Disease relevance of Retin-A

• BACKGROUND: Acute promyelocytic leukemia (APL) is associated with a hemorrhagic disorder of unknown cause that responds to treatment with all-trans-retinoic acid [1].
• Tretinoin for hyperpigmentation in black patients [2].
• Retinoid dermatitis developed in 12 of the 24 tretinoin-treated subjects who completed the study (50 percent) and in 1 tretinoin-treated subject who withdrew from the study, but diminished as the study progressed [3].
• Treatment with all-trans-retinoic acid reversed these changes providing nonsurgical remediation of emphysema and suggesting the possibility of a similar effect in humans [4].
• The amount of the heterotrimeric G protein subunit G alpha i2 decreases after the induction of F9 teratocarcinoma cells to become primitive endoderm in the presence of retinoic acid (RA) [5].

Psychiatry related information on Retin-A

• In a previously reported study on the anti-photoageing effects of topical tretinoin, the following regimen produced good patient compliance: 0.01% for 1 month, 0.025% for 1 month; and 0.05% for 4 months [6].
• Suppression of the forebrain genes has a narrow critical period of RA response during the early culture phase [7].

High impact information on Retin-A

• We show that both PML and Tif1alpha are growth suppressors required for the growth-inhibitory activity of RA [8].
• T18, similar to PML-RARalpha, disrupts the RA-dependent activity of this complex in a dominant-negative manner resulting in a growth advantage [8].
• In Pml-/- cells, the RA-dependent induction of genes such as RARB2 and the ability of Tif1alpha and CBP to act as transcriptional coactivators on RA are impaired [8].
• We also determined the effect of all-trans-retinoic acid on the expression of annexin II and the generation of cell-surface plasmin [1].
• Here we show that PML, Tif1alpha and RXRalpha/RARalpha function together in a transcription complex that is dependent on retinoic acid (RA) [8].

Chemical compound and disease context of Retin-A

• The present results show that, unlike all-trans-retinoic acid, 9-cis-retinoic acid induces both differentiation and apoptosis in N-type SH SY 5Y neuroblastoma cells [9].
• METHODS: RAR-beta2 expression was studied by reverse transcription-polymerase chain reaction (RT-PCR) analysis in eight breast cancer cell lines that were either treated with the demethylating agent 5-aza-2'-deoxycytidine and subsequently with all-trans-retinoic acid (ATRA) or left untreated [10].
• The results showed that the SR11302, an AP-1 inhibition-specific retinoid, and other AP-1 inhibitors such as trans-retinoic acid and fluocinolone acetonide, markedly inhibit both 12-O-tetradecanoylphorbol-13-acetate-induced papilloma formation and AP-1 activation in 7,12-dimethyl benz(a)anthracene-initiated mouse skin (P < 0.05) [11].
• Retinol inhibits the growth of all-trans-retinoic acid-sensitive and all-trans-retinoic acid-resistant colon cancer cells through a retinoic acid receptor-independent mechanism [12].
• The explants keratinized in 6 to 8 days and, when cultured in the presence of beta-retinoic acid (RA), inhibition of keratinization occurred and a mucous metaplasia developed [13].

Biological context of Retin-A

• To determine whether 9-cis retinoic acid receptors (RXRs) regulate the biological activity of all-trans retinoic acid (tRA) and its receptors (RARs) in skin, we have targeted a dominant-negative RXR alpha (dnRXR alpha) lacking transactivation function AF-2 to differentiated suprabasal keratinocytes in the epidermis of transgenic mice [14].
• CONCLUSIONS: Previous studies have demonstrated differential responses to all-trans-retinoic acid in N- and S-type (substrate-adherent or Schwann-like) neuroblastoma cells: Apoptosis is induced in S-type cells, whereas differentiation occurs in N-type cells [9].
• Dose-dependent pharmacokinetics of all-trans-retinoic acid [15].
• Recently, the all-trans-retinoic acid (RA)-induced proteolysis of cyclin D1 that leads to the arrest of cells in G1 phase of the cell cycle was described in human bronchial epithelial cells and is a promising candidate for such a mechanism [16].
• Variability in the oral bioavailability of all-trans-retinoic acid [17].

