Article(id=1208795422408183865, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208795418612339683, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2021.10.12, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1610467200000, receivedDateStr=2021-01-13, revisedDate=1614700800000, revisedDateStr=2021-03-03, acceptedDate=null, acceptedDateStr=null, onlineDate=1766128887034, onlineDateStr=2025-12-19, pubDate=1635350400000, pubDateStr=2021-10-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1766128887034, onlineIssueDateStr=2025-12-19, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1766128887034, creator=13701087609, updateTime=1766128887034, updator=13701087609, issue=Issue{id=1208795418612339683, tenantId=1146029695717560320, journalId=1189873630562394117, year='2021', volume='46', issue='10', pageStart='955', pageEnd='1060', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1766128886129, creator=13701087609, updateTime=1766128956061, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1208795711982924071, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208795418612339683, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1208795711982924072, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208795418612339683, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1029, endPage=1033, ext={EN=ArticleExt(id=1208795422714368079, articleId=1208795422408183865, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Current status and perspectives of patient-derived xenograft models in liver cancer research, columnId=1190243275882729994, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Review, runingTitle=null, highlight=null, articleAbstract=
Patient-derived xenograft (PDX) model of liver cancer is created by transplanting the primary tumor tissue of patients with liver cancer into immunodeficient mice to simulate the biological characteristics of primary tumors, similar genetic characteristics and tumor heterogeneity with patients, which has been widely used in liver cancer research and plays an important role in drug research and clinical tumor treatment. This review firstly summarize the methodology to establish PDX models of liver cancer, four new PDX models of live cancer, and then go over recent application and function of liver cancer PDX models in basic cancer research and in preclinical explorations and finally give our perspectives on the future prospects of liver cancer PDX models.
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肝癌人源肿瘤异种移植(PDX)模型是将肝癌患者的原发肿瘤组织移植到免疫缺陷小鼠体内,能较好地模拟原代肿瘤的生物学特性及与患者相似的遗传特性和肿瘤异质性,已广泛用于肝癌研究,在药物研究、临床肿瘤治疗中具有重要地位。该文总结了国内外建立肝癌PDX模型的方法,概述了4种新型肝癌PDX模型,回顾了肝癌PDX模型在基础研究与临床前研究中的应用现状,以期为肝癌研究提供新的视角并为后续研究提供参考。
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1Department of Pharmacy, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
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27(8): 60-65.], articleTitle=肝癌人源肿瘤异种移植模型构建及初步应用, refAbstract=null)], funds=[Fund(id=1208795434412282216, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208795422408183865, awardId=81803019, language=EN, fundingSource=National Natural Science Foundation of China(81803019), fundOrder=null, country=null), Fund(id=1208795434521334124, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208795422408183865, awardId=81803019, language=CN, fundingSource=国家自然科学基金(81803019), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1208795423322542201, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208795422408183865, xref=1, ext=[AuthorCompanyExt(id=1208795423339319419, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208795422408183865, companyId=1208795423322542201, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=
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4西南医科大学附属医院肝胆外科,四川泸州 646000)])], figs=[ArticleFig(id=1208795432566788425, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208795422408183865, language=EN, label=Tab. 1, caption=
Mouse strains commonly used for PDX models of liver cancer
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| 品系 | 特点 | 寿命(年) | 价格(元) |
|---|
| C57BL/6-nu | 无毛无胸腺,易于种植及观察;缺乏T细胞,移植率低 | 1.5~2 | 120~140 |
| CB17-scid | 缺乏成熟T、B细胞;存在固有免疫和NK细胞;渗漏现象 | >1 | 180~200 |
| NOD-scid | 缺乏成熟T、B细胞;固有免疫和NK细胞活性低下;移植率高;寿命短,淋巴瘤发生率高 | <1 | 250~280 |
| NSG、NOG | 缺乏成熟T、B、NK细胞;固有免疫低下;移植率高;寿命长 | <1.5 | >300 |
), ArticleFig(id=1208795432684228942, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208795422408183865, language=CN, label=表1, caption=
肝癌PDX模型常用小鼠品系
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| 品系 | 特点 | 寿命(年) | 价格(元) |
|---|
| C57BL/6-nu | 无毛无胸腺,易于种植及观察;缺乏T细胞,移植率低 | 1.5~2 | 120~140 |
| CB17-scid | 缺乏成熟T、B细胞;存在固有免疫和NK细胞;渗漏现象 | >1 | 180~200 |
| NOD-scid | 缺乏成熟T、B细胞;固有免疫和NK细胞活性低下;移植率高;寿命短,淋巴瘤发生率高 | <1 | 250~280 |
| NSG、NOG | 缺乏成熟T、B、NK细胞;固有免疫低下;移植率高;寿命长 | <1.5 | >300 |
), ArticleFig(id=1208795432759726419, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208795422408183865, language=EN, label=Tab. 2, caption=
Methodology to establish PDX models of liver cancer
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| 移植方式 | 部位 | 特点 | 不足 |
|---|
| 原位移植 | 肝脏,多位于肝左叶 | 能更准确地模拟肿瘤微环境,模拟包括浸润、转移、腹水在内的各种肝癌特征性生物学行为,较好地保留了患者肝癌的生物学特性;最理想的移植模型[10] | 操作相对复杂;不能直接观察肿瘤的生长情况,需要借助超声或腔镜等方法确认肿瘤 |
| 异位移植 |
| | 皮下 | 双侧腹股沟、背部、腋下或前腹侧壁 | 操作简单,局部成瘤快,易于监测;广泛采用的移植模型 | 成瘤率较低;皮下缺乏肝癌相关基质成分;肝癌组织难以突破基膜而表现为成团生长,以致较少出现扩散和转移[11] |
| | 肾包膜下 | 肾包膜下 | 血供丰富,基质含量高,为肝癌细胞的存活及生长提供充足的条件,有利于肝癌转移;生长、浸润能力明显增强[12] | 操作难度大,不易观察测量;损伤较大,易引起小鼠感染 |
| 皮下-原位移植 | 皮下生长后移植至肝脏 | 操作相对原位方式简单,效率增高,为原位移植提供了大量瘤源[13] | 不能直接观察肿瘤的生长情况,需要借助超声或腔镜等方法确认肿瘤 |
), ArticleFig(id=1208795432889749850, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208795422408183865, language=CN, label=表2, caption=
不同肝癌移植方式的特征
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| 移植方式 | 部位 | 特点 | 不足 |
|---|
| 原位移植 | 肝脏,多位于肝左叶 | 能更准确地模拟肿瘤微环境,模拟包括浸润、转移、腹水在内的各种肝癌特征性生物学行为,较好地保留了患者肝癌的生物学特性;最理想的移植模型[10] | 操作相对复杂;不能直接观察肿瘤的生长情况,需要借助超声或腔镜等方法确认肿瘤 |
| 异位移植 |
| | 皮下 | 双侧腹股沟、背部、腋下或前腹侧壁 | 操作简单,局部成瘤快,易于监测;广泛采用的移植模型 | 成瘤率较低;皮下缺乏肝癌相关基质成分;肝癌组织难以突破基膜而表现为成团生长,以致较少出现扩散和转移[11] |
| | 肾包膜下 | 肾包膜下 | 血供丰富,基质含量高,为肝癌细胞的存活及生长提供充足的条件,有利于肝癌转移;生长、浸润能力明显增强[12] | 操作难度大,不易观察测量;损伤较大,易引起小鼠感染 |
| 皮下-原位移植 | 皮下生长后移植至肝脏 | 操作相对原位方式简单,效率增高,为原位移植提供了大量瘤源[13] | 不能直接观察肿瘤的生长情况,需要借助超声或腔镜等方法确认肿瘤 |
), ArticleFig(id=1208795434106098013, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208795422408183865, language=EN, label=Tab. 3, caption=
Characteristics of the novel PDX models of liver cancer
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| 新型肝癌PDX模型 | 特点 | 局限性 | 适用范围 | 优势 |
|---|
| 诱导多能干细胞来源的PDX模型 | 可在移植前进行细胞遗传操作 | 肝癌细胞重编程的效率以及将肝癌诱导多能干细胞分化为目标细胞类型的能力 | 不能直接植入小鼠体内的肿瘤 | 研究基因对肝癌体内生长的影响 |
| 组合模型 | 对患者进行治疗的同时可以进行药物敏感性分析及基因组分析 | 需要更先进的技术支持 | 探索潜在的治疗方法 | 多途径进行有效的肝癌个性化治疗 |
| 肝脏疾病介导的PDX模型 | 将肝脏疾病与PDX模型结合 | 人和动物病理背景的差异 | 肝损伤背景下的肝癌 | 更好地模拟了肿瘤生长的微环境 |
| 人源化小鼠PDX模型 | 采用人源化免疫系统小鼠或靶点基因人源化小鼠构建肝癌PDX模型 | 操作复杂,昂贵 | 采用免疫疗法治疗的肝癌 | 研究免疫系统与肝癌的相互作用,对肝癌免疫疗法进行临床前评估 |
), ArticleFig(id=1208795434248704352, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208795422408183865, language=CN, label=表3, caption=
新型肝癌PDX模型的特征
, figureFileSmall=null, figureFileBig=null, tableContent=
| 新型肝癌PDX模型 | 特点 | 局限性 | 适用范围 | 优势 |
|---|
| 诱导多能干细胞来源的PDX模型 | 可在移植前进行细胞遗传操作 | 肝癌细胞重编程的效率以及将肝癌诱导多能干细胞分化为目标细胞类型的能力 | 不能直接植入小鼠体内的肿瘤 | 研究基因对肝癌体内生长的影响 |
| 组合模型 | 对患者进行治疗的同时可以进行药物敏感性分析及基因组分析 | 需要更先进的技术支持 | 探索潜在的治疗方法 | 多途径进行有效的肝癌个性化治疗 |
| 肝脏疾病介导的PDX模型 | 将肝脏疾病与PDX模型结合 | 人和动物病理背景的差异 | 肝损伤背景下的肝癌 | 更好地模拟了肿瘤生长的微环境 |
| 人源化小鼠PDX模型 | 采用人源化免疫系统小鼠或靶点基因人源化小鼠构建肝癌PDX模型 | 操作复杂,昂贵 | 采用免疫疗法治疗的肝癌 | 研究免疫系统与肝癌的相互作用,对肝癌免疫疗法进行临床前评估 |
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