检索结果-南通市图书馆

Cyclin-dependent kinases-based synthetic lethality: Evidence, concept, and strategy

在线全文

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2021年第9期11卷 2738-2748页

作者： Kailin Li Jieqiong You Qian Wu Wen Meng Qiaojun He Bo Yang Chengliang Zhu Ji Cao College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310058China Innovation Institute for Artificial Intelligence in Medicine Zhejiang UniversityHangzhou 310058China Affiliated Hangzhou First People’s Hospital Zhejiang University School of MedicineHangzhou 310058China Cancer Center of Zhejiang University Hangzhou 310058China

synthetic lethality is a proven effective antitumor strategy that has attracted great ***-scale screening has revealed many synthetic lethal genetic phenotypes,and relevant smallmolecule drugs have also been implemented in clinical *** evidence suggests that CDKs,constituting a kinase family predominantly involved in cell cycle control,are synthetic lethal factors when combined with certain oncogenes,such as MFC,TP53,and RAS,which facilitate numerous antitumor treatment options based on CDK-related synthetic *** this review,we focus on the synthetic lethal phenotype and mechanism related to CDKs and summarize the preclinical and clinical discoveries of CDK inhibitors to explore the prospect of CDK inhibitors as antitumor compounds for strategic synthesis lethality in the future.

关键词： synthetic lethality Cyclin-dependent kinase Antitumor therapy Oncogenes MYC P53 RAS PARP

DNA repair and synthetic lethality

在线全文

学校读者我要写书评

暂无评论

International Journal of Oral Science 2011年第4期3卷 176-179页

作者： Gong-she Guo Feng-mei Zhang Rui-jie Gao Robert Delsite Zhi-hui Feng Simon N. Powell School of Public Health Shandong University Jinan 250012 China Second People＇s Hospital of Weifang Weifang 261041 China Department of Radiation Oncology Washington University in St Louis St Louis MO 63108 USA Department of Radiation Oncology Memorial Sloan Kettering Cancer Center New York NY10065 USA

Tumors often have DNA repair defects, suggesting additional inhibition of other DNA repair pathways in tumors may lead to synthetic lethality. Accumulating data demonstrate that DNA repair-defective tumors, in particular homologous recombination （HR）, are highly sensitive to DNA-damaging agents. Thus, HR-defective tumors exhibit potential vulnerability to the synthetic lethality approach, which may lead to new therapeutic strategies. It is well known that poly （adenosine diphosphate （ADP）-ribose） polymerase （PARP） inhibitors show the synthetically lethal effect in tumors defective in BRCA1 or BRCA2 genes encoded proteins that are required for efficient HR. In this review, we summarize the strategies of targeting DNA repair pathways and other DNA metabolic functions to cause synthetic lethality in HR-defective tumor cells.

关键词： DNA repair homologous recombination synthetic lethality BRCA Rad52

MOF负载Weel抑制剂实现p53突变胆囊癌的合成致死靶向治疗

在线全文

学校读者我要写书评

暂无评论

Science Bulletin 2024年第9期69卷 1286-1301页

作者：郦仕杰 Sarun Juengpanich Win Topatana 谢天傲侯丽丹朱怡远陈佳东单煜凯韩依纳陆子毅陈天恩 Charlie Topatana 张斌曹佳胜胡家豪严加费陈迎鑫顾臻俞计成蔡秀军陈鸣宇 Department of General Surgery Sir Run-Run Shaw HospitalZhejiang UniversityHangzhou 310016China School of Medicine Zhejiang UniversityHangzhou 310058China National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments Sir Run-Run Shaw HospitalZhejiang UniversityHangzhou 310016China School of Materials Science and Engineering Zhejiang UniversityHangzhou 310058China Department of Chemistry Zhejiang UniversityHangzhou 310016China Department of Pathology Sir Run-Run Shaw HospitalZhejiang UniversityHangzhou 310016China International College Zhejiang UniversityHangzhou 310058China Institute of Advanced Magnetic Materials and International Research Center for EM Metamaterials College of Materials&Environmental EngineeringHangzhou Dianzi UniversityHangzhou 310018China Zhejiang Provincial Key Laboratory for Advanced Drug Delivery Systems College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China National Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang UniversityHangzhou 310058China Liangzhu Laboratory Zhejiang UniversityHangzhou 311121China Jinhua Institute of Zhejiang University Jinhua 321299China MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China

