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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2022, Vol. 42 Issue (8): 74-84    DOI: 10.13523/j.cb.2202036
综述     
人源性食管癌异种移植模型的建立及应用进展*
梁帆1,程洪伟1,**(),张俊河1,2,**()
1.新乡医学院健康中原研究院 新乡 453003
2.新乡医学院生物化学与分子生物学系 新乡 453003
Establishment and Application Progress of Patient-derived Xenograft Model of Esophageal Cancer
LIANG Fan1,CHENG Hong-wei1,**(),ZHANG Jun-he1,2,**()
1. Institutes of Health Central Plains, Xinxiang Medical University, Xinxiang 453003, China
2. Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang 453003, China
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摘要：

食管癌是全球第十大常见癌症,其发病率和病死率较高,主要包括食管鳞状细胞癌(ESCC)和食管腺癌(EAC),通常发展到晚期才被诊断发现。食管癌的标准治疗方法包括放化疗、内窥镜疗法和外科手术,但其预后效果不甚理想。良好的动物模型可用于研究食管癌的发生发展和生物学机制。患者来源的异种移植(PDX)模型最大程度上保留了原始肿瘤的细胞形态、组织结构特征和与患者相似的遗传特征。PDX模型为研究食管癌患者对放化疗的反应性,寻求新的治疗靶点,改善预后效果提供了新的平台,使个性化精准治疗研究迈入新阶段。就食管癌PDX模型的特点、构建时常用的实验动物、优化模型建立的方法以及PDX模型在食管癌研究中的应用进行综述,并讨论了食管癌PDX模型的局限性和未来发展前景,以期为食管癌的个性化精准治疗、改善患者预后提供新的研究方向。
关键词： 患者来源的异种移植模型;  食管癌;  治疗靶点;  生物标志物    
Abstract:

Esophageal cancer is the tenth most common cancer in the world, with high morbidity and mortality. The main subtypes of esophageal cancer include esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), the patients of which are usually diagnosed at a late stage. The standard treatment methods of esophageal cancer include radiotherapy and chemotherapy, endoscopic therapy and surgery, but the prognosis is still not good as expected. The patient-derived xenograft (PDX) model retains the cellular morphology, tissue structure and genetic characteristics of the original tumor to the greatest extent. The PDX model provides a new platform and guarantee for studying the reactivity of patients with esophageal cancer to radiotherapy and chemotherapy, seeking new therapeutic targets and improving prognosis, which makes personalized precision therapy research enter a new stage. This article first reviews the characteristics of esophageal cancer PDX model, the commonly used experimental animals, the ways and methods for optimizing the model establishment, and the application of PDX model in the research of esophageal cancer, and then discusses the limitations and future development prospects of esophageal cancer PDX model, in order to provide a new research direction for personalized precision therapy and improve the prognosis of patients with esophageal cancer.
Key words: Patient-derived xenograft model    Esophageal cancer    Therapeutic targets    Biomarkers
收稿日期: 2022-02-22 出版日期: 2022-09-07
ZTFLH:  Q819  
基金资助: * 河南省重点研发与推广专项(科技攻关)(212102310634);新乡市科技攻关计划(GG2021008)
通讯作者: 程洪伟,张俊河     E-mail: zjh@xxmu.edu.cn;chenghongwei2014@gmail.com
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引用本文:

梁帆,程洪伟,张俊河. 人源性食管癌异种移植模型的建立及应用进展*[J]. 中国生物工程杂志, 2022, 42(8): 74-84.

