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Drug resistance mechanisms in cancers:Execution of prosurvival strategies 被引量:1
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作者 Pavan Kumar Dhanyamraju 《Journal of Biomedical Research》 CAS CSCD 2024年第2期95-121,共27页
One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon o... One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions. 展开更多
关键词 cancer drug resistance MECHANISMS MICRORNAS treatment strategies
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Role of targeting ferroptosis as a component of combination therapy in combating drug resistance in colorectal cancer 被引量:1
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作者 Xiao-Ting Xie Qiang-Hu Pang Lian-Xiang Luo 《World Journal of Clinical Oncology》 2024年第3期375-377,共3页
Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a ty... Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers. 展开更多
关键词 Colorectal cancer Ferroptosis IMMUNOTHERAPY drug resistance CHEMOTHERAPY Nanodrug delivery systems
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MATHEMATICAL MODELING AND BIFURCATION ANALYSIS FOR A BIOLOGICAL MECHANISM OF CANCER DRUG RESISTANCE
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作者 包康博 梁桂珍 +1 位作者 田天海 张兴安 《Acta Mathematica Scientia》 SCIE CSCD 2024年第3期1165-1188,共24页
Drug resistance is one of the most intractable issues in targeted therapy for cancer diseases.It has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory ca... Drug resistance is one of the most intractable issues in targeted therapy for cancer diseases.It has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory cancer cell populations.Focusing on how cancer cells develop resistance during the encounter with targeted drugs and the immune system,we propose a mathematical model for studying the dynamics of drug resistance in a conjoint heterogeneous tumor-immune setting.We analyze the local geometric properties of the equilibria of the model.Numerical simulations show that the selectively targeted removal of sensitive cancer cells may cause the initially heterogeneous population to become a more resistant population.Moreover,the decline of immune recruitment is a stronger determinant of cancer escape from immune surveillance or targeted therapy than the decay in immune predation strength.Sensitivity analysis of model parameters provides insight into the roles of the immune system combined with targeted therapy in determining treatment outcomes. 展开更多
关键词 mathematical model drug resistance cancer heterogeneity immune system targeted therapy
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Prox1 Suppresses Proliferation and Drug Resistance of Retinoblastoma Cells via Targeting Notch1
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作者 Hong-li ZHANG Na LI +2 位作者 Lin DONG Hong-xia MA Mo-chi YANG 《Current Medical Science》 SCIE CAS 2024年第1期223-231,共9页
Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,h... Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,hepatocyte,pancreatic,heart,lens,retinal,and cancer cells.The goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance,as well as to explore the underlying Notch1 mechanism.Methods Human RB cell lines(SO-RB50 and Y79)and a primary human retinal microvascular endothelial cell line(ACBRI-181)were used in this study.The expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction(RT-qPCR)and Western blotting.Cell proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTS assay.Drug-resistant cell lines(SO-RB50/vincristine)were generated and treated with Prox1 to investigate the role of Prox1 in drug resistance.We employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of Prox1.Finally,a xenograft model was constructed to assess the effect of Prox1 on RB in vivo.Results Prox1 was significantly downregulated in RB cells.Overexpression of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to vincristine.Notch1 was involved in Prox1’s regulatory effects.Notch1 was identified as a target gene of Prox1,which was found to be upregulated in RB cells and repressed by increased Prox1 expression.When pcDNA-Notch1 was transfected,the effect of Prox1 overexpression on RB was removed.Furthermore,by downregulating Notch1,Prox1 overexpression slowed tumor development and increased vincristine sensitivity in vivo.Conclusion These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1,implying that Prox1 could be a potential therapeutic target for RB. 展开更多
关键词 Proxl NOTCH1 retinoblastoma cells PROLIFERATION drug resistance
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Inferring Mycobacterium Tuberculosis Drug Resistance and Transmission using Whole-genome Sequencing in a High TB-burden Setting in China