Anatomical context of Retin-A

• Pretreatment of skin with tretinoin (all-trans-retinoic acid) inhibited the induction of matrix metalloproteinase proteins and activity (by 70 to 80 percent) in both connective tissue and outer layers of irradiated skin [18].
• Fifty-eight patients completed a 10-month randomized, double-blind study in which they applied either 0.1 percent tretinoin (n = 28) or vehicle (n = 30) cream daily to the face, upper extremities, or both [19].
• Surprisingly, in adult animals, the suprabasal expression of dnRXR alpha significantly reduced the ability of topically applied tRA to stimulate proliferation of undifferentiated keratinocytes in the basal layer of epidermis [14].
• We speculate that increased numbers of collagenous anchoring fibrils within the papillary dermis of human skin is one of the connective-tissue correlates of the clinical improvement observed in photoaged skin after treatment with topical tretinoin [20].
• Induction of terminal differentiation of two variant sublines derived from the human monocytic leukemia cell line THP-1 by all-trans-beta-retinoic acid (RA) was studied [21].

Associations of Retin-A with other chemical compounds

• As a drug, all-trans-retinoic acid has certain undesirable pharmacologic properties that might be overcome by the use of alternative retinoids, such as 9-cis-retinoic acid, that are equally active against acute promyelocytic leukemia cells in vitro [22].
• METHODS: Three hundred forty-six patients with previously untreated acute promyelocytic leukemia were randomly assigned to receive all-trans-retinoic acid or daunorubicin plus cytarabine as induction treatment [23].
• To determine modes of retinoid action in the modulation of inflammatory responses, we explored effects of all-trans-retinoic acid (t-RA) on the TNFalpha-induced expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin in cultured human dermal microvascular endothelial cells [24].
• The inducibility of 1 alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] binding by all-trans-retinoic acid (RA) was examined in tumor-derived clonal bone cell lines, in established clonal cell lines derived from normal embryonic bone, and in cultured bone cell populations freshly isolated from 18- and 21-day fetal and 5-day-old neonatal rat calvaria [25].
• Neither progesterone, testosterone, dexamethasone, thyroid hormone, all-trans-retinoic acid, nor 5alpha-androstane-3alpha,I7beta-diol could stimulate reporter gene activity, whereas estrone and 5alpha-androstane-3beta,17beta-diol did [26].

Gene context of Retin-A

• On the other hand, TGF-beta, as well as all-trans-retinoic acid, inhibited colony growth [27].
• Disruption of retinoic acid receptor (RAR) gamma in F9 embryonal carcinoma cells leads to aberrent differentiation and reduced activation of expression of several all-trans-retinoic acid (RA)-induced genes [28].
• RA treatment also decreased TNF receptors on acute monocytic leukemia cell line THP-1 [29].
• All-trans-retinoic acid (atRA) receptor (RAR) was tethered constitutively to the AP1 promoter [30].
• All-trans-retinoic acid induced reorganization of the PML nuclear body (NB) and reappearance of the IR-induced TopBP1 foci [31].

Analytical, diagnostic and therapeutic context of Retin-A

• By intention-to-treat analysis, the rates of overall survival at one, two, and three years after entry into the study were 75, 57, and 50 percent, respectively, among patients assigned to chemotherapy, and 82, 72, and 67 percent among those assigned to all-trans-retinoic acid (P= 0.003) [23].
• The t(15;17)-positive APL cells contained abundant messenger RNA for annexin II, which disappeared through a transcriptional mechanism after treatment with all-trans-retinoic acid [1].
• At the end of treatment, colorimetry demonstrated a 40 percent lightening of the lesions toward normal skin color in the tretinoin-treated lesions, as compared with an 18 percent lightening in vehicle-treated lesions (P = 0.05) [3].
• Eleven patients with acute promyelocytic leukemia were treated with tretinoin administered orally at a dose of 45 mg per square meter of body-surface area per day [32].
• The effect of beta-retinoic acid (RA) on carcinogen-induced hyperplasia was studied in organ cultures of mouse prostate gland [33].

References