Disease relevance of FENRETINIDE

• CONCLUSIONS: Fenretinide treatment of women with breast cancer for 5 years appears to have no statistically significant effect on the incidence of second breast malignancies overall, although a possible benefit was detected in premenopausal women [1].
• N-(4-hydroxyphenyl)retinamide: a potent inducer of apoptosis in human neuroblastoma cells [2].
• Can fenretinide protect women against ovarian cancer [3]?
• Growth inhibition and induction of apoptosis by fenretinide in small-cell lung cancer cell lines [4].
• BACKGROUND: The synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR or fenretinide) is toxic to myeloid leukemia and cervical carcinoma cell lines, probably in part due to its ability to increase levels of reactive oxygen species (ROS) [5].
• PLAB up-modulation by 4-HPR also occurred in vivo: in ascitic cells collected from patients with ovarian cancer before and after 4-HPR treatment, PLAB was upmodulated in 2/4 patients [6].
• These mRNAs are shown to be rapidly induced in 4-HBR-treated and 4-HPR-treated breast cancer cells, and this up-regulation is also shown to be independent of the RARs [7].
• In vivo, 4-HPR + ABT-737 increased the event-free survival of the MDR human neuroblastoma line CHLA-119 implanted subcutaneously in nu/nu mice (194.5 days for the combination vs. 68 days for ABT-737 and 99 days for 4-HPR) [8].

Psychiatry related information on FENRETINIDE

• When compared to control-fed animals, dietary fenretinide reduced the tumor incidence by 49% and the tumor mass by 52% of ras+myc-induced cancers in the mouse prostate reconstitution model system, which was modified to prolong the latency period before cancer development [9].
• The younger were the women, the greater was the risk reduction associated with fenretinide, which attained 50% in women aged 40 years or younger and disappeared after age 55 (P-age*treatment interaction = 0.023) [10].

High impact information on FENRETINIDE

• Effects of N-(4-hydroxyphenyl)retinamide on hTERT expression in the bronchial epithelium of cigarette smokers [11].
• Some novel retinoids, such as fenretinide, i.e., N-(4-hydroxyphenyl)retinamide (4-HPR), induce apoptosis through retinoic acid receptor-independent mechanisms; however, they appear to do so only at concentrations above those achieved in clinical chemoprevention trials [12].
• Re: Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer [13].
• BACKGROUND: 9-cis-Retinoic acid (9-cis-RA) and N-(4-hydroxyphenyl)retinamide (4-HPR) are effective chemopreventive agents against epithelial tumors in the oral cavity, breast, and prostate [14].
• BACKGROUND: We previously reported that N-(4-hydroxyphenyl)retinamide (4-HPR, fenretinide) treatment caused large increases of ceramide levels in neuroblastoma cell lines and induced cell death by a combination of apoptosis and necrosis through p53 (also known as TP53)-independent and caspase-independent pathways [15].

Chemical compound and disease context of FENRETINIDE

• PURPOSE: To determine (1) whether nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs) are differentially expressed in normal and in cancerous human prostate tissues and (2) whether oral fenretinide therapy impacts the expression of these receptors in prostate cancer [16].
• Use of tamoxifen combined with hormone replacement therapy or use of raloxifene, any aromatase inhibitor or inactivator, or fenretinide to lower the risk of developing breast cancer is not recommended outside of a clinical trial setting [17].
• We hypothesize that targeting minimal residual disease with the cytotoxic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR; fenretinide) may decrease relapse [18].
• Synthetic retinoid fenretinide is effective against a human ovarian carcinoma xenograft and potentiates cisplatin activity [19].
• We evaluated the ability of dietary N-(4-hydroxyphenyl)retinamide; 1 alpha,25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalcifero l (Ro24-5531); and tamoxifen to inhibit the development of androgen-promoted carcinomas of the accessory sex organs of male Lobund-Wistar rats [20].