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作者 FAN Yu Feng LIU Dong Xin +11 位作者 CHEN Yi Wang OU Xi Chao MAO Qi Zhi YANG Ting Ting WANG Xi Jiang HE Wen Cong ZHAO Bing LIU Zhen Jiang ABULIMITI Maiweilanjiang AIHEMUTI Maimaitiaili GAO Qian ZHAO Yan Lin 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2024年第2期157-169,共13页
Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of th... Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking.Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns.Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023–1.954;P=0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains.Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar. 展开更多
关键词 Mycobacterium tuberculosis Whole-genome sequencing(WGS) Transmission drug resistance XINJIANG
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PHLDA2 reshapes the immune microenvironment and induces drug resistance in hepatocellular carcinoma
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作者 KUN FENG HAO PENG +1 位作者 QINGPENG LV YEWEI ZHANG 《Oncology Research》 SCIE 2024年第6期1063-1078,共16页
Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable prognosis.The dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment fai... Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable prognosis.The dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment failure.The elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also underestimated.Here,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of HCC.Then,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT assays.Our findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer prognosis.The methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver tissues.Besides,noteworthy associations were observed between PHLDA2 expression and immune infiltration in HCC.In addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in HCC.In vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy drugs.Meanwhile,we found that TGF-βinduced the expression of PHLDA2 in vitro.The GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling pathway.Our study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC. 展开更多
关键词 HCC Immune infiltration drug resistance TME PHLDA2
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Research progress in tumor angiogenesis and drug resistance in breast cancer
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作者 Jiancheng Mou Chenhong Li +2 位作者 Qinghui Zheng Xuli Meng Hongchao Tang 《Cancer Biology & Medicine》 SCIE CAS CSCD 2024年第7期571-585,共15页
Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer tre... Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer treatments, via exacerbation of tumor hypoxia, decreased effective drug concentrations within tumors, and immune-related mechanisms. Antiangiogenic therapy can counteract these breast cancer resistance factors by promoting tumor vascular normalization. The combination of antiangiogenic therapy with chemotherapy, targeted therapy, or immunotherapy has emerged as a promising approach for overcoming drug resistance in breast cancer. This review examines the mechanisms associated with angiogenesis and the interactions among tumor angiogenesis, the hypoxic tumor microenvironment, drug distribution, and immune mechanisms in breast cancer. Furthermore, this review provides a comprehensive summary of specific antiangiogenic drugs, and relevant studies assessing the reversal of drug resistance in breast cancer. The potential mechanisms underlying these interventions are discussed, and prospects for the clinical application of antiangiogenic therapy to overcome breast cancer treatment resistance are highlighted. 展开更多
关键词 ANGIOGENESIS breast cancer CHEMOTHERAPY drug resistance vascular normalization immunologic therapy tumor microenvironment(TME)
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Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review
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作者 EFFAT ALEMZADEH LEILA ALLAHQOLI +4 位作者 AFROOZ MAZIDIMORADI ESMAT ALEMZADEH FAHIMEH GHASEMI HAMID SALEHINIYA IBRAHIM ALKATOUT 《Oncology Research》 SCIE 2024年第5期831-847,共17页
Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most sign... Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most significant challenge in treating patients with existing drugs.The Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance therapy.However,resistance to these new drugs has emerged.Therefore,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management.In this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR. 展开更多
关键词 CHEMOTHERAPY drug resistance mechanisms Ovarian cancer PARP inhibitors VEGF inhibitor
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HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province,China,2014–2020
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作者 YU De E XU Yu Jun +13 位作者 LI Mu YANG Yuan LIANG Hua Yue ZHONG Shan Mei QIN Cai LAN Ya Nan LI Da Wei YU Ji Peng PANG Yuan QIN Xue Qiu LIANG Hao ZHU Kao Kao YE Li LIANG Bing Yu 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2023年第9期800-813,共14页
Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted ... Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period. 展开更多
关键词 HIV-1 subtypes Antiretroviral therapy Virological failure drug resistance
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Distribution and Drug Resistance Analysis of 2287 Strains of Pathogenic Bacteria in Children’s Blood Culture 被引量:2
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作者 Tiefu Fang Qiang Wang +3 位作者 Wanqi Li Yanhuan Mao Peiqing Li Guangming Liu 《Advances in Microbiology》 CAS 2023年第1期24-31,共8页
Background: Bloodstream infection is a serious infectious disease. In recent years, the drug resistance of pathogenic bacteria to commonly used anti-infective drugs has been widely concerned, which also makes the trea... Background: Bloodstream infection is a serious infectious disease. In recent years, the drug resistance of pathogenic bacteria to commonly used anti-infective drugs has been widely concerned, which also makes the treatment of bloodstream infection face severe challenges. Objective: To explore the distribution characteristics of blood culture-positive pathogens and the resistance to antibacterial drugs, so as to provide clinicians with accurate laboratory evidence, so as to guide clinicians to rationally apply antibiotics, improve clinical treatment effects, and reduce the emergence of drug-resistant strains. Methods: From January 2019 to June 2022, 2287 positive blood culture specimens of patients in Guangzhou Women and Children’s Medical Center were retrospectively analyzed, and the proportion of different pathogenic bacteria, the distribution of pathogenic bacteria in different departments, and the multi-drug resistance of different pathogenic bacteria were counted. Results: Among the 2287 blood culture positive samples, 1560 strains (68.20%) of gram-positive bacteria and 727 strains (31.80%) of gram-negative bacteria were strained. The top three departments in the distribution of pathogenic bacteria were pediatric intensive care unit (600 strains), pediatric internal medicine (514 strains), and pediatric emergency comprehensive ward (400 strains). The pathogens with high detection rates were: Staphylococcus epidermidis (24.09%), Staphylococcus humans (23.74%), Escherichia coli (13.21%) and Klebsiella pneumoniae (8.71%). The pathogens with high multi-drug resistance rates were: Streptococcus pneumoniae (93%), Staphylococcus epidermidis (83.76%), Enterobacter cloacae (75.61%) and Staphylococcus humans (62.43%). Conclusion: In our hospital, gram-positive bacteria were the main pathogenic bacteria in the blood culture of children patients. The children’s intensive care unit was the department with the largest distribution of pathogenic bacteria, and the multiple drug resistance rate of Streptococcus pneumoniae was the highest. 展开更多
关键词 CHILDREN Blood Culture Pathogen drug resistance
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Smart drug delivery systems to overcome drug resistance in cancer immunotherapy 被引量:1
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作者 Wenzhe Yi Dan Yan +1 位作者 Dangge Wang Yaping Li 《Cancer Biology & Medicine》 SCIE CAS CSCD 2023年第4期248-267,共20页
Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resi... Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resistance to immune surveillance,resulting in poor response rates and low therapeutic efficacy.In addition,changes in genes and signaling pathways in tumor cells prevent susceptibility to immunotherapeutic agents.Furthermore,tumors create an immunosuppressive microenvironment via immunosuppressive cells and secrete molecules that hinder immune cell and immune modulator infiltration or induce immune cell malfunction.To address these challenges,smart drug delivery systems(SDDSs)have been developed to overcome tumor cell resistance to immunomodulators,restore or boost immune cell activity,and magnify immune responses.To combat resistance to small molecules and monoclonal antibodies,SDDSs are used to co-deliver numerous therapeutic agents to tumor cells or immunosuppressive cells,thus increasing the drug concentration at the target site and improving efficacy.Herein,we discuss how SDDSs overcome drug resistance during cancer immunotherapy,with a focus on recent SDDS advances in thwarting drug resistance in immunotherapy by combining immunogenic cell death with immunotherapy and reversing the tumor immunosuppressive microenvironment.SDDSs that modulate the interferon signaling pathway and improve the efficacy of cell therapies are also presented.Finally,we discuss potential future SDDS perspectives in overcoming drug resistance in cancer immunotherapy.We believe that this review will contribute to the rational design of SDDSs and development of novel techniques to overcome immunotherapy resistance. 展开更多
