-
Targeted dual degradation of HER2 and EGFR obliterates oncogenic signaling, overcomes therapy resistance, and inhibits metastatic lesions in HER2-positive breast cancer models Drug Resist. Updat. (IF 24.3) Pub Date : 2024-03-13 Lu Yang, Arup Bhattacharya, Darrell Peterson, Yun Li, Xiaozhuo Liu, Elisabetta Marangoni, Valentina Robila, Yuesheng Zhang
Human epidermal growth factor receptor 2 (HER2) is an oncogenic receptor tyrosine kinase amplified in approximately 20% of breast cancer (BC). HER2-targeted therapies are the linchpin of treating HER2-positive BC. However, drug resistance is common, and the main resistance mechanism is unknown. We tested the hypothesis that drug resistance results mainly from inadequate or lack of inhibition of HER2
-
TRIM29 facilitates gemcitabine resistance via MEK/ERK pathway and is modulated by circRPS29/miR-770-5p axis in PDAC Drug Resist. Updat. (IF 24.3) Pub Date : 2024-03-12 Wenjie Huang, Xiaojun Hu, Xiang He, Dongyue Pan, Zhaorong Huang, Zhanfeng Gu, Guobing Huang, Ping Wang, Chunhui Cui, Yingfang Fan
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease. Chemotherapy based on gemcitabine (GEM) remains the first-line drug for patients with advanced PDAC. However, GEM resistance impairs its therapeutic effectiveness. Therefore, identifying effective therapeutic targets are urgently needed to overcome GEM resistance. The clinical significance of Tripartite Motif Containing 29 (TRIM29)
-
A Novel SIK2 Inhibitor SIC-19 exhibits Synthetic Lethality with PARP inhibitors in Ovarian Cancer Drug Resist. Updat. (IF 24.3) Pub Date : 2024-03-06 Fang Wang, Xuejiao Yu, Jun Qian, Yumin Cao, Shunli Dong, Shenghua Zhan, Zhen Lu, Robert C. Bast Jr., Qingxia Song, Youguo Chen, Yi Zhang, Jinhua Zhou
Ovarian cancer patients with HR proficiency (HRP) have had limited benefits from PARP inhibitor treatment, highlighting the need for improved therapeutic strategies. In this study, we developed a novel SIK2 inhibitor, SIC-19, and investigated its potential to enhance the sensitivity and expand the clinical utility of PARP inhibitors in ovarian cancer. The SIK2 protein was modeled using a Molecular
-
Solving the antibacterial resistance in Europe: The multipronged approach of the COST Action CA21145 EURESTOP Drug Resist. Updat. (IF 24.3) Pub Date : 2024-02-17 Carole Seguin-Devaux, Tomislav Mestrovic, Jacobus J. Arts, Didem Sen Karaman, Cristina Nativi, Dana Reichmann, Priyanka Sahariah, Younes Smani, Patricia Rijo, Mattia Mori, on behalf of the COST Action CA21145 EURESTOP
-
Development and evaluation of a human CD47/HER2 bispecific antibody for Trastuzumab-resistant breast cancer immunotherapy Drug Resist. Updat. (IF 24.3) Pub Date : 2024-02-13 Binglei Zhang, Jianxiang Shi, Xiaojing Shi, Xiaolu Xu, Le Gao, Song Li, Mengmeng Liu, Mengya Gao, Shuiling Jin, Jian Zhou, Dandan Fan, Fang Wang, Zhenyu Ji, Zhilei Bian, Yongping Song, Wenzhi Tian, Yichao Zheng, Linping Xu, Wei Li
The treatment for trastuzumab-resistant breast cancer (BC) remains a challenge in clinical settings. It was known that CD47 is preferentially upregulated in HER2 BC cells, which is correlated with drug resistance to trastuzumab. Here, we developed a novel anti-CD47/HER2 bispecific antibody (BsAb) against trastuzumab-resistant BC, named IMM2902. IMM2902 demonstrated high binding affinity, blocking activity
-
AI in infectious diseases: The role of datasets Drug Resist. Updat. (IF 24.3) Pub Date : 2024-02-10 C, e, s, a, r, , d, e, , l, a, , F, u, e, n, t, e, -, N, u, n, e, z
-
Tumor-acquired somatic mutation affects conformation to abolish ABCG2-mediated drug resistance Drug Resist. Updat. (IF 24.3) Pub Date : 2024-02-06 Tomoka Gose, Ali Rasouli, Sepehr Dehghani-Ghahnaviyeh, Po-Chao Wen, Yao Wang, John Lynch, Yu Fukuda, Talha Shafi, Robert C. Ford, Emad Tajkhorshid, John D. Schuetz
ABCG2 is an important ATP-binding cassette transporter impacting the absorption and distribution of over 200 chemical toxins and drugs. ABCG2 also reduces the cellular accumulation of diverse chemotherapeutic agents. Acquired somatic mutations in the phylogenetically conserved amino acids of ABCG2 might provide unique insights into its molecular mechanisms of transport. Here, we identify a tumor-derived
-
ABCB1-dependent collateral sensitivity of multidrug-resistant colorectal cancer cells to the survivin inhibitor MX106-4C Drug Resist. Updat. (IF 24.3) Pub Date : 2024-02-06 Zi-Ning Lei, Najah Albadari, Qiu-Xu Teng, Hadiar Rahman, Jing-Quan Wang, Zhongzhi Wu, Dejian Ma, Suresh V. Ambudkar, John N.D. Wurpel, Yihang Pan, Wei Li, Zhe-Sheng Chen
To investigate the collateral sensitivity (CS) of ABCB1-positive multidrug resistant (MDR) colorectal cancer cells to the survivin inhibitor MX106–4C and the mechanism. Biochemical assays (MTT, ATPase, drug accumulation/efflux, Western blot, RT-qPCR, immunofluorescence, flow cytometry) and bioinformatic analyses (mRNA-sequencing, reversed-phase protein array) were performed to investigate the hypersensitivity
-
