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Inhibitor Valproic Acid (inhibitor + valproic_acid)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Photocarcinogenesis of topical tazarotene and isotretinoin alone and in combination with valproic acid in hairless mice

EXPERIMENTAL DERMATOLOGY, Issue 11 2008
Catharina M. Lerche
Abstract:, Retinoids and the histone deacetylase inhibitor valproic acid have shown anticancer properties, but the photocarcinogenic or photoprotective effect is unclear. Therefore, we investigated whether a topical formulation of valproic acid is photocarcinogenic or photoprotective in hairless female C3.Cg/TifBomTac immunocompetent mice exposed to simulated solar radiation (SSR) and whether valproic acid changes the effect of the retinoids: tazarotene and isotretinoin. The products were applied on the dorsal skin of 400 mice (five times weekly) followed by SSR (three times weekly) 3,4 h after the application. This was performed during 12 months or until death. Tumors appeared sooner in groups treated with tazarotene and isotretinoin compared with that of the group treated with valproic acid and the control group. The present study shows that valproic acid alone is not photocarcinogenic or photoprotective in hairless mice. When valproic acid is combined with tazarotene or isotretinoin, it does not change their photocarcinogenicity significantly. [source]

HDAC inhibitor valproic acid enhances tumor cell kill in adenovirus-HSVtk mediated suicide gene therapy in HNSCC xenograft mouse model

INTERNATIONAL JOURNAL OF CANCER, Issue 3 2010
Vishal Kothari
Abstract Safety, efficacy and enhanced transgene expression are the primary concerns while using any vector for gene therapy. One of the widely used vectors in clinical trials is adenovirus which provides a safe way to deliver the therapeutic gene. However, adenovirus has poor transduction efficiency in vivo since most tumor cells express low coxsackie and adenovirus receptors. Similarly transgene expression remains low, possibly because of the chromatization of adenoviral genome upon infection in eukaryotic cells, an effect mediated by histone deacetylases (HDACs). Using a recombinant adenovirus (Ad-HSVtk) carrying the herpes simplex thymidine kinase (HSVtk) and GFP genes we demonstrate that HDAC inhibitor valproic acid can bring about an increase in CAR expression on host cells and thereby enhanced Ad-HSVtk infectivity. It also resulted in an increase in transgene (HSVtk and GFP) expression. This, in turn, resulted in increased cell kill of HNSCC cells, following ganciclovir treatment in vitro as well as in vivo in a xenograft nude mouse model. [source]

Valproic acid blocks adhesion of renal cell carcinoma cells to endothelium and extracellular matrix

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009
Jon Jones
Abstract Treatment strategies for metastatic renal cell carcinoma (RCC) have been limited due to chemotherapy and radiotherapy resistance. The development of targeted drugs has now opened novel therapeutic options. In the present study, anti-tumoral properties of the histone deacetylase inhibitor valproic acid (VPA) were tested in vitro and in vivo on pre-clinical RCC models. RCC cell lines Caki-1, KTC-26 or A498 were treated with various concentrations of VPA to evaluate tumour cell adhesion to vascular endothelial cells or to immobilized extracellular matrix proteins. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. VPA was also combined with low dosed interferon-, (IFN-,) and the efficacy of the combination therapy, as opposed to VPA monotherapy, was compared. VPA significantly and dose-dependently prevented tumour cell attachment to endothelium or matrix proteins, accompanied by elevated histones H3 and H4 acetylation. VPA altered integrin-, and -, subtype expression, in particular ,3, ,5 and ,3, and blocked integrin-dependent signalling. In vivo, VPA significantly inhibited the growth of Caki-1 in subcutaneous xenografts with the 200 mg/kg being superior to the 400 mg/kg dosing schedule. VPA-IFN-, combination markedly enhanced the effects of VPA on RCC adhesion, and in vivo tumour growth was further reduced by the 400 mg/kg but not by the 200 mg/kg VPA dosing schedule. VPA profoundly blocked the interaction of RCC cells with endothelium and extracellular matrix and reduced tumour growth in vivo. Therefore, VPA should be considered an attractive candidate for clinical trials. [source]

Increase in platelet count in older, poor-risk patients with acute myeloid leukemia or myelodysplastic syndrome treated with valproic acid and all-trans retinoic acid

CANCER, Issue 1 2005
Chiara Pilatrino M.D.
Abstract BACKGROUND The authors investigated the efficacy and safety of the histone deacetylase inhibitors valproic acid (VPA) and all-trans retinoic acid (ATRA) as differentiation agents in a cohort of older, poor-risk patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). METHODS Twenty older patients with recurrent or refractory AML or MDS were treated in a Phase II protocol with sequential VPA and ATRA therapy. VPA was started at a dose of 10 mg/kg per day and then escalated to achieve the serum concentration of 45,100 ,g/mL. ATRA was added at 45 mg/square meters (sm) per day when VPA reached the target serum concentration. Only patients treated continuously for , 2 months were considered evaluable. RESULTS Hematologic improvement, according to World Health Organization criteria, was observed in 6 of 20 patients enrolled in the protocol but in 6 of 11 considered evaluable. In five patients, a major platelet response was observed, achieving platelet transfusion independence. Three of these five patients also exhibited a minor erythroid response. A sixth patient showed both a minor erythroid response and a platelet response. The median duration of response was 189 days (range, 63,550 days). No significant reduction in the blast count was observed. Grade 3 neurocortical toxicity was observed in four patients. Severe bone pain was experienced by 4 patients (2 Grade 4 and 2 Grade 3) and was associated with an increase in the peripheral blast cell count. Treatment with ATRA did not modify the response observed with VPA alone. CONCLUSIONS Differentiation therapy with VPA was of clinical benefit in approximately 30% of elderly patients with AML and MDS of the refractory anemia with excess of blast type with unfavorable prognostic features. A striking platelet transfusion independence lasting several months may be obtained in some patients, reducing the burden of palliative care and improving the quality of life. Cancer 2005;. © 2005 American Cancer Society. [source]