关键词 Cancer immunotherapy drug resistance smart drug delivery system immunosuppressive microenvironment immune cell
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KCNJ15 deficiency promotes drug resistance via affecting the function of lysosomes 被引量:1
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作者 Xinbo Qiao Yixiao Zhang +10 位作者 Zhan Zhang Nan Niu Haonan Li Lisha Sun Qingtian Ma Jiawen Bu Jinchi Liu Guanglei Chen Jinqi Xue Yongliang Yang Caigang Liu 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2023年第3期132-145,共14页
The altered lysosomal function can induce drug redistribution which leads to drug resistance and poor prognosis for cancer patients.V-ATPase,an ATP-driven proton pump positioned at lysosomal surfaces,is responsible fo... The altered lysosomal function can induce drug redistribution which leads to drug resistance and poor prognosis for cancer patients.V-ATPase,an ATP-driven proton pump positioned at lysosomal surfaces,is responsible for maintaining the stability of lysosome.Herein,we reported that the potassium voltage-gated channel subfamily J member 15(KCNJ15)protein,which may bind to V-ATPase,can regulate the function of lysosome.The deficiency of KCNJ15 protein in breast cancer cells led to drug aggregation as well as reduction of drug efficacy.The application of the V-ATPase inhibitor could inhibit the binding between KCNJ15 and V-ATPase,contributing to the amelioration of drug resistance.Clinical data analysis revealed that KCNJ15 deficiency was associated with higher histological grading,advanced stages,more metastases of lymph nodes,and shorter disease free survival of patients with breast cancer.KCNJ15 expression level is positively correlated with a high response rate after receiving neoadjuvant chemotherapy.Moreover,we revealed that the small molecule drug CMA/BAF can reverse drug resistance by disrupting the interaction between KCNJ15 and lysosomes.In conclusion,KCNJ15 could be identified as an underlying indicator for drug resistance and survival of breast cancer,which might guide the choice of therapeutic strategies. 展开更多
关键词 Breast cancer Cancer progression drug resistance LYSOSOME KCNJ15
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A Pleiotropic Drug Resistance Family Protein Gene Is Required for Rice Growth, Seed Development and Zinc Homeostasis
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作者 LI Chao LI He +1 位作者 ZHANG Xianduo YANG Zhimin 《Rice science》 SCIE CSCD 2023年第2期127-137,I0035-I0038,共15页
Zinc(Zn) is an essential mineral element for plant growth and development. Zn deficiency in crops frequently occurs in many types of soils. It is therefore crucial to identify genetic resources linking Zn acquisition ... Zinc(Zn) is an essential mineral element for plant growth and development. Zn deficiency in crops frequently occurs in many types of soils. It is therefore crucial to identify genetic resources linking Zn acquisition traits and development of crops with improved Zn-use efficiency for sustainable crop production. In this study, we functionally identified a rice uncharacterized ABCG(ATP-binding cassette G-subfamily) gene encoding a PDR20(pleiotropic drug resistance 20) metal transporter for mediation of rice growth, seed development and Zn accumulation. OsPDR20 was localized to the plasma membrane, but it was not transcriptionally induced under Zn deficiency, rather was sufficiently up-regulated under high level of Zn stress. Yeast(Saccharomyces cerevisiae) transformed with OsPDR20 displayed a relatively lower Zn accumulation with attenuated cellular growth, suggesting that OsPDR20 had an activity for Zn transport. Knocking-down OsPDR20 by RNA interference(RNAi) compromised rice growth with shorter plant height and decreased biomass in rice plantlets grown under hydroponic media. Zn concentration in the roots of OsPDR20 knocked-down rice lines declined under Zn deficiency, while they remained unchanged compared with the wild type under normal Zn supply. A rice lifelong field trial demonstrated that OsPDR20 mutation impaired the capacity of seed development, with shortened panicle and seed length, compromised spikelet fertility, and reduced grain number per plant or grain weight per unit area. Interestingly, OsPDR20 mutation elevated the accumulation of Zn in husk and brown rice over the wild type. Overall, this study pointed out that OsPDR20 is fundamentally required for rice growth and seed development through Zn transport and homeostasis. 展开更多
关键词 OsPDR20 zinc transport RICE seed development ABCG53 pleiotropic drug resistance
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Roles of lncRNAs in pancreatic ductal adenocarcinoma: Diagnosis,treatment, and the development of drug resistance
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作者 Xiao-Yin Jiang Qi-Cong Zhu +5 位作者 Xiao-Jian Zhang Ting Duan Jiao Feng Xin-Bing Sui Xue-Ni Sun Yi-Ping Mou 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2023年第2期128-139,共12页
Background: Pancreatic ductal adenocarcinoma(PDAC) is one of the most lethal cancers, primarily due to its late diagnosis, high propensity to metastasis, and the development of resistance to chemo-/radiotherapy. Accum... Background: Pancreatic ductal adenocarcinoma(PDAC) is one of the most lethal cancers, primarily due to its late diagnosis, high propensity to metastasis, and the development of resistance to chemo-/radiotherapy. Accumulating evidence suggests that long non-coding RNAs(lnc RNAs) are intimately involved in the treatment resistance of pancreatic cancer cells via interacting with critical signaling pathways and may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. Data sources: We carried out a systematic review on lnc RNAs-based research in the context of pancreatic cancer and presented an overview of the updated information regarding the molecular mechanisms underlying lnc RNAs-modulated pancreatic cancer progression and drug resistance, together with their potential value in diagnosis, prognosis, and treatment of PDAC. Literature mining was performed in Pub Med with the following keywords: long non-coding RNA, pancreatic ductal adenocarcinoma, pancreatic cancer up to January 2022. Publications relevant to the roles of lnc RNAs in diagnosis, prognosis, drug resistance, and therapy of PDAC were collected and systematically reviewed. Results: Lnc RNAs, such as HOTAIR, HOTTIP, and PVT1, play essential roles in regulating pancreatic cancer cell proliferation, invasion, migration, and drug resistance, thus may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. They participate in tumorigenesis mainly by targeting mi RNAs, interacting with signaling molecules, and involving in the epithelial-mesenchymal transition process. Conclusions: The functional lnc RNAs play essential roles in pancreatic cancer cell proliferation, invasion, migration, and drug resistance and have potential values in diagnosis, prognostic prediction, and treatment of PDAC. 展开更多
关键词 Long non-coding RNA Pancreatic ductal adenocarcinoma drug resistance Diagnostic indicator Therapeutic targets Molecular mechanism
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Advances in drug resistance of triple negative breast cancer caused by pregnane X receptor
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作者 Zhou-Zhou Rao Zhong-Wen Tang Jie Wen 《World Journal of Clinical Oncology》 2023年第9期335-342,共8页
Breast cancer is the most common malignancy in women worldwide.Triplenegative breast cancer(TNBC),refers breast cancer negative for estrogen receptor,progesterone receptor and human epidermal growth factor receptor 2,... Breast cancer is the most common malignancy in women worldwide.Triplenegative breast cancer(TNBC),refers breast cancer negative for estrogen receptor,progesterone receptor and human epidermal growth factor receptor 2,characterized by high drug resistance,high metastasis and high recurrence,treatment of which is a difficult problem in the clinical treatment of breast cancer.In order to better treat TNBC clinically,it is a very urgent task to explore the mechanism of TNBC resistance in basic breast cancer research.Pregnane X receptor(PXR)is a nuclear receptor whose main biological function is to participate in the metabolism,transport and clearance of allobiological agents in PXR.PXR plays an important role in drug metabolism and clearance,and PXR is highly expressed in tumor tissues of TNBC patients,which is related to the prognosis of breast cancer patients.This reviews synthesized the important role of PXR in the process of high drug resistance to TNBC chemotherapeutic drugs and related research progress. 展开更多
关键词 Triple-negative breast cancer Pregnane X receptor drug resistance Cytochrome P450 Uridinediphosphate glucuronyl transferases Glutathione transferases ATP-binding cassette transporter
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Clinical Distribution and Drug Resistance of Acinetobacter baumannii in a Hospital from 2019 to 2021
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作者 Wei Liu Yiminghui Long +1 位作者 Yu Liu Xu Zhou 《Journal of Clinical and Nursing Research》 2023年第3期124-129,共6页
