Retinoids in Clinical Use

Njar, Vincent C.O.

doi:10.1002/9783527623297.ch12

Cited by 4 publications

(4 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Derivatives of vitamin A are essential for a number of biological processes, and retinoic acid and its derivatives have been used extensively to treat skin conditions associated with increased cell proliferation and hyperkeratosis [23,24] . Retinoid responses are believed to be mediated by retinoid-dependent transcription factors, specifically retinoic acid receptor and retinoid X receptor [25,26] .…”

Section: Discussionmentioning

confidence: 99%

Claudin 2 mRNA and Protein Are Present in Human Keratinocytes and May Be Regulated by All-<i>trans-</i>Retinoic Acid

Telgenhoff¹,

Ramsay²,

Hilz³

et al. 2008

Skin Pharmacol Physiol

View full text Add to dashboard Cite

Tight junctions are composed of claudins, occludins, junctional adhesion molecules and plaque proteins. Claudin 2 protein forms a cation-selective channel which confers increased permeability in renal epithelial cells and in the intestine where its expression is restricted to the leaky epithelium. Immunohistochemical staining revealed claudin 2 staining in the granular layer of adult epidermis. Analysis of Western blots revealed bands corresponding to the molecular weight of claudin 2 in Madin-Darby canine kidney II cells, human kidney, adult skin and neonatal keratinocytes. Reverse transcriptase polymerase chain reaction on mRNA and cDNA sequence analysis found a 99% sequence homology between our cDNA and human claudin 2 (NIH BLAST sequence). Further, we show that all-trans-retinoic acid increases the expression of claudin 2 in keratinocytes in a dose-dependent manner. The discovery of claudin 2 transcript and protein in the skin could be of importance in epidermal differentiation, barrier function and pathological conditions.

show abstract

Section: Discussionmentioning

confidence: 99%

Claudin 2 mRNA and Protein Are Present in Human Keratinocytes and May Be Regulated by All-<i>trans-</i>Retinoic Acid

Telgenhoff¹,

Ramsay²,

Hilz³

et al. 2008

Skin Pharmacol Physiol

View full text Add to dashboard Cite

show abstract

“…Since PCa is one of the leading causes of deaths worldwide, there is an urgent need to identify effective agents against this disease. Retinoids, rexinoids, retinoid-related molecules (RRMs) and histone deacetylase inhibitors (HDACIs) have shown promising biological activities as single agents in several preclinical studies of both haematological and solid malignancies (Altucci and Gronemeyer, 2001;Lindemann et al, 2004;Bolden et al, 2006;Njar et al, 2006a). Because of the heterogeneous nature of PCa, we hypothesise that agents/ combination of agents affecting various pathways involved in PCa growth and survival may be advantageous.…”

mentioning

confidence: 99%

MS-275 synergistically enhances the growth inhibitory effects of RAMBA VN/66-1 in hormone-insensitive PC-3 prostate cancer cells and tumours

2008

View full text Add to dashboard Cite

Combining drugs, which target different signalling pathways, often decreases adverse side effects while increasing the efficacy of treatment. The objective of our study was to determine if the combination of our novel atypical retinoic acid metabolism-blocking agent (RAMBA) VN/66-1 and a promising histone deacetylase inhibitor N-(2-aminophenyl)4-[N-(pyridine-3-yl-methoxycarbonyl)aminomethyl]benzamide (MS-275) would show enhanced antineoplastic activity on human PC-3 prostate cancer cells/ tumours and also to decipher the molecular mechanisms of action. The combination of VN/66-1 þ MS-275 was found to be synergistic in inhibiting PC-3 cell growth, caused cell cytostaticity/cytotoxicity and induced marked G2/M phase arrest and apoptosis. In mice with well-established PC-3 tumours, VN/66-1 (5 and 10 mg kg À1 day À1 ) caused significant suppression of tumour growth compared with mice receiving vehicle alone. Furthermore, treatment with VN/66-1 (10 mg kg À1 day À1 ) þ MS-275 (2.5 mg kg À1 day À1 ) for 18 days resulted in an 85% reduction in final mean tumour volume compared with control and was more effective than either agent alone. Mechanistic studies indicated that treatment of PC-3 cells/tumours with VN/66-1 þ MS-275 caused DNA damage (upregulation of gH2AX), hyperacetylation of histones H3 and H4, upregulation of retinoic acid receptor-b, p21 WAF1/CIP1 , E-cadherin, and Bad and downregulation of Bcl-2. These data suggest that the mechanism of action of the combination of agents is DNA damage-induced p21 activation, resulting in inhibition of the Cdc2/cyclin B complex and accumulation of cells in G2/M phase. In addition, the combination caused modulation and induction of apoptosis. These results suggest that VN/66-1 or its combination with MS-275 may be a novel therapy for the treatment of prostate carcinoma.

show abstract

“…Adapalene is a naphthoic acid derivative with a methoxyphenil adamant side‐chain and is a commonly used anti‐acne drug. It also has selective affinity only for nuclear retinoic acid receptor‐β and retinoic acid receptor‐γ, which are associated with terminal differentiation in the epidermal keratinocytes, and has similar efficacy to that of other retinoids 8,9 . In contrast, tretinoin, one of the retinoids, is a retinoic acid receptor‐α, ‐β and ‐γ agonist, and it can act on increasing the turnover of follicular epithelial cells through EGFR signaling 8,10 .…”

mentioning

confidence: 99%

“…It also has selective affinity only for nuclear retinoic acid receptor‐β and retinoic acid receptor‐γ, which are associated with terminal differentiation in the epidermal keratinocytes, and has similar efficacy to that of other retinoids 8,9 . In contrast, tretinoin, one of the retinoids, is a retinoic acid receptor‐α, ‐β and ‐γ agonist, and it can act on increasing the turnover of follicular epithelial cells through EGFR signaling 8,10 . EGFR inhibitors such cetuximab result in impairing the turnover of follicular epithelial cells and give rise to acneiform eruptions 7,10 .…”

mentioning

confidence: 99%