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            <i>cis</i>
            -Retinoic Acid: Inhibition of Bladder Carcinogenesis in the Rat

Sporn, Michael B.; Squire, Robert A.; Brown, Charles; Smith, Joseph M.; Wenk, Martin L.; Springer, Stephanie

doi:10.1126/science.835006

Cited by 230 publications

(48 citation statements)

References 12 publications

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“…Animal studies evaluating the chemopreventive effects of retinoids have found that a range of synthetic and naturally occurring retinoids inhibit chemically induced bladder carcinogenesis in rats and mice (5)(6)(7)55). Furthermore, in human studies, serum vitamin A levels were shown to be lower in patients with bladder cancer (4), whereas a reduced incidence of bladder cancer was noted in patients with a high dietary intake of vitamin A or carotenoids (56,57).…”

Section: Discussionmentioning

confidence: 99%

Reduced Lecithin

Boorjian¹,

Tickoo²,

Mongan³

et al. 2004

Clinical Cancer Research

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Purpose: Retinoids, which include vitamin A (retinol; ROL) and its derivatives, have been investigated in the treatment of bladder cancer. We have shown that expression of the enzyme lecithin:ROL acyltransferase (LRAT), which converts ROL to retinyl esters, is reduced in several human cancers. Here we evaluated expression of LRAT protein and mRNA in normal and malignant bladder tissue specimens from human patients. We also examined the effect of retinoids on LRAT expression in bladder cancer cell lines.Experimental Design: We evaluated 49 bladder cancer specimens for LRAT protein expression using immunohistochemistry with affinity-purified antibodies to human LRAT. LRAT mRNA expression was assessed using reverse transcription-PCR in bladder specimens from an additional 16 patients. We examined the effect of retinoic acid and ROL on LRAT mRNA expression in five human bladder cancer cell lines.Results: LRAT protein was detected throughout the nonneoplastic bladder epithelium in all of the specimens. In bladder tumors, LRAT protein expression was reduced compared with the nonneoplastic epithelium or was completely absent in 7 of 32 (21.9%) superficial tumors versus 16 of 17 (94.1%) invasive tumors (P < 0.001). All of the nonneoplastic bladder specimens tested (11 of 11) showed LRAT mRNA expression, compared with 5 of 8 (62%) superficial tumors and 0 of 5 (0%) invasive tumors (P ‫؍‬ 0.001). Three of five human bladder cancer cell lines expressed LRAT mRNA independent of retinoid exposure, whereas in two cell lines LRAT mRNA expression was induced by retinoid treatment.Conclusions: We report a significant reduction in LRAT expression in bladder cancer. Moreover, we demonstrate an inverse correlation of LRAT mRNA and protein expression with increasing tumor stage. These data suggest that loss of LRAT expression is associated with invasive bladder cancer.

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Section: Discussionmentioning

confidence: 99%

Reduced Lecithin

Boorjian¹,

Tickoo²,

Mongan³

et al. 2004

Clinical Cancer Research

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“…[11][12][13] Initially, this interest was fuelled by reports that 13-cis-retinoic acid and the synthetic amide of retinoic acid N-(4-hydroxyphenyl)retinamide (4-HPR) are effective in inhibiting bladder carcinogenesis in animal models. [14][15][16][17] Retinoids bind to and activate the following 2 classes of receptors: retinoic acid receptors (RARa, b, and g) and retinoid X receptors (RXRa, b and g). All-trans retinoic acid (ATRA), the physiologically active derivative of vitamin A, activates RARs, whilst both RARs and RXRs are activated by 9-cis retinoic acid (9-cis RA).…”

mentioning

confidence: 99%

Retinoid‐related molecule AGN193198 potently induces G₂M arrest and apoptosis in bladder cancer cells

Reitmair

Shurland

Tsang

et al. 2005

Intl Journal of Cancer

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The novel synthetic retinoid-related molecule 4-[3-(1-heptyl-4,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-oxo-propenyl]-benzoic acid (AGN193198) neither binds effectively to retinoic acid receptors (RARs) and retinoid X receptors (RXRs) nor transactivates in RAR-and RXR-mediated reporter assays. Even so, AGN193198 is potent in inducing apoptosis in human prostate and breast carcinoma cells (Keedwell et al., Cancer Res 2004;64:3302-12). Here, we extend these findings to show that AGN193198 potently and rapidly induces apoptosis in bladder carcinoma cell lines. One micromolar of AGN193198 completely abolished the growth of the transitional cell carcinoma lines UM-UC-3 and J82, and the squamous cell carcinoma line SCaBER; the transitional cell papilloma line RT-4 was slightly less sensitive to the growth inhibitory effect of AGN193198. Treated cells accumulated in the G 2 M phase of the cell cycle. This was accompanied by apoptosis, as revealed by staining cells for exposure of phosphatidylserine at their surface (binding of Annexin V) and FACS analysis of propidium iodide labeled cells. As reported for prostate cancer cells, AGN193198 provoked rapid activation of caspases-3 (by 6 hr), -8 (by 16 hr) and -9 (by 6 hr) in bladder cancer cells. These findings suggest that AGN193198 and related compounds, whose mechanism of action does not appear to involve RARs and RXRs, may be useful in the treatment of bladder cancer. ' 2005 Wiley-Liss, Inc.

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“…Several retinoids are used clinically for treatment of recalcitrant cystic and conglobate acne, Darier's disease, pustular psoriasis , lichen ruber planus, basal cell carcinoma, keratoacanthoma and melanoma (Peck, 1982;Orfanos, 1980). In mice certain retinoids exert a therapeutic influence on chemically-induced papillomas and carcinomas of the skin (Bollag, 1975), and in rats certain retinoids prevent cancer of the urinary bladder (Sporn et al , 1977) and mammary gland (Moon and McCormick, 1982;Hartmann and Bollag, 1985).…”

Section: List Of Figuresmentioning

confidence: 99%

“…Some of these are in clinical use for treatment of recalcitrant cystic acne, Darier's disease, pustular psoriasis, lichen ruber planus, basal cell carcinomas, keratoacanthomas, and melanomas. Certain retinoids exert a therapeutic influence on chemically induced papillomas and carcinomas of the skin of mice (Bollag, 1975) and prevent carcinogenesis in the urinary bladder (Sporn et al, 1977) and mammary gland (Moon and McCormick, 1982;Hartman and Bollag, 1985) of rats. The use of retinoids in anticancer and dermatologic therapy has been reviewed (Bollag, 1979;Cunningham and Ehmann, 1983;Hill and Grubbs , 1982;Lauharanta, 1980;Meyskens, 1983;Orfanos, 1980;Peck, 1981;Peck, 1982;Sporn and Roberts, 1983 (Eaton, 1978;Jowsey and Riggs, 1968;Gerber eta!., 1954).…”

Section: Introductionmentioning

confidence: 99%