Adavosertib(ADA)is a WEE1 inhibitor that exhibits a synthetic lethal effect on p53-mutated gallbladder cancer(GBC).However,drug resistance due to DNA damage response compensation pathways and high toxicity limits further ***,estrone-targeted ADA-encapsulated metal–organic frameworks(ADA@MOF-EPL)for GBC synthetic lethal treatment by inducing conditional factors are *** high expression of estrogen receptors in GBC enables ADA@MOF-EPL to quickly enter and accumulate near the cell nucleus through estrone-mediated endocytosis and release ADA to inhibit WEE1 upon entering the acidic tumor *** irradiation induces ADA@MOF-EPL to generate reactive oxygen species(ROS),which leads to a further increase in DNA damage,resulting in a higher sensitivity of p53-mutated cancer cells to WEE1 inhibitor and promoting cell death via conditional synthetic *** conditional factor induced by ADA@MOF-EPL further enhances the antitumor efficacy while significantly reducing systemic ***,ADA@MOF-EPL demonstrates similar antitumor abilities in other p53-mutated solid tumors,revealing its potential as a broad-spectrum antitumor drug.

关键词： synthetic lethality Nanomedicine Sonodynamic therapy Gallbladder cancer Metal-organic frameworks DNA damage response

synthetic Lethal Interactions Prediction Based on Multiple Similarity Measures Fusion

在线全文

学校读者我要写书评

暂无评论

Journal of Computer Science & Technology 2021年第2期36卷 261-275页

作者： Lian-Lian Wu Yu-Qi Wen Xiao-Xi Yang Bo-Wei Yan Song He Xiao-Chen Bo Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjin 300072China Department of Biotechnology Beijing Institute of Radiation MedicineBeijing 100850China Experimental Center Beijing Friendship HospitalCapital Medical UniversityBeijing 100850China

The synthetic lethality(SL)relationship arises when a combination of deficiencies in two genes leads to cell death,whereas a deficiency in either one of the two genes does *** survival of the mutant tumor cells depends on the SL partners of the mutant gene,thereby the cancer cells could be selectively killed by inhibiting the SL partners of the oncogenic genes but normal cells could ***,there is an urgent need to develop more efficient computational methods of SL pairs identification for cancer targeted *** this paper,we propose a new approach based on similarity fusion to predict SL *** types of gene similarity measures are integrated and/c-nearest neighbors algorithm(k-NN)is applied to achieve the similarity-based classification task between gene *** a similarity-based method,our method demonstrated excellent performance in multiple *** the effectiveness of our method,the ease of use and expansibility can also make our method more widely used in practice.

关键词： synthetic lethality similarity measures fusion k-nearest neighbor multi-dimensional data

Epigenetic silencing of BEND4,a novel DNA damage repair gene,is a synthetic lethal marker for ATM inhibitor in pancreatic cancer

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Frontiers of Medicine 2024年第4期18卷 721-734页

作者： Yuanxin Yao Honghui Lv Meiying Zhang Yuan Li James G.Herman Malcolm V.Brock Aiai Gao Qian Wang Francois Fuks Lirong Zhang Mingzhou Guo Department of Gastroenterology and Hepatology the First Medical CenterChinese PLA General HospitalBeijing100853China Department of Pharmacology School of Basic Medical SciencesZhengzhou UniversityZhengzhou450001China Henan Institute of Advanced Technology Zhengzhou UniversityZhengzhou450001China UPMC Hillman Cancer Center University of Pittsburgh Medical CenterPittsburghPA15213USA Department of surgery School of MedicineJohns Hopkins School of MedicineBaltimoreMD21287USA Laboratory of Cancer Epigenetics Faculty of MedicineULB-Cancer Research Center(U-CRC)Universite Libre de Bruxelles(ULB)Brussels1070Belgium National Key Laboratory of Kidney Diseases the First Medical CenterChinese PLA General HospitalBeijing100853China