LIANG Fan,CHENG Hong-wei,ZHANG Jun-he. Establishment and Application Progress of Patient-derived Xenograft Model of Esophageal Cancer. China Biotechnology, 2022, 42(8): 74-84.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2202036    或    https://manu60.magtech.com.cn/biotech/CN/Y2022/V42/I8/74

免疫缺陷小鼠 特点 局限性
裸鼠 缺乏体毛,易于观察肿瘤生长情况
缺乏功能性T淋巴细胞		 存在功能性B淋巴细胞和NK细胞
随着年龄增长功能性T淋巴细胞数目增多
SCID小鼠 功能性T淋巴细胞和B淋巴细胞缺失 NK细胞残留
随着年龄增长,免疫功能有不同程度的恢复
对辐射敏感
NOD/SCID小鼠 功能性T淋巴细胞和B淋巴细胞缺失
NK细胞活性低
PDX移植成功率高		 对辐射敏感
小鼠寿命较短
易产生自发性淋巴瘤
NOG小鼠和NSG小鼠 无功能性T淋巴细胞、B淋巴细胞、NK细胞
IL-2受体蛋白γ链缺陷		 饲养难度大
价格昂贵
表1  PDX模型常用免疫缺陷小鼠的特点和局限性
植入部位 优势 局限性 参考文献
原位 模拟食管癌在人体内的发生发展过程,及时了解肿瘤对实验制剂的反应,接近原始肿瘤微环境 无法直接观察肿瘤生长情况,手术操作复杂、致死率高、成瘤率低 [31]
皮下 操作便捷,易于观察 淋巴增殖性病变替换移植组织,成功率低 [32]
肌肉 血液供应更充足, 异种移植物产生淋巴瘤转化 [38]
肾包膜 保持肿瘤组织学特征活体组织来源广,供血丰富,利于肿瘤转移 易感染 [39]
表2  PDX模型不同植入部位的建模比较
作用因素 治疗靶点 组织学 实验动物 参考文献
吉马替康 TOP1 ESCC NOD/SCID小鼠 [52]
HCPT TOP1 ESCC SCID小鼠 [53]
吲哚美辛 ITGAV ESCC 无胸腺裸鼠 [58]
西妥昔单抗 EGFR ESCC BALB/c裸鼠 [60]
塞利替尼 EGFR ESCC NOD/SCID小鼠 [62]
西利替尼 EGFR ESCC NOD/SCID小鼠 [62]
阿法替尼 EGFR/SFK ESCC NOD/SCID小鼠 [63]
曲妥珠单抗 HER2 EC NSG小鼠 [65]
5-FU/顺铂联合作用 HER2 ESCC 无胸腺裸鼠 [67]
拉帕提尼 HER2/EGFR ESCC 无胸腺裸鼠 [68]
MEDI3622 ADAM10 EC 无胸腺裸鼠 [72]
GPC-1单克隆抗体 GPC-1 ESCC NOD/SCID小鼠 [76]
GPC-1-ADC(MMAE) GPC-1 ESCC NOG小鼠 [78]
MET/EGFR联合抑制剂 MET/EGFR EAC NOD/SCID小鼠 [79]
反义寡核苷酸 LncRNA AGPG ESCC 无胸腺裸鼠 [80]
AdSOCS1 SOCS1 ESCC NOD/SCID小鼠 [81]
黄腐酚 AKT激酶 ESCC SCID小鼠 [82]
antagomiR-455-3p miR-455-3p ESCC NOG小鼠 [83]
茶素/NQO1抑制剂联合 NQO1 ESCC 无毛SCID小鼠 [84]
NSC74859 STAT3 ESCC BALB/c裸鼠 [85]
Ad-TD-nsIL12 Ki67 ESCC NDG小鼠、BALB/c裸鼠、转基因免疫缺陷仓鼠 [86]
BAY1143572 CDK9 EAC 无胸腺裸鼠 [87]
帕博西尼 CDK4/6 ESCC 无胸腺裸鼠 [88]
没食子酸乙醇 ERK1/2 ESCC SCID小鼠 [89]
γ-分泌酶抑制剂 Notch EAC NSG小鼠 [90]
CD276靶向抗体/CAR-T细胞 CD276 ESCC NSG小鼠 [91]
杠柳苷元 STAT3 ESCC NOD/SCID小鼠 [92]
奥昔卡因 AURKA ESCC SCID小鼠 [93]
EZH2/PI3Kα联合抑制剂 EZH2/PI3Kα联合抑制剂 ESCC BALB/c裸鼠 [94]
表3  食管癌PDX模型中测试的药物成分和其作用位点
[1] Sung H, Ferlay J, Siegel R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 2021, 71(3): 209-249.
doi: 10.3322/caac.21660
[2] Watanabe M, Otake R, Kozuki R, et al. Recent progress in multidisciplinary treatment for patients with esophageal cancer. Surgery Today, 2020, 50(1): 12-20.
doi: 10.1007/s00595-019-01878-7
[3] Huang F L, Yu S J. Esophageal cancer: risk factors, genetic association, and treatment. Asian Journal of Surgery, 2018, 41(3): 210-215.
doi: 10.1016/j.asjsur.2016.10.005
[4] Rustgi A K, El-Serag H B. Esophageal carcinoma. The New England Journal of Medicine, 2014, 371(26): 2499-2509.
doi: 10.1056/NEJMra1314530 pmid: 25539106
[5] Shi M C, Wang Y, Lin D, et al. Patient-derived xenograft models of neuroendocrine prostate cancer. Cancer Letters, 2022, 525: 160-169.
doi: 10.1016/j.canlet.2021.11.004
[6] Meehan T F. Know thy PDX model. Cancer Research, 2019, 79(17): 4324-4325.
