Michael W Sim1, Patrick T Grogan2, Chitra Subramanian3, Carol R Bradford1, Thomas E Carey1, M Laird Forrest4, Mark E Prince1, Mark S Cohen3. 1. Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, Ann Arbor, Michigan. 2. University of Kansas School of Medicine, Kansas City, Kansas. 3. Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan. 4. University of Kansas School of Pharmacy, Kansas City, Kansas, U.S.A.
Abstract
OBJECTIVES/HYPOTHESIS: To evaluate the efficacy of peritumoral hyaluronic acid (HA)-cisplatin therapy in a murine model of laryngeal squamous cell carcinoma and to evaluate its effect on cancer stem cells (CSCs). STUDY DESIGN: An orthotopic murine study utilizing University of Michigan squamous cell carcinoma-12 (UMSCC-12) laryngeal cancer cells was conducted in randomized controlled fashion with three treatment arms: saline, systemic cisplatin, and peritumoral HA-cisplatin. METHODS: UMSCC-12 laryngeal cancer cells were inoculated into the buccal mucosa of athymic nude mice followed by weekly treatment with saline, systemic cisplatin, or peritumoral HA-cisplatin for 3 weeks. Tumor response and animal weight was monitored and change in CD44 proportion was analyzed ex vivo. RESULTS: HA-cisplatin demonstrated superior antitumor efficacy and greater reduction in CD44 positivity on ex vivo analysis. CONCLUSIONS: Peritumoral nanoconjugated HA-cisplatin provides superior antitumor efficacy compared to standard cisplatin therapy in an in vivo laryngeal cancer model. There was also selective targeting of CD44+ cancer cells with HA-cisplatin. This therapeutic strategy could represent the first selective laryngeal CSC-targeted therapy. Further preclinical investigation is warranted to evaluate its role for locally advanced head and neck cancer treatment. LEVEL OF EVIDENCE: NA Laryngoscope, 126:E184-E190, 2016.
OBJECTIVES/HYPOTHESIS: To evaluate the efficacy of peritumoralhyaluronic acid (HA)-cisplatin therapy in a murine model of laryngeal squamous cell carcinoma and to evaluate its effect on cancer stem cells (CSCs). STUDY DESIGN: An orthotopic murine study utilizing University of Michigan squamous cell carcinoma-12 (UMSCC-12) laryngeal cancer cells was conducted in randomized controlled fashion with three treatment arms: saline, systemic cisplatin, and peritumoralHA-cisplatin. METHODS:UMSCC-12laryngeal cancer cells were inoculated into the buccal mucosa of athymic nude mice followed by weekly treatment with saline, systemic cisplatin, or peritumoralHA-cisplatin for 3 weeks. Tumor response and animal weight was monitored and change in CD44 proportion was analyzed ex vivo. RESULTS:HA-cisplatin demonstrated superior antitumor efficacy and greater reduction in CD44 positivity on ex vivo analysis. CONCLUSIONS:Peritumoral nanoconjugated HA-cisplatin provides superior antitumor efficacy compared to standard cisplatin therapy in an in vivo laryngeal cancer model. There was also selective targeting of CD44+ cancer cells with HA-cisplatin. This therapeutic strategy could represent the first selective laryngeal CSC-targeted therapy. Further preclinical investigation is warranted to evaluate its role for locally advanced head and neck cancer treatment. LEVEL OF EVIDENCE: NA Laryngoscope, 126:E184-E190, 2016.
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