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
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.
摘要：
Polymeric micelles (PMs) play a vital role in multidrug co-delivery and cancer treatment. However, the development of intelligent PMs further allows PMs to accurately -target tumour, selectively release cargo multidrug and increase uptake. Therefore, targets, controlled release and uptake of intelligent PMs should be paid more attention to improvement synergistic therapeutic outcomes and minimize side effects. In this review, tumour targeting of co-delivery intelligent PMs and its intracellular trafficking mechanisms were overviewed. And this review provides a comprehensive summarization of several intelligent co-delivery PMs. Such a system could control the multidrug to be released simultaneously or sequentially by special properties of tumour microenvironment (TME) (including acidic PH, redox, overexpressed enzyme, excessive temperature) and external environment trigger. Additionally, limitations, clinical translation and future perspectives of intelligent co-delivery PMs were also being discussed in this article.
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.
摘要：
Cervical cancer is the second most commonly diagnosed cancer and the third leading cause of cancer deaths among females in underdeveloped countries. This study aimed to identify several novel cervical cancer-specific targeting peptides (CSPs) to provide new methods for the effective diagnosis and treatment of cervical cancer. Peptide library screening in vivo was performed on human cervical cancer xenografts with Ph.D.™-12 and C7C phage display peptide libraries. Two specific peptide sequences (GDALFSVPLEVY and KQNLAEG), which were enriched in tumors, were screened, and respectively, named CSP-GD and CSP-KQ through three rounds of biopanning. The in vivo tumor-targeting ability of these peptides was identified by injecting them into mice with cervical cancer xenograft. CSPs were compounded and labeled with fluorescein isothiocyanate (FITC). The specificity and affinity of FITC-CSPs were evaluated in human cervical cancer cell lines and tissue microarrays in vitro by immunofluorescent staining. Results showed that FITC-CSP-GD and FITC-CSP-KQ evidently and specifically bound to the cell membrane and cytoplasm of SiHa, ME-180, and C-33A cells in vitro. In human cervical cancer tissue, FITC-CSP-GD and FITC-CSP-KQ strongly targeted human cervical adenocarcinoma and cervical squamous cell carcinoma tissues, respectively. A bright FITC signal was located mainly on the cell membrane and cytoplasm of tumor cells. In conclusion, the novel 12-residue peptide CSP-GD and 7-residue peptide CSP-KQ could specifically target human cervical cancer and may have the potential to be used in the diagnosis and targeted therapy of cervical cancer.
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.