[7] Fujii E, Kato A, Suzuki M. Patient-derived xenograft (PDX) models: characteristics and points to consider for the process of establishment. Journal of Toxicologic Pathology, 2020, 33(3): 153-160.
doi: 10.1293/tox.2020-0007
[8] Abdolahi S, Ghazvinian Z, Muhammadnejad S, et al. Patient-derived xenograft (PDX) models, applications and challenges in cancer research. Journal of Translational Medicine, 2022, 20(1): 206.
doi: 10.1186/s12967-022-03405-8
[9] Saw P E, Chen J N, Song E W. Targeting CAFs to overcome anticancer therapeutic resistance. Trends in Cancer, 2022, 8(7): 527-555.
doi: 10.1016/j.trecan.2022.03.001
[10] Cho S Y, Kang W, Han J Y, et al. An integrative approach to precision cancer medicine using patient-derived xenografts. Molecules and Cells, 2016, 39(2): 77-86.
doi: 10.14348/molcells.2016.2350
[11] Sia D, Moeini A, Labgaa I, et al. The future of patient-derived tumor xenografts in cancer treatment. Pharmacogenomics, 2015, 16(14): 1671-1683.
doi: 10.2217/pgs.15.102
[12] Dobbin Z C, Katre A A, Steg A D, et al. Using heterogeneity of the patient-derived xenograft model to identify the chemoresistant population in ovarian cancer. Oncotarget, 2014, 5(18): 8750-8764.
doi: 10.18632/oncotarget.2373
[13] Lohse I, Borgida A, Cao P, et al. BRCA1 and BRCA 2 mutations sensitize to chemotherapy in patient-derived pancreatic cancer xenografts. British Journal of Cancer, 2015, 113(3): 425-432.
doi: 10.1038/bjc.2015.220 pmid: 26180923
[14] Lai Y X, Wei X R, Lin S H, et al. Current status and perspectives of patient-derived xenograft models in cancer research. Journal of Hematology & Oncology, 2017, 10(1): 106.
[15] Okada S, Vaeteewoottacharn K, Kariya R. Application of highly immunocompromised mice for the establishment of patient-derived xenograft (PDX) models. Cells, 2019, 8(8): 889.
doi: 10.3390/cells8080889
[16] Flanagan S P. ‘Nude’, a new hairless gene with pleiotropic effects in the mouse. Genetical Research, 1966, 8(3): 295-309.
doi: 10.1017/S0016672300010168
[17] 李晓娟, 冯帆, 李瑞生, 等. 肝细胞癌人源异种移植模型应用研究进展. 传染病信息, 2021, 34(3): 202-207, 217.
Li X J, Feng F, Li R S, et al. Advances in application of patient-derived xenograft model for hepatocellular carcinoma. Infectious Disease Information, 2021, 34(3): 202-207, 217.
[18] Pan B H, Wei X Y, Xu X. Patient-derived xenograft models in hepatopancreatobiliary cancer. Cancer Cell International, 2022, 22(1): 41.
doi: 10.1186/s12935-022-02454-9
[19] Giovanella B C, Fogh J. The nude mouse in cancer research. Advances in Cancer Research, 1985, 44: 69-120.
pmid: 3898740
[20] Bosma G C, Custer R P, Bosma M J. A severe combined immunodeficiency mutation in the mouse. Nature, 1983, 301(5900): 527-530.
doi: 10.1038/301527a0
[21] 张楠楠, 卢荣梦, 孟廷薪. 免疫缺陷动物模型研究进展. 华南国防医学杂志, 2021, 35(7): 541-545.
Zhang N N, Lu R M, Meng T X. Research progress of immunodeficiency animal model. Military Medical Journal of South China, 2021, 35(7): 541-545.
[22] Makino S, Kunimoto K, Muraoka Y, et al. Breeding of a non-obese, diabetic strain of mice. Jikken Dobutsu Experimental Animals, 1980, 29(1): 1-13.
pmid: 6995140
[23] Kikutani H, Makino S. The murine autoimmune diabetes model: nod and related strains. Advances in Immunology, 1992, 51: 285-322.
pmid: 1323922
[24] Shultz L D, Schweitzer P A, Christianson S W, et al. Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice. Journal of Immunology (Baltimore, Md: 1950), 1995, 154(1): 180-191.
