence CBX3 and senescence-associated β-galactosidase activity. Our results suggested that the expression of Twist increased during the progression and metastasis of cervical cancer. Furthermore, Twist-induced senescence bypass is important in this process.
关键词: cervical cancer senescence Twist CBX3 lymph node metastasis
Biqiong Fu, Jie Yang, Jia Chen, Lirong Lin, Kehong Chen, Weiwei Zhang, Jianguo Zhang, Yani He
《医学前沿(英文)》 2019年 第13卷 第2期 页码 267-276 doi: 10.1007/s11684-017-0586-8
关键词: Shenkang injection senescence renal tubular epithelial cells diabetic nephropathy
Taking advantage of drug resistance, a new approach in the war on cancer
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《医学前沿(英文)》 2018年 第12卷 第4期 页码 490-495 doi: 10.1007/s11684-018-0647-7
Identification of the driver mutations in cancer has resulted in the development of a new category of molecularly targeted anti-cancer drugs. However, as was the case with conventional chemotherapies, the effectiveness of these drugs is limited by the emergence of drug-resistant variants. While most cancer therapies are given in combinations that are designed to avoid drug resistance, we discuss here therapeutic approaches that take advantage of the changes in cancer cells that arise upon development of drug resistance. This approach is based on notion that drug resistance comes at a fitness cost to the cancer cell that can be exploited for therapeutic benefit. We discuss the development of sequential drug therapies in which the first therapy is not given with curative intent, but to induce a major new sensitivity that can be targeted with a second drug that selectively targets the acquired vulnerability. This concept of collateral sensitivity has hitherto not been used on a large scale in the clinic and holds great promise for future cancer therapy.
关键词: cancer drug resistance genetic screens senescence targeted therapy
ECRG4: a new potential target in precision medicine
Xin Qin, Ping Zhang
《医学前沿(英文)》 2019年 第13卷 第5期 页码 540-546 doi: 10.1007/s11684-018-0637-9
关键词: ECRG4 tumor suppressor gene sentinel molecule precision medicine cell senescence epithelium homeostasis
Qi RUI, Qin LU, Dayong WANG
《医学前沿(英文)》 2009年 第3卷 第1期 页码 76-90 doi: 10.1007/s11684-009-0002-0
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标题 作者 时间 类型 操作
Reactive oxygen species generation is essential for cisplatin-induced accelerated senescence in hepatocellular
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期刊论文
Correlation of Twist upregulation and senescence bypass during the progression and metastasis of cervical
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期刊论文
Preventive effect of Shenkang injection against high glucose-induced senescence of renal tubular cells
Biqiong Fu, Jie Yang, Jia Chen, Lirong Lin, Kehong Chen, Weiwei Zhang, Jianguo Zhang, Yani He
期刊论文