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cxcl5在2型糖尿病与恶性肿瘤相关性研究进展

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西南医科大学学报 2024年第2期47卷 111-116页

作者：贺阿敏侯绍章宁夏医科大学总医院第一临床医学院银川750003 宁夏医科大学基础医学院病理学系银川750004

糖尿病(diabetes mellitus,DM)和恶性肿瘤(malignant tumor,MT)是影响人类身心健康的两大疾病,胰岛素抵抗是2型糖尿病(type II diabetes mellitus,T2DM)的主要发病机制。巨噬细胞在肿瘤免疫应答过程中起重要作用,且在糖尿病患者中高度... 详细信息

糖尿病(diabetes mellitus,DM)和恶性肿瘤(malignant tumor,MT)是影响人类身心健康的两大疾病,胰岛素抵抗是2型糖尿病(type II diabetes mellitus,T2DM)的主要发病机制。巨噬细胞在肿瘤免疫应答过程中起重要作用,且在糖尿病患者中高度浸润并产生C-X-C基序趋化因子配体5(chemokine C-X-C motif ligand 5,cxcl5)。肿瘤相关巨噬细胞(tumourassociated Macrophages,TAMs)/M2型巨噬细胞高度浸润于肿瘤微环境(tumor microenvironment,TME)中并分泌cxcl5,cxcl5可通过促进肿瘤微血管生成及与其靶基因结合进一步调节TME进而影响MT的发生、发展及预后。本文就cxcl5的分子特征、相关通路以及cxcl5在T2DM与MT相关性中的研究进展做一评述,以期为临床在T2DM与MT的治疗和改善结局方面开启新思路与新方法。

关键词： cxcl5 2型糖尿病恶性肿瘤肿瘤相关巨噬细胞肿瘤微环境

cxcl5在Ⅱ型糖尿病与恶性肿瘤相关性的研究进展

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西南医科大学学报 2024年

作者：贺阿敏侯绍章宁夏医科大学总医院第一临床医学院宁夏医科大学基础医学院病理学系

糖尿病（diabetes mellitus，DM）和恶性肿瘤（malignant tumor， MT）是影响人类身心健康的两大疾病，胰岛素抵抗是Ⅱ型糖尿病（type II diabetes mellitus，T2DM）的主要发病机制，巨噬细胞在肿瘤免疫应答过程中起重要作用，且在糖尿... 详细信息

糖尿病（diabetes mellitus，DM）和恶性肿瘤（malignant tumor， MT）是影响人类身心健康的两大疾病，胰岛素抵抗是Ⅱ型糖尿病（type II diabetes mellitus，T2DM）的主要发病机制，巨噬细胞在肿瘤免疫应答过程中起重要作用，且在糖尿病患者中高度浸润并产生C-X-C基序趋化因子配体5 (chemokine C-X-C motif ligand 5， cxcl5)，肿瘤相关巨噬细胞(tumourassociated Macrophages， TAMs) / M2型巨噬细胞高度浸润于肿瘤微环境（tumor microenvironment，TME）中并分泌cxcl5，cxcl5可通过促进肿瘤微血管生成及与其靶基因结合进一步调节TME进而影响MT的发生、发展及预后。本文就cxcl5的分子特征，相关通路以及cxcl5在T2DM与MT相关性中的研究进展做一评述，以期望为临床在T2DM与MT的治疗和改善结局方面开启新思路与新方法。

关键词： cxcl5 Ⅱ型糖尿病恶性肿瘤肿瘤相关巨噬细胞肿瘤微环境

铂耐药上皮性卵巢癌组织中cxcl5的表达与患者临床特征的关系

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宁夏医学杂志 2024年第2期46卷 96-100,F0002页

作者：何滢马晓玲高璐璐祖逸峥张瑞琪哈春芳宁夏医科大学临床医学院宁夏银川750004 甘肃省庆阳市第一人民医院甘肃庆阳745000 福建医科大学妇儿临床医学院福建福州350001 宁夏医科大学总医院宁夏银川750004