[25] Ito M, Hiramatsu H, Kobayashi K, et al. NOD/SCID/gammac(null)mouse: an excellent recipient mouse model for engraftment of human cells. Blood, 2002, 100(9): 3175-3182.
doi: 10.1182/blood-2001-12-0207
[26] McDermott S P, Eppert K, Lechman E R, et al. Comparison of human cord blood engraftment between immunocompromised mouse strains. Blood, 2010, 116(2): 193-200.
doi: 10.1182/blood-2010-02-271841 pmid: 20404133
[27] Nagatani M, Kodera T, Suzuki D, et al. Comparison of biological features between severely immuno-deficient NOD/Shi-scid Il2rg null and NOD/LtSz-scid Il2rg null mice. Experimental Animals, 2019, 68(4): 471-482.
doi: 10.1538/expanim.19-0024 pmid: 31118345
[28] 李媛, 闫平. 免疫缺陷小鼠平台上的人肿瘤异种移植研究进展. 武汉大学学报(医学版), 2012, 33(1): 137-140.
Li Y, Yan P. Advances of patient-derived human tumor tissue xenografts research in immunodeficient mice. Medical Journal of Wuhan University, 2012, 33(1): 137-140.
[29] Shin H Y, Lee E J, Yang W, et al. Identification of prognostic markers of gynecologic cancers utilizing patient-derived xenograft mouse models. Cancers, 2022, 14(3): 829.
doi: 10.3390/cancers14030829
[30] Jung J, Seol H S, Chang S. The generation and application of patient-derived xenograft model for cancer research. Cancer Research and Treatment, 2018, 50(1): 1-10.
doi: 10.4143/crt.2017.307
[31] Veeranki O L, Tong Z M, Mejia A, et al. A novel patient-derived orthotopic xenograft model of esophageal adenocarcinoma provides a platform for translational discoveries. Disease Models & Mechanisms, 2019, 12(12): dmm041004.
[32] Lan T F, Xue X, Dunmall L C, et al. Patient-derived xenograft: a developing tool for screening biomarkers and potential therapeutic targets for human esophageal cancers. Aging (Albany NY), 2021, 13(8): 12273-12293.
[33] 管柳柳, 邹晴晴, 刘倩, 等. 食管鳞癌患者来源移植瘤模型: B-NDG(R)小鼠与BALB/c裸鼠的比较. 南方医科大学学报, 2020, 40(8): 1200-1206.
Guan L L, Zou Q Q, Liu Q, et al. Comparison of B-NDG(R) and BALB/c mouse models bearing patient-derived xenografts of esophageal squamous cell carcinoma. Journal of Southern Medical University, 2020, 40(8): 1200-1206.
[34] Fujii E, Kato A, Chen Y J, et al. Characterization of EBV-related lymphoproliferative lesions arising in donor lymphocytes of transplanted human tumor tissues in the NOG mouse. Experimental Animals, 2014, 63(3): 289-296.
doi: 10.1538/expanim.63.289
[35] Tse E, Kwong Y L. Epstein Barr virus-associated lymphoproliferative diseases: the virus as a therapeutic target. Experimental & Molecular Medicine, 2015, 47(1): e136.
[36] Kanda T R, Yajima M, Ikuta K. Epstein-Barr virus strain variation and cancer. Cancer Science, 2019, 110(4): 1132-1139.
doi: 10.1111/cas.13954 pmid: 30697862
[37] Fujii E, Kato A, Chen Y J, et al. The status of donor cancer tissues affects the fate of patient-derived colorectal cancer xenografts in NOG mice. Experimental Animals, 2015, 64(2): 181-190.
doi: 10.1538/expanim.14-0080
[38] Read M, Liu D, Duong C P, et al. Intramuscular transplantation improves engraftment rates for esophageal patient-derived tumor xenografts. Annals of Surgical Oncology, 2016, 23(1): 305-311.
doi: 10.1245/s10434-015-4425-3
[39] Cutz J C, Guan J, Bayani J, et al. Establishment in severe combined immunodeficiency mice of subrenal capsule xenografts and transplantable tumor lines from a variety of primary human lung cancers: potential models for studying tumor progression-related changes. Clinical Cancer Research, 2006, 12(13): 4043-4054.
doi: 10.1158/1078-0432.CCR-06-0252
[40] Huang P G, Westmoreland S V, Jain R K, et al. Spontaneous nonthymic tumors in SCID mice. Comparative Medicine, 2011, 61(3): 227-234.
