{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T08:03:25Z","timestamp":1782288205331,"version":"3.54.5"},"reference-count":42,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Biological Macromolecules"],"published-print":{"date-parts":[[2022,2]]},"DOI":"10.1016\/j.ijbiomac.2022.01.015","type":"journal-article","created":{"date-parts":[[2022,1,8]],"date-time":"2022-01-08T02:03:40Z","timestamp":1641607420000},"page":"298-306","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["Targeting and neutralizing human epididymis protein 4 by novel nanobodies to suppress ovarian cancer cells and attenuate cisplatin resistance"],"prefix":"10.1016","volume":"199","author":[{"given":"Jianli","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haipeng","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Nian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiying","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenshuai","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.ijbiomac.2022.01.015_bb0005","first-page":"7","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. Clin."},{"issue":"18","key":"10.1016\/j.ijbiomac.2022.01.015_bb0010","doi-asserted-by":"crossref","first-page":"5404","DOI":"10.7150\/jca.57880","article-title":"A promising diagnosis biomarker of ovarian cancer","volume":"12","author":"Zhang","year":"2021","journal-title":"J. Cancer"},{"issue":"9","key":"10.1016\/j.ijbiomac.2022.01.015_bb0015","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1080\/14737140.2017.1360138","article-title":"The role of novel biomarker HE4 in the diagnosis, prognosis and follow-up of ovarian cancer: a systematic review","volume":"17","author":"Scaletta","year":"2017","journal-title":"Expert. Rev. Anticancer. Ther."},{"key":"10.1016\/j.ijbiomac.2022.01.015_bb0020","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.cca.2021.11.018","article-title":"A combined strategy of TK1, HE4 and CA125 shows better diagnostic performance than risk of ovarian malignancy algorithm (ROMA) in ovarian carcinoma","volume":"524","author":"Zhu","year":"2022","journal-title":"Clin. Chim. Acta"},{"issue":"1","key":"10.1016\/j.ijbiomac.2022.01.015_bb0025","doi-asserted-by":"crossref","first-page":"21945","DOI":"10.1038\/s41598-021-01544-4","article-title":"Recurrence monitoring for ovarian cancer using a cell phone-integrated paper device to measure the ovarian cancer biomarker HE4\/CRE ratio in urine","volume":"11","author":"Kight","year":"2021","journal-title":"Sci. Rep."},{"issue":"1","key":"10.1016\/j.ijbiomac.2022.01.015_bb0030","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13048-019-0503-7","article-title":"Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review","volume":"12","author":"Dochez","year":"2019","journal-title":"J. Ovarian Res."},{"issue":"9","key":"10.1016\/j.ijbiomac.2022.01.015_bb0035","doi-asserted-by":"crossref","first-page":"bio043570","DOI":"10.1242\/bio.043570","article-title":"Knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK\/STAT3 pathway","volume":"8","author":"Wang","year":"2019","journal-title":"Biol. Open"},{"issue":"1","key":"10.1016\/j.ijbiomac.2022.01.015_bb0040","doi-asserted-by":"crossref","first-page":"403","DOI":"10.3892\/or.2014.3549","article-title":"Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells","volume":"33","author":"Wang","year":"2015","journal-title":"Oncol. Rep."},{"issue":"1","key":"10.1016\/j.ijbiomac.2022.01.015_bb0045","doi-asserted-by":"crossref","first-page":"729","DOI":"10.18632\/oncotarget.6327","article-title":"Overexpression of HE4 (human epididymis protein 4) enhances proliferation, invasion and metastasis of ovarian cancer","volume":"7","author":"Zhu","year":"2016","journal-title":"Oncotarget"},{"issue":"4","key":"10.1016\/j.ijbiomac.2022.01.015_bb0050","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S1995-7645(13)60055-3","article-title":"Effect of WFDC 2 silencing on the proliferation, motility and invasion of human serous ovarian cancer cells in vitro","volume":"6","author":"Zhu","year":"2013","journal-title":"Asian Pac. J. Trop. Med."},{"key":"10.1016\/j.ijbiomac.2022.01.015_bb0055","doi-asserted-by":"crossref","first-page":"3574","DOI":"10.1038\/srep03574","article-title":"HE4 (WFDC2) gene overexpression promotes ovarian tumor growth","volume":"4","author":"Moore","year":"2014","journal-title":"Sci. Rep."},{"issue":"1","key":"10.1016\/j.ijbiomac.2022.01.015_bb0060","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13048-016-0240-0","article-title":"HE4 promotes collateral resistance to cisplatin and paclitaxel in ovarian cancer cells","volume":"9","author":"Ribeiro","year":"2016","journal-title":"J. Ovarian Res."},{"issue":"1","key":"10.1016\/j.ijbiomac.2022.01.015_bb0065","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1111\/jog.13181","article-title":"Role of human epididymis protein 4 in chemoresistance and prognosis of epithelial ovarian cancer","volume":"43","author":"Lee","year":"2017","journal-title":"J. Obstet. Gynaecol. Res."},{"issue":"1","key":"10.1016\/j.ijbiomac.2022.01.015_bb0070","doi-asserted-by":"crossref","first-page":"496","DOI":"10.3892\/mmr.2021.12135","article-title":"Human epididymis protein 4 promotes P-glycoprotein-mediated chemoresistance in ovarian cancer cells through interactions with annexin II","volume":"24","author":"Liu","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.ijbiomac.2022.01.015_bb0075","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1186\/1476-4598-13-243","article-title":"Human epididymis protein 4 in association with annexin II promotes invasion and metastasis of ovarian cancer cells","volume":"13","author":"Zhuang","year":"2014","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.ijbiomac.2022.01.015_bb0080","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/s12935-019-0864-4","article-title":"Interaction of HE4 and ANXA2 exists in various malignant cells\u2014HE4\u2013ANXA2\u2013MMP2 protein complex promotes cell migration","volume":"19","author":"Wang","year":"2019","journal-title":"Cancer Cell Int."},{"key":"10.1016\/j.ijbiomac.2022.01.015_bb0085","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1146\/annurev-biochem-063011-092449","article-title":"Nanobodies: natural single-domain antibodies","volume":"82","author":"Muyldermans","year":"2013","journal-title":"Annu. Rev. Biochem."},{"key":"10.1016\/j.ijbiomac.2022.01.015_bb0090","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev-animal-021419-083831","article-title":"Applications of nanobodies","volume":"9","author":"Muyldermans","year":"2021","journal-title":"Annu. Rev. Anim. Biosci."},{"issue":"1","key":"10.1016\/j.ijbiomac.2022.01.015_bb0095","first-page":"751","article-title":"Production of a mono-biotinylated EGFR nanobody in the E. Coli periplasm using the pET22b vector, BMC res","volume":"11","author":"Noor","year":"2018","journal-title":"Notes"},{"key":"10.1016\/j.ijbiomac.2022.01.015_bb0100","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.pep.2018.11.001","article-title":"An efficient constitutive expression system for anti-CEACAM5 nanobody production in the yeast Pichia pastoris","volume":"155","author":"Chen","year":"2019","journal-title":"Protein Expr. Purif."},{"key":"10.1016\/j.ijbiomac.2022.01.015_bb0105","doi-asserted-by":"crossref","DOI":"10.1016\/j.pep.2020.105607","article-title":"Nanobody production can be simplified by direct secretion from Escherichia coli","volume":"170","author":"Iwaki","year":"2020","journal-title":"Protein Expr. Purif."},{"key":"10.1016\/j.ijbiomac.2022.01.015_bb0110","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.molimm.2018.02.012","article-title":"Recent advances in the selection and identification of antigen-specific nanobodies","volume":"96","author":"Liu","year":"2018","journal-title":"Mol. Immunol."},{"key":"10.1016\/j.ijbiomac.2022.01.015_bb0115","article-title":"Bispecific single-domain antibodies as highly standardized synthetic calibrators for immunodiagnosis","author":"Santos","year":"2021","journal-title":"Anal. Chem."},{"issue":"6530","key":"10.1016\/j.ijbiomac.2022.01.015_bb0120","doi-asserted-by":"crossref","first-page":"eabe6230","DOI":"10.1126\/science.abe6230","article-title":"Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape","volume":"371","author":"Koenig","year":"2021","journal-title":"Science"},{"key":"10.1016\/j.ijbiomac.2022.01.015_bb0125","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.coi.2016.02.003","article-title":"Distinct antibody species: structural differences creating therapeutic opportunities","volume":"40","author":"Muyldermans","year":"2016","journal-title":"Curr. Opin. Immunol."},{"issue":"10","key":"10.1016\/j.ijbiomac.2022.01.015_bb0130","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1128\/AAC.45.10.2807-2812.2001","article-title":"Beta-lactamase inhibitors derived from single-domain antibody fragments elicited in the camelidae","volume":"45","author":"Conrath","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"issue":"11","key":"10.1016\/j.ijbiomac.2022.01.015_bb0135","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1111\/j.1538-7836.2011.04495.x","article-title":"TAFIa inhibiting nanobodies as profibrinolytic tools and discovery of a new TAFIa conformation","volume":"9","author":"Hendrickx","year":"2011","journal-title":"J. Thromb. Haemost."},{"issue":"7514","key":"10.1016\/j.ijbiomac.2022.01.015_bb0140","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/nature13552","article-title":"X-ray structure of the mouse serotonin 5-HT3 receptor","volume":"512","author":"Hassaine","year":"2014","journal-title":"Nature"},{"issue":"3","key":"10.1016\/j.ijbiomac.2022.01.015_bb0145","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nprot.2014.039","article-title":"A general protocol for the generation of nanobodies for structural biology","volume":"9","author":"Pardon","year":"2014","journal-title":"Nat. Protoc."},{"issue":"8","key":"10.1016\/j.ijbiomac.2022.01.015_bb0150","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1007\/s00216-020-02456-4","article-title":"Development of a highly thermostable immunoassay based on a nanobody-alkaline phosphatase fusion protein for carcinoembryonic antigen detection","volume":"412","author":"Lin","year":"2019","journal-title":"Anal. Bioanal. Chem."