title: Modulation of the opioid growth factor ([Met(5)]-enkephalin)-opioid growth factor receptor axis: novel therapies for squamous cell carcinoma of the head and neck.
abstract: BACKGROUND
  The opioid growth factor (OGF)-OGF receptor (OGFr) axis is a constitutively expressed biologic pathway regulating cell proliferation of squamous cell carcinoma of the head and neck (SCCHN). This study investigated modulation of the OGF-OGFr system by (1) exogenous OGF, (2) upregulation of OGFr using imiquimod, or (3) intermittent opioid receptor blockade with a low dose of naltrexone on progression of established SCCHN.
  
  
  METHODS
  Nude mice with visible human SCCHN SCC-1 tumors received (1) OGF or low-dose naltrexone either 1, 3, or 7 times/week or (2) imiquimod 1 or 3 times/week. Tumor growth and DNA synthesis were monitored.
  
  
  RESULTS
  OGF and low-dose naltrexone increased the latency from visible to measurable tumors up to 1.6-fold. OGF, low-dose naltrexone, and imiquimod treatment markedly reduced tumor volume and weight, and decreased DNA synthesis in tumors.
  
  
  CONCLUSIONS
  Modulation of the native OGF-OGFr regulatory network in SCCHN represents a novel nontoxic and highly efficacious approach for treatment of SCCHN.
authors.affiliation: Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA. pxm9@psu.edu
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: McLaughlin
authors.forename: Jaimon K
authors.initials: JK
authors.lastname: Stucki
authors.forename: Ian S
authors.initials: IS
authors.lastname: Zagon
mesh_terms: D000634:Aminoquinolines / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D004247:DNA / Q000096:biosynthesis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000077271:Imiquimod; D007274:Injections, Intraperitoneal; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental; D011957:Receptors, Opioid / Q000187:drug effects* / Q000235:genetics; D012016:Reference Values; D000077195:Squamous Cell Carcinoma of Head and Neck; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D047368:Tumor Burden; D015854:Up-Regulation
chemical_list: D000634:Aminoquinolines; D011957:Receptors, Opioid; C033593:methionine-enkephalin receptor; D004247:DNA; D000077271:Imiquimod