作者机构:
[Lei, Xiaoyong; Tang, Shengsong; Xing, Jichen] Univ South China, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hengyang 421001, Peoples R China.;[Lei, Xiaoyong; Tang, Shengsong; Xing, Jichen] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Tang, Shengsong; Xing, Jichen; Ning, Qian] Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua, Peoples R China.;[Tang, Diya] Cent South Univ, Dept Med Oncol, Xiangya Hosp, Changsha, Peoples R China.;[Mo, Zhongcheng] Guilin Med Univ, Coll Basic Med, Inst Basic Med Sci, Guilin, Guangxi, Peoples R China.
通讯机构:
[Tang, Shengsong] U;Univ South China, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hengyang 421001, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
关键词:
drug resistance;extrachromosomal DNA;oncogene amplification;tumor heterogeneity
摘要:
The amplification of oncogenes on extrachromosomal DNA (ecDNA) provides a new mechanism for cancer cells to adapt to the changes in the tumor microenvironment and accelerate tumor evolution. These extrachromosomal elements contain oncogenes, and their chromatin structures are more open than linear chromosomes and therefore have stronger oncogene transcriptional activity. ecDNA always contains enhancer elements, and genes on ecDNA can be reintegrated into the linear genome to regulate the selective expression of genes. ecDNA lacks centromeres, and the inheritance from the parent cell to the daughter cell is uneven. This non-Mendelian genetic mechanism results in the increase of tumor heterogeneity with daughter cells that can gain a competitive advantage through a large number of copies of oncogenes. ecDNA promotes tumor invasiveness and provides a mechanism for drug resistance associated with poorer survival outcomes. Recent studies have demonstrated that the overall proportion of ecDNA in tumors is approximately 40%. In this review, we summarize the current knowledge of ecDNA in the field of tumorigenesis and development.
期刊:
Journal of Drug Targeting,2021年29(7):703-715 ISSN:1061-186X
通讯作者:
Xianhui Zhang<&wdkj&>Linxi Chen
作者机构:
[Tang, Shengsong; Zhou, Qun] Hunan Univ Med, Sch Pharmaceut Sci, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua, Peoples R China.;[Zhang, Xianhui] Dongkou Peoples Hosp, Orthoped Dept, Dongkou 422300, Hunan, Peoples R China.;[Chen, Linxi] Univ South China, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hunan Prov Cooperat Innovat Ctr Mol Target, New Drug Study,Inst Pharm & Pharmacol, 28 Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Xianhui Zhang] O;[Linxi Chen] H;Orthopedics Department, Dongkou People’s Hospital, Dongkou, China<&wdkj&>Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target, New Drug Study, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, China
摘要:
Proline-rich Akt substrate of 40 kD (PRAS40) is not only the substrate of protein kinase B (PKB/Akt), but also the binding protein of 14-3-3 protein. PRAS40 is expressed in a variety of tissues in vivo and has multiple phosphorylation sites, which its activity is closely related to phosphorylation. Studies have shown that PRAS40 is involved in regulating cell growth, cell apoptosis, oxidative stress, autophagy and angiogenesis, as well as various of signalling pathways such as mammalian target of mammalian target rapamycin (mTOR), protein kinase B (PKB/Akt), nuclear factor kappa-B(NF-κB), proto-oncogene serine/threonine-protein kinase PIM-1(PIM1) and pyruvate kinase M2 (PKM2). The interactive roles between PRAS40 and these signal proteins were analysed by bioinformatics in this paper. Moreover, it is of great necessity for analyse the important roles of PRAS40 in some human diseases including cardiovascular disease, ischaemia-reperfusion injury, neurodegenerative disease, cancer, diabetes and other metabolic diseases. Finally, the effects of miRNA on the regulation of PRAS40 function and the occurrence and development of PRAS40-related diseases are also discussed. Overall, PRAS40 is expected to be a drug target and provide a new treatment strategy for human diseases.
期刊:
International Immunopharmacology,2020年86:106700 ISSN:1567-5769
通讯作者:
Tang, Shengsong
作者机构:
[Tang, Sha; Tang, Shengsong; Yang, Ling] Univ South China, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hengyang 421001, Peoples R China.;[Tang, Sha; Tang, Shengsong; Yang, Ling] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;[Tang, Sha; Tang, Shengsong; Yang, Ling; Ning, Qian] Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Peoples R China.;[Mo, Zhongcheng] Guilin Med Univ, Coll Basic Med, Inst Basic Med Sci, Guilin 541199, Guangxi, Peoples R China.