目的探讨铂耐药上皮性卵巢癌组织中CXC趋化因子配体-5(cxcl5)的表达与患者临床特征的关系。方法收集行满意肿瘤细胞减灭术后联合铂类为主规范化疗的134名上皮性卵巢癌患者,根据患者停止化疗后6个月的复发情况分为铂耐药组70例(实验组)... 详细信息

目的探讨铂耐药上皮性卵巢癌组织中CXC趋化因子配体-5(cxcl5)的表达与患者临床特征的关系。方法收集行满意肿瘤细胞减灭术后联合铂类为主规范化疗的134名上皮性卵巢癌患者,根据患者停止化疗后6个月的复发情况分为铂耐药组70例(实验组)和铂敏感组64例(对照组)。采用免疫组化法检测卵巢癌组织cxcl5表达,分析其与上皮性卵巢癌铂耐药的相关性。结果cxcl5在铂耐药上皮性卵巢癌患者组织中的表达主要位于癌细胞的细胞质中;cxcl5在铂耐药型卵巢癌组织中的表达水平明显低于铂敏感型,2组差异有统计学意义(P5);cxcl5在铂耐药组上皮性卵巢癌患者组织中的表达与新辅助化疗、总化疗次数、人附睾蛋白4(HE4)、中性粒细胞绝对值(NEUT)、血小板(PLT)、FIGO分期、组织学分化程度、腹水量有显著相关性(P5);其中与新辅助化疗、总化疗次数、HE4、FIGO分期、腹水量呈负相关,与NEUT、PLT、组织学分化程度呈正相关;与糖类抗原(CA125)、年龄、绝经状态、病灶大小、肿瘤单双侧、脉管阳性无明显相关性(P>0.05)。结论铂耐药上皮性卵巢癌患者组织中cxcl5的表达降低与新辅助化疗、总化疗次数、HE4、NEUT、PLT、FIGO分期、组织学分化程度、腹水量有关,cxcl5的低表达可能与上皮性卵巢癌产生铂耐药相关。

关键词： cxcl5 铂耐药上皮性卵巢癌临床特征

cxcl5/CXCR2 axis in tumor microenvironment as potential diagnostic biomarker and therapeutic target

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Cancer Communications 2020年第2期40卷 69-80页

作者： Wen Zhang Huishan Wang Mingyang Sun Xueting Deng Xueru Wu Yilan Ma Mengjing Li Said Maisam Shuoa Qiang You Lin Miao Medical Center for Digestive Diseases The Second Affiliated Hospital of Nanjing Medical UniversityNanjing 210011JiangsuP.R.China Department of Surgery The Second Affiliated Hospital of Nanjing Medical UniversityNanjing 210011JiangsuP.R.China Department of Biotherapy The Second Affiliated Hospital of Nanjing Medical UniversityNanjing 210011JiangsuP.R.China Key Laboratory for Aging and Disease Nanjing Medical UniversityNanjing 210011JiangsuP.R.China

The components of the tumor microenvironment(TME)in solid tumors,especially chemokines,are currently attracting much attention from scientists.C-X-C motif chemokine ligand 5(cxcl5)is one of the important chemokines in TME.Over-expression of cxcl5 is closely related to the survival time,recurrence and metasta-sis of cancer patients.In TME,cxcl5 binds to its receptors,such as C-X-C motif chemokine receptor 2(CXCR2),to participate in the recruitment of immune cells and promote angiogenesis,tumor growth,and metastasis.The cxcl5/CXCR2 axis can act as a bridge between tumor cells and host cells in TME.Blocking the trans-mission of cxcl5/CXCR2 signals can increase the sensitivity and effectiveness of immunotherapy and slow down tumor progression.cxcl5 and CXCR2 are also regarded as biomarkers for predicting prognosis and molecular targets for customiz-ing the treatment.In this review,we summarized the current literature regarding the biological functions and clinical significance of cxcl5/CXCR2 axis in TME.The possibility to use cxcl5 and CXCR2 as potential prognostic biomarkers and thera-peutic targets in cancer is also discussed.

