PMID- 11975681
OWN - NLM
STAT- MEDLINE
DCOM- 20020624
LR  - 20231213
IS  - 1048-891X (Print)
IS  - 1048-891X (Linking)
VI  - 12
IP  - 2
DP  - 2002 Mar-Apr
TI  - Activity of ALRT 1550, a new retinoid, with interferon-gamma on ovarian cancer 
      cell lines.
PG  - 202-7
AB  - Retinoids have been shown to be effective regulators of cell proliferation and 
      differentiation in many human cancers. The major biologic activity of the 
      retinoids is mediated by two families of nuclear receptors: retinoic acid 
      receptors (RARs) and retinoid X receptors (RXRs). ALRT 1550 is one of the most 
      potent RAR selective retinoids discovered to date, with 10-100 times more 
      activity than ATRA in competitive binding and cotransfection assays and 300 times 
      more inhibiting activity against proliferation of cervical carcinoma cell. To 
      evaluate the role of ALRT 1550 in ovarian cancer, the growth inhibitory activity 
      of ALRT 1550 was determined in the ATRA-resistant ovarian cancer cell line SKOV-3 
      and ovarian cancer cell line 2774 after exposure to concentrations of 0.1, 1, 
      2.5, 5, and 10 microM for 7 days. SKOV-3 showed 51%, 53%, and 68% cell growth 
      inhibition after treatment with ALRT 1550 at concentrations of 2.5, 5, and 10 
      microM, respectively, and the 2774 cell line showed 46% inhibition after 
      treatment at 10 microM. Because interferon (IFN)-gamma was found to 
      synergistically amplify the growth inhibition of retinoids in cultured breast 
      cancer cells, we investigated the combination of ALRT 1550 with IFN-gamma in two 
      ovarian cancer cell lines. ALRT 1550 (5 microM) in combination with IFN-gamma at 
      a concentration of 500 U/ml inhibited cell growth of SKOV-3 by as much as 81% (CI 
      = 1.88). This is a 28% greater effect than with ALRT alone. Cell line 2774 showed 
      a 69% cell growth inhibitory effect with ALRT 1550 (5 microM) in combination with 
      IFN-gamma at a concentration of 1000 U/ml (CI = 1.03). ALRT 1550 and IFN-gamma 
      may act synergistically in the SKOV-3 ovarian cancer cell line and additively in 
      the 2774 cell line. In conclusion, ALRT 1550 may be a promising drug with a high 
      biologic modulating activity against ovarian cancer. In combination with 
      IFN-gamma, additive and perhaps synergistic effects may be seen in some ovarian 
      cancer cell lines. Combining these two biologic modifiers for the treatment of 
      ovarian cancer may lower the effective dose of the retinoids, thus decreasing 
      their side effects.
FAU - Hu, Wei
AU  - Hu W
AD  - Department of Gynecologic Medical Oncology, University of Texas, M. D. Anderson 
      Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. 
      weihu@mdanderson.org
FAU - Verschraegen, C F
AU  - Verschraegen CF
FAU - Wu, W G
AU  - Wu WG
FAU - Nash, M
AU  - Nash M
FAU - Freedman, R S
AU  - Freedman RS
FAU - Kudelka, A
AU  - Kudelka A
FAU - Kavanagh, J J
AU  - Kavanagh JJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Int J Gynecol Cancer
JT  - International journal of gynecological cancer : official journal of the 
      International Gynecological Cancer Society
JID - 9111626
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoids)
RN  - 82115-62-6 (Interferon-gamma)
RN  - H62AOA2IYF (ALRT 1550)
SB  - IM
MH  - Antineoplastic Agents/*therapeutic use
MH  - Blotting, Western
MH  - Drug Synergism
MH  - Drug Therapy, Combination
MH  - Female
MH  - Humans
MH  - Interferon-gamma/*therapeutic use
MH  - Ovarian Neoplasms/*drug therapy
MH  - Receptors, Retinoic Acid/metabolism
MH  - Retinoids/*therapeutic use
MH  - Tumor Cells, Cultured/drug effects
MH  - Tumor Stem Cell Assay
MH  - Retinoic Acid Receptor gamma
EDAT- 2002/04/27 10:00
MHDA- 2002/06/25 10:01
CRDT- 2002/04/27 10:00
PHST- 2002/04/27 10:00 [pubmed]
PHST- 2002/06/25 10:01 [medline]
PHST- 2002/04/27 10:00 [entrez]
AID - ijg01084 [pii]
AID - 10.1046/j.1525-1438.2002.01084.x [doi]
PST - ppublish
SO  - Int J Gynecol Cancer. 2002 Mar-Apr;12(2):202-7. doi: 
      10.1046/j.1525-1438.2002.01084.x.