Drug Resistance Updates最新文献

{"title":"Editorial: ABC transporters and drug resistance","authors":"Qisi Lu, Suresh V. Ambudkar, Dong-Hua Yang","doi":"10.1016/j.drup.2024.101135","DOIUrl":"10.1016/j.drup.2024.101135","url":null,"abstract":"","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101135"},"PeriodicalIF":15.8,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional relay between Mph(A) enzyme and Mrx efflux pump mediates azithromycin resistance, a novel mechanism of bacterial antimicrobial resistance","authors":"Xuemei Yang , Haoshuai Zhang , Yang Tang , Heng Heng , Yan-Chu Cheung , Xuejiao Song , Hang-Kin Kong , Edward Wai-Chi Chan , Sheng Chen","doi":"10.1016/j.drup.2024.101127","DOIUrl":"10.1016/j.drup.2024.101127","url":null,"abstract":"","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101127"},"PeriodicalIF":15.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular and molecular mechanisms of gastrointestinal cancer liver metastases and drug resistance","authors":"Daosong Dong ,&nbsp;Xue Yu ,&nbsp;Jingjing Xu ,&nbsp;Na Yu ,&nbsp;Zhe Liu ,&nbsp;Yanbin Sun","doi":"10.1016/j.drup.2024.101125","DOIUrl":"10.1016/j.drup.2024.101125","url":null,"abstract":"<div><p>Distant metastases and drug resistance account for poor survival of patients with gastrointestinal (GI) malignancies such as gastric cancer, pancreatic cancer, and colorectal cancer. GI cancers most commonly metastasize to the liver, which provides a unique immunosuppressive tumour microenvironment to support the development of a premetastatic niche for tumor cell colonization and metastatic outgrowth. Metastatic tumors often exhibit greater resistance to drugs than primary tumors, posing extra challenges in treatment. The liver metastases and drug resistance of GI cancers are regulated by complex, intertwined, and tumor-dependent cellular and molecular mechanisms that influence tumor cell behavior (e.g. epithelial-to-mesenchymal transition, or EMT), tumor microenvironment (TME) (e.g. the extracellular matrix, cancer-associated fibroblasts, and tumor-infiltrating immune cells), tumor cell-TME interactions (e.g. through cytokines and exosomes), liver microenvironment (e.g. hepatic stellate cells and macrophages), and the route and mechanism of tumor cell dissemination (e.g. circulating tumor cells). This review provides an overview of recent advances in the research on cellular and molecular mechanisms that regulate liver metastases and drug resistance of GI cancers. We also discuss recent advances in the development of mechanism-based therapy for these GI cancers. Targeting these cellular and molecular mechanisms, either alone or in combination, may potentially provide novel approaches to treat metastatic GI malignancies.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101125"},"PeriodicalIF":15.8,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"crVDAC3 alleviates ferroptosis by impeding HSPB1 ubiquitination and confers trastuzumab deruxtecan resistance in HER2-low breast cancer","authors":"Yutian Zou ,&nbsp;Anli Yang ,&nbsp;Bo Chen ,&nbsp;Xinpei Deng ,&nbsp;Jindong Xie ,&nbsp;Danian Dai ,&nbsp;Jinhui Zhang ,&nbsp;Hailin Tang ,&nbsp;Tao Wu ,&nbsp;Zhigang Zhou ,&nbsp;Xiaoming Xie ,&nbsp;Jin Wang","doi":"10.1016/j.drup.2024.101126","DOIUrl":"10.1016/j.drup.2024.101126","url":null,"abstract":"<div><h3>Aims</h3><p>With the wide application of trastuzumab deruxtecan (T-DXd), the survival of HER2-low breast cancer patients is dramatically improved. However, resistance to T-DXd still exists in a subset of patients, and the molecular mechanism remains unclear.</p></div><div><h3>Methods</h3><p>An <em>in vivo</em> shRNA lentiviral library functional screening was performed to identify potential circular RNA (crRNA) that mediates T-DXd resistance. RNA pull-down, mass spectrometry, RNA immunoprecipitation, and co-immunoprecipitation assays were conducted to investigate the molecular mechanism. Ferroptosis was detected using C11-BODIPY, Liperfluo, FerroOrange staining, glutathione quantification, malondialdehyde quantification, and transmission electron microscopy. Molecular docking, virtual screening, and patient-derived xenograft (PDX) models were used to validate therapeutic agents.</p></div><div><h3>Results</h3><p>VDAC3-derived crRNA (crVDAC3) ranked first in functional shRNA library screening. Knockdown of crVDAC3 increased the sensitivity of HER2-low breast cancer cells to T-DXd treatment. Further mechanistic research revealed that crVDAC3 specifically binds to HSPB1 protein and inhibits its ubiquitination degradation, leading to intracellular accumulation and increased levels of HSPB1 protein. Notably, suppression of crVDAC3 dramatically increases excessive ROS levels and labile iron pool accumulation. Inhibition of crVDAC3 induces ferroptosis in breast cancer cells by reducing HSPB1 expression, thereby mediating T-DXd resistance. Through virtual screening and experimental validation, we identified that paritaprevir could effectively bind to crVDAC3 and prevent its interaction with HSPB1 protein, thereby increasing ubiquitination degradation of HSPB1 protein to overcome T-DXd resistance. Finally, we validated the enhanced therapeutic efficacy of T-DXd by paritaprevir in a HER2-low PDX model.</p></div><div><h3>Conclusion</h3><p>This finding reveals the molecular mechanisms underlying T-DXd resistance in HER2-low breast cancer. Our study provides a new strategy to overcome T-DXd resistance by inhibiting the interaction between crVDAC3 and HSPB1 protein.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101126"},"PeriodicalIF":15.8,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An increased prevalence of carbapenem-resistant hypervirulent Klebsiella pneumoniae associated with the COVID-19 pandemic","authors":"Chao Liu ,&nbsp;Jun Guo ,&nbsp;Shuaihua Fan ,&nbsp;Wei Guo ,&nbsp;Huaiqing Qi ,&nbsp;Stephen Baker ,&nbsp;Pengcheng Du ,&nbsp;Bin Cao","doi":"10.1016/j.drup.2024.101124","DOIUrl":"10.1016/j.drup.2024.101124","url":null,"abstract":"<div><h3>Background</h3><p><em>Klebsiella pneumoniae</em> (Kp) is a common community-acquired and nosocomial pathogen. Carbapenem-resistant and hypervirulent (CR-hvKp) variants can emerge rapidly within healthcare facilities and impacted by other infectious agents such as COVID-19 virus.</p></div><div><h3>Methods</h3><p>To understand the impact of COVID-19 virus on the prevalence of CR-hvKp, we accessed Kp genomes with corresponding metadata from GenBank. Sequence types (STs), antimicrobial resistance genes, and virulence genes, and those scores and CR-hvKp were identified. We analyzed population diversity and phylogenetic characteristics of five most common STs, measured the prevalence of CR-hvKp, identified CR-hvKp subtypes, and determined associations between carbapenem resistance gene subtypes with STs and plasmid types. These variables were compared pre- and during the COVID-19 pandemic.</p></div><div><h3>Findings</h3><p>The proportion of CR-hvKp isolates increased within multiple STs in different continents during the COVID-19 pandemic and persistent CR-hvKp subtypes were found in common STs. <em>bla</em>_KPC was dominant in CG258, <em>bla</em>_KPC-2 was detected in 97 % of the ST11 CR-hvKp, <em>bla</em>_NDM subtypes were prominent in ST147 (87.4 %) and ST307 (70.8 %); <em>bla</em>_OXA-48 and its subtypes were prevalent in ST15 (80.5 %). The possession of carbapenemase genes was different among subclades from different origins in different periods of time within each ST. IncFIB/IncHI1B hybrid plasmids contained virulence genes and carbapenemase genes and were predominant in ST147 (67.37 %) and ST307 (56.25 %).</p></div><div><h3>Interpretation</h3><p>The prevalence of CR-hvKp increased during the COVID-19 pandemic, which was evident by an increase in local endemic clones. This process was facilitated by the convergence of plasmids containing carbapenemase genes and virulence genes. These findings have implications for the appropriate use of antimicrobials and infection prevention and control during outbreaks of respiratory viruses and pandemic management.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101124"},"PeriodicalIF":15.8,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence of silent NDM-1 carbapenemase gene in carbapenem-susceptible Klebsiella pneumoniae: Clinical implications and epidemiological insights","authors":"Juanxiu Qin ,&nbsp;Yuan Zhu ,&nbsp;Yiwei Zhu ,&nbsp;Qianqian Gao ,&nbsp;Haomin Zhang ,&nbsp;Min Li ,&nbsp;Zhen Shen","doi":"10.1016/j.drup.2024.101123","DOIUrl":"10.1016/j.drup.2024.101123","url":null,"abstract":"<div><p>The global dissemination of carbapenemase genes, particularly <em>bla</em>_NDM-1, poses a significant threat to public health. While research has mainly focused on strains with phenotypic resistance, the impact of silent resistance genes has been largely overlooked. This study