PMID- 23213070
OWN - NLM
STAT- MEDLINE
DCOM- 20130719
LR  - 20131121
IS  - 1940-6215 (Electronic)
IS  - 1940-6215 (Linking)
VI  - 6
IP  - 2
DP  - 2013 Feb
TI  - A randomized, placebo-controlled, preoperative trial of allopurinol in subjects 
      with colorectal adenoma.
PG  - 74-81
LID - 10.1158/1940-6207.CAPR-12-0249 [doi]
AB  - Inflammation and oxidative stress play a crucial role in the development of 
      colorectal cancer (CRC) and interference with these mechanisms represents a 
      strategy in CRC chemoprevention. Allopurinol, a safe molecular scavenger largely 
      used as antigout agent, has been shown to increase survival of patients with 
      advanced CRC and to reduce CRC incidence in long-term gout users in epidemiologic 
      studies. We conducted a randomized, double-blind, placebo-controlled preoperative 
      trial in subjects with colorectal adenomatous polyps to assess the activity of 
      allopurinol on biomarkers of colorectal carcinogenesis. After complete 
      colonoscopy and biopsy of the index polyp, 73 subjects with colorectal adenomas 
      were assigned to either placebo or one of two doses of allopurinol (100 mg or 300 
      mg) and treated for four weeks before polyp removal. Change of Ki-67 labeling 
      index in adenomatous tissue was the primary endpoint. Secondary endpoints were 
      the immunohistochemical (IHC) expression of NF-kappaB, beta-catenin, topoisomerase-II-alpha, 
      and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) 
      in adenomatous polyps and normal adjacent colonic tissue. Compared with placebo, 
      Ki-67 levels were not significantly modulated by allopurinol, whereas beta-catenin 
      and NF-kappaB expression levels decreased significantly in adenomatous tissue, with a 
      mean change from baseline of -10.6%, 95% confidence interval (CI), -20.5 to -0.7, 
      and -8.1%, 95% CI, -22.7 to 6.5, respectively. NF-kappaB also decreased significantly 
      in normal adjacent tissue (-16.4%; 95% CI, -29.0 to -3.8). No dose-response 
      relationship was noted, except for NF-kappaB expression in normal tissue. Allopurinol 
      can inhibit biomarkers of oxidative activation in colon adenomatous polyps and 
      normal adjacent tissue. Further studies should define its potential 
      chemopreventive activity.
FAU - Puntoni, Matteo
AU  - Puntoni M
AD  - Office of the Scientific Director, E.O. Ospedali Galliera, Genova, Italy.
FAU - Branchi, Daniela
AU  - Branchi D
FAU - Argusti, Alessandra
AU  - Argusti A
FAU - Zanardi, Silvia
AU  - Zanardi S
FAU - Crosta, Cristiano
AU  - Crosta C
FAU - Meroni, Emanuele
AU  - Meroni E
FAU - Munizzi, Francesco
AU  - Munizzi F
FAU - Michetti, Paolo
AU  - Michetti P
FAU - Coccia, Gianni
AU  - Coccia G
FAU - De Roberto, Giuseppe
AU  - De Roberto G
FAU - Bandelloni, Roberto
AU  - Bandelloni R
FAU - Turbino, Laura
AU  - Turbino L
FAU - Minetti, Egle
AU  - Minetti E
FAU - Mori, Marco
AU  - Mori M
FAU - Salvi, Sandra
AU  - Salvi S
FAU - Boccardo, Simona
AU  - Boccardo S
FAU - Gatteschi, Beatrice
AU  - Gatteschi B
FAU - Benelli, Roberto
AU  - Benelli R
FAU - Sonzogni, Angelica
AU  - Sonzogni A
FAU - DeCensi, Andrea
AU  - DeCensi A
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20121204
PL  - United States
TA  - Cancer Prev Res (Phila)
JT  - Cancer prevention research (Philadelphia, Pa.)
JID - 101479409
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Placebos)
RN  - 63CZ7GJN5I (Allopurinol)
SB  - IM
CIN - Cancer Prev Res (Phila). 2013 Feb;6(2):71-3. PMID: 23333813
CIN - Cancer Prev Res (Phila). 2013 Apr;6(4):368. PMID: 23447560
CIN - Cancer Prev Res (Phila). 2013 Apr;6(4):369. PMID: 23447561
MH  - Adenoma/*drug therapy/*surgery
MH  - Adenomatous Polyps/drug therapy/surgery
MH  - Aged
MH  - Allopurinol/*administration & dosage
MH  - Antimetabolites, Antineoplastic/*administration & dosage
MH  - Chemotherapy, Adjuvant
MH  - Colorectal Neoplasms/*drug therapy/*surgery
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Placebos
MH  - *Preoperative Care
MH  - Preoperative Period
EDAT- 2012/12/06 06:00
MHDA- 2013/07/20 06:00
CRDT- 2012/12/06 06:00
PHST- 2012/12/06 06:00 [entrez]
PHST- 2012/12/06 06:00 [pubmed]
PHST- 2013/07/20 06:00 [medline]
AID - 1940-6207.CAPR-12-0249 [pii]
AID - 10.1158/1940-6207.CAPR-12-0249 [doi]
PST - ppublish
SO  - Cancer Prev Res (Phila). 2013 Feb;6(2):74-81. doi: 
      10.1158/1940-6207.CAPR-12-0249. Epub 2012 Dec 4.