title: Effect of celecoxib and the novel anti-cancer agent, dimethylamino-parthenolide, in a developmental model of pancreatic cancer.
abstract: OBJECTIVE
  Cancer of the exocrine pancreas is the fourth leading cause of cancer-related deaths in the United States. The efficacy of a novel bioavailable anticancer agent, dimethylamino-parthenolide (DMAPT), and the cyclooxygenase 2 inhibitor, celecoxib, was evaluated in a carcinogen-induced developmental model of pancreatic cancer.
  
  
  METHODS
  Syrian golden hamsters were injected with N-nitrosobis(2-oxopropyl)amine, once weekly for 6 weeks. Upon the first injection, hamsters were randomized as follows: placebo, low-/high-dose DMAPT (20 and 40 mg/kg per day), low-/high-dose celecoxib (10and 50 mg/kg per day), or combination DMAPT/celecoxib (low/low, high/high).
  
  
  RESULTS
  The 32-week trial showed that 40 mg/kg DMAPT alone significantly decreased the size of gross pancreatic cancers relative to placebo. No significant difference in gross tumor number was observed between the treatment groups and placebo with the exception of 50 mg/kg celecoxib with a higher tumor incidence; this group also exhibited lower lymphotactin levels suggestive of decreased immune surveillance. Tumor invasion into adjacent organs and metastasis were not observed in the DMAPT/celecoxib treatment groups. Drug targets including prostaglandin E2, prostaglandin E2 metabolite and activated nuclear factor kappaB were significantly decreased.
  
  
  CONCLUSIONS
  Dimethylamino-parthenolide and celecoxib have the potential to be novel chemotherapeutic agents for pancreatic cancer; however, further optimization or the use of other modalities may be required for chemoprevention.
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. myipschn@iupui.edu
authors.forename: Michele T
authors.initials: MT
authors.lastname: Yip-Schneider
authors.forename: Huangbing
authors.initials: H
authors.lastname: Wu
authors.forename: Victor
authors.initials: V
authors.lastname: Njoku
authors.forename: Matthew
authors.initials: M
authors.lastname: Ralstin
authors.forename: Bryan
authors.initials: B
authors.lastname: Holcomb
authors.forename: Peter A
authors.initials: PA
authors.lastname: Crooks
authors.forename: Sundar
authors.initials: S
authors.lastname: Neelakantan
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sweeney
authors.forename: C Max
authors.initials: CM
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects; D019744:Chemokines, C / Q000378:metabolism; D006224:Cricetinae; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D019394:Ki-67 Antigen / Q000378:metabolism; D008647:Mesocricetus; D009077:Mucins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009602:Nitrosamines; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011720:Pyrazoles / Q000008:administration & dosage; D012717:Sesquiterpenes / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D019744:Chemokines, C; D052246:Cyclooxygenase 2 Inhibitors; D019394:Ki-67 Antigen; C524858:LC-1 compound; D009077:Mucins; D016328:NF-kappa B; D009602:Nitrosamines; D011720:Pyrazoles; D012717:Sesquiterpenes; D013449:Sulfonamides; C486249:Xcl1 protein, mouse; C013622:nitrosobis(2-oxopropyl)amine; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D015232:Dinoprostone