documents the first instance of silent <em>bla</em>_NDM-1 in a cluster of clonally related carbapenem-susceptible <em>K. pneumoniae</em> strains from a single patient. Despite initial effectiveness of carbapenem therapy, the patient experienced four recurrent lung infections over five months, indicating persistent <em>K. pneumoniae</em> infection. Genomic sequencing revealed all strains harbored <em>bla</em>_NDM-1 on the epidemic IncX3 plasmid. A deletion within the upstream promoter region (P_{IS<em>Aba125</em>}) of <em>bla</em>_NDM-1 hindered its expression, resulting in phenotypic susceptibility to carbapenems. However, in vitro bactericidal assays and a mouse infection model showed that <em>K. pneumoniae</em> strains with silent <em>bla</em>_NDM-1 exhibited significant tolerance to carbapenem-mediated killing. These findings demonstrate that silent <em>bla</em>_NDM-1 can mediate both phenotypic susceptibility and antibiotic tolerance. In silico analysis of 1986 <em>bla</em>_NDM sequences showed that 1956 (98.5%) retained the original promoter P_{IS<em>Aba125</em>}. Given that previous genomic sequencing typically targets carbapenem-resistant strains, accurately assessing the prevalence of silent <em>bla</em>_NDM remains challenging. This study highlights the hidden threat of silent resistance genes to clinical antimicrobial therapy and calls for enhanced clinical awareness and laboratory detection.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"76 ","pages":"Article 101123"},"PeriodicalIF":15.8,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Framework nucleic acid-based nanoparticles enhance temozolomide sensitivity in glioblastoma","authors":"Yufei Lan ,&nbsp;Xiaodie Li ,&nbsp;Boyang Liu ,&nbsp;Jiankun Lu ,&nbsp;Boming Zuo ,&nbsp;Yue Wang ,&nbsp;Shuting Cao ,&nbsp;Xin Fu ,&nbsp;Qu Yue ,&nbsp;Xin Luo ,&nbsp;Xiangyang Zhong ,&nbsp;Yaoyuan Dong ,&nbsp;Zhao Wang ,&nbsp;Tao Yang ,&nbsp;Xinyun Xie ,&nbsp;Tianci Zeng ,&nbsp;Manqing Zhang ,&nbsp;Yuankai Wang ,&nbsp;Yixiong Shen ,&nbsp;Huaqin Zuo ,&nbsp;Hongbo Guo","doi":"10.1016/j.drup.2024.101122","DOIUrl":"10.1016/j.drup.2024.101122","url":null,"abstract":"<div><p>O⁶-methylguanine DNA methyltransferase (MGMT) is a crucial determinant of temozolomide (TMZ) sensitivity in patients with glioblastoma (GBM). The therapeutic potential of small interfering RNA (siRNA) targeting MGMT to enhance TMZ sensitivity has been hampered by serum nuclease degradation, off-target effects, poor accumulation at tumor sites, and low circulation in blood stream. In this study, we developed a framework nucleic acid-based nanoparticles (FNN), which is constructed from a six-helix DNA bundle, to encapsulate and protect siMGMT for improving TMZ sensitivity in GBM treatment. For better blood-brain barrier (BBB) penetration and GBM targeting, we conjugated Angiopep-2 (ANG) targeting modules to each end of the FNN. Nucleolin (NCL)-responsive locks were engineered along the sides of the six-helix DNA bundle, which safeguard siMGMT before tumor entry. Upon interaction with tumor-overexpressed NCL, these locks unlock, exposing siMGMT, this allows for effective suppression of MGMT, resulting in a significant improvement of TMZ therapeutic efficacy in GBM. This innovative strategy has the potential to transform the current treatment landscape for GBM.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"76 ","pages":"Article 101122"},"PeriodicalIF":15.8,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1368764624000803/pdfft?md5=47417d5307b912b981adbabff966005b&pid=1-s2.0-S1368764624000803-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141841138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BCL7A inhibits the progression and drug-resistance in acute myeloid leukemia","authors":"Tushuai Li ,&nbsp;Renjie Gao ,&nbsp;Kaiwen Xu ,&nbsp;Pengpeng Pan ,&nbsp;Congcong Chen ,&nbsp;Daokuan Wang ,&nbsp;Keyi Zhang ,&nbsp;Jilei Qiao ,&nbsp;Yue Gu","doi":"10.1016/j.drup.2024.101120","DOIUrl":"10.1016/j.drup.2024.101120","url":null,"abstract":"<div><h3>Aims</h3><p>This study aimed to elucidate the biological roles and regulatory mechanisms of B-cell lymphoma 7 protein family member A (BCL7A) in acute myeloid leukemia (AML), particularly its interaction with polypyrimidine tract binding protein 1 (PTBP1) and the effects on cancer progression and drug resistance.