Comparative subacute toxicity of all-trans- and 13-cis-retinoic acid in swiss mice

Hixson, E.Jane; Denine, E P

doi:10.1016/0041-008x(78)90281-8

Cited by 64 publications

(21 citation statements)

References 11 publications

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“…Longer treatment (Ͼ10 days), however, was associated with signs of retinoid toxicity, including weight loss, hair loss, and skin scaling. These findings are consistent with previous reports of retinoid toxicity (30).…”

Section: Resultssupporting

confidence: 83%

Systemic Retinoic Acid Treatment Induces Sodium/Iodide Symporter Expression and Radioiodide Uptake in Mouse Breast Cancer Models

Kogai¹,

Kanamoto²,

Lisa³

et al. 2004

Cancer Research

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Lactating breast tissue and some breast cancers express the sodium/ iodide symporter (NIS) and concentrate iodide. We recently demonstrated that all-trans retinoic acid (tRA) induces both NIS gene expression and iodide accumulation in vitro in well-differentiated human breast cancer cells (MCF-7). In the present study, we investigated the in vivo efficacy and specificity of tRA-stimulated iodide accumulation in mouse breast cancer models. Immunodeficient mice with MCF-7 xenograft tumors were treated with systemic tRA for 5 days. Iodide accumulation in the xenograft tumors was markedly increased, ϳ15-fold greater than levels without treatment, and the effects were tRA dose dependent. Iodide accumulation in other organs was not significantly influenced by tRA treatment. Significant induction of NIS mRNA and protein in the xenograft tumors was observed after tRA treatment. Iodide accumulation and NIS mRNA expression were also selectively induced in breast cancer tissues in transgenic mice expressing the oncogene, polyoma virus middle T antigen. These data demonstrate selective induction of functional NIS in breast cancer by tRA. Treatment with short-term systemic retinoic acid, followed by radioiodide administration, is a potential tool in the diagnosis and treatment of some differentiated breast cancer.

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Section: Resultssupporting

confidence: 83%

Systemic Retinoic Acid Treatment Induces Sodium/Iodide Symporter Expression and Radioiodide Uptake in Mouse Breast Cancer Models

Kogai¹,

Kanamoto²,

Lisa³

et al. 2004

Cancer Research

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“…Moreover, retinoid activity was assessed by measuring serum alkaline phosphatase (ALP) which is a measure of effects on bone resorption. 13 The relative levels of ALP when treated with 10 mg/kg of ATRA were at levels similar to that of ACR at 100 mg/kg, which were the dosages used for direct comparison in the present study (data not shown). Dosage of ACR at 100 mg/kg was therefore more potent than that of ATRA at 10 mg/kg.…”

Section: Acr Inhibits Vascular Remodelingmentioning

confidence: 85%

“…Moreover, abnormal blood chemistry such as liver dysfunction or hyperlipidemia, which is known to be associated with overdose of vitamin A, 13 was not seen (data not shown). Therefore, our results were likely attributable to the primary effects of the retinoid rather than secondary effects through adverse effects.…”

Section: Acr Inhibits Vascular Remodelingmentioning

confidence: 96%

Acyclic Retinoid Inhibits Neointima Formation Through Retinoic Acid Receptor Beta-Induced Apoptosis