Fibroblast growth factor receptor 1 inhibition suppresses pancreatic cancer chemoresistance and chemotherapy-driven aggressiveness Drug Resist. Updat. (IF 24.3) Pub Date : 2024-02-04 Qingxiang Lin, Andrea Serratore, Jin Niu, Shichen Shen, Tista Roy Chaudhuri, Wen Wee Ma, Jun Qu, Eugene S. Kandel, Robert M. Straubinger
Pancreatic ductal adenocarcinoma (PDAC) is often intrinsically-resistant to standard-of-care chemotherapies such as gemcitabine. Acquired gemcitabine resistance (GemR) can arise from treatment of initially-sensitive tumors, and chemotherapy can increase tumor aggressiveness. We investigated the molecular mechanisms of chemoresistance and chemotherapy-driven tumor aggressiveness, which are understood
-
Methylation of GPRC5A promotes liver metastasis and docetaxel resistance through activating mTOR signaling pathway in triple negative breast cancer Drug Resist. Updat. (IF 24.3) Pub Date : 2024-02-01 Xueqi Ou, Yeru Tan, Jindong Xie, Jingping Yuan, Xinpei Deng, Ruonan Shao, Cailu Song, Xi Cao, Xiaoming Xie, Rongfang He, Yuehua Li, Hailin Tang
This study aims to explore the function and mechanism of G Protein-coupled receptor class C group 5 member A (GPRC5A) in docetaxel-resistance and liver metastasis of breast cancer. Single-cell RNA transcriptomic analysis and bioinformatic analysis are used to screen relevant genes in breast cancer metastatic hepatic specimens. MeRIP, dual-luciferase analysis and bioinformation were used to detect m6A
-
The role of ABCC10/MRP7 in anti-cancer drug resistance and beyond Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-29 Da-Qian Chen, Yuhao Xie, Lu-Qi Cao, Joshua S. Fleishman, Yang Chen, Tiesong Wu, Dong-Hua Yang
Multidrug resistance protein 7 (MRP7), also known as ATP-binding cassette (ABC) transporter subfamily C10 (ABCC10), is an ABC transporter that was first identified in 2001. ABCC10/MRP7 is a 171 kDa protein located on the basolateral membrane of cells. ABCC10/MRP7 consists of three transmembrane domains and two nucleotide binding domains. It mediates multidrug resistance of tumor cells to a variety
-
Lipid oxidation in emulsions: New insights from the past two decades Prog. Lipid. Res. (IF 13.6) Pub Date : 2024-01-26 Marie Hennebelle, Pierre Villeneuve, Erwann Durand, Jérôme Lecomte, John van Duynhoven, Anne Meynier, Betül Yesiltas, Charlotte Jacobsen, Claire Berton-Carabin
Lipid oxidation constitutes the main source of degradation of lipid-rich foods, including food emulsions. The complexity of the reactions at play combined with the increased demand from consumers for less processed and more natural foods result in additional challenges in controlling this phenomenon. This review provides an overview of the insights acquired over the past two decades on the understanding
-
Phage-mediated colistin resistance in Acinetobacter baumannii Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-28 Massimiliano Lucidi, Francesco Imperi, Irene Artuso, Giulia Capecchi, Cinzia Spagnoli, Daniela Visaggio, Giordano Rampioni, Livia Leoni, Paolo Visca
Antimicrobial resistance is a global threat to human health, and is a paradigmatic example of how rapidly bacteria become resistant to clinically relevant antimicrobials. The emergence of multidrug-resistant . strains has forced the revival of colistin as a last-resort drug, suddenly leading to the emergence of colistin resistance. We investigated the genetic and molecular basis of colistin resistance
-
Target-based drug design strategies to overcome resistance to antiviral agents: opportunities and challenges Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-26 Shaoqing Du, Xueping Hu, Luis Menéndez-Arias, Peng Zhan, Xinyong Liu
Viral infections have a major impact in human health. Ongoing viral transmission and escalating selective pressure have the potential to favor the emergence of vaccine- and antiviral drug-resistant viruses. Target-based approaches for the design of antiviral drugs can play a pivotal role in combating drug-resistant challenges. Drug design computational tools facilitate the discovery of novel drugs
-
Acetaminophen Hepatotoxicity: Paradigm for Understanding Mechanisms of Drug-Induced Liver Injury Ann. Review Paleopathol. Mech. Disease (IF 36.2) Pub Date : 2024-01-24 Hartmut Jaeschke, Anup Ramachandran
Acetaminophen (APAP) overdose is the clinically most relevant drug hepatotoxicity in western countries, and, because of translational relevance of animal models, APAP is mechanistically the most studied drug. This review covers intracellular signaling events starting with drug metabolism and the central role of mitochondrial dysfunction involving oxidant stress and peroxynitrite. Mitochondria-derived
-
Chance and Opportunity: A Personal Story Ann. Review Paleopathol. Mech. Disease (IF 36.2) Pub Date : 2024-01-24 Abul K. Abbas
This article summarizes my personal life story, from early education in India to research, teaching, and other activities in Boston and San Francisco. I have tried to illustrate how unplanned events shape one's path, and why the willingness to go with the flow is among one's most valuable attributes.
