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Plasma proteome profiling reveals biomarkers of chemotherapy resistance in patients with advanced colorectal cancer

Quantitative Biology 2024年第2期12卷 215-224页

作者： Jingxin Yang Jin Chen Luobin Zhang Fangming Zhou Xiaozhen Cui Ruijun Tian Ruilian Xu Medical Genetic Center Affiliated Shenzhen Maternity and Child Healthcare HospitalSouthern Medical UniversityShenzhenChina Clinical Center for Molecular Diagnosis and Therapy The Second Affiliated Hospital of Fujian Medical UniversityQuanzhouChina Department of Chemistry and Research Center for Chemical Biology and Omics Analysis School of ScienceSouthern University of Science and TechnologyShenzhenChina Department of Oncology Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)ShenzhenChina

Colorectal cancer(CRC)is one of the most common *** with advanced CRC can only rely on chemotherapy to improve ***,primary drug resistance frequently occurs and is difficult to *** in plasma protein composition have shown potential in clinical ***,it is urgent to identify potential protein biomarkers for primary resistance to chemotherapy for patients with *** sample preparation and high-throughput analysis were used to explore potential plasma protein *** susceptibility testing of circulating tumor cells(CTCs)has been investigated,and the relationship between their values and protein expressions has been *** addition,the differential proteins in different chemotherapy outcomes have been ***,the potential biomarkers have been detected via enzyme-linked immunosorbent assay(ELISA).Plasma proteome of 60 CRC patients were *** correlation between plasma protein levels and the results of drug susceptibility testing of CTCs was performed,and 85 proteins showed a significant positive or negative correlation with chemotherapy ***-four CRC patients were then divided into three groups according to their chemotherapy outcomes(objective response,stable disease,and progressive disease),and 37 differential proteins were found to be related to chemotherapy *** overlapping proteins were further investigated in an additional group of 79 patients using *** levels of F5 and PROZ significantly increased in the progressive disease group compared to other outcome *** study indicated that F5 and PROZ proteins could represent potential biomarkers of resistance to chemotherapy in advanced CRC patients.

关键词： biomarker chemotherapy resistance colorectal cancer plasma proteome

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CK2αcauses stemness and chemotherapy resistance in liver cancer through the Hedgehog signaling pathway

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Hepatobiliary & Pancreatic Diseases International 2023年第4期22卷 383-391页

作者： Di Wu Yuan-Qin Yin Yan Li Ling Zhang You-Hong Jiang Zhe Wang Department of Tumor Biotherapy and Cancer Research the First Affiliated Hospital of China Medical UniversityShenyang 110001China Department of Pathology Shengjing Hospital of China Medical UniversityShenyang 110004China

Background:Liver cancer is one of the major causes of cancer-related deaths *** cell stem-ness and chemotherapy resistance contribute to the high *** evidence indicates that the alpha subunit of protein kinase 2(CK2α)is involved in several human cancers,its function in liver cancer remains *** the present study,we aimed to elucidate the role of CK2αin liver ***:We examined the role of CK2αregulation in stemness and chemotherapy resistance capacity of liver cancer *** assays,tumor sphere formation assays,RT-PCR,flow cytometry,Western blotting assay,clonogenicity assay,matrigel invasion assay and bioinformatics were conducted in this ***:CK2αexpression in the liver cancer tissues was notably upregulated compared with that in the corresponding non-tumorous *** overexpression of CK2αpromoted tumor sphere formation,increased the percentage of CD133(+)and side population cells,caused the resistance of liver cancer cells to 5-FU treatment,increased the expression levels of NANOG,OCT4,SOX2,Gli1 and Ptch1,and enhanced the ability of CD133(+)cell clone formation and ***,the downregulation of CK2αhad the opposite ***2αsilencing inhibited the Hedgehog pathway by reducing the expression of Gli1 and ***,CK2αregulation on liver cancer cell stemness and chemotherapy resistance was found to be involved in the Hedgehog signaling ***:Our study may bring some new insights into the occurrence of liver ***,these findings suggest that targeting CK2αmay be a novel therapeutic strategy for patients with liver cancer.

