PMID- 10433621
OWN - NLM
STAT- MEDLINE
DCOM- 19991118
LR  - 20190513
IS  - 0027-8874 (Print)
IS  - 0027-8874 (Linking)
VI  - 91
IP  - 15
DP  - 1999 Aug 4
TI  - Nuclear retinoid acid receptor beta in bronchial epithelium of smokers before and 
      during chemoprevention.
PG  - 1317-21
AB  - BACKGROUND: Retinoids can reverse neoplastic lesions and prevent second primary 
      tumors in the aerodigestive tract. These effects are thought to be mediated by 
      nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), each 
      receptor group including three subtypes (alpha, beta, and gamma). Previously, we 
      found that RARbeta expression was suppressed in lung cancer. In this study, we 
      investigated whether expression of RARbeta is modulated by chemopreventive 
      intervention. METHODS: Using in situ hybridization, we analyzed RARbeta messenger 
      RNA (mRNA) expression in bronchial biopsy specimens from heavy smokers, at 
      baseline and after 6 months of treatment with 13-cis-retinoic acid (13-cis-RA) or 
      placebo. Since we had previously detected RARbeta expression in 90% of bronchial 
      specimens from nonsmokers, we considered loss of RARbeta mRNA expression in at 
      least one of six biopsy specimens at baseline in this study to be aberrant. 
      RESULTS: RARbeta mRNA expression was aberrant in 30 (85.7%) of 35 subjects in the 
      13-cis-RA group and in 24 (72.7%) of 33 subjects in the placebo group. After 6 
      months of 13-cis-RA treatment, the number of subjects who were RARbeta positive 
      in all six biopsy specimens increased from five of 35 to 13 of 35 (2.6-fold), so 
      that the percentage of individuals with aberrant RARbeta expression decreased to 
      62.9% (22 of 35), which represents a statistically significant difference from 
      baseline expression (two-sided P =.01). In the placebo group, no statistically 
      significant difference in RARbeta expression was observed between baseline and 6 
      months. RARbeta expression was not related to current smoking status or reversal 
      of squamous metaplasia. CONCLUSIONS: These results indicate that RARbeta is an 
      independent marker of response to 13-cis-RA and may serve as an intermediate 
      biomarker in chemoprevention trials of upper aerodigestive tract cancers.
FAU - Xu, X C
AU  - Xu XC
AD  - Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson 
      Cancer Center, Houston, TX 77030, USA.
FAU - Lee, J S
AU  - Lee JS
FAU - Lee, J J
AU  - Lee JJ
FAU - Morice, R C
AU  - Morice RC
FAU - Liu, X
AU  - Liu X
FAU - Lippman, S M
AU  - Lippman SM
FAU - Hong, W K
AU  - Hong WK
FAU - Lotan, R
AU  - Lotan R
LA  - eng
GR  - U19CA68437/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Natl Cancer Inst
JT  - Journal of the National Cancer Institute
JID - 7503089
RN  - 0 (Anticarcinogenic Agents)
RN  - 0 (Biomarkers)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (retinoic acid receptor beta)
RN  - EH28UP18IF (Isotretinoin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anticarcinogenic Agents/*therapeutic use
MH  - Biomarkers
MH  - Biopsy
MH  - Bronchi/drug effects/*metabolism
MH  - Cell Nucleus/metabolism
MH  - Digestive System Neoplasms/etiology/*prevention & control
MH  - Epithelium/metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - In Situ Hybridization
MH  - Isotretinoin/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - RNA, Messenger/drug effects
MH  - Receptors, Retinoic Acid/*drug effects/genetics
MH  - Respiratory Tract Neoplasms/etiology/*prevention & control
MH  - Smoking/*adverse effects
MH  - Time Factors
MH  - Treatment Outcome
EDAT- 1999/08/05 00:00
MHDA- 1999/08/05 00:01
CRDT- 1999/08/05 00:00
PHST- 1999/08/05 00:00 [pubmed]
PHST- 1999/08/05 00:01 [medline]
PHST- 1999/08/05 00:00 [entrez]
AID - 10.1093/jnci/91.15.1317 [doi]
PST - ppublish
SO  - J Natl Cancer Inst. 1999 Aug 4;91(15):1317-21. doi: 10.1093/jnci/91.15.1317.