-
Pediatric Cholestatic Diseases: Common and Unique Pathogenic Mechanisms Ann. Review Paleopathol. Mech. Disease (IF 36.2) Pub Date : 2024-01-24 Harry Sutton, Saul J. Karpen, Binita M. Kamath
Cholestasis is the predominate feature of many pediatric hepatobiliary diseases. The physiologic flow of bile requires multiple complex processes working in concert. Bile acid (BA) synthesis and excretion, the formation and flow of bile, and the enterohepatic reuptake of BAs all function to maintain the circulation of BAs, a key molecule in lipid digestion, metabolic and cellular signaling, and, as
-
Neutrophils in Physiology and Pathology Ann. Review Paleopathol. Mech. Disease (IF 36.2) Pub Date : 2024-01-24 Alejandra Aroca-Crevillén, Tommaso Vicanolo, Samuel Ovadia, Andrés Hidalgo
Infections, cardiovascular disease, and cancer are major causes of disease and death worldwide. Neutrophils are inescapably associated with each of these health concerns, by either protecting from, instigating, or aggravating their impact on the host. However, each of these disorders has a very different etiology, and understanding how neutrophils contribute to each of them requires understanding the
-
Update on Epithelial-Mesenchymal Plasticity in Cancer Progression Ann. Review Paleopathol. Mech. Disease (IF 36.2) Pub Date : 2024-01-24 Rosa Fontana, Aida Mestre-Farrera, Jing Yang
Epithelial-mesenchymal transition (EMT) is a cellular process by which epithelial cells lose their characteristics and acquire mesenchymal traits to promote cell movement. This program is aberrantly activated in human cancers and endows tumor cells with increased abilities in tumor initiation, cell migration, invasion, metastasis, and therapy resistance. The EMT program in tumors is rarely binary and
-
Utilizing non-coding RNA-mediated regulation of ATP binding cassette (ABC) transporters to overcome multidrug resistance to cancer chemotherapy Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-20 Kenneth K.W. To, Zoufang Huang, Hang Zhang, Charles R. Ashby Jr., Liwu Fu
Multidrug resistance (MDR) is one of the primary factors that produces treatment failure in patients receiving cancer chemotherapy. MDR is a complex multifactorial phenomenon, characterized by a decrease or abrogation of the efficacy of a wide spectrum of anticancer drugs that are structurally and mechanistically distinct. The overexpression of the ATP-binding cassette (ABC) transporters, notably ABCG2
-
Polyphenol nanocomplex modulates lactate metabolic reprogramming and elicits immune responses to enhance cancer therapeutic effect Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-20 Zhan Zhang, Xinnan Li, Weiqiang Liu, Guanglei Chen, Jinchi Liu, Qingtian Ma, Pengjie Hou, Lu Liang, Caigang Liu
Cancer lactate metabolic reprogramming induces an elevated level of extracellular lactate and H, leading to an acidic immunosuppressive tumor microenvironment (TEM). High lactic acid level may affect the metabolic programs of various cells that comprise an antitumor immune response, therefore, restricting immune-mediated tumor destruction, and leading to therapeutic resistance and unsatisfactory prognosis
-
MAFF confers vulnerability to cisplatin-based and ionizing radiation treatments by modulating ferroptosis and cell cycle progression in lung adenocarcinoma Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-19 Jiaqi Liang, Guoshu Bi, Yiwei Huang, Guangyin Zhao, Qihai Sui, Huan Zhang, Yunyi Bian, Jiacheng Yin, Qun Wang, Zhencong Chen, Cheng Zhan
Lung cancer is the leading cause of cancer mortality and lung adenocarcinoma (LUAD) accounts for more than half of all lung cancer cases. Tumor elimination is mostly hindered by drug resistance and the mechanisms remain to be explored in LUAD. CRISPR screens in cell and murine models and single-cell RNA sequencing were conducted, which identified MAF bZIP transcription factor F (MAFF) as a critical
-
Drug resistance mechanisms in dopamine agonist-resistant prolactin pituitary neuroendocrine tumors and exploration for new drugs Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-19 Jianhua Cheng, Weiyan Xie, Yiyuan Chen, Yingxuan Sun, Lei Gong, Hongyun Wang, Chuzhong Li, Yazhuo Zhang
The treatment of dopamine agonists (DA) resistant prolactinomas remains a formidable challenge, as the mechanism of resistance is still unclear, and there are currently no viable alternative drug therapies available. This study seeks to investigate the mechanism of DA resistance in prolactinomas and identify new potentially effective drugs. To explore the mechanism of DA resistance in prolactinomas