关键词： biomarker cxcl5 CXCR2 molecular targeted therapy tumor microenvironment

Role of neutrophil chemoattractant cxcl5 in SARS-CoV-2 infection-induced lung inflammatory innate immune response in an in vivo hACE2 transfection mouse model

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Zoological Research 2020年第6期41卷 621-631页

作者： Yan Liang Heng Li Jing Li Ze-Ning Yang Jia-Li Li Hui-Wen Zheng Yan-Li Chen Hai-Jing Shi Lei Guo Long-Ding Liu Institute of Medical Biology Chinese Academy of Medical SciencesKunmingYunnan 650118China

Understanding the pathogenesis of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and clarifying antiviral immunity in hosts are critical aspects for the development of vaccines and antivirals.Mice are frequently used to generate animal models of infectious diseases due to their convenience and ability to undergo genetic manipulation.However,normal adult mice are not susceptible to SARS-CoV-2.Here,we developed a viral receptor(human angiotensin-converting enzyme 2,hACE2)pulmonary transfection mouse model to establish SARS-CoV-2 infection rapidly in the mouse lung.Based on the model,the virus successfully infected the mouse lung 2 days after transfection.Viral RNA/protein,innate immune cell infiltration,inflammatory cytokine expression,and pathological changes in the infected lungs were observed after infection.Further studies indicated that neutrophils were the first and most abundant leukocytes to infiltrate the infected lungs after viral infection.In addition,using infected cxcl5-knockout mice,chemokine cxcl5 was responsible for neutrophil recruitment.cxcl5 knockout decreased lung inflammation without diminishing viral clearance,suggesting a potential target for controlling pneumonia.

关键词： SARS-CoV-2 Mouse model Lung infection ACE2 Neutrophil cxcl5

Efficacy of bevacizumab-containing chemotherapy in metastatic colorectal cancer and cxcl5 expression: Six case reports

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World Journal of Gastroenterology 2020年第16期26卷 1979-1986页

作者： Apolonia Novillo María Gaibar Alicia Romero-Lorca María Fuencisla Gilsanz Laura Beltrán Miguel Galán Beatriz Antón Diego Malón Amalia Moreno Ana Fernández-Santander Department of Pre-clinical Dentistry Health Sciences FacultyUniversidad Europea de MadridVillaviciosa de OdónMadrid 28670Spain Department of Health Sciences Health Sciences FacultyUniversidad Europea de MadridVillaviciosa de OdónMadrid 28670Spain Department of Medicine Health Sciences FacultyUniversidad Europea de MadridVillaviciosa de OdónMadrid 28670Spain Department of Oncology University Hospital of FuenlabradaFuenlabradaMadrid 28942Spain Department of Pathological Anatomy University Hospital of FuenlabradaFuenlabradaMadrid 28942Spain

BACKGROUND In metastatic colorectal cancer(mCRC),the anti-vascular endothelial growth factor drug bevacizumab(BVZ)plus chemotherapy significantly improves progression-free survival compared to chemotherapy(CT)alone.This benefit is not,however,observed in all patients.While increased chemokine cxcl5 gene expression promoting angiogenesis has been proposed as a prognostic mCRC biomarker,few studies have examined its relationship with drug efficacy.This study sought to analyze tumor cxcl5 gene expression in six patients with different efficacy of BVZ-containing CT in terms of the tumor response to treatment.CASE SUMMARY We report six cases of stage IV KRAS-mutated mCRC.Patients were given first line treatment with BVZ-containing chemotherapy in University Hospital of Fuenlabrada.The six patients differed in terms of primary tumor location(right/left side),tumor burden(mostly hepatic and peritoneal disease)and clinical disease course.Before treatment onset,total RNA was isolated from paraffinated tumor biopsy specimens and cxcl5 gene expression quantified through conventional RT-qPCR procedures.Our main finding was that cxcl5 expression levels were several times higher in three patients with lower progression free survival(under 6 mo)from the start of treatment.CONCLUSION A higher expression of cxcl5 was observed in the three patients showing worse tumor response to treatment.

