{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T06:58:01Z","timestamp":1778309881820,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T00:00:00Z","timestamp":1468540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81373315"],"award-info":[{"award-number":["81373315"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81472536"],"award-info":[{"award-number":["81472536"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2016,10]]},"abstract":"Objective<\/jats:title>To evaluate the antitumor effects of fusion protein hGrB<\/jats:styled-content>\u2010TV<\/jats:styled-content> of human granzyme B (hGrB<\/jats:styled-content>) and truncated vascular endothelial growth factor (tVEGF<\/jats:styled-content>) on human oral squamous cell carcinoma (OSCC<\/jats:styled-content>) in\u00a0vitro<\/jats:italic> and in\u00a0vivo<\/jats:italic>.<\/jats:p><\/jats:sec>Methods<\/jats:title>The fusion protein hGrB<\/jats:styled-content>\u2010TV<\/jats:styled-content> was expressed and purified from E.\u00a0coli<\/jats:italic> bacteria by affinity chromatography. The cytotoxcity of hGrB<\/jats:styled-content>\u2010TV<\/jats:styled-content> on VEGFR<\/jats:styled-content>\u20102 (Flk\u20101)+<\/jats:sup> OSCC<\/jats:styled-content>\u00a0cells was analyzed in\u00a0vitro<\/jats:italic>. The antitumor therapeutic study was conducted on OSCC<\/jats:styled-content> xenografts in\u00a0vivo<\/jats:italic>.<\/jats:p><\/jats:sec>Results<\/jats:title>The purified hGrB<\/jats:styled-content>\u2010TV<\/jats:styled-content> fusion protein was selectively internalized into VEGFR<\/jats:styled-content>\u20102 (Flk\u20101)+<\/jats:sup> OSCC<\/jats:styled-content> cells\u00a0and endothelial cells. It can cleave inactive caspase 3 into its active p20 form. The hGrB<\/jats:styled-content>\u2010TV<\/jats:styled-content> showed dose\u2010dependent cytotoxicity on VEGFR<\/jats:styled-content>\u20102+<\/jats:sup> SCC<\/jats:styled-content>\u20109 cells. The morphological changes and cytolysis were appeared within dozen minutes. However, no cytotoxicity was observed on VEGFR<\/jats:styled-content>\u20102\u2212<\/jats:sup> cells. The hGrB<\/jats:styled-content> alone or tVEGF<\/jats:styled-content> alone did not have any toxicity on SCC<\/jats:styled-content>\u20109 cells. In addition, hGrB<\/jats:styled-content>\u2010TV<\/jats:styled-content> treatment completely destroyed the vasculature of the chick chorioallantoic membrane (CAM<\/jats:styled-content>) in\u00a0vivo<\/jats:italic> and consequently led to chick embryo development arrest. Most importantly, the fusion protein hGrB<\/jats:styled-content>\u2010TV<\/jats:styled-content> inhibited tumor angiogenesis and growth of human\u00a0OSCC<\/jats:styled-content> xenografts in nude mice without any apparent toxicity.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>The fusion protein hGrB<\/jats:styled-content>\u2010TV<\/jats:styled-content> specifically inhibits angiogenesis and tumor growth of OSCC<\/jats:styled-content>; hGrB<\/jats:styled-content>\u2010TV<\/jats:styled-content> is a powerful and safe therapeutic molecule for tumor therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/odi.12522","type":"journal-article","created":{"date-parts":[[2016,6,13]],"date-time":"2016-06-13T07:16:48Z","timestamp":1465802208000},"page":"688-696","source":"Crossref","is-referenced-by-count":11,"title":["Granzyme B\u2010truncated VEGF<\/scp> fusion protein represses angiogenesis and tumor growth of OSCC<\/scp>"],"prefix":"10.1111","volume":"22","author":[{"given":"X\u2010Z","family":"Lv","sequence":"first","affiliation":[{"name":"Department Oral &\u00a0Head and Neck Surgery Nan Fang Hospital Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u2010Y","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Cell Biology School of Basic Medicine Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Z\u2010Q","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Cell Biology School of Basic Medicine Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department Oral &\u00a0Head and Neck Surgery Nan Fang Hospital Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology School of Basic Medicine Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W\u2010S","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Cell Biology School of Basic Medicine Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,7,15]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"230","volume-title":"Methods in Enzymology","author":"Abelson JN","year":"1995"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80550-6"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-015-3454-7"},{"key":"e_1_2_7_5_1","first-page":"183","article-title":"Vascular endothelial growth factor chimeric toxin is highly active against endothelial cells","volume":"59","author":"Arora N","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.33.21261"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2126(03)00256-X"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.5566\/ias.v24.p169-180"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/377446a0"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.36.21709"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81810-3"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.10.5519"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.10.5638"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2010.00894.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(04)00187-5"},{"key":"e_1_2_7_16_1","first-page":"1341","article-title":"Targeted delivery of human pro\u2010apoptotic enzymes to tumor\u00a0cells: in\u00a0vitro studies describing a novel class of recombinant\u00a0highly cytotoxic agents","volume":"2","author":"Liu Y","year":"2003","journal-title":"Mol Cancer Ther"},{"key":"e_1_2_7_17_1","first-page":"949","article-title":"Mechanistic\u00a0studies of a novel human fusion toxin composed of vascular\u00a0endothelial growth factor (VEGF)121 and the serine protease\u00a0granzyme B: directed apoptotic events in vascular endothelial\u00a0cells","volume":"2","author":"Liu Y","year":"2003","journal-title":"Mol Cancer Ther"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830271250"},{"key":"e_1_2_7_19_1","first-page":"4185","article-title":"Tumor growth modulation by sense and antisense vascular endothelial growth factor gene expression: effects on angiogenesis, vascular permeability, blood volume, blood flow, fluorodeoxyglucose uptake, and proliferation of human melanoma intracerebral xenografts","volume":"58","author":"Oku T","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2014.12.030"},{"key":"e_1_2_7_21_1","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1182\/blood.V92.3.1044","article-title":"Entry and trafficking of granzyme B in target cells during granzyme\u00a0B\u2010perforin\u2010mediated apoptosis","volume":"92","author":"Pinkoski MJ","year":"1998","journal-title":"Blood"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056836"},{"key":"e_1_2_7_23_1","first-page":"1189","article-title":"The chick embryo chorioallantoic\u00a0membrane as a model for in\u00a0vivo research on angiogenesis","volume":"40","author":"Ribatti D","year":"1996","journal-title":"Int J Dev Biol"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.12.3101"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.5.855"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24028"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-0554"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.8.1323"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.2.603"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.122157899"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M312648200"}],"container-title":["Oral Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fodi.12522","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/odi.12522","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T20:54:28Z","timestamp":1695761668000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/odi.12522"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,15]]},"references-count":30,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1111\/odi.12522"],"URL":"https:\/\/doi.org\/10.1111\/odi.12522","archive":["Portico"],"relation":{},"ISSN":["1354-523X","1601-0825"],"issn-type":[{"value":"1354-523X","type":"print"},{"value":"1601-0825","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,15]]}}}