通讯机构:
[Tang, Shengsong] H;Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Peoples R China.
关键词:
Cancer immune cycle;Immune checkpoint;Immune escape;Immunotherapy
摘要:
Cancer is a critical issue globally with high incidence and mortality, imposing great burden on the society. Although great progress has been made in immunotherapy based on immune checkpoint, only a subset of patients responds to this treatment, suggesting that cancer immune evasion is still a major barrier in current immunotherapy. There are a series of factors contributing to immune evasion despite in an immunocompetent environment. Given that these factors are involved in different steps of the cancer immune cycle. In this review, we discuss the mechanisms of immune escape in each step of the cancer immune cycle and then present therapeutic strategies for overcoming immune escape, with the potential to better understand the determinants of immune escape and make anti-tumor immunity more effective.
摘要:
With the arrival of the precision medicine and personalized treatment era, targeted therapy that improves efficacy and reduces side effects has become the mainstream approach of cancer treatment. Antibody fragments that further enhance penetration and retain the most critical antigen-specific binding functions are considered the focus of research targeting cancer imaging and therapy. Thanks to the superior penetration and rapid blood clearance of antibody fragments, antibody fragment-based imaging agents enable efficient and sensitive imaging of tumour sites. In tumour-targeted therapy, antibody fragments can directly inhibit tumour proliferation and growth, serve as an ideal carrier for delivery of anti-tumour drugs, or manipulate the immune system to eliminate tumour cells. In this review, the excellent physicochemical properties and the basic structure of antibody fragments are expressly depicted depicted, the progress of antibody fragments in cancer therapy and imaging are thoroughly summarized, and the future development of antibody fragments is predicted.
作者机构:
[Zhang, Mengxia] Hunan Univ Chinese Med, Dept Histol & Embryol, Changsha 410208, Hunan, Peoples R China.;[Tang, Shengsong] Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Hunan, Peoples R China.;[Zhang, Mengxia; Liu, Qi; Mo, Zhongcheng] Univ South China, Clin Anat & Reprod Med Applicat Inst, Dept Histol & Embryol, Hengyang 421001, Hunan, Peoples R China.;[Tang, Shengsong; Lei, Xiaoyong; Tu, Jian; Li, Lijun] Univ South China, Insitute Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Ning, Jing; Tang, Shengsong] Hunan Univ Med, Dept Pharmacol, Huaihua 418000, Hunan, Peoples R China.
通讯机构:
[Tang, Shengsong] H;Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Hunan, Peoples R China.
关键词:
macrophage colony-stimulating factor;breast cancer;apoptosis;HIF-1 and BINP3
摘要:
Macrophage colony-stimulating factor (M-CSF), a tumour marker, is related to tumour cell anti-apoptosis and drug resistance. However, the role of M-CSF in MCF-7 cells is unknown. In the present study, the effect and mechanism of M-CSF on hypoxia-inducible factor-1 (HIF-1)/BCL2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3)/Apoptosis Regulator BAX signalling in human breast cancer MCF-7 cells were investigated. Western blotting revealed that the expression of HIF-1, BNIP3, Bax, caspase-3 and caspase-9 was lower in MCF-7-M cells compared to MCF-7 and MCF-7-C cells treated with adriamycin (ADM). Immunoprecipitation combined with western blotting was used to detect the interaction between Bcl-2 and BNIP3 or Bax protein. MCF-7-M cells had a higher amount of Bax binding to Bcl-2 compared to MCF-7 cells or MCF-7-C cells, while the amount of BNIP3 binding to Bcl-2 was decreased in MCF-7-M cells. Hoechst 33342 staining and flow cytometry were utilized to evaluate the effect of M-CSF on apoptosis in MCF-7 cells treated with ADM. Compared to ADM-treated MCF-7 cells, the apoptotic rate of MCF-7-M cells was significantly decreased. These effects were dependent on the concentration of ADM. In conclusion, cytoplasmic M-CSF suppressed apoptosis by inhibiting the HIF-1/BNIP3/Bax signalling pathway, which potentiated the dissociation of Bcl-2 from Bcl-2-BNIP3 compounds and the formation of Bcl-2-Bax compounds.