</p></div><div><h3>Methods</h3><p>BCL7A expression levels were analyzed in AML tissues and cell lines, focusing on associations with promoter hypermethylation. Interaction with PTBP1 and effects of differential expression of BCL7A were examined in vitro and in vivo. The impacts on cell proliferation, cycle progression, apoptosis, and differentiation were studied. Additionally, the regulatory roles of BCL7A on interferon regulatory factor 7 (IRF7) and 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) were assessed.</p></div><div><h3>Results</h3><p>BCL7A was downregulated in AML due to promoter hypermethylation and negatively regulated by PTBP1. Upregulation of BCL7A impeded AML cell growth, induced apoptosis, promoted cell differentiation, and decreased cell infiltration into lymph nodes, enhancing survival in mouse models. Overexpression of BCL7A upregulated IRF7 and downregulated HMGCS1, linking to reduced AML cell malignancy and decreased resistance to cytarabine.</p></div><div><h3>Conclusions</h3><p>BCL7A acts as a tumor suppressor in AML, inhibiting malignant progression and enhancing drug sensitivity through the IRF7/HMGCS1 pathway. These findings suggest potential therapeutic targets for improving AML treatment outcomes.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"76 ","pages":"Article 101120"},"PeriodicalIF":15.8,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1368764624000785/pdfft?md5=fea43ab3d6711381539b5ee4322205d8&pid=1-s2.0-S1368764624000785-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intersecting pathways: The role of hybrid E/M cells and circulating tumor cells in cancer metastasis and drug resistance","authors":"Amirali Hariri ,&nbsp;Mina Mirian ,&nbsp;Arezoo Khosravi ,&nbsp;Atefeh Zarepour ,&nbsp;Siavash Iravani ,&nbsp;Ali Zarrabi","doi":"10.1016/j.drup.2024.101119","DOIUrl":"10.1016/j.drup.2024.101119","url":null,"abstract":"<div><p>Cancer metastasis and therapy resistance are intricately linked with the dynamics of Epithelial-Mesenchymal Transition (EMT) and Circulating Tumor Cells (CTCs). EMT hybrid cells, characterized by a blend of epithelial and mesenchymal traits, have emerged as pivotal in metastasis and demonstrate remarkable plasticity, enabling transitions across cellular states crucial for intravasation, survival in circulation, and extravasation at distal sites. Concurrently, CTCs, which are detached from primary tumors and travel through the bloodstream, are crucial as potential biomarkers for cancer prognosis and therapeutic response. There is a significant interplay between EMT hybrid cells and CTCs, revealing a complex, bidirectional relationship that significantly influences metastatic progression and has a critical role in cancer drug resistance. This resistance is further influenced by the tumor microenvironment, with factors such as tumor-associated macrophages, cancer-associated fibroblasts, and hypoxic conditions driving EMT and contributing to therapeutic resistance. It is important to understand the molecular mechanisms of EMT, characteristics of EMT hybrid cells and CTCs, and their roles in both metastasis and drug resistance. This comprehensive understanding sheds light on the complexities of cancer metastasis and opens avenues for novel diagnostic approaches and targeted therapies and has significant advancements in combating cancer metastasis and overcoming drug resistance.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"76 ","pages":"Article 101119"},"PeriodicalIF":15.8,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141699106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Point mutation P174L of the penA gene endowing ceftazidime resistance to Burkholderia pseudomallei in China","authors":"Shen Tian ,&nbsp;Xingyong Wu ,&nbsp;Lin Liu ,&nbsp;Anyang Li ,&nbsp;Xuemiao Li ,&nbsp;Hua Pei ,&nbsp;Yanshuang Wang ,&nbsp;David A.B. Dance ,&nbsp;Hai Chen ,&nbsp;Qianfeng Xia","doi":"10.1016/j.drup.2024.101121","DOIUrl":"10.1016/j.drup.2024.101121","url":null,"abstract":"<div><p>In a clinical isolate of <em>Burkholderia pseudomallei</em> from Hainan, the association between the emergence of ceftazidime resistance and a novel PenA P174L allele was identified for the first time, providing an understanding of one mechanism by which ceftazidime resistance arises in <em>B. pseudomallei</em>.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"76 ","pages":"Article 101121"},"PeriodicalIF":15.8,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141630330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}