关键词： CK2α Liver cancer Hedgehog signaling pathway Stemness chemotherapy resistance

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The DMRTA1-SOX2 positive feedback loop promotes progression and chemotherapy resistance of esophageal squamous cell carcinoma

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肿瘤学研究(英文) 2023年第6期31卷 887-897页

作者： RUI ZHANG PENG ZHOU XIA OU PEIZHU ZHAO XIJING GUO MIAN XI CHEN QING School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products Kunming Medical UniversityKunming650500China Department of Radiotherapy The First Affiliated Hospital of Kunming Medical UniversityKunming650032China Department of Pharmacy The Second Affiliated Hospital of Kunming Medical UniversityKunming650101China Medical School Kunming University of Science and TechnologyKunming650504China Department of Radiation Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou510060China

Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients *** to immunotherapy and chemotherapy results in worse survival outcomes in *** is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ***,we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy *** found that DMRTA1 was extremely upregulated in the non-pathologic complete response(non-pCR)*** proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression,which could increase cisplatin sensitivity in ***,suppression of DMRTA1 could decrease the immune escape of esophageal squamous carcinoma *** mechanistic studies suggest that DMRTA1 can promote its expression by binding to the promoter of SOX2,which plays important roles in the progression and chemoresistance of ESCC in the form of positive ***,DMRTA1 could be a potential target to suppress immune escape and overcome chemoresistance in ESCC.

关键词： Esophageal squamous cell carcinoma DMRTA1 SOX2 chemotherapy resistance Immune escape

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ABCA1 is associated with the development of acquired chemotherapy resistance and predicts poor ovarian cancer outcome

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Cancer Drug resistance 2021年第2期4卷 485-502页

作者： Wanqi Wang Noor A Lokman Tannith M Noye Anne M Macpherson Martin K Oehler Carmela Ricciardelli Adelaide Medical School Robinson Research InstituteUniversity of AdelaideAdelaideSA 5000Australia Department of Gynaecological Oncology Royal Adelaide HospitalAdelaideSA 5000Australia.

Aim:This study investigated the ATP binding cassette(ABC)transporter(ABCA1,ABCB1,ABCB3,ABCC2 and ABCG2)expression in high grade serous ovarian cancer(HGSOC)tissues,cell lines and primary cells to determine their potential relationship with acquired chemotherapy resistance and patient ***:ABC transporter mRNA and protein expression(ABCA1,ABCB1,ABCB3,ABCC2 and ABCG2)was assessed in publicly available datasets and in a tissue microarray(TMA)cohort of HGSOC at diagnosis,*** transporter mRNA expression was also assessed in chemosensitive ovarian cancer cell lines(OVCAR-5 and CaOV3)versus matching cell lines with acquired carboplatin resistance and in primary HGSOC cells from patients with chemosensitive disease at diagnosis(n=10)as well as patients with acquired chemotherapy resistance at relapse(n=6).The effects of the ABCA1 inhibitor apabetalone in carboplatin-sensitive and-resistant cell lines were also ***:High ABCA1 mRNA and protein expression was found to be significantly associated with poor patient ***1 mRNA and protein levels were significantly increased in ovarian cancer cell lines(OVCAR-5 CBPR and CaOV3 CBPR)with acquired carboplatin ***1 mRNA was significantly increased in primary HGSOC cells obtained from patients with acquired chemotherapy *** treatment reduced ABCA1 protein expression and increased the sensitivity of both parental and carboplatin-resistant ovarian cancer cells to ***: These results suggest that inhibiting ABCA1 transporter may be useful in overcoming acquired chemotherapy resistance and improving outcome for patients with HGSOC.

关键词： HGSOC chemotherapy resistance ABC transporter ABCA1 ABCB1 TAP2 ABCB3 ABCC2 ABCG2 apabetalone

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MGMT activated by Wnt pathway promotes cisplatin tolerance through inducing slow-cycling cells and nonhomologous end joining in colorectal cancer

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Journal of Pharmaceutical Analysis 2024年第6期14卷 863-877页

作者： Haowei Zhang Qixin Li Xiaolong Guo Hong Wu Chenhao Hu Gaixia Liu Tianyu Yu Xiake Hu Quanpeng Qiu Gang Guo Junjun She Yinnan Chen Department of General Surgery The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China Center for Gut Microbiome Research Med-X InstituteThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China Department of High Talent The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China

chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA *** the elements that lead to DDP resistance,O^(6)-methylguanine(O^(6)-MG)-DNA-methyltransferase(MGMT),a DNA-repair enzyme,performs a quintessential *** this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in ***,in cancer cells,MGMT overexpression abolishes their sensitivity to DDP ***,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of ***,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy *** transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant *** summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.

