Randomized placebo-controlled trial of isotretinoin in chemoprevention of bronchial squamous metaplasia

Js, Lee; Lippman, S. M.; Benner, Steven E.; Lee, Joseph; Ro, JY; Jm, Lukeman

doi:10.1016/0169-5002(94)92175-x

Cited by 23 publications

(25 citation statements)

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“…24 In addition, we included in the current study a total of 77 bronchial biopsy samples that were taken from 15 healthy smokers as an initial screening for a previously reported bronchial chemoprevention trial. 25 …”

Section: Patient Selectionmentioning

confidence: 99%

Expression of cyclooxygenase‐1 and cyclooxygenase‐2 in bronchial epithelium and nonsmall cell lung carcinoma

Hastürk¹,

Kemp²,

Kalapurakal³

et al. 2002

Cancer

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Section: Patient Selectionmentioning

confidence: 99%

Expression of cyclooxygenase‐1 and cyclooxygenase‐2 in bronchial epithelium and nonsmall cell lung carcinoma

Hastürk¹,

Kemp²,

Kalapurakal³

et al. 2002

Cancer

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“…[4][5][6] In human lung cancer, epidemiological evidence supports a role for vitamin A-rich foods and supplements in protection against the development of lung cancer in smokers and nonsmokers alike 7 ; however, clinical trials assessing the efficacy of retinoid supplementation against lung cancer have yielded inconsistent and inconclusive results. [8][9][10][11] Difficulties in human trials have included differential responses between smokers, former smokers, and never smokers, and treatment noncompliance, possibly related to the toxic effects of high-dose retinoids.Retinoids regulate biological activity through two types of nuclear receptors: retinoic acid receptors (RARs) and retinoid X receptors (RXRs). 12 While much research has focused on RARb as a tumor suppressor and has utilized ligands specific for the RARs (such as all-trans retinoic acid), fewer studies have investigated ligands that also bind RXRs, including 9cRA.…”

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confidence: 99%

mentioning

confidence: 99%

Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D₃ and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Mernitz

Smith

Wood

et al. 2007

Intl Journal of Cancer

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9-cis-Retinoic acid (9cRA) and 1a, 25-dihydroxyvitamin D 3 (1,25D) show promise as potential chemopreventive agents. We examined 9cRA and 1,25D, alone and in combination, for their potential to inhibit carcinogen (NNK)-induced lung carcinogenesis in A/J mice. A/J mice (n 5 14/group) were treated with 9cRA (7.5, 15, or 30 mg/kg diet), 1,25D (2.5 or 5.0 lg/kg diet), or a combination of 9cRA (15 mg/kg diet) plus 1,25D (2.5 lg/kg diet) for 3 weeks before and 17 weeks after carcinogen injection. Lung tumor incidence, tumor multiplicity, plasma 1,25D levels and kidney expression of vitamin D 24-hydroxylase (CYP24) were determined. Compared to carcinogen-injected controls, mice receiving 9cRA supplementation had significantly lower tumor multiplicity at all doses (decreased 68-85%), with body weight loss at the higher doses of 9cRA. Mice receiving 1,25D supplementation had significantly lower tumor incidence (decreased 36 and 82%) and tumor multiplicity (decreased 85 and 98%), but experienced significant body weight loss, kidney calcium deposition, elevated kidney CYP24 expression and decreased fasting plasma 1,25D levels. Although, there was no apparent influence on chemopreventive efficacy, addition of 9cRA to 1,25D treatment effectively prevented the weight loss and kidney calcification associated with 1,25D treatment alone. These data demonstrate that 9cRA and 1,25D, alone or combined, can inhibit lung tumor promotion in the A/J mouse model. Combining 1,25D with 9cRA has the potential to mitigate the toxicity of 1,25D, while preserving the significant effect of 1,25D treatment against lung carcinogenesis. The underlying mechanism behind this effect does not appear to be related to retinoid modulation of vitamin D catabolism. ' 2006 Wiley-Liss, Inc.Key words: lung cancer; 9-cis retinoic acid; 1a,25-dihydroxyvitamin D 3Chemoprevention by diet or drug intervention may offer a realistic and practical means of modifying the risk of lung cancer, the leading cause of cancer deaths in both men and women in the United States. 1 Two classes of chemopreventive compounds that have been considered are the retinoids and the active form of vitamin D, 1a,25-dihydroxyvitamin D 3 (1,25D, also calcitriol).Retinoids are required for proper differentiation of lung and upper airway epithelium, 2 and both 9-cis retinoic acid (9cRA, also 9-cis tretinoin) and all-trans retinoic acid have been shown to inhibit cell growth and proliferation in lung cancer cell lines. 3 Studies in animal models of lung cancer suggest that retinoids may be effective in cancer chemoprevention in vivo, but results have varied with species, dose and timing of treatment in relation to induction of carcinogenesis. [4][5][6] In human lung cancer, epidemiological evidence supports a role for vitamin A-rich foods and supplements in protection against the development of lung cancer in smokers and nonsmokers alike 7 ; however, clinical trials assessing the efficacy of retinoid supplementation against lung cancer have yielded inconsistent and inconclusive results. [8][...