Biological context of FENRETINIDE

• Involvement of reactive oxygen species in N-(4-hydroxyphenyl)retinamide-induced apoptosis in cervical carcinoma cells [21].
• Effect of the synthetic retinoid fenretinide on dark adaptation and the ocular surface [22].
• 4-oxo-fenretinide, a recently identified fenretinide metabolite, induces marked G2-M cell cycle arrest and apoptosis in fenretinide-sensitive and fenretinide-resistant cell lines [23].
• The levels of the retinoid receptors, retinoic acid receptor alpha and retinoid X receptor gamma, were up-regulated in response to fenretinide, suggestive of ligand-induced receptor up-regulation [24].
• Because of these findings, we investigated whether dietary fenretinide could alter the incidence of phenotype of oncogene-induced prostate cancer in the mouse prostate reconstitution model system [9].

Anatomical context of FENRETINIDE

• We found that mac25 accumulates in senescent cells and is up-regulated in normal, growing mammary epithelial cells by all-trans-retinoic acid or the synthetic retinoid fenretinide [25].
• Fenretinide enhances rituximab-induced cytotoxicity against B-cell lymphoma xenografts through a caspase-dependent mechanism [26].
• Bilateral ovariectomy and dietary administration of the retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) are both effective inhibitors of chemical carcinogenesis in the rat mammary gland [27].
• Fenretinide treatment also increased levels of the death receptor DR5 and caused mitochondrial membrane depolarization [24].
• 6-[3-(1-Admantyl)]-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) and fenretinide N-[4-hydroxyphenyl] retinamide (4-HPR) are conformationally restricted synthetic retinoids that induce growth arrest and apoptosis in both ATRA-sensitive and ATRA-resistant ovarian tumor cell lines [28].

Associations of FENRETINIDE with other chemical compounds

• The CD437-resistant cell line maintains sensitivity to the antiproliferative and apoptotic action of all-trans-retinoic acid, AM580, and fenretinide, though it shows partial resistance to the cytodifferentiating effects of the first 2 compounds [29].
• Five-year administration of fenretinide: pharmacokinetics and effects on plasma retinol concentrations [30].
• Fenretinide or N-(4-hydroxyphenyl)retinamide is a vitamin A analogue synthesized in the United States in the late 1960s [31].
• The activity of dietary and topical administration of three retinoids, all-trans-retinoic acid, 13-cis-retinoic acid, and N-(4-hydroxyphenyl)retinamide (4-HPR), as promoters of skin tumor induction in SENCAR mice was studied [32].
• Conversely, Bak induction was blocked by the antioxidant vitamin C. Overexpression of Bak increased apoptosis in both the presence and absence of fenretinide, whereas expression of antisense Bak inhibited fenretinide-induced apoptosis [33].

Gene context of FENRETINIDE

• The synthetic retinoid N-(4-hydroxyphenyl)retinamide, which does not bind effectively to RAR-beta, had no effect on COX-2 suppression [34].
• BBC3 mediates fenretinide-induced cell death in neuroblastoma [35].
• Fenretinide induced reductions of IGF-I, IGFBP-3, and IGF-I:IGFBP-3 of 8% (95% CI, 2-12%; P = 0.004), 3% (95% CI, 1-5%; P = 0.002), and 5% (95% CI, 0-10%; P = 0.050), respectively [36].
• We aimed at determining the effect of cyclin D1 level on the response to fenretinide treatment [37].
• Cell death induced by N-(4-hydroxyphenyl)retinamide in human epidermal keratinocytes is modulated by TGF-beta and diminishes during the progression of squamous cell carcinoma [38].

Analytical, diagnostic and therapeutic context of FENRETINIDE

• Phase IIa study of fenretinide in superficial bladder cancer, using DNA flow cytometry as an intermediate end point [39].
• Enhanced inhibition of mammary carcinogenesis by combined treatment with N-(4-hydroxyphenyl)retinamide and ovariectomy [27].
• In an attempt to characterize the mechanism of action of fenretinide, cDNA array filters were screened to identify apoptotic genes regulated in response to treatment of SH-SY5Y cells with fenretinide [40].
• Fenretinide is currently being evaluated in phase I and phase II clinical trials as an agent for both the treatment and chemoprevention of human prostate cancer [9].
• The genes involved in the enhanced fenretinide-induced apoptosis by parthenolide were identified using the differential display-PCR method and subsequent Northern blot or semiquantitative reverse transcriptase PCR analysis [41].

References