关键词： Colorectal cancer MGMT chemotherapy resistance Slow-cycling cells Nonhomologous end joining Wnt pathway

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resistance mechanisms and potential therapeutic strategies in relapsed or refractory natural killer/T cell lymphoma

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中华医学杂志(英文版) 2024年第19期137卷 2024 Aug 23页

作者： Wang Chengji Wang Liang Department of Hematology Beijing Tongren Hospital Capital Medical University Beijing China

Natural killer/T cell lymphoma (NKTCL) is a malignant tumor originating from NK or T cells, characterized by its highly aggressive and heterogeneous nature. NKTCL is predominantly associated with Epstein–Barr virus infection, disproportionately affecting Asian and Latin American populations. Owing to the application of asparaginase and immunotherapy, clinical outcomes have improved significantly. However, for patients in whom first-line treatment fails, the prognosis is exceedingly poor. Overexpression of multidrug resistance genes, abnormal signaling pathways, epigenetic modifications and active Epstein–Barr virus infection may be responsible for resistance. This review summarized the mechanisms of resistance for NKTCL and proposed potential therapeutic approaches.

关键词： Natural killer/T cell lymphoma Epstein–Barr virus chemotherapy resistance Asparaginase Immunotherapy

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Gastric cancer derived mesenchymal stem cells induce resistance to chemotherapy through up-regulating PD-L1-CTCF

Gastric cancer derived mesenchymal stem cells induce resista...

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第十四届全国免疫学学术大会

作者： Qianqian Wang Ying Ding Bin Chen Shuwei Guo Qiuzhi Gao Chao Huang Yuanyuan Zhao Mei Wang Bo Shen Wei Zhu Jiangsu University 四川省疾病预防控制中心济宁医学院附属医院江苏省肿瘤医院

Background:Gastric cancer(GC) is the fourth leading cause of death worldwide due to the resistance to chemotherapy and lack of effective *** cells,especially mesenchymal stem cells(MSCs),residing in the tumor microenvironment plays a significant role in the development of therapy ***-1/PD-L1 crosstalk between cancer and immune cells has been *** addition,emerging evidence suggests that PD-L1 also contributes to tumor resistance to ***:In this analysis,we aims to demonstrate the interactions between GC derived MSCs(GCMSCs) and tumor cells which was mediated by the PD-L1-CTCF axis leading to chemotherapy resistance within the tumor ***:GC cell lines HGC-27 and SGC-7901 cells were co-cultured with or without conditioned medium of GCMSCs(GCMSCs-CM) and PD-L1 neutralizing antibody(Anti-PD-L1) for 48 *** cell viability and apoptosis were detected by CCK-8 assay and flow cytometry after 5-FU or paclitaxel *** also analyzed the colony forming ability and the expression of PD-L1,MDR1,LRP and CD44 by western *** shRNA against PD-L1 and PD-L1-expressing lentivirus were used to analyze the effects of PD-L1 on GCMSCs-induced ***,siRNA targeting human CTCF were transfected into GC cells to observe interaction between PD-L1 and *** vivo experiment,we used immunohistochemistry and western blot to investigate the effect of PD-L1-CTCF axis on GCMSCs-induced resistance to 5-FU in ***:In response to 5-FU or paclitaxel therapy,GCMSCs-CM could enhance the GC cell viability and stemness and decrease apoptosis rate as well as increase the expression of PD-L1,MDR1,LRP and ***,blocking PDL1 or CTCF in GC cells could both prevent GCMSCs-induced resistance to 5-FU and paclitaxel accompanied by a decline in stemness and self-renewal of *** with these in vitro observations,we observed that mice in GCMSCs-CM group showed lower sensitivity to 5-FU treatme

关键词： mesenchymal stem cells gastric cancer PD-L1 CTCF stemness chemotherapy resistance

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Niclosamide(NA)overcomes cisplatin resistance in human ovarian cancer

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Genes & Diseases 2023年第4期10卷 1687-1701页

作者： Linjuan Huang Jing Zhang Youling Deng Hao Wang Piao Zhao Guozhi Zhao Wei Zeng Yonghui Wang Connie Chen William Wagstaff Rex C.Haydon Russell R.Reid Tong-Chuan He Le Shen Hue H.Luu Ling Zhao Departments of Obstetrics and Gynecology Orthopaedic Surgery and UrologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing 400046China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Neurology The Second Affiliated Hospital of Jianghan UniversityWuhanHubei 430050China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Surgery The University of Chicago Medical CenterChicagoIL 60637USA

