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Cancer Drug resistance 2022年第4期5卷 1016-1024页

作者： Danilo Rocco Luigi Della Gravara Giovanni Palazzolo Cesare Gridelli Department of Pulmonary Oncology AORN dei Colli MonaldiNaples 80131Italy Department of Experimental Medicine Universitàdegli studi della Campania“Luigi Vanvitelli”Naples 80138Italy UO Oncologia “ULSS 6 Euganea”Cittadella(PD)35131Italy Division of Medical Oncology “S.G.Moscati”HospitalAvellino 83100Italy.

As of today, only two antiangiogenic monoclonal antibodies plus epidermal growth factor receptor-tyrosine kinaseinhibitor (EGFR-TKI) combinations are FDA and EMA-approved and are recommended by American Society ofClinical Oncology, European Society for Medical Oncology, and National Comprehensive Cancer Network for thefirst-line treatment of EGFR+ advanced non-small cell lung cancer patients: erlotinib plus bevacizumab anderlotinib plus ramucirumab. However, all treated patients eventually become unresponsive to such drugs, due toseveral different acquired resistance mechanisms, mainly represented by T790M substitutions and METamplifications. While osimertinib treatment in T790M+ patients still represents the only approved treatment,MET-TKIs will likely change this status quo in the near future. In fact, existing clinical data strongly support a rolefor MET-TKI-based combinations in EGFR+ MET-amplified patients, possibly revolutionizing our current treatmentalgorithm. Chemotherapy plus immunotherapy plus antiangiogenic therapy combinations could also representanother useful addition.

关键词： NSCLC EGFR T790M MET bevacizumab ramucirumab TKI resistance mechanisms

Acinetobacter baumannii biofilm resistance mechanisms and prevention and control of progress

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Discussion of Clinical Cases 2016年第2期3卷 22-26页

作者： Liying Wang Lingfeng Wang The Third Affiliated Hospital of Inner Mongolia Medical University BaotouChina

At present,the multiple drug resistance of Acinetobacter baumannii outbreaks worldwide and has intensified the trend,especially in the intensive care unit and burn *** drug resistant Acinetobacter baumannii is known as the 21st century gram-negative bacterium“MRSA”,“Superbugs”.In recent years,researches have shown that this is associated with pathogenic bacteria to form *** this paper,the status of Acinetobacter baumannii infection,biofilm formation,resistance mechanism and prevention in recent years were summarized.

关键词： Acinetobacter baumannii Biofilms resistance mechanisms

Antimicrobial resistance and underlying mechanisms in Staphylococcus aureus isolates

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Asian Pacific Journal of Tropical Medicine 2017年第11期10卷 1059-1064页

作者： Ebru Sebnem Yilmaz Ozkan Aslantas Department of Biology Faculty of Art and Sciences Mustafa Kemal University Department of Microbiology Faculty of Veterinary Medicine Mustafa Kemal University

Objective: To investigate the antimicrobial susceptibility of 97 clinical Staphylococcus aureus(S. aureus) strains against 14 antimicrobials and corresponding resistance ***: The antimicrobial susceptibility of the isolates was determined using a disk diffusion method and antimicrobial resistance genes were screened by polymerase chain reaction. Mutations responsible for ciprofloxacin and rifampicin resistance were investigated by polymerase chain reaction and DNA ***: All isolates were found to be susceptible to vancomycin. Various rates of resistance to penicillin(83.5%), ampicillin(77.3%), erythromycin(63.9%), tetracycline(16.5%), amoxicillin/clavulanic acid(16.5%), ciprofloxacin(15.5%), trimethoprim/sulfamethoxazole(15.5%), oxacillin(13.4%), fusidic acid(12.4%), rifampin(6.2%), clindamycin(6.2%), gentamicin(6.2%) and mupirocin(5.2%) were determined. In addition,different combinations of resistance genes were identified among resistant *** resistant isolates had mutations in codon 84(Ser84 Leu) and 106(Gly106 Asp) in the gyr A gene. Mutations in grl A were mostly related to Ser80 Phe substitution. Leu466 Ser mutation in the rpo B gene was detected in all rifampin resistant isolates. All methicillin resistant S. aureus isolates were SCCmec type ***: In conclusion, it was determined that the isolates were resistant to different classes of antimicrobials at varying rates and resistance was mediated by different genetic mechanisms. Therefore, continuous monitoring of resistance in S. aureus strains is necessary to control their resistance for clinically important antimicrobials.

