title: Effect of docetaxel on the surgical tumor microenvironment of head and neck cancer in murine models.
abstract: OBJECTIVE
  To identify the antitumor activity and wound-healing effect of docetaxel delivered in the surgical tumor microenvironment of head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  Control and experimental series.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  BALB/c and severe combined immunodeficiency mice.
  
  
  METHODS
  Intrawound (IW) docetaxel therapy was tested in 3 HNSCC xenograft and 2 taxane-resistant models. Intratumoral (IT) docetaxel therapy was further tested in the 2 taxane-resistant models.
  
  
  METHODS
  Tumor size, survival, and wound toxic effects were measured. The effect of docetaxel on various factors involved in wound healing and tumor growth within the surgical tumor microenvironment was also analyzed.
  
  
  RESULTS
  In a pilot study using BALB/c mice, IW docetaxel therapy was not associated with problems in wound healing. Using the HN6, HN12, and HN30 HNSCC xenograft model, IW docetaxel prevented tumor growth and improved survival when compared with controls. No local or systemic toxic effect or wound-healing problem was noted. Using taxane-resistant xenograft lung cancer (H460/T800) and syngeneic salivary cancer (BALB/c mucoepidermoid carcinoma) models, IW therapy did not delay tumor growth. An antitumor effect was detected with repeated docetaxel injections in the H460/T800 taxane-resistant model but not in the BALB/c mucoepidermoid carcinoma model. Docetaxel inhibited the expression of growth factors and receptors in tumor cells; however, it did not inhibit the level of wound-healing growth factors in the surgical tumor microenvironment.
  
  
  CONCLUSIONS
  These preclinical results support further testing of IW docetaxel treatment in HNSCC. Docetaxel appears to exert antitumor activity without affecting factors involved in wound healing in the tumor microenvironment.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Wayne State University, 5E University Health Center, 4201 St Antoine, Detroit, MI 48201, USA. gyoo@med.wayne.edu
authors.forename: George H
authors.initials: GH
authors.lastname: Yoo
authors.forename: Geetha
authors.initials: G
authors.lastname: Subramanian
authors.forename: Marie P
authors.initials: MP
authors.lastname: Piechocki
authors.forename: John F
authors.initials: JF
authors.lastname: Ensley
authors.forename: Omer
authors.initials: O
authors.lastname: Kucuk
authors.forename: Ozlem E
authors.initials: OE
authors.lastname: Tulunay
authors.forename: Fulvio
authors.initials: F
authors.lastname: Lonardo
authors.forename: Harold
authors.initials: H
authors.lastname: Kim
authors.forename: Joshua
authors.initials: J
authors.lastname: Won
authors.forename: Timothy
authors.initials: T
authors.lastname: Stevens
authors.forename: Ho-Sheng
authors.initials: HS
authors.lastname: Lin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D018277:Carcinoma, Mucoepidermoid / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D015552:Injections, Intralesional; D008175:Lung Neoplasms / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010039:Otorhinolaryngologic Neoplasms / Q000473:pathology*; D010865:Pilot Projects; D012468:Salivary Gland Neoplasms / Q000473:pathology; D043823:Taxoids / Q000494:pharmacology* / Q000633:toxicity; D047368:Tumor Burden; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel