The high sensitivity of the rabbit to the teratogenic effects of 13-cis-retinoic acid (isotretinoin) is a consequence of prolonged exposure of the embryo to 13-cis-retinoic acid and 13-cis-4-oxo-retinoic acid, and not of isomerization to all-trans-retinoic acid

1994 ◽  
Vol 68 (2) ◽  
pp. 119-128 ◽  
Author(s):  
Georg Tzimas ◽  
Heinrich Bürgin ◽  
Michael D. Collins ◽  
Hans Hummler ◽  
Heinz Nau
Keyword(s):  
Retinoic Acid ◽  
Prolonged Exposure ◽  
High Sensitivity ◽  
Teratogenic Effects ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

scholarly journals Characterization of acute promyelocytic leukemia cases with PML-RAR alpha break/fusion sites in PML exon 6: identification of a subgroup with decreased in vitro responsiveness to all-trans retinoic acid

Blood ◽  
1995 ◽  
Vol 86 (4) ◽  
pp. 1540-1547 ◽  
Author(s):  
RE Gallagher ◽  
YP Li ◽  
S Rao ◽  
E Paietta ◽  
J Andersen ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
High Sensitivity ◽  
Promyelocytic Leukemia ◽  
Reaction Products ◽  
Reading Frame ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Fusion Site

Of 113 acute promyelocytic leukemia cases documented to have diagnostic PML-RAR alpha hybrid mRNA, 10 cases (8.8%) had fusion sites in PML gene exon 6 (V-forms) rather than in the two common hybrid mRNA configurations resulting from breaksites in either PML gene intron 6 (L- forms) or intron 3 (S-forms). In 4 V-form cases, a common break/fusion site was discovered at PML gene nucleotide (nt) 1685, abutting a 3′ cryptic splice donor sequence. The fusion site was proximal to the common site in 1 case and more distal in 5 cases. The open reading frame encoding a PML-RAR alpha gene was consistently preserved, either by an in-frame fusion site or by the insertion of 3 to 127 unidentified nts. In 2 V-form cases, hybridization analysis of the reverse transcriptase-polymerase chain reaction products with a PML-RAR alpha juction probe was required for discrimination from L-form cases. Two V- form subgroups were defined by in vitro sensitivity to all-trans retinoic acid (tRA)-induced differentiation: 4 of 4 cases tested with fusion sites at or 5′ to nt 1685 (subgroup E6S) had reduced sensitivity (EC50 > or = 10(-7) mol/L), whereas 4 of 4 cases with fusion sites at or 3′ to nt 1709 (subgroup E6L) had high sensitivity (EC50 < 10(-8) mol/L) indistinguishable from that of L-form and S-form cases. These results provide the first link between PML-RAR alpha configuration and tRA sensitivity in vitro and support the importance of subclassifying APL cases according to PML-RAR alpha transcript type.

Simultaneous determination of endogenous retinoic acid isomers and retinol in human plasma by isocratic normal-phase HPLC with ultraviolet detection

1994 ◽  
Vol 40 (1) ◽  
pp. 48-51 ◽  
Author(s):  
E Meyer ◽  
W E Lambert ◽  
A P De Leenheer
Keyword(s):  
Retinoic Acid ◽  
Human Plasma ◽  
Simple Procedure ◽  
Internal Standard ◽  
High Sensitivity ◽  
Normal Phase ◽  
Ultraviolet Detection ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Normal Phase Hplc

Abstract We describe a rapid and simple procedure for the simultaneous quantitation of endogenous 13-cis-retinoic acid, all-trans-retinoic acid, and retinol by isocratic normal-phase HPLC with ultraviolet detection, in 0.5 mL of human plasma. A silica adsorption column was eluted with n-hexane:2-propanol:acetic acid (200:0.7:0.135 by vol) at 0.9 mL/min, and the effluent monitored at 350 nm. The arotinoid ethylsulfonic acid Ro 15-1570 was used as the internal standard. High sensitivity, allowing quantitation of physiological concentrations, was achieved, particularly for the retinoic acid isomers. The detection limits were 0.5 microgram/L in plasma for both 13-cis- and trans-retinoic acid, and 10 micrograms/L for retinol. The CVs for between-day determinations of the lowest quality-control concentration (n = 12) were 4.8% for 13-cis-retinoic acid, 3.4% for trans-retinoic acid, and 3.0% for retinol. The mean (+/- SD) concentrations of 13-cis-retinoic acid (1.79 +/- 0.56 microgram/L), trans-retinoic acid (1.35 +/- 0.42 microgram/L), and retinol (533 +/- 58 micrograms/L) measured in plasma from 22 healthy volunteers agreed well with those previously reported.

