PMID- 22901127
OWN - NLM
STAT- MEDLINE
DCOM- 20130122
LR  - 20190606
IS  - 2476-762X (Electronic)
IS  - 1513-7368 (Linking)
VI  - 13
IP  - 5
DP  - 2012
TI  - Retinoid receptors in gastric cancer: expression and influence on prognosis.
PG  - 1809-17
AB  - BACKGROUND: Gastric cancer is frequently lethal despite aggressive multimodal 
      therapies, and new treatment approaches are therefore needed. Retinoids are 
      potential candidate drugs: they prevent cell differentiation, proliferation and 
      malignant transformation in gastric cancer cell lines. They interact with nuclear 
      retinoid receptors (the retinoic acid receptors [RARs] and retinoid X receptors 
      [RXRs]), which function as transcription factors, each with three subclasses, alpha, 
      beta and gamma. At present, little is known about retinoid expression and influence on 
      prognosis in gastric cancers. PATIENTS AND METHODS: We retrospectively analyzed 
      the expression of the subtypes RARalpha, RARbeta, RARgamma, RXRalpha, RXRbeta, RXRgamma by 
      immunohistochemistry in 147 gastric cancers and 51 normal gastric epithelium 
      tissues for whom clinical follow-up data were available and correlated the 
      results with clinical characteristics. In addition, we quantified the expression 
      of retinoid receptor mRNA using real- time PCR (RT-PCR) in another 6 gastric 
      adenocarcinoma and 3 normal gastric tissues. From 2008 to 2010, 80 patients with 
      gastric cancers were enrolled onto therapy with all-trans-retinoic acid (ATRA). 
      RESULTS: RARalpha, RARbeta, RARgamma and RXRgamma positively correlated with each other 
      (p<0.001) and demonstrated significantly lower levels in the carcinoma tissue 
      sections (p<0.01), with lower RARbeta, RARgamma and RXRalpha expression significantly 
      related to advanced stages (p<=0.01). Tumors with poor histopathologic grade had 
      lower levels of RARalpha and RARbeta in different histological types of gastric 
      carcinoma (p<0.01). Patients whose tumors exhibited low levels of RARa expression 
      had significantly lower overall survival compared with patients who had higher 
      expression levels of this receptor (p<0.001, HR=0.42, 95.0% CI 0.24-0.73), and 
      patients undergoing ATRA treatment had significantly longer median survival times 
      (p=0.007, HR=0.41, 95.0% CI 0.21-0.80). CONCLUSIONS: Retinoic acid receptors are 
      frequently expressed in epithelial gastric cancer with a decreased tendency of 
      expression and RARa may be an indicator of a positive prognosis. This study 
      provides a molecular basis for the therapeutic use of retinoids against gastric 
      cancer.
FAU - Hu, Kong-Wang
AU  - Hu KW
AD  - Department of General Surgery, the First Hospital of Anhui Medical University, 
      School of Pharmacology, Anhui Medical University, Hefei, China.
FAU - Chen, Fei-Hu
AU  - Chen FH
FAU - Ge, Jin-Fang
AU  - Ge JF
FAU - Cao, Li-Yu
AU  - Cao LY
FAU - Li, Hao
AU  - Li H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Thailand
TA  - Asian Pac J Cancer Prev
JT  - Asian Pacific journal of cancer prevention : APJCP
JID - 101130625
RN  - 0 (Antineoplastic Agents)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Adenocarcinoma/drug therapy/*metabolism/mortality
MH  - Aged
MH  - Antineoplastic Agents/therapeutic use
MH  - Female
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Prognosis
MH  - RNA, Messenger/genetics
MH  - Receptors, Retinoic Acid/*genetics/*metabolism
MH  - Retrospective Studies
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stomach Neoplasms/drug therapy/*metabolism/mortality
MH  - Survival Rate
MH  - Tretinoin/therapeutic use
EDAT- 2012/08/21 06:00
MHDA- 2013/01/23 06:00
CRDT- 2012/08/21 06:00
PHST- 2012/08/21 06:00 [entrez]
PHST- 2012/08/21 06:00 [pubmed]
PHST- 2013/01/23 06:00 [medline]
AID - 10.7314/apjcp.2012.13.5.1809 [doi]
PST - ppublish
SO  - Asian Pac J Cancer Prev. 2012;13(5):1809-17. doi: 10.7314/apjcp.2012.13.5.1809.