关键词： Colorectal cancer Bevacizumab Chemokine cxcl5 Gene expression Progression-free survival Case report

紫花前胡苷通过调控cxcl5-ERK/MEK信号轴发挥抗肝癌作用

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天然产物研究与开发 2022年第6期34卷 1014-1020页

作者：王鹏利王国泰闫曙光李京涛罗璐白垚周小燕陕西中医药大学附属医院咸阳712000

本文探讨紫花前胡苷(nodakenin,NK)对肝癌细胞的作用及机制。不同浓度紫花前胡苷处理HepG2和MHCC-97H细胞,CCK-8检测细胞增殖变化,细胞划痕和Trans-wells实验观察细胞迁移和侵袭能力变化。紫花前胡苷能够显著抑制HepG2和MHCC-97H细胞增... 详细信息

本文探讨紫花前胡苷(nodakenin,NK)对肝癌细胞的作用及机制。不同浓度紫花前胡苷处理HepG2和MHCC-97H细胞,CCK-8检测细胞增殖变化,细胞划痕和Trans-wells实验观察细胞迁移和侵袭能力变化。紫花前胡苷能够显著抑制HepG2和MHCC-97H细胞增殖、体外迁移和侵袭;RNA-seq分析紫花前胡苷给药前后各基因表达,qRT-PCR、Western blotting和细胞免疫荧光进行验证分析,结果表明紫花前胡苷给药后趋化因子5(cxcl5)的表达显著降低,同时ERK和MEK磷酸化被抑制。综上所述紫花前胡苷通过下调cxcl5抑制ERK/MEK信号通路从而发挥抗肝癌作用。

关键词：紫花前胡苷 cxcl5 ERK/MEK 肝癌

The effects of glycyrrhizic acid and glabridin in the regulation of cxcl5 inflammation gene on acceleration of wound healing

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Asian Pacific Journal of Tropical Biomedicine 2016年第2期6卷 108-113页

作者： Hong Yung Yip Melissa Su Wei Poh Yoke Yin Chia School of Biosciences Division of Medicine Pharmacy and Health Sciences Taylor's University

Objective: To evaluate the anti-inflammatory property of both glycyrrhizic acid(GA)and glabridin in reducing inflammation to accelerate wound regeneration on 3T3-L1 and NIH-3T3 fibroblast cell lines.Methods: Cell proliferation and viability assay(MTT assay), scratch wound healing assays,and quantitative real-time PCR were conducted to investigate the effects on cell proliferation,cell migration, and expression of CXC chemokine ligand 5 inflammation gene respectively.Results: Results showed that at a low concentration of 1 × 10^(-8)mol/L, glabridin down regulated cell proliferation in NIH-3T3 significantly, suggesting its involvement in ERK1/2 signaling pathway. GA and glabridin significantly accelerated cell migration through wound healing in both 3T3-L1 and NIH-3T3 and significantly down regulated the expression of CXC chemokine ligand 5 in 3T3-L1 at concentration 1 × 10^(-8)mol/L,indicating the possible involvement of nuclear factor-k B and cyclooxygenase 2 transcriptions modulation.Conclusions: Both GA and glabridin can serve as potential treatment for chronic inflammatory disease, and glabridin as an oncogenic inhibitor due to its anti-proliferative property.