-
Single-cell transcriptome analysis reveals the association between histone lactylation and cisplatin resistance in bladder cancer Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-19 Fei Li, Henghui Zhang, Yuan Huang, Dongqing Li, Zaosong Zheng, Kunfeng Xie, Chun Cao, Qiong Wang, Xinlei Zhao, Zehai Huang, Shijun Chen, Haiyong Chen, Qin Fan, Fan Deng, Lina Hou, Xiaolin Deng, Wanlong Tan
Patients with bladder cancer (BCa) frequently acquires resistance to platinum-based chemotherapy, particularly cisplatin. This study centered on the mechanism of cisplatin resistance in BCa and highlighted the pivotal role of lactylation in driving this phenomenon. Utilizing single-cell RNA sequencing, we delineated the single-cell landscape of Bca, pinpointing a distinctive subset of BCa cells that
-
Tumor-associated macrophage (TAM)-secreted CCL22 confers cisplatin resistance of esophageal squamous cell carcinoma (ESCC) cells via regulating the activity of diacylglycerol kinase α (DGKα)/NOX4 axis Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-18 Jie Chen, Di Zhao, Lingyuan Zhang, Jing Zhang, Yuanfan Xiao, Qingnan Wu, Yan Wang, Qimin Zhan
Tumor-associated macrophages (TAMs) are often associated with chemoresistance and resultant poor clinical outcome in solid tumors. Here, we demonstrated that TAMs-released chemokine-C-C motif chemokine 22 (CCL22) in esophageal squamous cell carcinoma (ESCC) stroma was tightly correlated with the chemoresistance of ESCC patients. TAMs-secreted CCL22 was able to block the growth inhibitory and apoptosis-promoting
-
Inhibition of SIRT7 overcomes sorafenib acquired resistance by suppressing ERK1/2 phosphorylation via the DDX3X-mediated NLRP3 inflammasome in hepatocellular carcinoma Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-17 Yuna Kim, Kwan-Young Jung, Yun Hak Kim, Pan Xu, Baeki E. Kang, Yunju Jo, Navin Pandit, Jeongho Kwon, Karim Gariani, Joanna Gariani, Junguee Lee, Jef Verbeek, Seungyoon Nam, Sung-Jin Bae, Ki-Tae Ha, Hyon-Seung Yi, Minho Shong, Kyun-Hwan Kim, Doyoun Kim, Hee Jung Jung, Chang-Woo Lee, Kwang Rok Kim, Kristina Schoonjans, Johan Auwerx, Dongryeol Ryu
-
-
Mitochondrial phospholipid transport: Role of contact sites and lipid transport proteins Prog. Lipid. Res. (IF 13.6) Pub Date : 2024-01-07 Vijay Aditya Mavuduru, Lavanya Vadupu, Krishna Kanta Ghosh, Sabyasachi Chakrabortty, Balázs Gulyás, Parasuraman Padmanabhan, Writoban Basu Ball
One of the major constituents of mitochondrial membranes is the phospholipids, which play a key role in maintaining the structure and the functions of the mitochondria. However, mitochondria do not synthesize most of the phospholipids in situ, necessitating the presence of phospholipid import pathways. Even for the phospholipids, which are synthesized within the inner mitochondrial membrane (IMM),
-
Dual specific phosphatase 4 suppresses ferroptosis and enhances sorafenib resistance in hepatocellular carcinoma Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-10 Shi-Hui Hao, Xiao-Dan Ma, Li Xu, Jing-Dun Xie, Zi-Hao Feng, Jie-Wei Chen, Ri-Xin Chen, Feng-Wei Wang, Yu-Hao Tang, Dan Xie, Mu-Yan Cai
-
Tyrosine phosphorylation-mediated YAP1-TFAP2A interactions coordinate transcription and trastuzumab resistance in HER2+ breast cancer Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-09 Hailin Zou, Juan Luo, Yibo Guo, Liang Deng, Leli Zeng, Yihang Pan, Peng Li
Trastuzumab resistance in HER2+ breast cancer (BC) is the major reason leading to poor prognosis of BC patients. Oncogenic gene overexpression or aberrant activation of tyrosine kinase SRC is identified to be the key modulator of trastuzumab response. However, the detailed regulatory mechanisms underlying SRC activation-associated trastuzumab resistance remain poorly understood. In the present study
-
NDRG1 overcomes resistance to immunotherapy of pancreatic ductal adenocarcinoma through inhibiting ATG9A-dependent degradation of MHC-1 Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-09 Zhiheng Zhang, Bojiao Song, Haowei Wei, Yang Liu, Wenjie Zhang, Yuhong Yang, Beicheng Sun
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that is resistant to immune checkpoint blockade (ICB) therapies. Emerging evidence suggests that NDRG1 may be an important target for the development of new therapies for PDAC. Herein, we investigated the novel roles of NDRG1 and Combretastatin A-4 (CA-4) in the treatment of PDAC ICB resistance. Enrichment of MHC class I was detected by RNA
-
-