[41] Santagostino S F, Arbona R, Nashat M A, et al. Pathology of aging in NOD scid gamma female mice. Veterinary Pathology, 2017, 54(5): 855-869.
doi: 10.1177/0300985817698210 pmid: 28355107
[42] Plaks V, Kong N W, Werb Z. The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells? Cell Stem Cell, 2015, 16(3): 225-238.
doi: 10.1016/j.stem.2015.02.015
[43] Liu Z C, Wu K Q, Gu S R, et al. A methyltransferase-like 14/miR-99a-5p/tribble 2 positive feedback circuit promotes cancer stem cell persistence and radioresistance via histone deacetylase 2-mediated epigenetic modulation in esophageal squamous cell carcinoma. Clinical and Translational Medicine, 2021, 11(9): e545.
[44] Liu D S H, Read M, Cullinane C, et al. APR-246 potently inhibits tumour growth and overcomes chemoresistance in preclinical models of oesophageal adenocarcinoma. Gut, 2015, 64(10): 1506-1516.
doi: 10.1136/gutjnl-2015-309770
[45] Zhang C J, Zhang J X, Wu Q, et al. Sulforaphene induces apoptosis and inhibits the invasion of esophageal cancer cells through MSK2/CREB/Bcl-2 and cadherin pathway in vivo and in vitro. Cancer Cell International, 2019, 19: 342.
doi: 10.1186/s12935-019-1061-1
[46] Talukdar A, Kundu B, Sarkar D, et al. Topoisomerase I inhibitors: Challenges, progress and the road ahead. European Journal of Medicinal Chemistry, 2022, 236: 114304.
doi: 10.1016/j.ejmech.2022.114304
[47] Wu J H, Phatnani H P, Hsieh T S, et al. The phosphoCTD-interacting domain of topoisomerase I. Biochemical and Biophysical Research Communications, 2010, 397(1): 117-119.
doi: 10.1016/j.bbrc.2010.05.081
[48] Pommier Y, Sun Y L, Huang S Y N, et al. Roles of eukaryotic topoisomerases in transcription, replication and genomic stability. Nature Reviews Molecular Cell Biology, 2016, 17(11): 703-721.
doi: 10.1038/nrm.2016.111 pmid: 27649880
[49] Hanagiri T, Ono K, Kuwata T, et al. Evaluation of topoisomerase I/topoisomerase IIalpha status in esophageal cancer. Journal of UOEH, 2011, 33(3): 205-216.
pmid: 21913377
[50] Mohinudeen I A H K, Kanumuri R, Soujanya K N, et al. Sustainable production of camptothecin from an Alternaria sp. isolated from Nothapodytes nimmoniana. Scientific Reports, 2021, 11: 1478.
doi: 10.1038/s41598-020-79239-5 pmid: 33446714
[51] Hsiang Y H, Hertzberg R, Hecht S, et al. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. The Journal of Biological Chemistry, 1985, 260(27): 14873-14878.
doi: 10.1016/S0021-9258(17)38654-4
[52] Zou J L, Li S, Chen Z H, et al. A novel oral camptothecin analog, gimatecan, exhibits superior antitumor efficacy than irinotecan toward esophageal squamous cell carcinoma in vitro and in vivo. Cell Death & Disease, 2018, 9: 661.
[53] Song M Q, Yin S Y, Zhao R, et al. (S)-10-hydroxycamptothecin inhibits esophageal squamous cell carcinoma growth in vitro and in vivo via decreasing topoisomerase I enzyme activity. Cancers, 2019, 11(12): 1964.
doi: 10.3390/cancers11121964
[54] Hynes R O. Integrins: bidirectional, allosteric signaling machines. Cell, 2002, 110(6): 673-687.
doi: 10.1016/S0092-8674(02)00971-6
[55] Fan Z, Chang Y, Cui C C, et al. Near infrared fluorescent peptide nanoparticles for enhancing esophageal cancer therapeutic efficacy. Nature Communications, 2018, 9: 2605.
