{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:23:37Z","timestamp":1790882617164,"version":"4.1.0"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T00:00:00Z","timestamp":1524009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T00:00:00Z","timestamp":1524009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Princess Alexandra Hospital Research Foundation"},{"name":"Queensland Head and Neck Cancer Centre"},{"name":"QBiotics Ltd"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Invest New Drugs"],"published-print":{"date-parts":[[2019,2,15]]},"abstract":"<jats:title>Summary<\/jats:title>\n          <jats:p>The five-year survival rate for patients with head and neck squamous cell carcinoma (HNSCC) has remained at ~50% for the past 30\u00a0years despite advances in treatment. Tigilanol tiglate (TT, also known as EBC-46) is a novel diterpene ester that induces cell death in HNSCC in vitro and in mouse models, and has recently completed Phase I human clinical trials. The aim of this study was to optimise efficacy of TT treatment by altering different administration parameters. The tongue SCC cell line (SCC-15) was identified as the line with the lowest efficacy to treatment. Subcutaneous xenografts of SCC-15 cells were grown in BALB\/c <jats:italic>Foxn1<\/jats:italic><jats:sup>nu<\/jats:sup> and NOD\/SCID mice and treated with intratumoral injection of 30 \u03bcg TT or a vehicle only control (40% propylene glycol (PG)). Greater efficacy of TT treatment was found in the BALB\/c <jats:italic>Foxn1<\/jats:italic><jats:sup><jats:italic>nu<\/jats:italic><\/jats:sup> mice compared to NOD\/SCID mice. Immunohistochemical analysis indicated a potential role of the host\u2019s innate immune system in this difference, specifically neutrophil infiltration. Neither fractionated doses of TT nor the use of a different excipiant led to significantly increased efficacy. This study confirmed that TT in 40% PG given intratumorally as a single bolus dose was the most efficacious treatment for a tongue SCC mouse model.<\/jats:p>","DOI":"10.1007\/s10637-018-0604-y","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T02:35:08Z","timestamp":1524018908000},"page":"1-8","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Optimising intratumoral treatment of head and neck squamous cell carcinoma models with the diterpene ester Tigilanol tiglate"],"prefix":"10.1007","volume":"37","author":[{"given":"Catherine M. E.","family":"Barnett","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasa","family":"Broit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Yi","family":"Yap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason K.","family":"Cullen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G.","family":"Parsons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedict J.","family":"Panizza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glen M.","family":"Boyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,4,18]]},"reference":[{"key":"604_CR1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.3322\/caac.20107","volume":"61","author":"A Jemal","year":"2011","unstructured":"Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69\u201390","journal-title":"CA Cancer J Clin"},{"key":"604_CR2","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1002\/ijc.28112","volume":"133","author":"P Bose","year":"2013","unstructured":"Bose P, Brockton NT, Dort JC (2013) Head and neck cancer: from anatomy to biology. Int J Cancer 133:2013\u20132023","journal-title":"Int J Cancer"},{"key":"604_CR3","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1097\/01.cco.0000264952.98166.99","volume":"19","author":"D Murdoch","year":"2007","unstructured":"Murdoch D (2007) Standard, and novel cytotoxic and molecular-targeted, therapies for HNSCC: an evidence-based review. Curr Opin Oncol 19:216\u2013221","journal-title":"Curr Opin Oncol"},{"key":"604_CR4","doi-asserted-by":"publisher","first-page":"e108887","DOI":"10.1371\/journal.pone.0108887","volume":"9","author":"GM Boyle","year":"2014","unstructured":"Boyle GM, D'Souza MM, Pierce CJ, Adams RA, Cantor AS et al (2014) Intra-lesional injection of the novel PKC activator EBC-46 rapidly ablates tumors in mouse models. PLoS One 9:e108887","journal-title":"PLoS One"},{"key":"604_CR5","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.ijpharm.2012.06.055","volume":"453","author":"SV Kurkov","year":"2013","unstructured":"Kurkov SV, Loftsson T (2013) Cyclodextrins. Int J Pharm 453:167\u2013180","journal-title":"Int J Pharm"},{"key":"604_CR6","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1002\/hed.10261","volume":"25","author":"DJ Castro","year":"2003","unstructured":"Castro DJ, Sridhar KS, Garewal HS, Mills GM, Wenig BL, Dunphy FR, Costantino PD, Leavitt RD, Stewart ME, Orenberg EK (2003) Intratumoral cisplatin\/epinephrine gel in advanced head and neck cancer: a multicenter, randomized, double-blind, phase III study in North America. Head Neck 25:717\u2013731","journal-title":"Head Neck"},{"key":"604_CR7","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1089\/pho.2005.23.531","volume":"23","author":"MB Paiva","year":"2005","unstructured":"Paiva MB, Bublik M, Castro DJ, Udewitz M, Wang MB, Kowalski LP, Sercarz J (2005) Intratumor injections of cisplatin and laser thermal therapy for palliative treatment of recurrent cancer. Photomed Laser Surg 23:531\u2013535","journal-title":"Photomed Laser Surg"},{"key":"604_CR8","doi-asserted-by":"publisher","first-page":"2354","DOI":"10.1002\/ijc.23756","volume":"123","author":"CM van Herpen","year":"2008","unstructured":"van Herpen CM, van der Voort R, van der Laak JA, Klasen IS, de Graaf AO et al (2008) Intratumoral rhIL-12 administration in head and neck squamous cell carcinoma patients induces B cell activation. Int J Cancer 123:2354\u20132361","journal-title":"Int J Cancer"},{"key":"604_CR9","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1200\/JCO.2001.19.2.289","volume":"19","author":"J Nemunaitis","year":"2001","unstructured":"Nemunaitis J, Khuri F, Ganly I, Arseneau J, Posner M, Vokes E, Kuhn J, McCarty T, Landers S, Blackburn A, Romel L, Randlev B, Kaye S, Kirn D (2001) Phase II trial of intratumoral administration of ONYX-015, a replication-selective adenovirus, in patients with refractory head and neck cancer. J Clin Oncol 19:289\u2013298","journal-title":"J Clin Oncol"},{"key":"604_CR10","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1080\/00016480600702100","volume":"126","author":"Y Fujimoto","year":"2006","unstructured":"Fujimoto Y, Mizuno T, Sugiura S, Goshima F, Kohno S et al (2006) Intratumoral injection of herpes simplex virus HF10 in recurrent head and neck squamous cell carcinoma. Acta Otolaryngol 126:1115\u20131117","journal-title":"Acta Otolaryngol"},{"key":"604_CR11","doi-asserted-by":"crossref","first-page":"180","DOI":"10.4049\/jimmunol.154.1.180","volume":"154","author":"LD Shultz","year":"1995","unstructured":"Shultz LD, Schweitzer PA, Christianson SW, Gott B, Schweitzer IB et al (1995) Multiple defects in innate and adaptive immunologic function in NOD\/LtSz-scid mice. J Immunol 154:180\u2013191","journal-title":"J Immunol"},{"key":"604_CR12","doi-asserted-by":"publisher","first-page":"4600","DOI":"10.1158\/1078-0432.CCR-09-0090","volume":"15","author":"TY Juan","year":"2009","unstructured":"Juan TY, Roffler SR, Hou HS, Huang SM, Chen KC, Leu YL, Prijovich ZM, Yu CP, Wu CC, Sun GH, Cha TL (2009) Antiangiogenesis targeting tumor microenvironment synergizes glucuronide prodrug antitumor activity. Clin Cancer Res 15:4600\u20134611","journal-title":"Clin Cancer Res"}],"container-title":["Investigational New Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-018-0604-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10637-018-0604-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-018-0604-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,11]],"date-time":"2023-03-11T18:27:30Z","timestamp":1678559250000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10637-018-0604-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,18]]},"references-count":12,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,2,15]]}},"alternative-id":["604"],"URL":"https:\/\/doi.org\/10.1007\/s10637-018-0604-y","relation":{},"ISSN":["0167-6997","1573-0646"],"issn-type":[{"value":"0167-6997","type":"print"},{"value":"1573-0646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,18]]},"assertion":[{"value":"15 March 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 April 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"Peter G. Parsons declares consulting payments and contract research funding from QBiotics Ltd. Benedict J. Panizza declares consulting payments from QBiotics Ltd. Glen M. Boyle declares he was a recipient of a fellowship co-sponsored by QBiotics Ltd. and contract research funding from QBiotics Ltd. For the remaining authors no conflicts of interest were declared.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This article does not contain any studies with human participants performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"For this type of study, informed consent is not required.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}