核酸适配体技术在胰腺癌诊断和治疗中的应用
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摘要
胰腺癌因其早期无特异性体征和症状,难以实现早期诊断,且由于缺乏有效的治疗手段,是目前死亡率最高的癌症之一,因此实现胰腺癌的早期诊断和有效治疗具有重大意义。核酸适配体是通过指数富集的配体系统进化技术筛选得到的具有高亲和性、高特异性,可识别靶标分子的寡核苷酸片段,具有类似抗体的特点。核酸适配体因其良好的特性,近年来成为研究的热点。目前已有多个可识别胰腺癌的核酸适配体被报道,有望实现癌症的早期诊断。核酸适配体偶联药物也是目前热门的研究方向,可提高胰腺癌治疗药物的靶向治疗能力。本文简要介绍核酸适配体技术的进展,并就其在胰腺癌早期诊断和治疗中的应用做一介绍。
引文
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[4]Rialon KL,White RR.Aptamers:potential applications to pancreatic cancer therapy[J].Anticancer Agents Med Chem,2011,11(5):434-441.
[5]Mayer G.The chemical biology of aptamers[J].Angew Chem Int Ed Engl,2009,48(15):2672-2689.
[6]Oldfield LE,Connor AA,Gallinger S.Molecular events in the natural history of pancreatic cancer[J].Trends Cancer,2017,3(5):336-346.
[7]Siegel RL,Miller KD,JemaL A.Cancer Statistics,2017[J].CA Cancer J Clin,2017,67(1):7-30.
[8]Hanada K,Okazaki A,Hirano N,et al.Diagnostic strategies for early pancreatic cancer[J].J Gastroenterol,2015,50(2):147-154.
[9]Ballehaninna UK,Chamberlain RS.The clinical utility of serum CA19-9 in the diagnosis,prognosis and management of pancreatic adenocarcinoma:An evidence based appraisal[J].JGastrointest Oncol,2012,3(2):105-119.
[10]Marrelli D,Caruso S,Pedrazzani C,et al.CA19-9 serum levels in obstructive jaundice:clinical value in benign and malignant conditions[J].Am J Surg,2009,198(3):333-339.
[11]Huang PH,Lu PJ,Ding LY,et al.TGFβpromotes mesenchymal phenotype of pancreatic cancer cells,in part,through epigenetic activation of VAV1[J].Oncogene,2017,36(16):2202-2214.
[12]Croker AK,Allan AL.Cancer stem cells:implications for the progression and treatment of metastatic disease[J].J Cell Mol Med,2008,12(2):374-390.
[13]Kim YJ,Lee HS,Jung DE,et al.The DNA aptamer binds stemness-enriched cancer cells in pancreatic cancer[J].J Mol Recognit,2017,30(4).Epub 2016 Nov 28.
[14]Dua P,Sajeesh S,Kim S,et al.ALPPL2 aptamer-mediated targeted delivery of 5-Fluoro-2'-Deoxyuridine to pancreatic cancer[J].Nucleic Acid Ther,2015,25(4):180-187.
[15]Albers GH,Fleuren G,Escribano MJ.Immunohistochemistry of CEA in the human pancreas during development,in the adult,chronic pancreatitis,and pancreatic adenocarcinoma[J].Am J Clin Pathol,1988,90(1):17-22.
[16]Bates PJ,Reyes-Reyes EM,Malik MT,et al.G-quadruplex oligonucleotide AS1411 as a cancer-targeting agent:Uses and mechanisms[J].Biochim Biophys Acta Gen Subj,2017,1861(5 Pt B):1414-28.
[17]Bates PJ,Laber DA,Miller DM,et al.Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer[J].Exp Mol Pathol,2009,86(3):151-164.
[18]Park JY,Cho YL,Chae JR,et al.Gemcitabine-incorporated gquadruplex aptamer for targeted drug delivery into pancreas cancer[J].Mol Ther Nucleic Acids,2018,12:543-553.
[19]Ray P,Cheek MA,Sharaf ML,et al.Aptamer-mediated delivery of chemotherapy to pancreatic cancer cells[J].Nucleic Acid Ther,2012,22(5):295-305.
[20]Yoon S,Huang KW,Reebye V,et al.Aptamer-drug conjugates of active metabolites of nucleoside analogs and cytotoxic agents inhibit pancreatic tumor cell growth[J].Mol Ther Nucleic Acids,2017,6:80-88.
[21]Chu GC,Kimmelman AC,Hezel AF,et al.Stromal biology of pancreatic cancer[J].J Cell Biochem,2007,101(4):887-907.
[22]Bj?rnmalm M,Thurecht KJ,Michael M,et al.Bridging bionano science and cancer nanomedicine[J].ACS Nano,2017,11(10):9594-9613.
[23]He X,Chen X,Liu L,et al.Sequentially triggered nanoparticles with tumor penetration and intelligent drug release for pancreatic cancer therapy[J].Adv Sci(Weinh),2018,5(5):1701070.
[24]Healy JM,Lewis SD,Kurz M,et al.Pharmacokinetics and biodistribution of novel aptamer compositions[J].Pharm Res,2004,21(12):2234-2246.
[25]Burmeister PE,Lewis SD,Silva RF,et al.Direct in vitro selection of a 2'-O-methyl aptamer to VEGF[J].Chem Biol,2005,12(1):25-33.
[26]韩冬梅,邓叶茂.核酸适配体在胰腺癌中的应用研究进展[J].生命科学研究,2018,22(4):332-337.