Objective:To analyze the clinical distribution and drug resistance of Acinetobacter baumannii(AB)and provide reference for the treatment of AB infection.Methods:AB isolated from clinical specimens of Huaihua First Peo... Objective:To analyze the clinical distribution and drug resistance of Acinetobacter baumannii(AB)and provide reference for the treatment of AB infection.Methods:AB isolated from clinical specimens of Huaihua First People’s Hospital from 2019 to 2021 were collected and identified by VITEK 2 Compact,an automated microbial identification and susceptibility testing system,in which drug sensitivity test was also performed.Excel was used for statistical analysis.Results:Among the 1,311 AB strains,81.16%(1,064 strains)were from sputum samples,and the departments with the highest detections rates of AB were neurosurgery(24.33%),intensive care(15.48%)and infectious disease(11.44%).The drug sensitivity test showed that the resistance rate of 1,311 AB strains to compound sulfamethoxazole and amikacin was 28.38%and 20.54%,respectively,and the resistance rate to 10 other kinds of common antibiotics was more than 40%.Conclusion:The 1,311 AB strains isolated were widely distributed in clinical settings and had strong resistance to commonly used antibiotics.Therefore,it is necessary to strengthen the monitoring of pathogens and drug resistance,formulate reasonable and effective infection control measures,and ensure that antibiotics are used in a reasonable manner. 展开更多
关键词 Acinetobacter baumannii drug resistance drug sensitivity test
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Antiviral drug resistance increases hepatocellular carcinoma:A prospective decompensated cirrhosis cohort study 被引量:20
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作者 Lei Li Wei Liu +6 位作者 Yu-Han Chen Chun-Lei Fan Pei-Ling Dong Fei-Li Wei Bing Li De-Xi Chen Hui-Guo Ding 《World Journal of Gastroenterology》 SCIE CAS 2013年第45期8373-8381,共9页
AIM:To study the clinical outcome of antiviral therapy in hepatitis B-related decompensated cirrhotic patients.METHODS:Three hundred and twelve patients with decompensated hepatitis B cirrhosis were evaluated in a pro... AIM:To study the clinical outcome of antiviral therapy in hepatitis B-related decompensated cirrhotic patients.METHODS:Three hundred and twelve patients with decompensated hepatitis B cirrhosis were evaluated in a prospective cohort.With two years of follow-up,198patients in the group receiving antiviral therapy with nucleos(t)ide analogues and 39 patients in the control group without antiviral treatment were analysed.RESULTS:Among the antiviral treatment patients,162had a complete virological response(CVR),and 36 were drug-resistant(DR).The two-year cumulative incidence of hepatocellular carcinoma(HCC)in the DR patients(30.6%)was significantly higher than that in both the CVR patients(4.3%)and the control group(10.3%)(P<0.001).Among the DR patients in particular,the incidence of HCC was 55.6%(5/9)in those who failed rescue therapy,which was extremely high.The rtA181T mutation was closely associated with rescue therapy failure(P=0.006).The Child-Pugh scores of the CVR group were significantly decreased compared with the baseline(8.9±2.3 vs 6.0±1.3,P=0.043).CONCLUSION:This study showed that antiviral drug resistance increased the risk of HCC in decompensated hepatitis B-related cirrhotic patients,especially in those who failed rescue therapy. 展开更多
关键词 Hepatitis B DECOMPENSATED CIRRHOSIS Nucleos(t)ide ANALOGUES HEPATOCELLULAR carcinoma drug resistance
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Study of HIV-1 Drug Resistance in Patients Receiving Free Antiretroviral Therapy in China 被引量:9
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作者 Xin-ping LIP  Hui XING  +11 位作者 Zhe WANG  Xue-feng SI Lian-en WANG  Hua CHENG  Wei-guo CUI  Shu-lin JIANG  Ling-jie LIAO  Hai-wei ZHOU  Jiang-hong HUANG  Hong PENG  Peng-fei MA  Yi-ming SHAO 《中国病毒学》 CSCD 2007年第3期233-240,共8页
To investigate the prevalence of drug-resistance mutations,resistance to antiretroviral drugs,and the subsequent virological response to therapy in treatment-naive and antiretroviral-treated patients infected with HIV... To investigate the prevalence of drug-resistance mutations,resistance to antiretroviral drugs,and the subsequent virological response to therapy in treatment-naive and antiretroviral-treated patients infected with HIV/AIDS in Henan,China,a total of 431 plasma samples were collected in Queshan county between 2003 and 2004,from patients undergoing the antiretroviral regimen Zidovudine + Didanosine + Nevirapine(Azt+Ddi+Nvp).Personal information was collected by face to face interview.Viral load and genotypic drug resistance were tested.Drug resistance mutation data were obtained by analyzing patient-derived sequences through the HIVdb Program(http://hivdb.stanford.edu).Overall,38.5% of treatment-naive patients had undetectable plasma viral load(VL),the rate significantly increased to 61.9% in 0 to 6 months treatment patients(mean 3 months)(P<0.005)but again significantly decrease to 38.6% in 6 to 12 months treatment patients(mean 9 months)(P<0.001)and 40.0% in patients receiving more than 12 months treatment(mean 16 months)(P<0.005).The prevalence of drug resistance in patients who had a detectable VL and available sequences were 7.0%,48.6%,70.8%,72.3% in treatment-na?ve,0 to 6 months treatment,6 to 12 months treatment,and treatment for greater than 12 months