Inhibition of NF-κB signaling unveils novel strategies to overcome drug resistance in cancers Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-04 Yuanfang Li, Baiwei Zhao, Juzheng Peng, Hailin Tang, Sicheng Wang, Sicheng Peng, Feng Ye, Junye Wang, Kai Ouyang, Jianjun Li, Manbo Cai, Yongming Chen
Drug resistance in cancer remains a major challenge in oncology, impeding the effectiveness of various treatment modalities. The nuclear factor-kappa B (NF-κB) signaling pathway has emerged as a critical player in the development of drug resistance in cancer cells. This comprehensive review explores the intricate relationship between NF-κB and drug resistance in cancer. We delve into the molecular
-
The promising role of tumor-associated macrophages in the treatment of cancer Drug Resist. Updat. (IF 24.3) Pub Date : 2024-01-03 Hongbin Wang, Xueying Wang, Xin Zhang, Wanhai Xu
Macrophages are important components of the immune system. Mature macrophages can be recruited to tumor microenvironment that affect tumor cell proliferation, invasion and metastasis, extracellular matrix remodeling, immune suppression, as well as chemotherapy resistance. Classically activated type I macrophages (M1) exhibited marked tumor killing and phagocytosis. Therefore, using macrophages for
-
Phosphatidic acid signaling and function in nuclei Prog. Lipid. Res. (IF 13.6) Pub Date : 2023-12-26 Shuaibing Yao, Sang-Chul Kim, Jianwu Li, Shan Tang, Xuemin Wang
Membrane lipidomes are dynamic and their changes generate lipid mediators affecting various biological processes. Phosphatidic acid (PA) has emerged as an important class of lipid mediators involved in a wide range of cellular and physiological responses in plants, animals, and microbes. The regulatory functions of PA have been studied primarily outside the nuclei, but an increasing number of recent
-
Vaccine effects on COVID-19 infection with bivalent boosting by age group Drug Resist. Updat. (IF 24.3) Pub Date : 2023-12-27 Y, o, s, h, i, y, a, s, u, , T, a, k, e, f, u, j, i
This paper examines time-series vaccine effectiveness on COVID-19 infection with/without a bivalent booster dose by 6 age groups such as 18–29, 30–49, 50–64, 65–79, 80+, and all_ages respectively. CDC’s COVID data on rates of COVID-19 cases and deaths by updated (bivalent) booster status was used in this study. This result concludes that there is no difference between vaccines with or without a bivalent
-
Dynamic within-host cefiderocol heteroresistance caused by blaSHV-12 amplification in pandrug-resistant and hypervirulent Klebsiella pneumoniae sequence type 11 Drug Resist. Updat. (IF 24.3) Pub Date : 2023-12-27 Chao Liu, Juan Yi, Ming Lu, Ping Yang, Chunjing Du, Fan Jiang, Pengcheng Du, Ning Shen
Although cefiderocol (FDC) is not prescribed in China, FDC-resistant pandrug-resistant hypervirulent (PDR-hvKp) is emerging. In this study, we performed FDC susceptibility testing of clinical Kp isolates to explore the prevalence of FDC-resistant isolates and the mechanism of FDC-resistance. We retrospectively selected 151 carbapenem-resistant Kp isolates to assess FDC susceptibility. Seven isolates
-
Rewiring chaperone-mediated autophagy in cancer by a prion-like chemical inducer of proximity to counteract adaptive immune resistance Drug Resist. Updat. (IF 24.3) Pub Date : 2023-12-25 Jin Yan, Dan Liu, Jingmei Wang, Weiming You, Wenguang Yang, Siqi Yan, Wangxiao He
Chaperone-mediated autophagy (CMA), a proteolytic system contributing to the degradation of intracellular proteins in lysosomes, is upregulated in tumors for pro-tumorigenic and pro-survival purposes. In this study, bioinformatics analysis revealed the co-occurrence of upregulated CMA and PD-L1 accumulation in metastatic melanoma with adaptive immune resistance (AIR) to anti-PD1 treatment, suggesting
-
Global spread characteristics of CTX-M-type extended-spectrum β-lactamases: A genomic epidemiology analysis Drug Resist. Updat. (IF 24.3) Pub Date : 2023-12-23 Keyi Yu, Zhenzhou Huang, Yue Xiao, He Gao, Xuemei Bai, Duochun Wang
Extended-spectrum β-lactamases (ESBLs) producing bacteria have spread worldwide and become a global public health concern. Plasmid-mediated transfer of ESBLs is an important route for resistance acquisition. We collected 1345 complete sequences of plasmids containing CTX-Ms from public database. The global transmission pattern of plasmids and evolutionary dynamics of CTX-Ms have been inferred. We applied
-
Cefiderocol: Clinical application and emergence of resistance Drug Resist. Updat. (IF 24.3) Pub Date : 2023-12-18 Liang Wang, Jie Zhu, Liang Chen, Hong Du