doi: 10.1038/s41467-018-04763-y
[56] Hussain M, le Moulec S, Gimmi C, et al. Differential effect on bone lesions of targeting integrins: randomized phase II trial of abituzumab in patients with metastatic castration-resistant prostate cancer. Clinical Cancer Research: an Official Journal of the American Association for Cancer Research, 2016, 22(13): 3192-3200.
doi: 10.1158/1078-0432.CCR-15-2512
[57] Vane J, Botting R. Mechanism of action of antiinflammatory drugs. Adv Exp Med Biol, 1997, 433:131-138.
pmid: 9561120
[58] Liu F F, Wu Q, Han W, et al. Targeting integrin αvβ 3 with indomethacin inhibits patient-derived xenograft tumour growth and recurrence in oesophageal squamous cell carcinoma. Clinical and Translational Medicine, 2021, 11(10): e548.
[59] He S M, Zhao C Y, Tao H Y, et al. A recombinant scFv antibody-based fusion protein that targets EGFR associated with IMPDH 2 downregulation and its drug conjugate show therapeutic efficacy against esophageal cancer. Drug Delivery, 2022, 29(1): 1243-1256.
doi: 10.1080/10717544.2022.2063454
[60] Zhu H T, Wang C Y, Wang J J, et al. A subset of esophageal squamous cell carcinoma patient-derived xenografts respond to cetuximab, which is predicted by high EGFR expression and amplification. Journal of Thoracic Disease, 2018, 10(9): 5328-5338.
doi: 10.21037/jtd.2018.09.18
[61] Yang Y M, Hong P, Xu W W, et al. Advances in targeted therapy for esophageal cancer. Signal Transduction and Targeted Therapy, 2020, 5: 229.
doi: 10.1038/s41392-020-00323-3 pmid: 33028804
[62] Ren Y X, Zheng J M, Fan S M, et al. Anti-tumor efficacy of theliatinib in esophageal cancer patient-derived xenografts models with epidermal growth factor receptor (EGFR) overexpression and gene amplification. Oncotarget, 2017, 8(31): 50832-50844.
doi: 10.18632/oncotarget.17243
[63] Liu Z T, Chen Z H, Wang J Y, et al. Mouse avatar models of esophageal squamous cell carcinoma proved the potential for EGFR-TKI afatinib and uncovered Src family kinases involved in acquired resistance. Journal of Hematology & Oncology, 2018, 11(1): 109.
[64] Chong C R, Jänne P A. The quest to overcome resistance to EGFR-targeted therapies in cancer. Nature Medicine, 2013, 19(11): 1389-1400.
doi: 10.1038/nm.3388
[65] Ebbing E A, Medema J P, Damhofer H, et al. ADAM10-mediated release of heregulin confers resistance to trastuzumab by activating HER3. Oncotarget, 2016, 7(9): 10243-10254.
doi: 10.18632/oncotarget.7200 pmid: 26863569
[66] Wu X H, Zhang J C, Zhen R H, et al. Trastuzumab anti-tumor efficacy in patient-derived esophageal squamous cell carcinoma xenograft (PDECX) mouse models. Journal of Translational Medicine, 2012, 10: 180.
doi: 10.1186/1479-5876-10-180
[67] Zhang J C, Jiang D X, Li X J, et al. Establishment and characterization of esophageal squamous cell carcinoma patient-derived xenograft mouse models for preclinical drug discovery. Laboratory Investigation, 2014, 94(8): 917-926.
doi: 10.1038/labinvest.2014.77
[68] Hou W M, Qin X, Zhu X H, et al. Lapatinib inhibits the growth of esophageal squamous cell carcinoma and synergistically interacts with 5-fluorouracil in patient-derived xenograft models. Oncology Reports, 2013, 30(2): 707-714.
doi: 10.3892/or.2013.2500
[69] Pahl R, Brunke G, Steubesand N, et al. IL-1β and ADAM 17 are central regulators of β-defensin expression in Candida esophagitis. American Journal of Physiology Gastrointestinal and Liver Physiology, 2011, 300(4): G547-G553.
doi: 10.1152/ajpgi.00251.2010
[70] Liu H B, Zhu Y, Yang Q C, et al. Expression and clinical significance of ADAM 17 protein in esophageal squamous cell carcinoma. Genetics and Molecular Research: GMR, 2015, 14(2): 4391-4398.
doi: 10.4238/2015.April.30.12
[71] Gao L, Liu H, Xu R, et al. ADAM17 and NF-kappaB p 65 form a positive feedback loop that facilitates human esophageal squamous cell carcinoma cell viability. Int J Clin Exp Pathol, 2021, 14(7):845-854.