patients,respectively.No mutation associated with resistance to Protease inhibitor(PI)was detected in this study.Nucleoside RT inhibitor(NRTI)mutations always emerged after non-nucleoside RT inhibitor(NNRTI)mutations,and were only found in patients treated for more than 6 months,with a frequency less than 5%,with the exception of mutation T215Y(12.8%,6/47)which occurred in patients treated for more than 12 months.NNRTI mutations emerged quickly after therapy begun,and increased significantly in patients treated for more than 6 months(P<0.005),and the most frequent mutations were K103N,V106A,Y181C,G190A.There had been optimal viral suppression in patients undergoing treatment for less than 6 months in Queshan,Henan.The drug resistance strains were highly prevalent in antiretroviral-treated patients,and increased with the continuation of therapy,with many patients encountering virological failure after 6 months therapy. 展开更多
关键词 艾滋病病毒 艾滋病 治疗 抗药性 逆转录酶
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Effects of Taxotere on invasive potential and multidrug resistance phenotype in pancreatic carcinoma cell line SUIT-2 被引量:12
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作者 Edgar Staren Takeshi Iwamura +1 位作者 Hubert Appert John Howard 《World Journal of Gastroenterology》 SCIE CAS CSCD 2001年第1期143-148,共6页
INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relatio... INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10]. 展开更多
关键词 Carcinoma Pancreatic Neoplasms TAXOIDS Antineoplastic Agents Phytogenic Biocompatible Materials Collagen drug Combinations drug resistance Multiple drug resistance Neoplasm Fluorescent Dyes Humans In Vitro LAMININ Neoplasm Invasiveness P-Glycoprotein Paclitaxel derivatives Phenotype PROTEOGLYCANS RNA Neoplasm Research Support Non-U.S. Gov't Rhodamine 123 Tumor Cells Cultured
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Drug sensitivity and drug resistance profiles of human intrahepatic cholangiocarcinoma cell lines 被引量:10
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作者 Nisana Tepsiri Liengchai Chaturat +4 位作者 Banchob Sripa Wises Namwat Sopit Wongkham Vajarabhongsa Bhudhisawasdi Wichittra Tassaneeyakul 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第18期2748-2753,共6页
AIM: To study the effect of a number of chemotherapeutic drugs on five human intrahepatic cholangiocarcinoma (CCA) cell lines. The expressions of genes that have been proposed to influence the resistance of chemothera... AIM: To study the effect of a number of chemotherapeutic drugs on five human intrahepatic cholangiocarcinoma (CCA) cell lines. The expressions of genes that have been proposed to influence the resistance of chemotherapeutic drugs including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), glutathione-S-transferase PI (GSTP1), multidrug resistance protein (MDR1) and multidrug resistance-associated proteins (MRPs) were also determined. METHODS: Five human CCA cell lines (KKU-100, KKU-M055, KKU-M156, KKU-M214 and KKU-OCA17) were treated with various chemotherapeutic drugs and growth inhibition was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Semi-quantitative levels of gene expression were determined by a reverse transcriptase polymerase chain reaction (RT-PCR). Results of IC_(50) values and the ratios of gene expression were analyzed by linear regression to predict their relationship. RESULTS: Among five CCA cell lines, KKU-M055 was the most sensitive cell line towards all chemotherapeutic drugs investigated, particularly taxane derivatives with IC_(50) values of 0.02-3 nmol/L, whereas KKU-100 was apparently the least sensitive cell line. When compared to other chemotherapeutic agents, doxorubicin and pirarubicin showed the lowest IC_(50) values (<5 μmol/L) in all five CCA cell lines. Results from RT-PCR showed that TS, MRP1, MRP3 and GSTP1 were highly expressed in these five CCA cell lines while DPD and MRP2 were only moderately expressed. It should be noted that MDR1 expression was detected only in KKU-OCA17 cell lines. A strong correlation was only found between the level of MRP3 expression and the IC_(50) values of etoposide, doxorubicin and pirarubicin (r=0.86-0.98, P<0.05). CONCLUSION: Sensitivity to chemotherapeutic agents is not associated with the histological type of CCA. Choosing of the appropriate chemotherapeutic regimen for the treatment of CCA requires knowledge of drug sensitivity. MRP3 was correlated with resistance of CCA cell lines to etoposide, doxorubicin and pirarubicin, whereas other chemotherapeutic drugs showed no association. The role of this multidrug resistance-associated protein, MRP3, in chemotherapeutic resistance in CCA patients needs to be further investigated. 展开更多
关键词 CHOLANGIOCARCINOMA Chemotherapeutic agents drug sensitivity drug resistance Multidrug resistance protein MRP
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