Antibacterial drug resistance of gram-negative bacteria (GNB) results in high morbidity and mortality of GNB infection, seriously threaten human health globally. Developing new antibiotics has become the critical need for dealing with drug-resistant bacterial infections. Cefiderocol is an iron carrier cephalosporin that achieves drug accumulation through a unique “Trojan horse” strategy into the bacterial
-
Progress in characterizing ABC multidrug transporters in zebrafish Drug Resist. Updat. (IF 24.3) Pub Date : 2023-12-17 Joanna R. Thomas, William J.E. Frye, Robert W. Robey, Michael M. Gottesman
Zebrafish have proved to be invaluable for modeling complex physiological processes shared by all vertebrate animals. Resistance of cancers and other diseases to drug treatment can occur owing to expression of the ATP-dependent multidrug transporters ABCB1, ABCG2, and ABCC1, either because of expression of these transporters by the target cells to reduce intracellular concentrations of cytotoxic drugs
-
Upregulation of CoQ shifts ferroptosis dependence from GPX4 to FSP1 in acquired radioresistance Drug Resist. Updat. (IF 24.3) Pub Date : 2023-12-09 Xu Lin, Qingyi Zhang, Qi Li, Jun Deng, Shuying Shen, Muhu Tang, Xianghua Ye, Cong Ji, Yuhong Yang, Yuxiao Chen, Liping Zeng, Jiangang Zhao, M.B.N. Kouwenhoven, Don Eliseo Lucero-Prisno III, Junjie Huang, Yangling Li, Bo Zhang, Jian Hu
-
TRAIL-driven targeting and reversing cervical cancer radioresistance by seleno-nanotherapeutics through regulating cell metabolism Drug Resist. Updat. (IF 24.3) Pub Date : 2023-12-09 Wenxiao Jiang, Guanning Huang, Shuya Pan, Xin Chen, Ting Liu, Ziyi Yang, Tianfeng Chen, Xueqiong Zhu
-
Combating bacterial infections with host defense peptides: Shifting focus from bacteria to host immunity Drug Resist. Updat. (IF 24.3) Pub Date : 2023-11-30 Nan Gao, Jiajun Wang, Chunyang Fang, Pengfei Bai, Yu Sun, Wanpeng Wu, Anshan Shan
The increasing prevalence of multidrug-resistant bacterial infections necessitates the exploration of novel paradigms for anti-infective therapy. Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), have garnered extensive recognition as immunomodulatory molecules that leverage natural host mechanisms to enhance therapeutic benefits. The unique immune mechanism exhibited by certain
-
Global distribution and genomic characteristics of carbapenemase-producing Escherichia coli among humans, 2005–2023 Drug Resist. Updat. (IF 24.3) Pub Date : 2023-12-03 Yan Li, Xinran Sun, Ning Dong, Zhiqiang Wang, Ruichao Li
Carbapenem-resistant Escherichia coli (CREC) has become a major public health problem worldwide. To date, there is a limited understanding of the global distribution of CREC. In this study, we performed a comprehensive genomic analysis of 7, 731 CRECs of human origin collected from different countries worldwide between 2005 and 2023. Our results showed that these CRECs were distributed in 75 countries
-
Patient- and xenograft-derived organoids recapitulate pediatric brain tumor features and patient treatments EMBO Mol. Med. (IF 11.1) Pub Date : 2023-11-30 Chiara Lago, Aniello Federico, Gloria Leva, Norman L Mack, Benjamin Schwalm, Claudio Ballabio, Matteo Gianesello, Luana Abballe, Isabella Giovannoni, Sofia Reddel, Sabrina Rossi, Nicolas Leone, Andrea Carai, Angela Mastronuzzi, Alessandra Bisio, Alessia Soldano, Concetta Quintarelli, Franco Locatelli, Marcel Kool, Evelina Miele, Luca Tiberi
Brain tumors are the leading cause of cancer-related death in children. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of pediatric brain cancers are limited and hard to establish. We present a protocol that enables efficient generation, expansion, and biobanking of pediatric brain cancer organoids. Utilizing our protocol, we have established patient-derived
-
Deciphering the genetic basis of resistome and virulome diversity among multidrug-resistant Mycoplasma hominis Drug Resist. Updat. (IF 24.3) Pub Date : 2023-11-30 Wenwen Liu, Yawen Yu, Yuting Wang, Ting Yang, Yingying Kong, Xinyou Xie, Jun Zhang
Mycoplasma hominis, a commensal bacterium that commonly inhabits the genital tract, leading to infections in both the genitourinary and extragenital regions. However, the antimicrobial resistance and pathogenic mechanisms of M. hominis isolated from extra-urogenital cystic abscess is largely unknown. This study reports the genomic epidemiological characteristics of a M. hominis isolate recovered from
-
Overexpression of ABCC1 and ABCG2 confers resistance to talazoparib, a poly (ADP-Ribose) polymerase inhibitor Drug Resist. Updat. (IF 24.3) Pub Date : 2023-11-29 Qiu-Xu Teng, Zi-Ning Lei, Jing-Quan Wang, Yuqi Yang, Zhuo-Xun Wu, Nikita Dilip Acharekar, Wei Zhang, Sabesan Yoganathan, Yihang Pan, John Wurpel, Zhe-Sheng Chen, Shuo Fang