作者机构:
[Tang, SS; Mo, Zhongcheng; Ou, Hanxiao; Tang, Shengsong; Liu, Chuhao; Xiao, Xinwen; Feng, Wenjie] Univ South China, Inst Pharm & Pharmacol, Clin Anat & Reprod Med Applicat Inst, Hengyang 421001, Peoples R China.;[Tang, Shengsong] Hunan Univ Med, Ctr Life Sci, Huaihua 418000, Peoples R China.;[Liu, Chuhao; Xiao, Xinwen; Feng, Wenjie] Univ South China, Med Sch, Hengyang 421001, Peoples R China.
通讯机构:
[Tang, SS; Mo, ZC] U;[Tang, Shengsong] H;Univ South China, Inst Pharm & Pharmacol, Clin Anat & Reprod Med Applicat Inst, Hengyang 421001, Peoples R China.;Hunan Univ Med, Ctr Life Sci, Huaihua 418000, Peoples R China.
关键词:
adenosine monophosphate-activated protein kinase;autophagy;lipid metabolism;atherosclerosis-associated cell;atherosclerosis
摘要:
Atherosclerosis is characterized by the accumulation of lipids and deposition of fibrous elements in the vascular wall, which is the primary cause of cardiovascular diseases. Adenosine monophosphate-activated protein kinase (AMPK) is a metabolic sensor of energy metabolism that regulates multiple physiological processes, including lipid and glucose metabolism and the normalization of energy imbalances. Overwhelming evidence indicates that AMPK activation markedly attenuates atherosclerosis development. Autophagy inhibits cell apoptosis and inflammation and promotes cholesterol efflux and efferocytosis. Physiological autophagy is essential for maintaining normal cardiovascular function. Increasing evidence demonstrates that autophagy occurs in developing atherosclerotic plaques. Emerging evidence indicates that AMPK regulates autophagy via a downstream signaling pathway. The complex relationship between AMPK and autophagy has attracted the attention of many researchers because of this close relationship to atherosclerosis development. This review demonstrates the role of AMPK and autophagy in atherosclerosis. An improved understanding of this interrelationship will create novel preventive and therapeutic strategies for atherosclerosis.
通讯机构:
[Tang, Shengsong] H;[Tang, Shengsong] U;Hunan Univ Med, Biomed Res Ctr, Huaihua 418000, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Dept Histol & Embryol, Hengyang 421001, Peoples R China.
关键词:
Macrophage colony-stimulating factor;chemoresistance;apoptosis;autophagy;breast cancer
摘要:
Macrophage colony-stimulating factor is a vital factor in maintaining the biological function of monocyte–macrophage lineage. It is expressed in many tumor tissues and cancer cells. Recent findings indicate that macrophage colony-stimulating factor might contribute to chemoresistance, but the precise mechanisms are unclear. This study was to explore the effect of macrophage colony-stimulating factor on doxorubicin resistance in MCF-7 breast cancer cells and the possible mechanism. In the study, the human breast cancer cells, MCF-7, were transfected with macrophage colony-stimulating factor. We document that cytoplasmic macrophage colony-stimulating factor induces doxorubicin resistance and inhibits apoptosis in MCF-7 cells. Further studies demonstrated that cytoplasmic macrophage colony-stimulating factor-mediated apoptosis inhibition was dependent on the activation of PI3K/Akt/Survivin pathway. More importantly, we found that macrophage colony-stimulating factor-induced autophagic cell death in doxorubicin-treated MCF-7 cells. Taken together, we show for the first time that macrophage colony-stimulating factor-induced doxorubicin resistance is associated with the changes in cell death response with defective apoptosis and promotion of autophagic cell death.
摘要:
Isolation rearing induces profound behavioral and neurochemical abnormalities in rodents. However there have been many controversies with its anxiogenic-like effects using models like elevated-plus maze. In the current study we aimed to address this by using one novelty-based anxiety paradigm that has been largely overlooked in previous isolation rearing studies. We found that eight-week isolation rearing produced potent anxiogenic-like effects in novelty-induced hypophagia test in mice. We also demonstrated PSD-95 levels were elevated in the hippocampus and amygdala and reduced in the frontal cortex after social isolation. This study provides further behavioral and neurochemical evidence to support that isolation rearing can produce anxiogenic-like effects in rodents. (C) 2012 Elsevier Ireland Ltd. All rights reserved.