Enhancement of Regression of Cervical Intraepithelial Neoplasia II (Moderate Dysplasia) With Topically Applied All- trans -Retinoic Acid: a Randomized Trial

Meyskens, Frank L.; Surwit, Earl A.; Moon, Thomas E.; Childers, Joel M.; Davis, John R.; Dorr, Robert T.; Johnson, Cynthia S.; Alberts, David S.

doi:10.1093/jnci/86.7.539

Cited by 229 publications

(109 citation statements)

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“…The first goal of our cancer chemoprevention trials was to define a dose of DFMO that was both safe and effective. Our dose de-escalation studies and subsequent randomized placebo-controlled studies demonstrated that oral doses of DFMO between 0.25 and 0.5 g/m 2 /day for times as short as 1 month and as long as 1 year were effective in reducing rectal polyamine content in humans [85][86][87] . These studies also demonstrated that these doses, which can reduce rectal polyamine levels, did not produce detectable toxicities in excess of those observed in the group receiving placebo.…”

Section: Box 3 | Measuring Polyamine Variables In Clinical Studiesmentioning

confidence: 71%

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Polyamines and cancer: old molecules, new understanding

2004

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| The amino-acid-derived polyamines have long been associated with cell growth and cancer, and specific oncogenes and tumour-suppressor genes regulate polyamine metabolism. Inhibition of polyamine synthesis has proven to be generally ineffective as an anticancer strategy in clinical trials, but it is a potent cancer chemoprevention strategy in preclinical studies. Clinical trials, with well-defined goals, are now underway to evaluate the chemopreventive efficacy of inhibitors of polyamine synthesis in a range of tissues. UREA CYCLEThe key metabolic pathway in mammals for eliminating cellular breakdown products containing nitrogen. NATURE REVIEWS | CANCER VOLUME 4 | OCTOBER 2004 | 7 8 1

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Section: Box 3 | Measuring Polyamine Variables In Clinical Studiesmentioning

confidence: 71%

“…'Proof of principle' for chemoprevention of cancer in humans has been established [85][86][87] . However, toxicity has abrogated the widespread adoption of agents, such as retinoids, for the prevention of cervical and oral cancers 89 .…”

Section: Implications and Future Directionsmentioning

confidence: 99%

Polyamines and cancer: old molecules, new understanding

2004

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“…Cancer of the cervix, which develops in a multistep fashion through progressive intra-epithelial neoplasia (CINI-III) is another logical candidate for a chemoprevention approach. Topical application of ATRAinduced regression in 43% of patients with moderate dysplasia (CIN II) in comparison to a spontaneous regression in 27% of patients treated with placebo, but had no effect on more severe dysplasia (Meyskens et al, 1994). Moreover, N-(4-ethoxycarbophenyl) retinamide decreased the incidence and increased survival in a population at high risk of oesophageal cancer (Han, 1993), but retinoids have had consistently no effect on reversal of bronchial metaplasia (Lee et al, 1994).…”

Section: Clinical Datamentioning

confidence: 99%

Retinoids: present role and future potential

1999

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Summary Vitamin A and its biologically active derivatives, retinal and retinoic acid (RA), together with a large repertoire of synthetic analogues are collectively referred to as retinoids. Naturally occurring retinoids regulate the growth and differentiation of a wide variety of cell types and play a crucial role in the physiology of vision and as morphogenic agents during embryonic development. Retinoids and their analogues have been evaluated as chemoprevention agents, and also in the management of acute promyelocytic leukaemia. Retinoids exert most of their effects by binding to specific receptors and modulating gene expression. The development of new active retinoids and the identification of two distinct families of retinoid receptors has led to an increased understanding of the cellular effects of activation of these receptors. In this article we review the use of retinoids in chemoprevention strategies, discuss the cellular consequences of activated retinoid receptors, and speculate on how our increasing understanding of retinoid-induced signalling pathways may contribute to future therapeutic strategies in the management of malignant disease.

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“…Other successful retinoid trials have been reported, including cervical dysplasia (20) and xeroderma pigmentosum (21). Treatment with all-trans-retinoic acid is a relatively standard therapy for the treatment of acute promyelocytic leukemias (22).…”

Section: Introductionmentioning

confidence: 99%

Organ-specific expression profiles of rat mammary gland, liver, and lung tissues treated with targretin, 9-cis retinoic acid, and 4-hydroxyphenylretinamide

Wang¹,

Yao²,

Maciąg³

et al. 2006

Molecular Cancer Therapeutics

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A rexinoid, targretin, and two retinoids, 9-cis retinoic acid (9cRA) and 4-hydroxyphenylretinamide (4HPR), were examined for their effects on gene expression in rat mammary gland, liver, and lung tissues. The chemopreventive effects of these agents have largely been attributed to their ability to interact with retinoic acid receptors (RAR) and/or retinoid X receptors (RXR). Targretin interacts with the RXR receptors. 9cRA interacts with both the RAR and RXR receptors, whereas 4HPR has a moderate affinity primarily for RAR ;. Based on previous studies on mammary chemoprevention, targretin (150 mg/ kg diet), 9cRA (100 mg/kg diet), and 4HPR (782 mg/kg diet), were administered to rats continually in their diet for 7 days. Tissue-and agent-specific expression differences were determined by comparing tissues from treated rats with those from rats given a control diet. There were significantly more changes associated with targretin than 9cRA or 4HPR. Only a limited number of expression changes were found with 4HPR treatment. For each organ, targretin-and 9cRA-treated tissues clustered closely together, whereas 4HPR-treated tissues clustered with the tissues from the control diet group. In contrast to 9cRA treatment, targretin treatment altered genes that involved fatty acid metabolism and modulation of various cytochromes P450 in the liver, clearly demonstrating the very disparate nature of these two retinoids. These expression signatures could provide useful pharmacodynamic biomarkers for retinoid treatment and chemoprevention.

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Enhancement of Regression of Cervical Intraepithelial Neoplasia II (Moderate Dysplasia) With Topically Applied All- trans -Retinoic Acid: a Randomized Trial

Abstract: A derivative of vitamin A can reverse or suppress an epithelial preneoplasia, lending further support to the notion that chemoprevention of human cancer is feasible.

Cited by 229 publications

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Polyamines and cancer: old molecules, new understanding

Polyamines and cancer: old molecules, new understanding

Retinoids: present role and future potential

Organ-specific expression profiles of rat mammary gland, liver, and lung tissues treated with targretin, 9-cis retinoic acid, and 4-hydroxyphenylretinamide

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