[72] Rios-Doria J, Sabol D, Chesebrough J, et al. A monoclonal antibody to ADAM 17 inhibits tumor growth by inhibiting EGFR and non-EGFR-mediated pathways. Molecular Cancer Therapeutics, 2015, 14(7): 1637-1649.
doi: 10.1158/1535-7163.MCT-14-1040 pmid: 25948294
[73] Nishigaki T, Takahashi T, Serada S, et al. Anti-glypican-1 antibody-drug conjugate is a potential therapy against pancreatic cancer. British Journal of Cancer, 2020, 122(9): 1333-1341.
doi: 10.1038/s41416-020-0781-2 pmid: 32152502
[74] Li J, Chen Y J, Zhan C, et al. Glypican-1 promotes tumorigenesis by regulating the PTEN/Akt/β-catenin signaling pathway in esophageal squamous cell carcinoma. Digestive Diseases and Sciences, 2019, 64(6): 1493-1502.
doi: 10.1007/s10620-019-5461-9
[75] Hara H, Takahashi T, Serada S, et al. Overexpression of glypican-1 implicates poor prognosis and their chemoresistance in oesophageal squamous cell carcinoma. British Journal of Cancer, 2016, 115(1): 66-75.
doi: 10.1038/bjc.2016.183
[76] Harada E, Serada S, Fujimoto M, et al. Glypican-1 targeted antibody-based therapy induces preclinical antitumor activity against esophageal squamous cell carcinoma. Oncotarget, 2017, 8(15): 24741-24752.
doi: 10.18632/oncotarget.15799 pmid: 28445969
[77] Birrer M J, Moore K N, Betella I, et al. Antibody-drug conjugate-based therapeutics: state of the science. JNCI: Journal of the National Cancer Institute, 2019, 111(6): 538-549.
doi: 10.1093/jnci/djz035
[78] Munekage E, Serada S, Tsujii S, et al. A glypican-1-targeted antibody-drug conjugate exhibits potent tumor growth inhibition in glypican-1-positive pancreatic cancer and esophageal squamous cell carcinoma. Neoplasia, 2021, 23(9): 939-950.
doi: 10.1016/j.neo.2021.07.006 pmid: 34332450
[79] Apicella M, Migliore C, Capelôa T, et al. Dual MET/EGFR therapy leads to complete response and resistance prevention in a MET-amplified gastroesophageal xenopatient cohort. Oncogene, 2017, 36(9): 1200-1210.
doi: 10.1038/onc.2016.283 pmid: 27524418
[80] Liu J, Liu Z X, Wu Q N, et al. Long noncoding RNA AGPG regulates PFKFB3-mediated tumor glycolytic reprogramming. Nature Communications, 2020, 11: 1507.
doi: 10.1038/s41467-020-15112-3
[81] Sugase T, Takahashi T, Serada S, et al. Suppressor of cytokine signaling-1 gene therapy induces potent antitumor effect in patient-derived esophageal squamous cell carcinoma xenograft mice. International Journal of Cancer, 2017, 140(11): 2608-2621.
doi: 10.1002/ijc.30666
[82] Liu X J, Song M Q, Wang P L, et al. Targeted therapy of the AKT kinase inhibits esophageal squamous cell carcinoma growth in vitro and in vivo. International Journal of Cancer, 2019, 145(4): 1007-1019.
doi: 10.1002/ijc.32285
[83] Liu A B, Zhu J R, Wu G Y, et al. Antagonizing miR-455-3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinoma. Molecular Cancer, 2017, 16(1): 106.
doi: 10.1186/s12943-017-0669-9
[84] Mizumoto A, Ohashi S, Kamada M, et al. Combination treatment with highly bioavailable curcumin and NQO 1 inhibitor exhibits potent antitumor effects on esophageal squamous cell carcinoma. Journal of Gastroenterology, 2019, 54(8): 687-698.
doi: 10.1007/s00535-019-01549-x pmid: 30737573
[85] 张琪琪, 刘清, 郑树涛, 等. NSC74859对食管鳞状细胞癌人源肿瘤异种移植模型的抗肿瘤作用研究. 新疆医科大学学报, 2021, 44(5): 528-533.
Zhang Q Q, Liu Q, Zheng S T, et al. Antitumor effect of NSC 74859 on patient-derived tumor xenograft of esophageal squamous cell carcinoma. Journal of Xinjiang Medical University, 2021, 44(5): 528-533.