The overexpression of ABC transporters on cancer cell membranes is one of the most common causes of multidrug resistance (MDR). This study investigates the impact of ABCC1 and ABCG2 on the resistance to talazoparib (BMN-673), a potent poly (ADP-ribose) polymerase (PARP) inhibitor, in ovarian cancer treatment. The cell viability test was used to indicate the effect of talazoparib in different cell lines
-
Biosynthesis of phosphatidylglycerol in photosynthetic organisms Prog. Lipid. Res. (IF 13.6) Pub Date : 2023-11-29 Koichi Kobayashi, Haruhiko Jimbo, Yuki Nakamura, Hajime Wada
Phosphatidylglycerol (PG) is a unique phospholipid class with its indispensable role in photosynthesis and growth in land plants, algae, and cyanobacteria. PG is the only major phospholipid in the thylakoid membrane of cyanobacteria and plant chloroplasts and a main lipid component in photosynthetic protein-cofactor complexes such as photosystem I and photosystem II. In plants and algae, PG is also
-
The role of histone H1.2 in pancreatic cancer metastasis and chemoresistance Drug Resist. Updat. (IF 24.3) Pub Date : 2023-11-28 Jianyou Gu, Junfeng Zhang, Renpei Xia, Xianxing Wang, Jiali Yang, Fuming Xie, Qiang Zhou, Jinghe Li, Tao Zhang, Qing Chen, Yingfang Fan, Shixiang Guo, Huaizhi Wang
Pancreatic cancer (PC) is a highly metastatic malignant tumor of the digestive system. Drug resistance frequently occurs during cancer treatment process. This study aimed to explore the link between chemoresistance and tumor metastasis in PC and its possible molecular and cellular mechanisms. A Metastasis and Chemoresistance Signature (MCS) scoring system was built and validated based on metastasis-
-
Tumor endothelial cell autophagy is a key vascular-immune checkpoint in melanoma EMBO Mol. Med. (IF 11.1) Pub Date : 2023-11-27 Jelle Verhoeven, Kathryn A Jacobs, Francesca Rizzollo, Francesca Lodi, Yichao Hua, Joanna Poźniak, Adhithya Narayanan Srinivasan, Diede Houbaert, Gautam Shankar, Sanket More, Marco B Schaaf, Nikolina Dubroja Lakic, Maarten Ganne, Jochen Lamote, Johan Van Weyenbergh, Louis Boon, Oliver Bechter, Francesca Bosisio, Yasuo Uchiyama, Mathieu JM Bertrand, Jean Christophe Marine, Diether Lambrechts, Gabriele
Tumor endothelial cells (TECs) actively repress inflammatory responses and maintain an immune-excluded tumor phenotype. However, the molecular mechanisms that sustain TEC-mediated immunosuppression remain largely elusive. Here, we show that autophagy ablation in TECs boosts antitumor immunity by supporting infiltration and effector function of T-cells, thereby restricting melanoma growth. In melanoma-bearing
-
HMBA ameliorates obesity by MYH9- and ACTG1-dependent regulation of hypothalamic neuropeptides EMBO Mol. Med. (IF 11.1) Pub Date : 2023-11-20 Seokjae Park, Sungjoon Oh, Nayoun Kim, Eun-Kyoung Kim
The global epidemic of obesity remains a daunting problem. Here, we report hexamethylene bisacetamide (HMBA) as a potent anti-obesity compound. Peripheral and central administration of HMBA to diet-induced obese mice regulated the expression of hypothalamic neuropeptides critical for energy balance, leading to beneficial metabolic effects such as anorexia and weight loss. We found that HMBA bound to
-
Enhancement of efferocytosis through biased FPR2 signaling attenuates intestinal inflammation EMBO Mol. Med. (IF 11.1) Pub Date : 2023-11-22 Ming-Yue Wu, Yun-Jun Ge, Er-Jin Wang, Qi-Wen Liao, Zheng-Yu Ren, Yang Yu, Guoyuan Zhu, Chun-Ping Liu, Meng-Ni Zhang, Huanxing Su, Han-Ming Shen, Ye Chen, Lei Wang, Yi-Tao Wang, Min Li, Zhaoxiang Bian, Jin Chai, Richard D Ye, Jia-Hong Lu
Efficient clearance of dying cells (efferocytosis) is an evolutionarily conserved process for tissue homeostasis. Genetic enhancement of efferocytosis exhibits therapeutic potential for inflammation resolution and tissue repair. However, pharmacological approaches to enhance efferocytosis remain sparse due to a lack of targets for modulation. Here, we report the identification of columbamine (COL)
-
Oxylipin transport by lipoprotein particles and its functional implications for cardiometabolic and neurological disorders Prog. Lipid. Res. (IF 13.6) Pub Date : 2023-11-17 Nuanyi Liang, Brian A. Harsch, Sitong Zhou, Alison Borkowska, Gregory C. Shearer, Rima Kaddurah-Daouk, John W. Newman, Kamil Borkowski