关键词： Staphylococcus aureus Antimicrobial resistance resistance mechanisms Point mutation

mechanisms of tigecycline resistance in Gram-negative bacteria:A narrative review

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Engineering Microbiology 2024年第3期4卷 54-61页

作者： Wenya Su Wenjia Wang Ling Li Mengge Zhang Hai Xu Chengzhang Fu Xiuhua Pang Mingyu Wang State Key Laboratory of Microbial Technology Microbial Technology InstituteShandong UniversityQingdao 266237PR China Helmholtz Institute for Pharmaceutical Research Saarland(HIPS) Helmholtz Centre for Infection Research(HZI)and Department of PharmacySaarland UniversitySaarbrücken 66123Germany

Tigecycline serves as a critical“final-resort”antibiotic for treating bacterial infections caused by multidrug-resistant bacteria for which treatment options are severely *** increasing prevalence of tigecycline resistance,particularly among Gram-negative bacteria,is a major *** mechanisms have been iden-tified as contributors to tigecycline resistance,including upregulation of nonspecific resistance Nodulation Divi-sion(RND)efflux pumps due to mutations in transcriptional regulators,enzymatic modification of tigecycline by monooxygenase enzymes,and mutations affecting tigecycline binding *** review aims to consolidate our understanding of tigecycline resistance mechanisms in Gram-negative bacteria and offer insights and perspectives for further drug development.

关键词： Gram-negative bacteria Tigecycline Tigecycline resistance resistance mechanisms RND efflux pump

Immune checkpoint inhibitors in breast cancer: development, mechanisms of resistance and potential management strategies

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Cancer Drug resistance 2023年第4期6卷 768-787页

作者： Rachel SJ Wong Rebecca JM Ong Joline SJ Lim Department of Haematology-Oncology National University Cancer InstituteNational University HospitalSingapore 119228Singapore Yong Loo Lin School of Medicine National University of SingaporeSingapore 119228Singapore

The use of immune checkpoint inhibitors(iCls)has increased exponentially in the past decade,although its progress specifically for breast cancer has been *** first *** and Drug Administration approval for ICl in breast cancer came in 2019,eight years after the first-ever approval of an *** present,current indications for ICls are relevant only to a subset of patients with triple-negative breast cancer,or those displaying high microsatellite instability or deficiency in the mismatch repair protein *** an increasing understanding of the limitations of using ICls,which stem from breast cancer being innately poorly immunogenic,as well as the presence of various intrinsic and acquired resistance pathways,ongoing trials are evaluating different combination therapies to overcome these *** this review,we aim to describe the development timeline of ICls and resistance mechanisms limiting their utility,and summarise the available approaches and ongoing trials relevant to overcoming each resistance mechanism.

关键词： Immunotherapy immune checkpoint inhibitors resistance mechanisms breast cancer

Overcoming the mechanisms of primary and acquired resistance to new generation hormonal therapies in advanced prostate cancer: focus on androgen receptor independent pathways

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Cancer Drug resistance 2020年第4期3卷 726-741页

作者： Maristella Bungaro Consuelo Buttigliero Marcello Tucci Medical Oncology University of TurinSan Luigi Gonzaga HospitalOrbassanoTurin 10043Italy Medical Oncology Cardinal Massaia HospitalAsti 14100Italy

In recent years,many therapeutic advances have been made in the management of castration-resistant prostate cancer,with the development and approval of many new *** androgen receptor(AR)is the main driver in prostate cancer growth and progression and the most effective therapeutic agents are still directed against this *** these,new generation hormonal agents(NHA)including enzalutamide,abiraterone acetate,apalutamide,and darolutamide have shown to improve overall survival and quality of life of prostate cancer ***,despite the demonstrated benefit,not all patients respond to treatment and almost all are destined to develop a resistant *** the resistance mechanisms are not fully understood,the most studied ones include the activation of both dependent and independent AR signalling *** findings about multiple growth-promoting and survival pathways in advanced prostate cancer suggest the presence of alternative mechanisms involved in disease progression,and an interplay between these pathways and AR *** this review we discuss the possible mechanisms of primary and acquired resistance to NHA with a focus on AR independent pathways.

