welcome to oneFAPvoice
- a positively charged Familial Adenomatous Polyposis community.- join today!
- login
Levels of Rectal Mucosal Polyamines and Prostaglandin E2 Predict Ability of DFMO and Sulindac to Prevent Colorectal Adenoma
source: Gastroenterology
year: 2010
authors: Patricia A. Thompson, Betsy C. Wertheim, Jason A. Zell, Wen-Pin Chen, Bonnie J. LaFleur, Frank L. Meyskens, Christine E. McLaren, Eugene W. Gerner
summary/abstract:BACKGROUND & AIMS : Combination of polyamine and prostaglandin E2 (PGE2)-synthesis inhibitors reduced the risk of colorectal adenoma (CRA) by 70% in patients who received polypectomies. We studied effects of the combination of difluoromethylornithine (DFMO) and sulindac on biomarkers and investigated factors that modify their efficacy.
METHODS : We analyzed rectal mucosal levels of polyamines (spermidine, spermine, and putrescine) and PGE2, treatment regimens, and risk of CRA in 267 participants of a phase IIb/III chemoprevention trial of DFMO/sulindac.
RESULTS : In the group that received DFMO/sulindac, spermidine-to-spermine ratio (Spd:Spm) in rectal mucosa decreased between baseline and 12- and 36-month follow-up examinations (0.30, 0.23, and 0.24, respectively; P < .001 for both comparisons to baseline). Putrescine levels decreased between baseline and 12 months (0.46 vs 0.15 nmol/mg protein; P < .001) but rebounded between 12 and 36 months (0.15 vs 0.36 nmol/mg protein; P = .001). PGE2 levels did not change, although aspirin use was significantly associated with lower baseline levels of PGE2. No significant associations were observed between changes in biomarker levels and efficacy. However, drug efficacy was greatest in subjects with low Spd:Spm and high PGE2 at baseline; none of these subjects, versus 39% of those given placebo, developed CRA (P < .001). Efficacy was lowest in subjects with high Spd:Spm and low PGE2 at baseline; 28% developed CRA, compared with 36% of patients given placebo (P = .563).
CONCLUSIONS : A combination of DFMO and sulindac significantly suppressed production of rectal mucosal polyamines but not PGE2. No relationship was found between changes in biomarker levels and response. However, baseline biomarker levels modified the effect of DFMO/sulindac for CRA prevention.
organization: University of ArizonaDOI: 10.1053/j.gastro.2010.06.005
read more full text source
expertly curated content related to this topic
-
Pharmacotherapy for Inherited Colorectal CancerIMPORTANCE OF THE FIELD : An important r...
-
Restorative Proctectomy with Ileal Pouch-Anal Anastomosis in Obese PatientsPURPOSE : The aim of this study was to a...
-
Study identifies enhanced impact of treatment for hereditary cancer patientsPeople with an inherited syndrome called...
-
A New Technique for Delivering a Polyglycolic Acid Sheet to Cover a Large Mucosal Defect: The Swiss Roll MethodEndoscopic tissue shielding with polygly...
-
Chemo: (Hair) Loss & Mane (Thinning)https://www.youtube.com/watch?v=TaGRE_J5...
-
Surgical Treatment of Familial Adenomatous Polyposis: Ileorectal Anastomosis or Restorative Proctolectomy?CONTEXT : Controversy regarding the best...
-
Starch Powder That can be Sprinkled on Food is Tested as Cure for Bowel CancerA powder made from starch that can b...