[86] Zhang Z F, Zhang C Y, Miao J X, et al. A tumor-targeted replicating oncolytic adenovirus ad-TD-nsIL 12 as a promising therapeutic agent for human esophageal squamous cell carcinoma. Cells, 2020, 9(11): 2438.
doi: 10.3390/cells9112438
[87] Veeranki O L, Tong Z M, Dokey R, et al. Targeting cyclin-dependent kinase 9 by a novel inhibitor enhances radiosensitization and identifies Axl as a novel downstream target in esophageal adenocarcinoma. Oncotarget, 2019, 10(45): 4703-4718.
doi: 10.18632/oncotarget.27095 pmid: 31384397
[88] Su D, Zhang D D, Jin J Y, et al. Identification of predictors of drug sensitivity using patient-derived models of esophageal squamous cell carcinoma. Nature Communications, 2019, 10: 5076.
doi: 10.1038/s41467-019-12846-7
[89] Liu F F, Zu X Y, Xie X M, et al. Ethyl gallate as a novel ERK1/ 2 inhibitor suppresses patient-derived esophageal tumor growth. Molecular Carcinogenesis, 2019, 58(4): 533-543.
doi: 10.1002/mc.22948
[90] Wang Z Q, da Silva T G, Jin K, et al. Notch signaling drives stemness and tumorigenicity of esophageal adenocarcinoma. Cancer Research, 2014, 74(21): 6364-6374.
doi: 10.1158/0008-5472.CAN-14-2051
[91] Xuan Y J, Sheng Y Q, Zhang D Q, et al. Targeting CD276 by CAR-T cells induces regression of esophagus squamous cell carcinoma in xenograft mouse models. Translational Oncology, 2021, 14(8): 101138.
doi: 10.1016/j.tranon.2021.101138
[92] Hu Y M, Liu F F, Jia X C, et al. Periplogenin suppresses the growth of esophageal squamous cell carcinoma in vitro and in vivo by targeting STAT3. Oncogene, 2021, 40(23): 3942-3958.
doi: 10.1038/s41388-021-01817-2
[93] Bao Z, Li A, Lu X B, et al. Oxethazaine inhibits esophageal squamous cell carcinoma proliferation and metastasis by targeting aurora kinase A. Cell Death & Disease, 2022, 13: 189.
[94] Xing H, Gao M S, Wang Y X, et al. Genome-wide gain-of-function screening identifies EZH 2 mediating resistance to PI3Kα inhibitors in oesophageal squamous cell carcinoma. Clinical and Translational Medicine, 2022, 12(5): e835.
[95] Shi J H, Li Y Y, Jia R B, et al. The fidelity of cancer cells in PDX models: Characteristics, mechanism and clinical significance. International Journal of Cancer, 2020, 146(8): 2078-2088.
doi: 10.1002/ijc.32662
[96] Miao J X, Wang J Y, Li H Z, et al. Promising xenograft animal model recapitulating the features of human pancreatic cancer. World Journal of Gastroenterology, 2020, 26(32): 4802-4816.
doi: 10.3748/wjg.v26.i32.4802
[97] 宋松, 祝献民, 范国平. 免疫缺陷大鼠模型的研究进展. 自然杂志, 2021, 43(5): 365-373.
Song S, Zhu X M, Fan G P. Recent progress in development of immunodeficient rat models. Chinese Journal of Nature, 2021, 43(5): 365-373.
[98] Lynch M, Ackerman M S, Gout J F, et al. Genetic drift, selection and the evolution of the mutation rate. Nature Reviews Genetics, 2016, 17(11): 704-714.
doi: 10.1038/nrg.2016.104
[1] 安龙飞, 金龙, 孙凤亮, 李凯, 闫成智, 秦钧, 张普民, 吴琛, 陈欢. 应用蛋白质组学筛选宫颈癌患者尿液中的肿瘤标志物[J]. 中国生物工程杂志, 2016, 36(9): 1-10.
[2] 王康, 贺春, 高伟, 王斌全, 王晓霞. IQGAP1基因干扰对人食管癌细胞同质粘附能力的影响[J]. 中国生物工程杂志, 2014, 34(9): 24-30.
[3] 邓孟垚, 曹亚. 血清分泌蛋白质组学在肿瘤中的研究进展[J]. 中国生物工程杂志, 2010, 30(11): 83-87.
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