},{"issue":"23","key":"10.1016\/j.ijbiomac.2022.01.015_bb0155","doi-asserted-by":"crossref","first-page":"5001","DOI":"10.1158\/0008-5472.CAN-15-0563","article-title":"p53: protection against tumor growth beyond effects on cell cycle and apoptosis","volume":"75","author":"Wang","year":"2015","journal-title":"Cancer Res."},{"issue":"3","key":"10.1016\/j.ijbiomac.2022.01.015_bb0160","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1097\/IGC.0000000000000078","article-title":"Human epididymis protein 4 inhibits proliferation of human ovarian cancer cells via the mitogen-activated protein kinase and phosphoinositide 3-kinase\/AKT pathways","volume":"24","author":"Kong","year":"2014","journal-title":"Int. J. Gynecol. Cancer"},{"key":"10.1016\/j.ijbiomac.2022.01.015_bb0165","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.pep.2017.09.005","article-title":"Preparation and characterization of a high-affinity monoclonal antibody against human epididymis protein-4","volume":"141","author":"Shen","year":"2018","journal-title":"Protein Expr. Purif."},{"issue":"4","key":"10.1016\/j.ijbiomac.2022.01.015_bb0170","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s00280-008-0881-9","article-title":"Cancer and the tumor microenvironment: a review of an essential relationship","volume":"63","author":"Mbeunkui","year":"2009","journal-title":"Cancer Chemother. Pharmacol."},{"key":"10.1016\/j.ijbiomac.2022.01.015_bb0175","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1016\/j.celrep.2018.01.053","article-title":"Commonly occurring cell subsets in high-grade serous ovarian tumors identified by single-cell mass cytometry","volume":"22","author":"Gonzalez","year":"2018","journal-title":"Cell Rep."},{"key":"10.1016\/j.ijbiomac.2022.01.015_bb0180","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.ygyno.2012.11.040","article-title":"Can the preoperative HE4 level predict optimal cytoreduction in patients with advanced ovarian carcinoma?","volume":"128","author":"Angioli","year":"2013","journal-title":"Gynecol. Oncol."},{"issue":"7","key":"10.1016\/j.ijbiomac.2022.01.015_bb0185","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1515\/cclm-2017-1176","article-title":"Prognostic value of HE4 in patients with ovarian cancer","volume":"56","author":"Yuan","year":"2018","journal-title":"Clin. Chem. Lab. Med."},{"key":"10.1016\/j.ijbiomac.2022.01.015_bb0190","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ejphar.2014.07.025","article-title":"Cisplatin in cancer therapy: molecular mechanisms of action","volume":"740","author":"Shaloam","year":"2014","journal-title":"Eur. J. Pharmacol."},{"issue":"12","key":"10.1016\/j.ijbiomac.2022.01.015_bb0195","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1007\/s00432-016-2235-z","article-title":"Vitamin C in synergism with cisplatin induces cell death in cervical cancer cells through altered redox cycling and p53 upregulation","volume":"142","author":"Leekha","year":"2016","journal-title":"J. Cancer Res. Clin. Oncol."},{"issue":"30","key":"10.1016\/j.ijbiomac.2022.01.015_bb0200","doi-asserted-by":"crossref","first-page":"49033","DOI":"10.18632\/oncotarget.16931","article-title":"WP1130 attenuates cisplatin resistance by decreasing P53 expression in non-small cell lung carcinomas","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.ijbiomac.2022.01.015_bb0205","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1146\/annurev-med-012017-043332","article-title":"Entering the modern era of gene therapy","volume":"70","author":"Angeula","year":"2019","journal-title":"Annu. Rev. Med."},{"issue":"7735","key":"10.1016\/j.ijbiomac.2022.01.015_bb0210","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1038\/d41586-018-07639-9","article-title":"Gene therapy","volume":"564","author":"Brody","year":"2018","journal-title":"Nature"}],"container-title":["International Journal of Biological Macromolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0141813022000162?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0141813022000162?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T09:20:29Z","timestamp":1758878429000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0141813022000162"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2]]},"references-count":42,"alternative-id":["S0141813022000162"],"URL":"https:\/\/doi.org\/10.1016\/j.ijbiomac.2022.01.015","relation":{},"ISSN":["0141-8130"],"issn-type":[{"value":"0141-8130","type":"print"}],"subject":[],"published":{"date-parts":[[2022,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Targeting and neutralizing human epididymis protein 4 by novel nanobodies to suppress ovarian cancer cells and attenuate cisplatin resistance","name":"articletitle","label":"Article Title"},{"value":"International Journal of Biological Macromolecules","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ijbiomac.2022.01.015","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}