关键词： castration-resistant prostate cancer androgen receptor signalling hormonal treatment enzalutamide abiraterone resistance mechanisms

mechanisms of resistance to PARP inhibitors - an evolving challenge in oncology

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Cancer Drug resistance 2019年第3期2卷 608-617页

作者： Angela Mweempwa Michelle K.Wilson Cancer and Blood Auckland City HospitalAuckland 1023New Zealand

Poly-adenosine diphosphate ribose polymerase inhibitors(PARPi)lead to synthetic lethality when used in cancers harbouring a BRCA mutation or homologous recombination *** are now four PARPi approved by the Food and Drug Administration for therapeutic use is ovarian and breast *** addition to this,there is data supporting its use in pancreatic adenocarcinoma and prostate ***,development of resistance to PARPi limits the duration of *** mechanisms found to date include:(1)restoration of homologous recombination;(2)changes in PARP1;(3)suppression of non-homologous end joining;(4)replication fork protection;and(5)drug *** a better understanding of resistance mechanisms may guide combination therapies to overcome the resistance and improve the efficacy of *** purpose of this review is to describe the resistance mechanisms to PARPi and discuss their early detection.

关键词： Poly-adenosine diphosphate ribose polymerase inhibition resistance mechanisms homologous recombination BRCA reversion ovarian cancer

Natural Products and Antiviral resistance

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Advances in Microbiology 2024年第7期14卷 366-388页

作者： Erute Magdalene Adongbede Janak Raj Khatiwada Rishipal Rastrapal Bansode Leonard Lamont Williams Department of Botany University of Lagos Lagos Nigeria Center for Excellence in Post-Harvest Technologies North Carolina A & T State University Kannapolis North Carolina USA

Viral diseases are minacious with the potential for causing pandemics and treatment is complicated because of their inherent ability to mutate and become resistant to drugs. Antiviral drug resistance is a persistent problem that needs continuous attention by scientists, medical professionals, and government agencies. To solve the problem, an in-depth understanding of the intricate interplay between causes of antiviral drug resistance and potential new drugs specifically natural products is imperative in the interest and safety of public health. This review delves into natural product as reservoir for antiviral agents with the peculiar potentials for addressing the complexities associated with multi-drug resistant and emerging viral strains. An evaluation of the mechanisms underlying antiviral drug activity, antiviral drug resistance is addressed, with emphasis on production of broad-spectrum antiviral agents from natural sources. There is a need for continued natural product-based research, identification of new species and novel compounds.

关键词： Drug resistance resistance mechanisms Phytochemicals Broad-Spectrum Drugs Antiviral Agents

Comprehensive Overview of Populus simonii Research in the Recent Years

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Open Journal of Ecology 2024年第5期14卷 419-434页

作者： Dandan Zhang Faujiah Nurhasanah Ritonga Tuya Siqin Runxian Song Zicheng Zhang Mingwei Tang Peilin Sun Wa Gao Heilongjiang Institute of Atomic Energy Harbin China Graduate School Padjadjaran University Bandung Indonesia Key Laboratory of Molecular Epigenetics of the Ministry of Education Northeast Normal University Changchun China

As an important ecological tree species in northern China, Populus simonii plays a crucial role in maintaining ecological balance and promoting environmental sustainability. The academic community has conducted a series of in-depth studies on this species, covering key areas such as genomics, survival mechanisms, and genetic breeding. Through the analysis of the genomic structure and function of P. simonii, we have not only revealed the molecular basis for its adaptation to harsh environments but also identified key genes that promote its growth and resistance to pests and diseases. Furthermore, exploring the survival mechanisms of P. simonii has deepened our understanding of its stress resistance traits, including how it effectively copes with abiotic stresses such as drought, salinization, and heavy metal pollution. In genetic breeding, significant progress has been made through the application of modern biotechnology, improving the growth rate and wood quality of P. simonii and enhancing its environmental adaptability and disease resistance. These research findings have not only enriched our knowledge of the biological characteristics of P. simonii but also provided a solid scientific foundation for its application in ecological restoration, forestry production, and environmental management.

关键词： Breeding Ecological Restoration Genomics Populus simonii resistance mechanisms

Prevalence and mechanisms of carbapenems-resistance in Enterobacteriaceae with decreased susceptibility to carbapenem,in Zhejiang Province

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Prevalence and mechanisms of carbapenems-resistance in Enter...