synthetic lethality is a novel model for cancer *** understand the function and mechanism of BEN domain-containing protein 4(BEND4)in pancreatic cancer,eight cell lines and a total of 492 cases of pancreatic neoplasia samples were included in this ***-specific polymerase chain reaction,CRISPR/Cas9,immunoprecipitation assay,comet assay,and xenograft mouse model were ***4 is a new member of the BEN domain *** expression of BEND4 is regulated by promoter region *** is methylated in 58.1%(176/303)of pancreatic ductal adenocarcinoma(PDAC),33.3%(14/42)of intraductal papillary mucinous neoplasm,31.0%(13/42)of pancreatic neuroendocrine tumor,14.3%(3/21)of mucinous cystic neoplasm,4.3%(2/47)of solid pseudopapillary neoplasm,and 2.7%(1/37)of serous cystic ***4 methylation is significantly associated with late-onset PDAC(>50 years,Psynthetic lethal marker for ATM inhibitor in PDAC treatment.

关键词： BEND4 DNA methylation synthetic lethality NHEJ pathway

Design, synthesis, and biological evaluation of quinazolin-4(3H)-one derivatives co-targeting poly (ADP-ribose) polymerase-1 and bromodomain containing protein 4 for breast cancer therapy

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2021年第1期11卷 156-180页

作者： Xiaosa Changy Dejuan Suny Danfeng Shiy Guan Wang Yanmei Chen Kai Zhang Huidan Tan Jie Liu Bo Liu Liang Ouyang State Key Laboratory of Biotherapy and Cancer Center West China HospitalCollaborative Innovation Center of BiotherapySichuan UniversityChengdu 610041China

This study was aimed to design the first dual-target small-molecule inhibitor co-targeting poly(ADP-ribose)polymerase-1(PARP1)and bromodomain containing protein 4(BRD4),which had important cross relation in the global network of breast cancer,reflecting the synthetic lethal effect.A series of new BRD4 and PARP1 dual-target inhibitors were discovered and synthesized by fragmentbased combinatorial screening and activity assays that together led to the chemical *** these compounds,19 d was selected and exhibited micromole enzymatic potencies against BRD4 and PARP1,*** 19 d was further shown to efficiently modulate the expression of BRD4 and ***,compound 19 d was found to induce breast cancer cell apoptosis and stimulate cell cycle arrest at G1 *** pharmacokinetic studies,compound 19 d showed its antitumor activity in breast cancer susceptibility gene 1/2(BRCA1/2)wild-type MDA-MB-468 and MCF-7 xenograft models without apparent toxicity and loss of body *** results together demonstrated that a highly potent dual-targeted inhibitor was successfully synthesized and indicated that co-targeting of BRD4 and PARP1 based on the concept of synthetic lethality would be a promising therapeutic strategy for breast cancer.

关键词： BRD4 PARP1 Dual-target inhibitor synthetic lethality Quinazolin-4(3H)-one derivatives

Emerging roles of Aurora-A kinase in cancer therapy resistance

在线全文

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2023年第7期13卷 2826-2843页

作者： Dayong Zheng Jun Li Han Yan Gang Zhang Wei Li Edward Chu Ning Wei School of Pharmacy North China University of Science and TechnologyTangshan 063210China Basic Medical Science College Liaoning University of Traditional Chinese MedicineShenyang 110032China Division of Biology and Biological Engineering California Institute of TechnologyPasadenaCA 91125USA Department of Oncology and Cancer Therapeutics Program Montefiore Einstein Cancer CenterAlbert Einstein College of MedicineBronxNY 10461USA