CNS Relapses of Acute Promyelocytic Leukemia after All-Trans Retinoic Acid

2002 ◽  
Vol 36 (12) ◽  
pp. 1900-1906 ◽  
Author(s):  
Lisa D Burry ◽  
Jack T Seki
Keyword(s):  
Retinoic Acid ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Peripheral Blood ◽  
Prolonged Exposure ◽  
Promyelocytic Leukemia ◽  
Treatment Modalities ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Cytogenetic Remission

OBJECTIVE: To review the role of all- trans retinoic acid (ATRA) and arsenic trioxide in central nervous system (CNS) relapses of acute promyelocytic leukemia (APL). CASE SUMMARY: A 69-year-old white man diagnosed with APL presented with bleeding diathesis. His molecular and cytogenetic studies were positive for promyelocytic leukemia—retinoic acid receptorα (PML-RARα) and t(15;17) transformation. Complete molecular and cytogenetic remission was achieved with ATRA, daunorubicin, and cytarabine. Within 6 months, the patient was readmitted for investigation of severe global headaches and an ataxic gait. His peripheral blood and cerebral spinal fluid were positive for PML-RARα fusion protein. Intrathecal chemotherapy and radiation, as well as ATRA, were the main treatment modalities provided. Molecular and cytogenetic remission was again obtained. Three months later, a second relapse occurred in the CNS and the peripheral blood. DISCUSSION: APL is typically treated with anthacycline-based chemotherapy and ATRA. Approximately 85–95% of patients achieve complete remission (CR); however, the relapse rate has been reported to be about 30–40%. A thorough literature search (MEDLINE, EMBASE, CANCERLIT, 1966–January 2002) revealed only 54 cases of extramedullary disease, of which 35 involved the CNS. CONCLUSIONS: The introduction of ATRA has improved patient survival dramatically. APL relapse, in general, has been in part attributable to repetitive or prolonged exposure to ATRA and the possibility of additional chromosomal changes, making the disease more refractory to treat. Given the evidence, one could argue that, with repeated ATRA treatment, CR duration may be shortened. However, limited data are available to guide the appropriate management of APL relapsed to the CNS with either ATRA, chemotherapy, or arsenic trioxide. In our opinion, treatment using arsenic trioxide is an unconventional option worthy of exploring.

v-erbA and citral reduce the teratogenic effects of all-trans retinoic acid and retinol, respectively, in Xenopus embryogenesis

Development ◽  
1993 ◽  
Vol 119 (3) ◽  
pp. 785-798 ◽  
Author(s):  
T.J. Schuh ◽  
B.L. Hall ◽  
J.C. Kraft ◽  
M.L. Privalsky ◽  
D. Kimelman
Keyword(s):  
Retinoic Acid ◽  
Neural Crest ◽  
Neural Crest Cells ◽  
Gastrula Stage ◽  
Teratogenic Effects ◽  
Retinoic Acid Signalling ◽  
Xenopus Development ◽  
Xenopus Embryos ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Treatment of late blastula/early gastrula stage Xenopus embryos with all-trans retinoic acid results in disruption of the primary body axis through effects on both mesoderm and neuroectoderm. This effect of retinoic acid, coupled with the known presence of retinoic acid in Xenopus embryos has led to the proposal that retinoic acid may be an endogenous morphogen providing positional information in early development. To further elucidate the role of retinoic acid in early Xenopus development, we have attempted to interfere with the retinoic acid signalling pathway both at the level of retinoic acid formation, by treatment with citral (3,7-dimethy-2,6-octadienal), and at the level of nuclear retinoic acid receptor function, by microinjection of v-erbA mRNA. The feasibility of this approach was demonstrated by the ability of citral treatment and v-erbA mRNA injection to reduce the teratogenic effects of exogenous retinol and retinoic acid, respectively, in early Xenopus development. Interestingly, v-erbA mRNA injection and citral treatment of gastrula stage embryos resulted in tadpoles with a similar set of developmental defects. The defects were chiefly found in tissues that received a contribution of cells from the neural crest, suggesting that at least a subset of neural crest cells may be sensitive to the endogenous level of retinoic acid. In accord with this proposal, it was found that the expression patterns of two early markers of cranial neural crest cells, Xtwi and XAP-2, were altered in embryos injected with v-erbA mRNA. These results indicate that structures in addition to the primary axis are regulated by retinoic acid signalling during early Xenopus development.

Antiproliferative effect of all-trans-retinoic acid in cholangiocarcinoma

2017 ◽  
Author(s):  
A Prawan ◽  
S Butsri ◽  
V Kukongviriyapan ◽  
L Senggunprai ◽  
S Kongpetch
Keyword(s):  
Retinoic Acid ◽  
Antiproliferative Effect ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid
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