Retinoid signaling in immortalized and carcinoma-derived human uroepithelial cells

Waliszewski, Przemysław; Waliszewska, Miroslawa; Gordon, Niquel; Hurst, Robert E.; Benbrook, Doris M.; Arindam, Dhar; Hemstreet, George P.

doi:10.1016/s0303-7207(98)00235-4

Cited by 8 publications

(14 citation statements)

References 42 publications

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“…This is consistent with our initial report of a lack of modulation of flow cytometric DNA content, conventional cytology, and recurrence-free survival by the retinoid after 3 years (16). Despite evidence of activity in animal studies (27)(28)(29) and its ability to induce apoptosis in bladder cancer cell lines at relevant pharmacologic concentrations (30), fenretinide has proved to be ineffective in two independent clinical trials (16,31). Accumulating evidence suggests that retinoids fail to modulate tobacco-related carcinogenesis (32,33).…”

Section: Discussionsupporting

confidence: 85%

Prognostic Effect of DNA Aneuploidy from Bladder Washings in Superficial Bladder Cancer

Puntoni¹,

Zanardi²,

Branchi³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Superficial (papillary) bladder cancer is associated with progression and death from muscle-invasive bladder cancer, but no reliable predictors of the outcomes have been identified. Methods: We analyzed the long-term prognostic effect of DNA flow cytometry in bladder washings from 93 subjects with previously resected T a and T 1 bladder tumors who participated in a chemoprevention trial of the synthetic retinoid fenretinide. Kaplan-Meier analysis and Cox regression were used to determine the prognostic effect of DNA aneuploidy on cancer progression and mortality in conjunction with conventional clinical factors after a median of 11.5 years (interquartile range, 9.5-11.7 years). Results: Overall, 58 of 93 (62%) specimens were DNA aneuploid at baseline. Progression-free survival was signif-

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Section: Discussionsupporting

confidence: 85%

Prognostic Effect of DNA Aneuploidy from Bladder Washings in Superficial Bladder Cancer

Puntoni¹,

Zanardi²,

Branchi³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…From a potential therapeutic standpoint, LRAT expression was restored here after retinoid treatment in two TCC cell lines, which demonstrated minimal or absent basal LRAT mRNA expression. Retinoid-induced mRNA expression of several retinoid-responsive genes has been shown previously in human bladder cancer cell lines (18); LRAT activity, meanwhile, has been demonstrated in the livers of vitamin A-deficient rats after retinoid exposure (24). Given the known impact of retinoids on cell growth and differentiation (19), along with the importance of LRAT in maintaining retinoid levels in tissues (25,26), restoration of LRAT expression may provide one molecular mechanism for the effects of retinoids in human bladder cancer, as reviewed previously (3,52,53).…”

Section: Discussionsupporting

confidence: 56%

“…The majority of actions of retinoids are thought to be mediated by two different families of nuclear receptors, RA receptors and retinoid X receptors, each consisting of three receptor types ␣, ␤, and ␥ (17). The expression profile of these receptors in bladder cancer has been explored previously in vitro for several human bladder carcinoma cell lines (9,18). The RA receptors and retinoid X receptors act as ligand-activated transcription factors to regulate the expression of a number of retinoidresponsive genes (19).…”

Section: Introductionmentioning

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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“…[32][33] Rationale of the present study was based on the mutual relationship of the bladder and retinoids as evident from: (1) The expression of not only the complete retinoid signal transduction cascade, synthesizing and catabolising enzymes but also retinoid storing ability. [34][35][36][37][38] (2) Abnormalities at the genetic and epigenetic levels involving these components correlated unfavorable bladder cancer prognosis and early disease. [34][35][36][37][38][39][40][41][42] (3) Epidemiologic studies connected the disease predisposition and/or prevention to abnormal plasma retinoid levels.…”

Section: Discussionmentioning

confidence: 99%

“…[34][35][36][37][38] (2) Abnormalities at the genetic and epigenetic levels involving these components correlated unfavorable bladder cancer prognosis and early disease. [34][35][36][37][38][39][40][41][42] (3) Epidemiologic studies connected the disease predisposition and/or prevention to abnormal plasma retinoid levels. [43][44][45] Bilharzial patients and bladder cancer patients with squamous cell carcinoma, the most prevalent type in Egypt, showed significantly lower levels of vitamin A than normal male subjects.…”

Section: Discussionmentioning

confidence: 99%

The effectiveness of retinoic acid treatment in bladder cancer: Impact on recurrence, survival and TGFα and VEGF as end-point biomarkers.

Hameed

2008

Cancer Biology & Therapy

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Introduction and aims: Being best-studied superficial bladder cancer (SBC) chemopreventives, retinoids' negative studies and toxicity were stumbling. With proper understanding of retinoid metabolism, we aimed at investigating combined ketoconazole (a strong inhibitor of retinoic acid-catabolizing cytochrome P450s) all-trans retinoic acid (Keto-atRA) SBC treatment. VEGF and TGFα levels are end-point pathogenetic biomarkers involved in early SBC.Results: Keto-atRA treatment significantly improved survival time and decreased recurrence rate compared to control disease group, with tolerable and reversible side-effects. Treatment normalized induced levels of VEGF and TGFα with a positive correlation between these cytokines.Material and methods: Seven days after TURT visible tumor(s), combined atRA 1 mg/kg for five days a week + Keto 200 mg twice daily for five days a week for three months were given to 16 patients with SBC stages Ta and T1 with various grades. Three months follow up/20 months used white light cystoscopy and urinary cytology. Recurrence rate and survival time were compared to a retrospective group of 25 patients of comparable age, stage and grade with TURT as sole treatment for SBC. VEGF and TGFα were measured in urine and serum of 12 normal subjects and treated patients. Samples were collected just before TURT, one week after TURT, at the end of one month and at the end of three months of treatment.Conclusions: The combination and schedule used for KetoatRA therapy effectively reduced recurrence rate and increased survival time of SBC patients probably through reduction of VEGF and TGFα as major mitogenic/angiogenic factors; possibly by eliminating malignant cells that produce them.

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Retinoid signaling in immortalized and carcinoma-derived human uroepithelial cells

Cited by 8 publications

References 42 publications

Prognostic Effect of DNA Aneuploidy from Bladder Washings in Superficial Bladder Cancer

Prognostic Effect of DNA Aneuploidy from Bladder Washings in Superficial Bladder Cancer

Reduced Lecithin

The effectiveness of retinoic acid treatment in bladder cancer: Impact on recurrence, survival and TGFα and VEGF as end-point biomarkers.

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