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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
Prevalence of antifolate drug resistance markers in in China
《医学前沿(英文)》 2022年 第16卷 第1期 页码 83-92 doi: 10.1007/s11684-021-0894-x
关键词: drug resistance antifolates molecular markers Plasmodium vivax China
Detection of AmpC β-lactamase and drug resistance of
Rong WANG, Shangwei WU, Xue LI, Ping HE, Yunde LIU
《医学前沿(英文)》 2009年 第3卷 第1期 页码 72-75 doi: 10.1007/s11684-009-0004-y
《医学前沿(英文)》 2022年 第16卷 第6期 页码 883-895 doi: 10.1007/s11684-022-0919-0
关键词: osteosarcoma autophagy metastasis drug resistance Beclin1 LC3B
Antibiotic resistome of : molecular determinants for the emergence of drug resistance
《医学前沿(英文)》 2021年 第15卷 第5期 页码 693-703 doi: 10.1007/s11684-020-0777-6
关键词: S. typhi antibiotic resistance mechanism resistome identification methods
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《医学前沿(英文)》 2018年 第12卷 第2期 页码 182-188 doi: 10.1007/s11684-017-0529-4
With the abuse of antimicrobial agents in developing countries, increasing number of carbapenem-resistant Enterobacteriaceae (CRE) attracted considerable public concern. A retrospective study was conducted based on 242 CRE strains from a tertiary hospital in Hangzhou, China to investigate prevalence and drug resistance characteristics of CRE in southeast China. Bacterial species were identified. Antimicrobial susceptibility was examined by broth microdilution method or epsilometer test. Resistant β-lactamase genes were identified by polymerase chain reaction and sequencing. Genotypes were investigated by phylogenetic analysis. and were the most prevalent types of species, with occurrence in 71.9% and 21.9% of the strains, respectively. All strains exhibited high resistance (>70%) against β-lactam antibiotics, ciprofloxacin, trimethoprim–sulfamethoxazole, and nitrofurantoin but exhibited low resistance against tigecycline (0.8%) and minocycline (8.3%). A total of 123 strains harbored more than two kinds of β-lactamase genes. , , , and were the predominant genotypes, with detection rates of 60.3%, 61.6%, 43.4%, and 16.5%, respectively, and were highly identical with reference sequences in different countries, indicating potential horizontal dissemination. IMP-4 was the most frequent class B metallo-lactamases in this study. In conclusion, continuous surveillance and effective prevention should be emphasized to reduce spread of CRE.
关键词: Enterobacteriaceae carbapenem β-lactamase genes phylogenetic analysis
Zhaoshi Bao, Yongzhi Wang, Qiangwei Wang, Shengyu Fang, Xia Shan, Jiguang Wang, Tao Jiang
《医学前沿(英文)》 2021年 第15卷 第4期 页码 551-561 doi: 10.1007/s11684-020-0760-2
关键词: glioma evolution mechanism strategies tumor heterogeneity secondary glioma
Role of the forkhead transcription factor FOXO-FOXM1 axis in cancer and drug resistance
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《医学前沿(英文)》 2012年 第6卷 第4期 页码 376-380 doi: 10.1007/s11684-012-0228-0
The forkhead transcription factors FOXO and FOXM1 have pivotal roles in tumorigenesis and in mediating chemotherapy sensitivity and resistance. Recent research shows that the forkhead transcription factor FOXM1 is a direct transcriptional target repressed by the forkhead protein FOXO3a, a vital downstream effector of the PI3K-AKT-FOXO signaling pathway. Intriguingly, FOXM1 and FOXO3a also compete for binding to the same gene targets, which have a role in chemotherapeutic drug action and sensitivity. An understanding of the role and regulation of the FOXO-FOXM1 axis will impact directly on our knowledge of chemotherapeutic drug action and resistance in patients, and provide new insights into the design of novel therapeutic strategy and reliable biomarkers for prediction of drug sensitivity.
关键词: FOXO3a FOXM1 transcription factor cancer drug resistance tumorigenesis
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《医学前沿(英文)》 2015年 第9卷 第2期 页码 134-138 doi: 10.1007/s11684-015-0396-9
Drug resistance is a major factor that limits the efficacy of targeted cancer therapies. In this review, we discuss the main known mechanisms of resistance to receptor tyrosine kinase inhibitors, which are the most prevalent class of targeted therapeutic agent in current clinical use. Here we focus on bypass track resistance, which involves the activation of alternate signaling molecules by tumor cells to bypass inhibition and maintain signaling output, and consider the problems of signaling pathway redundancy and how the activation of different receptor tyrosine kinases translates into intracellular signal transduction in different cancer types. This information is presented in the context of research strategies for the discovery of new targets for pharmacological intervention, with the goal of overcoming resistance in order to improve patient outcomes.
关键词: targeted therapy drug resistance receptor tyrosine kinases cancer
Progress and challenges in RET-targeted cancer therapy
《医学前沿(英文)》 2023年 第17卷 第2期 页码 207-219 doi: 10.1007/s11684-023-0985-y
关键词: pralsetinib selpercatinib RET-alteration lung cancer thyroid cancer tumor-agnostic therapy drug resistance
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《医学前沿(英文)》 2018年 第12卷 第1期 页码 92-97 doi: 10.1007/s11684-017-0610-z
Investigations on the genetic diversity of Mycobacterium tuberculosis in China have shown that Beijing genotype strains play a dominant role. To study the association between the M.?tuberculosis Beijing genotype and the drug-resistance phenotype, 1286 M. tuberculosis clinical isolates together with epidemiological and clinical information of patients were collected from the center for tuberculosis (TB) prevention and control or TB hospitals in Beijing municipality and nine provinces or autonomous regions in China. Drug resistance testing was conducted on all the isolates to the four first-line anti-TB drugs (isoniazid, rifampicin, streptomycin, and ethambutol). A total of 585 strains were found to be resistant to at least one of the four anti-TB drugs. The Beijing family strains consisted of 499 (53.20%) drug-sensitive strains and 439 (46.80%) drug-resistant strains, whereas the non-Beijing family strains comprised 202 (58.05%) drug-sensitive strains and 146 (41.95%) drug-resistant strains. No significant difference was observed in prevalence (c2=2.41, P>0.05) between the drug-resistant and drug-sensitive strains among the Beijing family strains. Analysis of monoresistance, multidrug-resistant TB, and geographic distribution of drug resistance did not find any relationships between the M.?tuberculosis Beijing genotype and drug-resistance phenotype in China. Results confirmed that the Beijing genotype, the predominant M. tuberculosis genotype in China, was not associated with drug resistance.
关键词: tuberculosis drug resistance genotype molecular biology
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《医学前沿(英文)》 2013年 第7卷 第4期 页码 462-476 doi: 10.1007/s11684-013-0270-6
Evaluating the effects of novel drugs on appropriate tumor models has become crucial for developing more effective therapies that target highly tumorigenic and drug-resistant cancer stem cell (CSC) populations. In this study, we demonstrate that a subset of cancer cells with CSC properties may be enriched into tumor spheroids under stem cell conditions from a non-small cell lung cancer cell line. Treating these CSC-like cells with gemcitabine alone and a combination of gemcitabine and the novel CHK1 inhibitor PF-00477736 revealed that PF-00477736 enhances the anti-proliferative effect of gemcitabine against both the parental and the CSC-like cell populations. However, the CSC-like cells exhibited resistance to gemcitabine-induced apoptosis. Collectively, the spheroid-forming CSC-like cells may serve as a model system for understanding the mechanism underlying the drug resistance of CSCs and for guiding the development of better therapies that can inhibit tumor growth and eradicate CSCs.
关键词: drug resistance cancer stem cell checkpoint kinase 1 (CHK1) PF-00477736 lung cancer tumorigenicity
Biodegradable polymethacrylic acid grafted psyllium for controlled drug delivery systems
Ranvijay KUMAR, Kaushlendra SHARMA
《化学科学与工程前沿(英文)》 2013年 第7卷 第1期 页码 116-122 doi: 10.1007/s11705-013-1310-0
关键词: psyllium acetyl salicylic acid in-vitro drug release swelling biodegradation
Protein microspheres for pulmonary drug delivery
Yongda SUN,
《化学科学与工程前沿(英文)》 2010年 第4卷 第1期 页码 82-86 doi: 10.1007/s11705-009-0307-1
关键词: advanced engineering improved pressure aqueous technique
Semi-solid materials for controlled release drug formulation: current status and future prospects
Michelle TRAN,Chun WANG
《化学科学与工程前沿(英文)》 2014年 第8卷 第2期 页码 225-232 doi: 10.1007/s11705-014-1429-7
关键词: controlled release drug delivery semi-solids polymer excipient
标题 作者 时间 类型 操作
Detection of AmpC β-lactamase and drug resistance of
Rong WANG, Shangwei WU, Xue LI, Ping HE, Yunde LIU
期刊论文
Superenhancers activate the autophagy-related genes Beclin1 and LC3B to drive metastasis and drug resistance
期刊论文
Prevalence and drug resistance characteristics of carbapenem-resistant Enterobacteriaceae in Hangzhou
null
期刊论文
Intratumor heterogeneity, microenvironment, and mechanisms of drug resistance in glioma recurrence and
Zhaoshi Bao, Yongzhi Wang, Qiangwei Wang, Shengyu Fang, Xia Shan, Jiguang Wang, Tao Jiang
期刊论文
Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies
null
期刊论文
Combined gemcitabine and CHK1 inhibitor treatment induces apoptosis resistance in cancer stem cell-like
null
期刊论文
Biodegradable polymethacrylic acid grafted psyllium for controlled drug delivery systems
Ranvijay KUMAR, Kaushlendra SHARMA
期刊论文