Disease relevance of Arotinoid

• Hypercalcemia induced with an arotinoid in thyroparathyroidectomized rats. New model to study bone resorption in vivo [1].
• Treatment of lichen planus with temarotene [2].
• Such marked toxicity was not evident with the arotinoid at doses having high antitumor activity [3].
• Comparison of the therapeutic effects of a new arotinoid, Ro 40-8757, and all-trans- and 13-cis-retinoic acids on rat breast cancer [3].
• The sodium sulfonate derivative, Ro-14-3899, is somewhat less active, whereas the ethyl sulfone (Ro-15-1570) and Ro-15-0778, an arotinoid lacking a terminal group, have little or no effect on embryonal carcinoma cell differentiation [4].

High impact information on Arotinoid

• The types of malformations induced by oral arotinoid treatment were essentially identical to those found after maternal treatment with all-trans-retinoic acid or other teratogenic retinoids during the same gestational age [5].
• Treatment of epidermal cells with arotinoid Ro 13-6298, a potent synthetic analog of retinoic acid, increased the abundance of mRNA for keratin 13 by 25-fold and for keratin 19 by greater than 40-fold but had no effect on the abundance of mRNA for keratins 5 and 6 [6].
• The induction of ODC activity by RA was itself inhibited by topical arotinoid ethyl ester treatment [7].
• Induction of epidermal ODC activity was inhibited by arotinoid ethyl ester but not by RA, 13-cis-RA, or aromatic retinoid when they were applied to the skin at 24 hr prior to tape stripping [7].
• In epidermal keratinocytes, the levels of keratins 5, 6, 14, and 17 decrease and keratins 13 and 19 increase in response to increasing concentrations of a potent synthetic trans-retinoic acid analog, arotinoid Ro 13-6298 [8].

Chemical compound and disease context of Arotinoid

• Topical application of 0.01-1.0 mg/kg arotinoid Ro 13-6298 resulted in dose-dependent mucocutaneous toxicity and an increase in the numbers of dead embryos and malformed offspring [9].
• Histologic examination of the epidermis revealed that a dose-dependent hyperplasia and thickening of the epidermis and the stratum granulosum was induced by the retinoids when given at subtoxic doses, being most marked after arotinoid or RA [10].
• Studies with murine bone marrow cells and human breast-cancer cell lines in vitro demonstrated that there was no interaction between the 2 drugs at the cellular level, indicating that the arotinoid does not enhance the ability of cells to metabolize 5-FU [11].
• They differed in their ability to normalize blood pressure (Ro-257386 > BMS-453 > arotinoid), albuminuria (BMS-453 > Ro-257386 > arotinoid), and creatinine clearance (arotinoid > BMS-453 > Ro-257386) [12].
• In this study, inhibitory effects of rh-CT against bone resorption were examined in thyroparathyroidectomized (TPTX) rats, the animal model of accelerated bone resorption induced by administering a synthetic retinoid (arotinoid) [13].

Biological context of Arotinoid

• Both induction and suppression responses show identical kinetics and both processes are half-maximal at 5 nM arotinoid and maximal at 10 nM [8].
• We examined the binding properties of RARs and RXRs for a series of synthetic retinoids and compared the ligand-binding properties of these arotinoid analogs with their ability to regulate gene expression via the retinoid receptors in a cotransfection assay [14].
• In rats treated for 3 days with ALLN, arotinoid-induced reduction in cortical bone mineral density measured by peripheral quantitative computed tomography (pQCT) was inhibited by 86.4% (p < 0.05) in rats treated with ALLN 100 mg/kg, i.p., and by 82% in rats treated with 50 mg/kg, i.p. (p < 0.05) [15].
• The arotinoid did not interact with receptor signal transduction pathways under the control of serum components, such as growth factors as half-maximal inhibiton of growth was similar in HT29-S-B6 cells cultured in the absence or presence of serum [16].
• Influence of food on the bioavailability of Ro 15-0778 in humans [17].