Ovarian cancer(OC)is one of the most lethal malignancies of the female reproduc-tive *** patients are usually diagnosed at advanced stages due to the lack of early *** standard treatment for OC includes a combination of debulking surgery and platinum-taxane chemotherapy,while several targeted therapies have recently been approved for maintenance *** vast majority of OC patients relapse with chemoresistant tu-mors after an initial ***,there is an unmet clinical need to develop new therapeu-tic agents to overcome the chemoresistance of *** anti-parasite agent niclosamide(NA)has been repurposed as an anti-cancer agent and exerts potent anti-cancer activities in human cancers including ***,we investigated whether NA could be repurposed as a therapeutic agent to overcome cisplatin-resistant(CR)in human OC *** this end,we first established two CR lines SKOV3CR and OVCAR8CR that exhibit the essential biological characteristics of cisplatin resistance in human *** showed that NA inhibited cell proliferation,sup-pressed cell migration,and induced cell apoptosis in both CR lines at a low micromole ***,NA inhibited multiple cancer-related pathways including AP1,ELK/SRF,HIF1,and TCF/LEF,in SKOV3CR and OVCAR8CR *** was further shown to effectively inhibit xenograft tumor growth of SKOV3CR ***,our findings strongly suggest that NA may be repurposed as an efficacious agent to combat cisplatin resistance in chemoresistant hu-man OC,and further clinical trials are highly warranted.

关键词： chemotherapy resistance Cisplatin Drug repurposing Niclosamide Ovarian cancer

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Current Progress of Phytomedicine in Glioblastoma Therapy

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Current Medical Science 2020年第6期40卷 1067-1074页

作者： Fahad Hassan Shah Saad Salman Jawaria Idrees Fariha Idrees Syed Turab Ali Shah Abid Ali Khan Bashir Ahmad Centre of Biotechnology and Microbiology University of PeshawarPeshawar 25120Pakistan Department of Pharmacy The University of LahoreIslamabad CampusIslamabad 45800Pakistan Islamia College University Peshawar Peshawar 25000Pakistan

Glioblastoma multiforme,an intrusive brain cancer,has the lowest survival rate of all brain *** chemotherapy utilized to prevent their proliferation and propagation is limited due to modulation of complex cancer signalling *** complex pathways provide infiltrative and drug evading properties leading to the development of chemotherapy ***,the development and discovery of such interventions or therapies that can bypass all these resistive barriers to ameliorate glioma prognosis and survival is of profound *** plants are comprised of an exorbitant range of phytochemicals that have the broad-spectrum capability to target intrusive brain cancers,modulate anti-cancer pathways and immunological responses to facilitate their eradication,and induce *** phytocompounds also interfere with several oncogenic proteins that promote cancer invasiveness and metastasis,chemotherapy resistance and *** plants are extremely vital for promising anti-glioma therapy to avert glioma proliferation and *** this review,we acquired recent literature on medicinal plants whose extracts/bioactive ingredients are newly exploited in glioma therapeutics,and also highlighted their mode of action and pharmacological profile.

关键词： phytomedicine phytochemicals glioblastoma chemotherapy resistance bioactive

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Annexin A2 promotion of hepatocellular carcinoma tumorigenesis via the immune microenvironment

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World Journal of Gastroenterology 2020年第18期26卷 2126-2137页

作者： Li-Wei Qiu Yi-Fei Liu Xiao-Qing Cao Yan Wang Xiao-Hong Cui Xian Ye Shuo-Wen Huang Hong-Jun Xie Hai-Jian Zhang Research Center of Clinical Medicine Affiliated Hospital of Nantong UniversityNantong 226001Jiangsu ProvinceChina Department of Pathology Affiliated Hospital of Nantong UniversityNantong 226001Jiangsu ProvinceChina Department of Thoracic Surgery Beijing Chest HospitalCapital Medical University(Beijing Tuberculosis and Thoracic Tumor Research Institute)Beijing 101149China Emergency Department Affiliated Hospital of Nantong UniversityNantong 226001Jiangsu ProvinceChina Department of General Surgery Shanghai Electric Power HospitalShanghai 200050China Medical School of Nantong University Nantong 226001Jiangsu ProvinceChina

Hepatocellular carcinoma(HCC) is the most common primary liver cancer with a dismal prognosis, especially when diagnosed at advanced stages. Annexin A2(ANXA2), is found to promote cancer progression and therapeutic ***, the underlining mechanisms of ANXA2 in immune escape of HCC remain poorly understood up to now. Herein, we summarized the molecular function of ANXA2 in HCC and its relationship with prognosis. Furthermore, we tentatively elucidated the underlying mechanism of ANXA2 immune escape of HCC by upregulating the proportion of regulatory T cells and the expression of several inhibitory molecules, and by downregulating the proportion of natural killer cells and dendritic cells and the expression of several inhibitory molecules or effector molecules. We expect a lot of in-depth studies to further reveal the underlying mechanism of ANXA2 in immune escape of HCC in the future.

关键词： Annexin A2 Hepatocellular carcinoma Immune microenvironment Overall survival chemotherapy resistance Checkpoint

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