Kada

Suzuki

Aizawa

et al. 2007

ATVB

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Objectives-Acyclic retinoid (ACR) is a synthetic retinoid with a high safety profile that has been pursued with high expectations for therapeutic use in prevention (recurrence) and treatment of malignancies. With the objective of addressing the therapeutic potential in the cardiovasculature, namely neointima formation, effects of ACR on neointima formation and the involved mechanisms were investigated. Methods and Results-ACR was administered to cuff-injured mice which showed inhibition of neointima formation.Investigation of involved mechanisms at the cellular and molecular levels showed that ACR induces apoptosis of neointimal cells and this to be mediated by selective induction of retinoic-acid receptor ␤ (RAR␤) which shows growth inhibitory and proapoptotic effects on smooth muscle cells. Key Words: smooth muscle cell Ⅲ cell growth Ⅲ retinoid R etinoids are natural and synthetic derivatives of vitamin A which modulate growth, apoptosis, and differentiation of cells. 1 Many retinoids have been pursued from therapeutic standpoints with the aim of chemotherapy of cancer, leukemia, and prevention of atherosclerosis. 1 The biological effects of retinoids are mainly mediated by their receptors, retinoicacid receptor (RAR) and retinoic-X receptor (RXR). 2 RAR interacts with both all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9cRA), and has 3 isoforms (␣, ␤, and ␥). 2 Among the retinoid receptors, RAR␤ plays a critical role in mediating the effects of retinoid on cell growth and tumor inhibition in various cancer cells. 3,4 RAR␤ expression diminishes with development of esophageal squamous cell carcinoma. 4 Induction of RAR␤ by ATRA and overexpression of RAR␤ also play important roles in mediating the growth-inhibitory effects of ATRA in human lung squamous cell carcinoma. 3 These findings indicate that modulation of expression of RAR␤ critically regulates cell growth inhibition. The role of RAR␤ in vascular SMCs (smooth muscle cells), however, has not been previously addressed. Conclusion-WeAcyclic retinoid (ACR) is a novel synthetic RAR-selective retinoid (supplemental Table I) which has been shown to inhibit the growth of hepatoma cells in vivo and in vitro. 5 ACR has been shown to inhibit the recurrence of hepatocellular carcinoma with oral administration in clinical trials, and has a high safety profile causing less side effects than other retinoids. 6 Recently, ACR has been shown to preferentially act on and to elicit biological effects mainly through RAR␤. 7,8 At the cellular level, ACR induces apoptosis in hepatoma cells. 9,10 ACR is therefore well-defined and safe, and is thus an attractive retinoid for therapeutic use. However, its effects on vascular remodeling have not been studied.In the present study, we investigated whether ACR shows effects on neointima formation. We also addressed the mechanism of action of ACR in the vasculature, namely through effects on expression of RARs in SMCs with a focus on the biological role of RAR␤. We show that expression of RAR␤ as induced by ACR exerts i...

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“…:illli-RA for 84 days to rats (Zbinden, 1975) increased the concentrations of serum alkaline phosphatase, a change indicative of increased osteoblast activity. Administration of all-trans-or 13-Q.s.-RA for 21 days induced dose-dependent fractures of the long bones, dermal and epidermal abnormalities, cartilage degeneration, and elevations in plasma alkaline phosphatase (Hixson and Denine, 1978). However, changes in alkaline phosphatase were not always associated with bone fractures .…”

Section: Bone and Co Nnective Tissuementioning

confidence: 96%

“…of vi tamin A daily between 6 and I 0 weeks of gestation was reported by Pilotti and Scorta ( 1965 (Kamm, 1982). Hixson and Denine (1978) reported the LDso for all-l! :llM-RA at 31 mg / kg i.p.…”

Section: Dysmorphogenicitymentioning

confidence: 99%

Structure-activity relationships of retinoids in developmental toxicology

Howard

Willhite

Dawson

et al. 1988

Toxicology and Applied Pharmacology

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Comparative subacute toxicity of all-trans- and 13-cis-retinoic acid in swiss mice

Cited by 64 publications

References 11 publications

Systemic Retinoic Acid Treatment Induces Sodium/Iodide Symporter Expression and Radioiodide Uptake in Mouse Breast Cancer Models

Systemic Retinoic Acid Treatment Induces Sodium/Iodide Symporter Expression and Radioiodide Uptake in Mouse Breast Cancer Models

Acyclic Retinoid Inhibits Neointima Formation Through Retinoic Acid Receptor Beta-Induced Apoptosis

Structure-activity relationships of retinoids in developmental toxicology

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