Anatomical context of Arotinoid

• This gene was down-regulated in the breast-cancer cell line MDA-MB-231 after treatment with the arotinoid for 3 to 6 hr [18].
• In addition to its anti-proliferative effects, this arotinoid may play a role in protection of bone marrow function after use of cytotoxic drugs [19].
• After applications of 0.1 ml of 0.1% RA, 0.1% 13-cis-RA, 0.1% aromatic retinoid, or 0.001% arotinoid in acetone to the dorsal skin for 5 days a week for 2 weeks, there was a reduction of utricle diameter to 45%, 52%, 30%, and 31% of acetone-treated controls, respectively [10].
• The half-lives of the retinoids in the dermis tended to be longer than in the epidermis, except for the arotinoid [20].
• After doses of 0.1% RA and 0.001% arotinoid , the utricles resembled the hair follicles of hairless mice [10].

Associations of Arotinoid with other chemical compounds

• Of all retinoids tested, only arotinoid ethylsulfone caused a drastic increase in EGF binding, while hydrocortisone had no effect [21].
• Inhibition of oral carcinogenesis by the arotinoid mofarotene (Ro 40-8757) in male F344 rats [22].
• The chemopreventive effect of dietary administration of a new arotinoid, mofarotene (Ro 40-8757), which contains a morpholine structure in the polar end group, during the initiation phase of 4-nitroquinoline 1-oxide (4-NQO)-induced oral carcinogenesis was investigated in male F344 rats [22].
• Quantitative analysis of retinoids in biological fluids by high-performance liquid chromatography using column switching. III. Determination of the arotinoid sumarotene and its Z-isomer in human and animal plasma [23].
• Structural modifications of the arotinoid molecule RO 13-7410 led to a difference in the teratogenic potencies of more than five orders of magnitude in mice in vivo and in micromass cultures of rat embryonic limb bud cells (Kistler et al. 1990) [24].

Gene context of Arotinoid

• Direct addition of Ro 40-8757 to mouse bone-marrow cells in clonogenic assay cultures containing WEHI-3-conditioned medium plus erythropoietin showed no significant enhancement by the arotinoid [25].
• The oncogene erbB2 (c-neu) and the growth factor EGF expression were more prominent in the small tumors of the mice treated with arotinoid than in the larger tumors of the control group [26].
• The experimental treatment modalities, interferon-alpha and retinoids, especially arotinoid, are most effective in early stages of CTCL; in advanced stages, the effectiveness can be increased by combination regimens [27].
• In this study, the effects of the arotinoid mofarotene on single cell motility and vinculin organization of the highly metastatic melanoma cell line K-1735-M2 were determined [28].
• Influence of 13-cis retinoic acid and of arotinoid on the cytochrome P-450 system in rat liver [29].

Analytical, diagnostic and therapeutic context of Arotinoid

• On Northern blot analysis, sPRP cDNA hybridized to RNAs of similar sizes in tracheal cells from cat, rabbit, and lamb. sPRP was not detected in tracheal cells that were cultured with 10(-9) M arotinoid [30].
• Arotinoid Ro 40-8757 caused marked decrease in the number and branching of mammary ducts, and inhibited mammary tumor development with significant decrease in the incidence, multiplicity, and tumor weights compared to the NTP-2000 diet control [26].
• Established, palpable and measurable rat mammary tumours, chemically induced by oral administration of 12 mg/animal 7,12-dimethylbenz[a]anthracene, were treated with Ro 15-0778 as a feed-admix in daily doses of 100 mg/kg for 6 weeks and 200 and 400 mg/kg for 9 weeks [31].
• A non-polar arotinoid, Ro 15-0778, has been investigated for its effect on carcinogen-induced changes in rodent respiratory epithelia in organ culture [32].
• Sixteen patients - 12 with cutaneous T cell lymphoma (CTCL), 1 with Sézary syndrome, 1 with actinic reticuloid, and 2 with parapsoriasis variegata - were treated with either a new, potent arotinoid alone or with combined etretinate (Tigason) and PUVA therapy (Re-PUVA) [33].

References