{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T16:43:38Z","timestamp":1782924218161,"version":"3.54.5"},"reference-count":44,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2008,1,25]],"date-time":"2008-01-25T00:00:00Z","timestamp":1201219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2008,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Head and neck squamous cell carcinomas (HNSCC) represent a group of metastasizing tumors with a high mortality rate in man and animals. Since the biomolecule ozone was found to inhibit growth of various carcinoma cells <jats:italic>in vitro<\/jats:italic> we here applied the highly aggressive and lethal VX2 carcinoma HNSCC tumor model of the New Zealand White rabbit to test whether ozone exerts antitumorous effects <jats:italic>in vivo<\/jats:italic>. Therapeutic insufflation of medical ozone\/oxygen (O<jats:sub>3<\/jats:sub>\/O<jats:sub>2<\/jats:sub>) gas mixture into the peritoneum (O<jats:sub>3<\/jats:sub>\/O<jats:sub>2<\/jats:sub>\u2010pneumoperitoneum) at an advanced stage of tumor disease led to a survival rate of 7\/14 rabbits. Six of the seven surviving rabbits presented full tumor regression and the absence of local or distant lung metastases. Insufflation of pure oxygen (O<jats:sub>2<\/jats:sub>) resulted in a survival rate of 3\/13 animals accompanied by full tumor remission in 2 of the 3 surviving animals. Of the 14 sham\u2010treated animals only 1 had spontaneous tumor remission and survived. No adverse effects or changes in standard blood parameters were observed after repeated intraperitoneal insufflations of the O<jats:sub>3<\/jats:sub>\/O<jats:sub>2<\/jats:sub> or O<jats:sub>2<\/jats:sub> gas. Animals with O<jats:sub>3<\/jats:sub>\/O<jats:sub>2<\/jats:sub>\u2010induced tumor eradication developed tolerance against reimplantation of the VX2 tumor. This could be reversed by immune suppression with a combination of dexamethasone and cyclosporin A suggesting an antitumorous effect of O<jats:sub>3<\/jats:sub>\/O<jats:sub>2<\/jats:sub>\u2010mediated activation of the body's own immunosurveillance. Although the exact mechanisms of action are still unclear the present data point to O<jats:sub>3<\/jats:sub>\/O<jats:sub>2<\/jats:sub>\u2010pneumoperitoneum as a promising new strategy in anticancer therapy. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.23382","type":"journal-article","created":{"date-parts":[[2008,1,25]],"date-time":"2008-01-25T18:17:30Z","timestamp":1201285050000},"page":"2360-2367","source":"Crossref","is-referenced-by-count":37,"title":["Treatment with ozone\/oxygen\u2010pneumoperitoneum results in complete remission of rabbit squamous cell carcinomas"],"prefix":"10.1002","volume":"122","author":[{"given":"Siegfried","family":"Schulz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"H\u00e4ussler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Mandic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes T.","family":"Heverhagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Neubauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja A.","family":"D\u00fcnne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen A.","family":"Werner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eberhard","family":"Weihe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,1,25]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"3273","article-title":"Lymphogenic metastatic spread of auricular VX2 carcinoma in New Zealand white rabbits","volume":"22","author":"Dunne AA","year":"2002","journal-title":"Anticancer Res"},{"key":"e_1_2_6_3_2","first-page":"4209","article-title":"The auricular VX2 carcinoma: feasibility of complete tumor resection","volume":"25","author":"Sapundzhiev N","year":"2005","journal-title":"Anticancer Res"},{"key":"e_1_2_6_4_2","first-page":"3523","article-title":"Effect of hyperthermia on the immunocompetence of VX2 tumor\u2010bearing rabbits","volume":"38","author":"Shah SA","year":"1978","journal-title":"Cancer Res"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1054\/jcms.2000.0165"},{"key":"e_1_2_6_6_2","first-page":"3281","article-title":"Expression of MMP\u20103. MMP\u201013, TIMP\u20102 and. TIMP\u20103 in the VX2 carcinoma of the New Zealand white rabbit","volume":"22","author":"Mandic R","year":"2002","journal-title":"Anticancer Res"},{"key":"e_1_2_6_7_2","first-page":"973","article-title":"Comparison of surface HLA class I levels in squamous cell carcinoma cell lines of the head and neck","volume":"24","author":"Mandic R","year":"2004","journal-title":"Anticancer Res"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1997.472"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602407"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2.8.827"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31202"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0303-269"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1102-991"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31405"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm990"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-003-0456-x"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32136"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31537"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0530251100"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00614.2005"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1080\/109374099281232"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1080\/15287398409530493"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1159\/000067032"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1077642"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/1811202a0"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7403859"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1258\/002367799780578372"},{"key":"e_1_2_6_28_2","volume-title":"CCAC guidelines on: choosing an appropriate endpoint in experiments using animals for research, teaching and testing","author":"Canadian Council on Animal Care","year":"1998"},{"key":"e_1_2_6_29_2","unstructured":"DCTD NCI NIH DHHS.Common Terminology Criteria for Adverse Events v3.0 (CTCAE): Cancer Therapy Evaluation Program 2006."},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.3109\/02841859309175412"},{"key":"e_1_2_6_31_2","first-page":"4163","article-title":"Perilesional IL\u20102 treatment of a VX2 head\u2010and\u2010neck cancer model can induce a systemic anti\u2010tumour activity","volume":"20","author":"van Es RJ","year":"2000","journal-title":"Anticancer Res"},{"key":"e_1_2_6_32_2","volume-title":"The laboratory rabbited","author":"Suckow MA","year":"1997"},{"key":"e_1_2_6_33_2","first-page":"231","article-title":"VX2 carcinoma, pulmonary metastases, and neutrophilic leukocytosis. Possible animal model of tumor\u2010associated granulocytosis","volume":"112","author":"Hough AJ","year":"1983","journal-title":"Am J Pathol"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1031601100"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602382103"},{"key":"e_1_2_6_36_2","first-page":"11","article-title":"Effector mechanisms of the anti\u2010cancer immune responses of macrophages in SR\/CR mice","volume":"6","author":"Hicks AM","year":"2006","journal-title":"Cancer Immun"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx00021a014"},{"key":"e_1_2_6_38_2","doi-asserted-by":"crossref","first-page":"3120","DOI":"10.1016\/S0021-9258(18)53667-X","article-title":"A kinetic model for the competitive reactions of ozone with amino acid residues in proteins in reverse micelles","volume":"268","author":"Pryor WA","year":"1993","journal-title":"JBiol Chem"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(92)90060-T"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(95)02033-7"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb\/9.6.594"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00666104"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.14.209"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00464-001-9166-7"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2005.02.001"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.23382","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.23382","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T07:27:39Z","timestamp":1697527659000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.23382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,25]]},"references-count":44,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2008,5,15]]}},"alternative-id":["10.1002\/ijc.23382"],"URL":"https:\/\/doi.org\/10.1002\/ijc.23382","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,1,25]]}}}