关键词： Wound healing Glycyrrhizic acid Glabridin cxcl5 Inflammation Cell proliferation Cell migration

cxcl5在铂耐药上皮性卵巢癌患者组织中的表达及其与临床特征的关系

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CXCL5在铂耐药上皮性卵巢癌患者组织中的表达及其与临床特征的关系

作者：何滢宁夏医科大学

学位级别：硕士

目的探讨CXC趋化因子配体-5(CXC cell chemokine ligand-5,cxcl5)在铂耐药上皮性卵巢癌患者组织中的表达情况,分析铂耐药型上皮性卵巢癌患者组织中cxcl5表达与临床特征的关系。方法选取在宁夏医科大学总医院妇科行手术治疗的3例铂耐药及... 详细信息

目的探讨CXC趋化因子配体-5(CXC cell chemokine ligand-5,cxcl5)在铂耐药上皮性卵巢癌患者组织中的表达情况,分析铂耐药型上皮性卵巢癌患者组织中cxcl5表达与临床特征的关系。方法选取在宁夏医科大学总医院妇科行手术治疗的3例铂耐药及3例铂敏感上皮性卵巢癌患者的组织,采用转录组测序筛选出上皮性卵巢癌患者差异基因5个,选取差异基因表达最明显的cxcl5为靶基因并行q RT-PCR验证。收集2015年1月～2021年12月在宁夏医科大学总医院妇科行满意肿瘤细胞减灭术后联合铂类为主规范化疗的134名上皮性卵巢癌患者,根据患者停化疗后六个月的复发情况分为铂耐药组患者70例和铂敏感组患者64例。取患者石蜡病理切块,采用免疫组织化学法检测两组患者卵巢癌组织中cxcl5蛋白的表达,分析cxcl5与上皮性卵巢癌铂耐药的关系。收集70例铂耐药组患者一般临床资料如年龄、绝经状态、病灶大小、是否接受新辅助化疗、总化疗次数;术前血清学指标如CA125、HE4、血清中血小板(Platelet,PLT)、白蛋白(Albumin,ALB)、中性粒细胞绝对值(Absolute neutrophil count,NEUT)、单核细胞绝对值(Absolute monocyte count,MXD),病理特征如FIGO分期、组织学分化程度、肿瘤单双侧情况、脉管阳性、淋巴结转移、腹水量、大网膜状态,通过单因素分析铂耐药组患者组织中cxcl5表达与患者一般临床资料等上述指标的关系,探讨cxcl5引起上皮性卵巢癌患者耐药的相关因素。结果(1)cxcl5在铂耐药上皮性卵巢癌患者组织中的表达主要位于癌细胞的细胞质中。cxcl5在耐药型卵巢癌组织中的表达水平明显低于敏感型,两组差异有统计学意义(P5)。(2)cxcl5在铂耐药组上皮性卵巢癌患者组织中的表达与新辅助化疗、总化疗次数、HE4、NEUT、PLT、ALB、FIGO分期、组织学分化程度、淋巴结转移、腹水量、大网膜状态有显著相关性(P5);其中与新辅助化疗、总化疗次数、HE4、FIGO分期、腹水量、大网膜状态呈负相关,与NEUT、PLT、ALB、组织学分化程度、淋巴结转移呈正相关;与CA125、MXD、年龄、绝经状态、病灶大小、肿瘤单双侧、脉管阳性无明显相关性(P>0.05)。结论1.cxcl5在铂耐药上皮性卵巢癌患者组织中的表达主要位于癌细胞的细胞质中且cxcl5在耐药型癌组织中的表达水平明显低于敏感型,提示cxcl5的低表达可能与上皮性卵巢癌铂耐药相关。2.cxcl5在铂耐药上皮性卵巢癌患者组织中的表达与新辅助化疗、总化疗次数、HE4、FIGO分期、腹水量、大网膜状态呈负相关,而与NEUT、PLT、ALB、组织学分化程度、淋巴结转移呈正相关。

关键词：上皮性卵巢癌铂耐药 cxcl5 临床特征