Lipoprotein metabolism is critical to inflammation. While the periphery and central nervous system (CNS) have separate yet connected lipoprotein systems, impaired lipoprotein metabolism is implicated in both cardiometabolic and neurological disorders. Despite the substantial investigation into the composition, structure and function of lipoproteins, the lipoprotein oxylipin profiles, their influence
-
A new chapter of healthy indoor air: antiviral air treatments EMBO Mol. Med. (IF 11.1) Pub Date : 2023-11-16 Irina Glas, Shannon C David
Aerosol transmission remains a major challenge for the control of respiratory viruses. To date, prevention strategies include masks, vaccinations, physical distancing, travel restrictions, and lockdowns. Such measures are effective but come with heavy societal burdens and rely on public compliance. Additionally, most are simply not suitable as long-term measures. Other strategies evolve around the
-
Propylene glycol inactivates respiratory viruses and prevents airborne transmission EMBO Mol. Med. (IF 11.1) Pub Date : 2023-11-16 Christine T Styles, Jie Zhou, Katie E Flight, Jonathan C Brown, Charlotte Lewis, Xinyu Wang, Michael Vanden Oever, Thomas P Peacock, Ziyin Wang, Rosie Millns, John S O'Neill, Alexander Borodavka, Joe Grove, Wendy S Barclay, John S Tregoning, Rachel S Edgar
Viruses are vulnerable as they transmit between hosts, and we aimed to exploit this critical window. We found that the ubiquitous, safe, inexpensive and biodegradable small molecule propylene glycol (PG) has robust virucidal activity. Propylene glycol rapidly inactivates a broad range of viruses including influenza A, SARS-CoV-2 and rotavirus and reduces disease burden in mice when administered intranasally
-
Immunotherapy targeting isoDGR-protein damage extends lifespan in a mouse model of protein deamidation EMBO Mol. Med. (IF 11.1) Pub Date : 2023-11-16 Pazhanichamy Kalailingam, Khalilatul-Hanisah Mohd-Kahliab, SoFong Cam Ngan, Ranjith Iyappan, Evelin Melekh, Tian Lu, Gan Wei Zien, Bhargy Sharma, Tiannan Guo, Adam J MacNeil, Rebecca EK MacPherson, Evangelia Litsa Tsiani, Deborah D O'Leary, Kah Leong Lim, I Hsin Su, Yong-Gui Gao, A Mark Richards, Raj N Kalaria, Christopher P Chen, Neil E McCarthy, Siu Kwan Sze
Aging results from the accumulation of molecular damage that impairs normal biochemical processes. We previously reported that age-linked damage to amino acid sequence NGR (Asn-Gly-Arg) results in “gain-of-function” conformational switching to isoDGR (isoAsp-Gly-Arg). This integrin-binding motif activates leukocytes and promotes chronic inflammation, which are characteristic features of age-linked
-
LKB1-SIK2 loss drives uveal melanoma proliferation and hypersensitivity to SLC8A1 and ROS inhibition EMBO Mol. Med. (IF 11.1) Pub Date : 2023-11-15 Sarah Proteau, Imène Krossa, Chrystel Husser, Maxime Guéguinou, Federica Sella, Karine Bille, Marie Irondelle, Mélanie Dalmasso, Thibault Barouillet, Yann Cheli, Céline Pisibon, Nicole Arrighi, Sacha Nahon-Estève, Arnaud Martel, Lauris Gastaud, Sandra Lassalle, Olivier Mignen, Patrick Brest, Nathalie M Mazure, Frédéric Bost, Stéphanie Baillif, Solange Landreville, Simon Turcotte, Dan Hasson, Saul Carcamo
Metastatic uveal melanomas are highly resistant to all existing treatments. To address this critical issue, we performed a kinome-wide CRISPR-Cas9 knockout screen, which revealed the LKB1-SIK2 module in restraining uveal melanoma tumorigenesis. Functionally, LKB1 loss enhances proliferation and survival through SIK2 inhibition and upregulation of the sodium/calcium (Na+/Ca2+) exchanger SLC8A1. This
-
Acquired immunity against SARS-CoV-2 infection and vaccination EMBO Mol. Med. (IF 11.1) Pub Date : 2023-11-15 Laurent Renia, Lisa FP Ng
The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused more than 700 million confirmed infections and ~7 million fatalities worldwide since its emergence in December 2019. SARS-CoV-2 is part of a family of positive-sense, enveloped RNA viruses known as coronaviruses. Today, at least seven human coronaviruses have been identified and are known to cause respiratory
-
MYC expression and fatty acid oxidation in EGFR-TKI acquired resistance Drug Resist. Updat. (IF 24.3) Pub Date : 2023-11-13 GuoSheng Wang, Tao Li, Yuan Wan, Qiang Li
This report expands on our previous research, highlighting a unique inverse correlation between MYC expression in tumor cells and immune cells during the development of EGFR-TKI resistance. It is observed that MYC expression and fatty acid oxidation (FAO) metabolism in tissue-resident memory (TRM) CD8 + T cells are significantly impaired. These findings offer new insights into the mechanisms of TKI