scholarly journals Retinoic acid receptor-^|^alpha; up-regulates proopiomelanocortin gene expression in AtT20 corticotroph cells

2014 ◽  
Vol 61 (11) ◽  
pp. 1105-1114 ◽  
Author(s):  
Akira Uruno ◽  
Akiko Saito-Hakoda ◽  
Atsushi Yokoyama ◽  
Naotaka Kogure ◽  
Ken Matsuda ◽  
...  
2021 ◽  
Author(s):  
Shahan Mamoor

Triple negative breast cancer (TNBC) shares overlap with the basal or basal-like molecular subtype of breast cancer and is more frequently diagnosed in women of African descent (black women) for reasons not understood (1, 2). To understand genes whose expression may be of pertinence to the development or progression of triple negative breast cancer, we mined published microarray data (3) comparing global gene expression profiles of TNBC cases, identifying genes whose expression was least different among TNBC cases, indicating conservation of expression patterns suggestive of importance for TNBC biology. We identified the gene encoding the retinoic acid receptor alpha (RARA), a fatty acid elongase (ELOVL1), as well as multiple genes encoding molecules involved in epigenetic functions or with nucleic acid binding or modification properties, including TDRD7, KDM1B, PHF7, TAF5L, as well as the microRNA hsa-miR-605. Kaplan-Meier survival analysis revealed that expression levels of each of these genes correlated with survival outcomes in the basal subtype of human breast cancer, which shares significant overlap with triple negative breast cancer at the level of gene expression (2). RARA, ELOVL1, TDRD7, KDM1B, PHF7, TAF5L and hsa-miR-605 may be of relevance in understanding the etiology or progression of triple negative breast cancer. Together with our previous findings, the data allude to a potential pathogenic mechanism involving transcriptional perturbation of epigenetic machinery in triple negative breast cancer (4, 5).


2013 ◽  
Vol 13 (5) ◽  
pp. 401-408 ◽  
Author(s):  
Samar Alsafadi ◽  
Caroline Even ◽  
Coralie Falet ◽  
Aicha Goubar ◽  
Frédéric Commo ◽  
...  

2017 ◽  
pp. 271-285
Author(s):  
Ganesan Padmavathi ◽  
Javadi Monisha ◽  
Anand Anip ◽  
Krishan Kumar Thakur ◽  
Ajaikumar B. Kunnumakkara

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 99-102 ◽  
Author(s):  
C Largman ◽  
K Detmer ◽  
JC Corral ◽  
FM Hack ◽  
HJ Lawrence

The expression of the newly described human retinoic acid receptor alpha (RAR alpha) in six nonlymphoid and six lymphoid leukemia cell lines and nine freshly obtained samples of leukemia cells from patients with acute nonlymphoid leukemia was assessed by Northern blot analysis, using a full length cDNA clone of RAR alpha as probe. RAR alpha was expressed in all 12 cell lines and in all fresh leukemia samples as two major transcripts of 2.6 and 3.5 kb in size. Levels of RAR alpha expression and transcript sizes in retinoid-sensitive cells (such as HL60 or fresh promyelocytic leukemia cells) were not different from those in other samples. Moreover, expression of RAR alpha was not significantly modulated by exposure to cis-retinoic acid (cisRA) in either cisRA-responsive or unresponsive cells. By using a 3′ fragment of the RAR alpha gene as a probe, we confirmed that the transcripts visualized did not represent the homologous RAR beta gene. RAR alpha appears to be expressed in most human leukemia cells regardless of the type of biologic response to retinoic acid.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS7071-TPS7071
Author(s):  
Rachel J. Cook ◽  
Eytan Stein ◽  
David P. Steensma ◽  
Mikkael A. Sekeres ◽  
Dale L. Bixby ◽  
...  

TPS7071 Background: SY-1425 (tamibarotene) is an orally available, synthetic retinoid approved in Japan for the treatment of relapsed/refractory (R/R) APL. SY-1425 is a more potent and selective retinoic acid receptor alpha (RARα) agonist with improved pharmacologic properties compared to all-trans retinoic acid (ATRA) including increased half-life and lack of metabolism by CYP26A1 resulting in extended relative exposures. SY-1425 binding to RARα relieves pathogenic repression of myeloid differentiation. Super-enhancers associated with RARA and upregulation of RARA expression correlate with increased sensitivity to SY-1425 in vitro and predict for response to SY-1425 with induced differentiation and reduced proliferation in RARA-high PDX AML models, but not in RARA-low models. SY-1425 also induces the RARα target gene DHRS3 in RARA-high AML cell lines. This study is designed to demonstrate pharmacodynamic (PD) and clinical effects of SY-1425 in non-APL AML and MDS patients (pts) positive for the RARA super-enhancer associated biomarker or exploratory RARA pathway biomarker, IRF8. Methods: This study is enrolling pts with R/R AML, R/R higher-risk MDS, newly-diagnosed AML ≥60 yrs unlikely to respond to or tolerate standard therapy, and transfusion dependent lower-risk MDS pts without del 5q who are unlikely to respond to or have failed ESAs. Pts must be biomarker positive based on centralized testing of tumor cells from blood. All pts receive SY-1425 at 6 mg/m2/day PO with continuous twice daily dosing. Primary objectives are to characterize the activity of SY-1425 by ORR in AML and higher-risk MDS pts or transfusion independence in lower-risk MDS pts. Secondary objectives include event-free and relapse-free survival, duration of response, overall survival, hematologic improvement and safety. PD evaluation includes induction of DHRS3 and expression of myeloid differentiation markers. Target enrollment is 80 pts. This trial opened in September 2016. Through a protocol amendment, SY-1425 treatment in combination with azacitidine will also be evaluated. ClinicalTrials.gov identifier: NCT02807558.


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