title: Effects of alpha-difluoromethylornithine on markers of proliferation, invasion, and apoptosis in breast cancer.
abstract: OBJECTIVE
  To examine changes in biomarkers expressed in breast tumors in response to patient treatment with the polyamine synthesis inhibitor alpha-difluoromethylornithine (DFMO).
  
  
  METHODS
  The expression of Ki-67 (MIB-1), matrix metalloproteinases (MMP) 2 and 9, urokinase-type plasminogen activator (uPA) were examined by immunohistochemistry in breast tissue specimens (controls: n=15, 13 evaluable, and DFMO group; n=27, 21 evaluable). Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL).
  
  
  RESULTS
  Significant increases in apoptosis, MMP-9 and uPA (tumor) were observed in 7 patients >or=50 years who received DFMO for >or=14 days relative to patients <50 years and/or who received <14 days of treatment (n=11). No other measured characteristics, including tumor estrogen and progesterone receptor status, hormone replacement therapy history, histopathological characteristics or tumor grade were correlated with these biomarker changes.
  
  
  CONCLUSIONS
  Unexpected correlation of proapoptotic DFMO activity in postmenopausal women with breast cancer warrants further study.
authors.affiliation: BTNS LLC, Box 810, Marion, TX 78124, USA. btns.llc@gmail.com
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Izbicka
authors.forename: Robert T
authors.initials: RT
authors.lastname: Streeper
authors.forename: I-Tien
authors.initials: IT
authors.lastname: Yeh
authors.forename: Oredius
authors.initials: O
authors.lastname: Pressley
authors.forename: Michael
authors.initials: M
authors.lastname: Grant
authors.forename: J Valerie R
authors.initials: JV
authors.lastname: Andrews
authors.forename: Joseph
authors.initials: J
authors.lastname: Kuhn
authors.forename: Joyce
authors.initials: J
authors.lastname: O'Shaughnessy
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D000518:Eflornithine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000032:analysis; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008875:Middle Aged; D009361:Neoplasm Invasiveness
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000518:Eflornithine