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“…All MDACC subjects were clinically free of cancer at enrollment and underwent a bronchoscopy at baseline. Bronchial brushes were done at six predetermined sites including the entry area at each of the five main lobes and the carina, as previously described (11). The study was approved by the MDACC Institutional Review Board, and all MDACC participants gave signed informed consent.…”

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confidence: 99%

Impact of Smoking Cessation on Global Gene Expression in the Bronchial Epithelium of Chronic Smokers

Zhang

Lee

Tang

et al. 2008

Cancer Prevention Research

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Cigarette smoke is the major cause of lung cancer and can interact in complex ways with drugs for lung cancer prevention or therapy. Molecular genetic research promises to elucidate the biological mechanisms underlying divergent drug effects in smokers versus nonsmokers and to help in developing new approaches for controlling lung cancer. The present study compared global gene expression profiles (determined via Affymetrix microarray measurements in bronchial epithelial cells) between chronic smokers, former smokers, and never smokers. Smoking effects on global gene expression were determined from a combined analysis of three independent data sets. Differential expression between current and never smokers occurred in 591 of 13,902 measured genes (P < 0.01 and >2-fold change; pooled data)-a profound effect. In contrast, differential expression between current and former smokers occurred in only 145 of the measured genes (P < 0.01 and >2-fold change; pooled data). Nine of these 145 genes showed consistent and significant changes in each of the three data sets (P < 0.01 and >2-fold change), with eight being down-regulated in former smokers. Seven of the eight down-regulated genes, including CYP1B1 and three AKR genes, influence the metabolism of carcinogens and/or therapeutic/chemopreventive agents. Our data comparing former and current smokers allowed us to pinpoint the genes involved in smoking-drug interactions in lung cancer prevention and therapy. These findings have important implications for developing new targeted and dosing approaches for prevention and therapy in the lung and other sites, highlighting the importance of monitoring smoking status in patients receiving oncologic drug interventions.

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Randomized placebo-controlled trial of isotretinoin in chemoprevention of bronchial squamous metaplasia

Cited by 23 publications

References 0 publications

Expression of cyclooxygenase‐1 and cyclooxygenase‐2 in bronchial epithelium and nonsmall cell lung carcinoma

Expression of cyclooxygenase‐1 and cyclooxygenase‐2 in bronchial epithelium and nonsmall cell lung carcinoma

Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D₃ and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Impact of Smoking Cessation on Global Gene Expression in the Bronchial Epithelium of Chronic Smokers

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Randomized placebo-controlled trial of isotretinoin in chemoprevention of bronchial squamous metaplasia

Cited by 23 publications

References 0 publications

Expression of cyclooxygenase‐1 and cyclooxygenase‐2 in bronchial epithelium and nonsmall cell lung carcinoma

Expression of cyclooxygenase‐1 and cyclooxygenase‐2 in bronchial epithelium and nonsmall cell lung carcinoma

Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D3 and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Impact of Smoking Cessation on Global Gene Expression in the Bronchial Epithelium of Chronic Smokers

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Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D₃ and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity