{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:03:53Z","timestamp":1785427433310,"version":"3.56.0"},"reference-count":21,"publisher":"American Veterinary Medical Association (AVMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>Objective<\/jats:bold>\u2014To establish the maximum tolerated dose of <jats:italic>Clostridium novyi<\/jats:italic>\u2013NT spores in tumor-bearing dogs and evaluate spore germination within tumors and tumor response.<\/jats:p>\n<jats:p><jats:bold>Animals<\/jats:bold>\u20146 client-owned dogs.<\/jats:p>\n<jats:p><jats:bold>Procedures<\/jats:bold>\u2014A standard dose-escalation study was planned, with maximum tolerated dose defined as the highest dose at which 0 or 1 of 6 dogs had dose-limiting toxicoses (DLT). Dogs received 1 dose of <jats:italic>C novyi<\/jats:italic>\u2013NT spores IV. Toxicoses were graded and interventions performed according to specific guidelines. Grade 3 or higher toxicosis or any toxicosis combination that substantially affected patient status was considered DLT. Clinical response was measured by use of response evaluation criteria in solid tumors at 28 days.<\/jats:p>\n<jats:p><jats:bold>Results<\/jats:bold>\u2014The first 2 dogs had DLT. The dose was decreased. Two of the next 4 dogs had DLT; therefore, dose administration was stopped because the study endpoint had been reached. The most common toxicosis was fever (n = 6 dogs). Two dogs developed abscesses (1 within a nasal carcinoma and 1 splenic abscess) attributable to <jats:italic>C novyi<\/jats:italic>\u2013NT infection; both required surgical intervention. <jats:italic>Clostridium novyi<\/jats:italic>\u2013NT was cultured from 1 of 6 tumors. Five dogs were available for response assessment (4 had stable disease; 1 had progressive disease).<\/jats:p>\n<jats:p><jats:bold>Conclusions and Clinical Relevance<\/jats:bold>\u2014Results indicated that <jats:italic>C novyi<\/jats:italic>\u2013NT can germinate within tumors of dogs. Toxicosis, although common and sometimes severe, was manageable with treatment. Further studies in dogs with superficial tumors may allow for continued dose escalation and provide information for use in clinical trials in veterinary and human oncology.<\/jats:p>","DOI":"10.2460\/ajvr.73.1.112","type":"journal-article","created":{"date-parts":[[2011,12,28]],"date-time":"2011-12-28T19:37:15Z","timestamp":1325101035000},"page":"112-118","source":"Crossref","is-referenced-by-count":63,"title":["Evaluation of Clostridium novyi\u2013NT spores in dogs with naturally occurring tumors"],"prefix":"10.2460","volume":"73","author":[{"given":"Erika L.","family":"Krick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin U.","family":"Sorenmo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelley C.","family":"Rankin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Cheong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Kobrin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Thornton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth W.","family":"Kinzler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert","family":"Vogelstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis A.","family":"Diaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1272","reference":[{"key":"ref1","series-title":"Angiogenesis","first-page":"231","author":"Sturk","year":"2005"},{"key":"ref2","series-title":"J Appl Microbiol","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1111\/j.1365-2672.2006.02886.x","article-title":"The use of clostridial spores for cancer treatment","volume":"101","author":"Barbe","year":"2006"},{"key":"ref3","series-title":"J Cancer Res","first-page":"334","article-title":"The treatment of Flexner-Jobling rat carcinomas with bacterial proteolytic ferments","volume":"11","author":"Torrey","year":"1927"},{"key":"ref4","series-title":"Can Med Assoc J","first-page":"364","article-title":"The study and treatment of cancer by proteolytic enzymes","volume":"33","author":"Connell","year":"1935"},{"key":"ref5","series-title":"Proc Soc Exp Biol Med","doi-asserted-by":"publisher","first-page":"461","DOI":"10.3181\/00379727-66-16124","article-title":"Effects of histolyticus infections and toxin on transplantable mouse tumors","volume":"66","author":"Parker","year":"1947"},{"key":"ref6","series-title":"Cancer Res","first-page":"743","article-title":"Localization of the vegetative form of Clostridium tetani in mouse tumors following intravenous spore administration","volume":"15","author":"Malmgren","year":"1955"},{"key":"ref7","series-title":"Cancer Res","first-page":"212","article-title":"Oncolysis by clostridia. 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