Aurora kinase A(Aurora-A),a serine/threonine kinase,plays a pivotal role in various cellular processes,including mitotic entry,centrosome maturation and spindle *** or gene-amplification/mutation of Aurora-A kinase occurs in different types of cancer,including lung cancer,colorectal cancer,and breast *** of Aurora-A impacts multiple cancer hallmarks,especially,immortalization,energy metabolism,immune escape and cell death resistance which are involved in cancer progression and *** review highlights the most recent advances in the oncogenic roles and related multiple cancer hallmarks of Aurora-A kinase-driving cancer therapy resistance,including chemoresistance(taxanes,cisplatin,cyclophosphamide),targeted therapy resistance(osimertinib,imatinib,sorafenib,etc.),endocrine therapy resistance(tamoxifen,fulvestrant) and ***,the mechanisms of Aurora-A kinase promote acquired resistance through modulating DNA damage repair,feedback activation bypass pathways,resistance to apoptosis,necroptosis and autophagy,metastasis,and ***,our review also summarizes the promising synthetic lethality strategy for Aurora-A inhibitors in RB1,ARID1A and MYC gene mutation tumors,and potential synergistic strategy for m TOR,PAK1,MDM2,MEK inhibitors or PD-L1 antibodies combined with targeting Aurora-A *** addition,we discuss the design and development of the novel class of Aurora-A inhibitors in precision medicine for cancer treatment.

关键词： Aurora-A Therapy resistance Chemoresistance Targeted therapy Radioresistance synthetic lethality Alisertib PROTAC

synthetic lethal approaches to target cancers with loss of PTEN function

在线全文

学校读者我要写书评

暂无评论

Genes & Diseases 2023年第6期10卷 2511-2527页

作者： Ayse Ertay Rob MEwing Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK

Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene and has a role in inhibiting the oncogenic AKT signaling pathway by dephosphorylating phosphatidylinositol 3,4,5-triphosphate (PIP3 ) into phosphatidylinositol 4,5-bisphosphate (PIP2 ). The function of PTEN is regulated by different mechanisms and inactive PTEN results in aggressive tumor phenotype and tumorigenesis. Identifying targeted therapies for inactive tumor suppressor genes such as PTEN has been challenging as it is difficult to restore the tumor suppressor functions. Therefore, focusing on the downstream signaling pathways to discover a targeted therapy for inactive tumor suppressor genes has highlighted the importance of synthetic lethality studies. This review focused on the potential synthetic lethality genes discovered in PTEN-inactive cancer types. These discovered genes could be potential targeted therapies for PTEN-inactive cancer types and may improve the treatment response rates for aggressive types of cancer.

关键词： Cancer PTEN synthetic lethality Tumour suppressor gene WDHD1

Structure-specific nucleases in genome dynamics and strategies for targeting cancers

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

JOURNAL OF MOLECULAR CELL BIOLOGY 2024年第5期16卷 mjae019页

作者： Sun, Haitao Luo, Megan Zhou, Mian Zheng, Li Li, Hongzhi Esworthy, R. Steven Shen, Binghui Chinese Acad Med Sci Inst Med Plant Dev Peking Union Med Coll Med Plant Resources & Protect Res Ctr Be?ing 100193 Peoples R China Beckman Res Inst City Hope Dept Canc Genet & Epigenet Duarte CA 91010 USA Univ Calif Berkeley Dept Mol & Cell Biol Berkeley CA 94720 USA

Nucleases are a super family of enzymes that hydrolyze phosphodiester bonds present in genomes. They widely vary in substrates, causing differentiation in cleavage patterns and havinga diversified role in maintaining genetic material. Through cellular evolution of prokaryotic to eukaryotic, nucleases become structure-specific in recognizing its own orforeign genomic DNA/RNA configurations as its substrates, including flaps, bubbles, and Holliday junctions. These special structural configurations are commonly found as intermediates in processes like DNA replication, repair, and recombination. The structure-specific nature and diversified functions make them essential to maintaining genome integrity and evolution in normal and cancer cells. In this article, we review their roles in various pathways, including Okazaki fragment maturation during DNA replication, end resection in homology-directed recombination repair of DNA double-strand breaks, DNA excision repair and apoptosis DNA fragmentation in response to exogenous DNA damage, and HIV life cycle. As the nucleases serve as key points for the DNA dynamics, cellular apoptosis, and cancer cell survival pathways, we discuss the efforts in the field in developing the therapeutic regimens, taking advantage of recently available knowledge of their diversified structures and functions.

关键词： structure-specific nucleases DNA replication nuclease inhibitors synthetic lethality