Disease relevance of Ro 4-3930

• Increase of ceramide and induction of mixed apoptosis/necrosis by N-(4-hydroxyphenyl)- retinamide in neuroblastoma cell lines [1].
• HPLC analysis of the bile of female rats injected intraperitoneally with a single dose of the retinamide [60 mg/kg (body weight)] showed that the excretion of the retinamide and its glucuronide were markedly suppressed by pretreatment with an oral dose of calcium glucarate [4.5 mmol/kg (body weight)] [2].
• We evaluated the efficacy of concurrent administration of another biologic agent, N-(4-hydroxyphenyl) retinamide (4HPR, fenretinide) with rituximab against a variety of human B-cell lymphoma cell lines (Ramos, DHL-4, and FL-18) in vivo [3].
• N-(4-hydroxyphenyl) retinamide [4-HPR], a synthetic retinoid, has been shown to inhibit tumor cell growth, invasion, and metastasis by a mechanism that is not fully understood [4].
• N-(4-hydroxyphenyl) retinamide (4HPR) enhances TRAIL-mediated apoptosis through enhancement of a mitochondrial-dependent amplification loop in ovarian cancer cell lines [5].

Psychiatry related information on Ro 4-3930

• Administration of 13-cis retinoic acid and N-(4-hydroxyphenyl) retinamide daily in the diet to female Sprague-Dawley rats beginning one day after intubation with 7,12-dimethylbenz(a)anthracene (DMBA) prolonged the latency periods and inhibited the percentage incidence of mammary tumors [6].

High impact information on Ro 4-3930

• Regulation of apoptosis induced by the retinoid N-(4-hydroxyphenyl) retinamide and effect of deregulated bcl-2 [7].
• Involvement of mitochondrial and akt signaling pathways in augmented apoptosis induced by a combination of low doses of celecoxib and N-(4-hydroxyphenyl) retinamide in premalignant human bronchial epithelial cells [8].
• While mean tumor incidence and latency were not significantly altered by any retinoid treatment, tumor growth rate (volume) and final tumor weight were inhibited (P less than 0.05) by 0.75 mmol/kg 13-cis retinoic acid and 1.5 mmol/kg N-(4-hydroxyphenyl) all-trans-retinamide [9].
• A concentration of 1.5 mmol/kg diet of 2-hydroxyethyl and N-(4-hydroxyphenyl) all-trans-retinamide significantly reduced the overall number of gross lung metastases in BALB/c and Swiss mice, and mean number of metastases in Swiss mice [9].
• N-[4-hydroxyphenyl] retinamide in rheumatoid arthritis: a pilot study [10].

Chemical compound and disease context of Ro 4-3930

• N-(4-hydroxyphenyl) retinamide (4-HPR), a derivative of all-trans-retinoic acid (RA) is currently in clinical trials as a chemopreventive agent for breast cancer [11].
• BCNU chemotherapy combined with retinamide markedly down-regulated levels of both Bcl-xL and Bcl-2 proteins in glioblastoma and enhanced the incidence of apoptosis in U87 cells [12].

Biological context of Ro 4-3930

• Role of antioxidants and intracellular free radicals in retinamide-induced cell death [13].
• N-(4-hydroxyphenyl) retinamide induces cell cycle specific growth inhibition in PC3 cells [14].
• Effect of N-(4-hydroxyphenyl) retinamide on food intake, growth, and mammary gland development in rats [15].
• Treatment of the antisense BAG-1-transfected cells with the anti-cancer drugs staurosporine, paclitaxel, all-trans retinoic acid (ATRA), and N-(4-hydroxyphenyl) retinamide (4-HPR) resulted in significantly enhanced apoptosis and reduced cell viability relative to vector-transfected cells [16].
• The in vitro esterification of retinol was competitively inhibited by all-trans-N-(4-hydroxyphenyl) retinamide (Ki = 154 microM) [17].

Anatomical context of Ro 4-3930

• Chemoprevention of cancer of uterine cervix: a study on chemoprevention of retinamide II from cervical precancerous lesions [18].

Associations of Ro 4-3930 with other chemical compounds

• Beginning 1 week after a single i.p. dose of 0, 50 or 100 mg DEN per kg body wt, groups of 35 mice received dietary supplements of (per kg diet): 0.1 mmol all-trans-retinoic acid (RA), 0.5 or 1.0 mmol all-trans-ethyl retinamide (ER), 0.5 or 1.0 mmol 13-cis-ethyl retinamide (13-cis-ER), or vehicle only [19].
• N-(4-hydroxphenyl) retinamide induced a dose-dependent decline in cell growth and survival associated with a maximal 10-fold increase in ceramide production at 10 microM [20].
• The retinamide-mediated apoptosis of promyelocytic cells was investigated using pHi- and DNA-sensitive fluorescent probes (BCECF and Hoechst 33342) [21].
• Differential effects of retinoic acid (RA) and N-(4-hydroxyphenyl) retinamide (4-HPR) on cell growth, induction of differentiation, and changes in p34cdc2, Bcl-2, and actin expression in the human promyelocytic HL-60 leukemic cells [22].
• Cells were treated with either retinamide alone or in combination with the chemotherapy agent, BCNU [12].

Gene context of Ro 4-3930

• Effects of N-(4-hydroxyphenyl) retinamide on urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in prostate adenocarcinoma cell lines [23].
• Retinamide treatment resulted in increased ratios of deamidated verses transamidated levels of Bcl-xL in U87 cells [12].
• Clinical studies have demonstrated that N-4-(carboxyphenyl) retinamide is effective against oral leukoplakia, vulvar leukoplakia, and dysplasia of the uterine cervix and stomach [24].
• The identification of agents that inhibit the progression of dysplastic lesions to esophageal SCC has proven difficult; however, the results of the trial with ATB and retinamide are encouraging [25].
• Cis/trans isomerization of each retinamide at C13 occurred, but only 15-20% of the total dose could be accounted for as parent retinamide and its C13 isomer [26].

Analytical, diagnostic and therapeutic context of Ro 4-3930

• RESULTS: Breast tissue and plasma retinamide (4-HPR plus 4-MPR) concentrations increased significantly with short-term oral administration of 4-HPR [27].
• The synthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR) has been demonstrated to inhibit the development of primary and metastatic neoplasms in several animal models [14].
• An NCI-sponsored, phase II trial of N-(4-hydroxyphenyl)- retinamide (4-HPR) in patients with organ-confined prostate cancer in the period prior to radical prostatectomy was carried out [28].
• Among the Retinoic Acid (RA) derivatives, retinamides, and in particular N-(4-hydroxyphenyl) retinamide (4-HPR), are currently being investigated in selected cases of cancer chemoprevention [29].
• Influence of hormones on N-(4-hydroxyphenyl) retinamide inhibition of 7,12-dimethylbenz[alpha]anthracene transformation of mammary cells in organ culture [30].

References