Retinoic trans

Retinal trans-Retinal [116-31-4] Retinaldehyde [116-31-4] Retinitis pigmentosa Retinoblastoma Retinoic acid... 

Tretinoin, the - -trans isomer of retinoic acid [302-79-4] was shown in the 1960s to be useful for the treatment of disorders associated with abnormal epithehal differentiation. 

Figure 10.12 Response elements for heterodimers of the nuclear receptor for ds-retinoic acid (RXR) with the receptors for vitamin D (VDR), thyroid hormone (TR) and trans-retinoic acid (RAR). The half-sites of these response elements have identical nucleotide sequences and are organized as direct repeats. They differ in the number of base pairs in the spacer region between the half-sites. This difference forms the basis for the ability of the heterodimers to discriminate between the different response elements.

Retinoids are needed for cellular differentiation and skin growth. Some retinoids even exert a prophylactic effect on preneoplastic and malignant skin lesions. Fenretlnide (54) is somewhat more selective and less toxic than retinyl acetate (vitamin A acetate) for this purpose. It is synthesized by reaction of all trans-retinoic acid (53), via its acid chloride, with g-aminophe-nol to give ester 54 (13). 

Agents which enhance the host s response against neoplasias or force them to differentiate are termed biological response modifiers. Examples include interleukin 2 which is used to treat renal cell carcinoma, interferon a which is active against hematologic neoplasias, and tretinoin (all-trans retinoic acid) which is a powerful inducer of differentiation in certain leukemia cells by acting on retinoid receptors. Side effects include influenza like symptoms, changes in blood pressure and edema. 

CYP26 consists of three enzymes each representing a separate subfamily (Table 1) probably are all involved in retinoic acid hydroxylation. CYP26A1 is an all trans retinoic acid hydroxylase which degrades retinoic acid, an important signalling molecule for vertebrate development. It acts through retinoic acid receptors. The other CYP26 isozymes are also retinoic acid hydroxylases. 

Since the theory and medical applications of collagen sponge were described by Chvapil et al. (52-54), they have been used to deliver steroid hormones (55), the anticancer drugs trans-retinoic acid (TRA) (56,57), and 5-fluorouracil (5-FU) (58), and antibiotics (59). 

A most important function of vitamin A is in the control of cell differentiation and mrnover. PsA-trans-retinoic acid and 9-cw-retinoic acid (Figure 45-1) regulate growth, development, and tissue differentiation they have different actions in different tissues. Like the steroid hormones and vitamin D, retinoic acid binds to nuclear receptors that bind to response elements of DNA and regulate the transcription of specific genes. There are two families of nuclear retinoid receptors the retinoic acid receptors (RARs) bind all-rrijw-retinoic acid or 9-c -retinoic acid, and the retinoid X receptors (RXRs) bind 9-cw-retinoic acid. 

Baillet, A., Corbeau, L., Rafidson, R, and Ferrier, D., Separation of isomeric compounds by reversed-phase high-performance liquid chromatography using Ag+ complexation. Application to cis-trans fatty acid methyl esters and retinoic acid photoisomers, /. Chromatogr., 634, 251, 1993. 

Tretinoin, also referred to ATRA, which stands for all-trans-retinoic acid, is a retinoic acid that is not cytotoxic but promotes the maturation of early promyelocytic cells and is specific to the t(15 17) cytogenetic marker. The time to peak concentrations is 1 to 2 hours after an oral dose. The elimination half-life is 21 to 51 minutes.32 These maroon-and-gold capsules are dosed at 45 mg/m2 per day divided into two doses. The most significant side effect is the retinoic acid syndrome, which may occur anywhere from the first couple of days of therapy until the end of therapy and consists of symptoms of... 

FIGURE 20.2 The involvement of RARE on apo-lO -lycopenoic acid-transactivated RARp expression. Upper panel Diagram of the RARp reporter vector with wild type and mutated R AREs. Lower panel HeLa cells transfected with the RARp reporter vector and an internal control vector were treated with 5 pmol/I. of apo-lO -lycopenoic acid or 1 pmol/L of all-trans retinoic acid for 24h. Luciferase activities were measured by dual-luciferase reporter system. Values are means of SEM of three replicate assays., statistically significantly different, as compared with control in the same group, P < 0.05. (Adapted from Lian, F. et al., Carcinogenesis, 28, 1567, 2007. With permission.)... 

Liu, Y., Chang, R.L., Cui, X.X., Newmark, H.L. and Conney, A.H. 1997. Synergistic effects of curcumin on all-trans retinoic acid- and 1 alpha,25-dihydroxyvitamin D3-induced differentiation in human promyelocytic leukemia HL-60 cells. Oncol Res 9 19-29. 

The tritium-labelled 9-cri-retinoic acid [11,12-3H2], 96, the natural ligand for retinoid X receptor (RXR)83, has been produced84 by small-scale photoisomerization of all-trans-retinoic acid [11,12-3H2(N)], 97, followed by HPLC purification (equation 37). 

Granulocyte differentiation acute promyelocytic leukemia PBMCs (in vivo) Cultured bone marrow mononuclear cells (in vitro) All-trans retinoic acid (ATRA) Promoter analysis of ATRA response genes suggest molecular mechanism underlying ATRA-induced granulocytic differentiation [30]... 

Baltes S, Nau H, and Lampen A [2004] All-trans retinoic acid enhances differentiation and influences permeability of intestinal Caco-2 cells under serum-free conditions. Dev Growth Differentiation 46 503-514... 

Benson MJ, Pino-Lagos K, Rosemblatt M, Noelle RJ AU-trans retinoic acid mediates enhanced Treg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. J Exp Med 2007 204 1765-1774. 

White JA, Guo YD, Baetz K, Beckett-Jones B, Bonasoro J, et al. 1996. Identification of the retinoic acid-inducible all-trans-retinoic acid 4-hydroxylase. J Biol Chem 271 29922-29927. 

White JA, Ramshaw H, Taimi M, Stangle W, Zhang A, et al. 2000. Identification of the human cytochrome P450, P450RAI-2, which is predominantly expressed in the adult cerebellum and is responsible for all-trans-retinoic acid metabolism. Proc Natl Acad Sci USA 97 6403-6408. 

H. Narahara, M. Tatsuta, H. lishi, M. Baba, N. Uedo, N. Sakai, H. Yano and S. Ishiguro, K-ras point mutation is associated with enhancement by deoxycholic acid of colon carcinogenesis induced by azoxymethane, but not with its attenuation by all-trans-retinoic acid, Int. J. Cancer, 2000, 88(2), 157. 

Tretinoin (Trans-Retinoic Acid Vitamin A Acid)... 

Lim S.-J. and Kim C.-K., Eormulation parameters determining the physicochemical characteristics of sohd hpid nanoparticles loaded with all-trans retinoic acid, Int. J. Pham., 243, 135, 2002. 

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