The Experts below are selected from a list of 165 Experts worldwide ranked by ideXlab platform
Myrna Candelaria - One of the best experts on this subject based on the ideXlab platform.
-
Antineoplastic effects of the DNA methylation inhibitor Hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines
Cancer Cell International, 2006Co-Authors: Alma Chavez-blanco, Carlos Perez-plasencia, Enrique Perez-cardenas, Claudia Carrasco-legleu, Edgar Rangel-lopez, Blanca Segura-pacheco, Lucia Taja-chayeb, Catalina Trejo-becerril, Aurora Gonzalez-fierro, Myrna CandelariaAbstract:Background Among the epigenetic alterations occurring in cancer, DNA hypermethylation and histone hypoacetylation are the focus of intense research because their pharmacological inhibition has shown to produce antineoplastic activity in a variety of experimental models. The objective of this study was to evaluate the combined antineoplastic effect of the DNA methylation inhibitor Hydralazine and the histone deacetylase inhibitor valproic acid in a panel of cancer cell lines. Results Hydralazine showed no growth inhibitory effect on cervical, colon, breast, sarcoma, glioma, and head & neck cancer cell lines when used alone. On the contrary, valproic acid showed a strong growth inhibitory effect that is potentiated by Hydralazine in some cell lines. Individually, Hydralazine and valproic acid displayed distinctive effects upon global gene over-expression but the number of genes over-expressed increased when cells were treated with the combination. Treatment of HeLa cells with Hydralazine and valproic acid lead to an increase in the cytotoxicity of gemcitabine, cisplatin and adriamycin. A higher antitumor effect of adriamycin was observed in mice xenografted with human fibrosarcoma cells when the animals were co-treated with Hydralazine and valproic acid. Conclusion Hydralazine and valproic acid, two widely used drugs for cardiovascular and neurological conditions respectively have promising antineoplastic effects when used concurrently and may increase the antitumor efficacy of current cytotoxic agents.
Alma Chavez-blanco - One of the best experts on this subject based on the ideXlab platform.
-
Antineoplastic effects of the DNA methylation inhibitor Hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines
Cancer Cell International, 2006Co-Authors: Alma Chavez-blanco, Carlos Perez-plasencia, Enrique Perez-cardenas, Claudia Carrasco-legleu, Edgar Rangel-lopez, Blanca Segura-pacheco, Lucia Taja-chayeb, Catalina Trejo-becerril, Aurora Gonzalez-fierro, Myrna CandelariaAbstract:Background Among the epigenetic alterations occurring in cancer, DNA hypermethylation and histone hypoacetylation are the focus of intense research because their pharmacological inhibition has shown to produce antineoplastic activity in a variety of experimental models. The objective of this study was to evaluate the combined antineoplastic effect of the DNA methylation inhibitor Hydralazine and the histone deacetylase inhibitor valproic acid in a panel of cancer cell lines. Results Hydralazine showed no growth inhibitory effect on cervical, colon, breast, sarcoma, glioma, and head & neck cancer cell lines when used alone. On the contrary, valproic acid showed a strong growth inhibitory effect that is potentiated by Hydralazine in some cell lines. Individually, Hydralazine and valproic acid displayed distinctive effects upon global gene over-expression but the number of genes over-expressed increased when cells were treated with the combination. Treatment of HeLa cells with Hydralazine and valproic acid lead to an increase in the cytotoxicity of gemcitabine, cisplatin and adriamycin. A higher antitumor effect of adriamycin was observed in mice xenografted with human fibrosarcoma cells when the animals were co-treated with Hydralazine and valproic acid. Conclusion Hydralazine and valproic acid, two widely used drugs for cardiovascular and neurological conditions respectively have promising antineoplastic effects when used concurrently and may increase the antitumor efficacy of current cytotoxic agents.
Dennie V Jones - One of the best experts on this subject based on the ideXlab platform.
-
a phase i protocol of Hydralazine and valproic acid in advanced previously treated solid cancers
Translational Oncology, 2014Co-Authors: Julie E Bauman, Monte Shaheen, Claire F Verschraegen, Steven A Belinsky, Houman M Fekrazad, Ian Rabinowitz, Meera Ravindranathan, Dennie V JonesAbstract:Smokers experience aberrant gene promoter methylation in their bronchial cells, which may predispose to the development of neoplasia. Hydralazine is a DNA demethylating agent, and valproic acid is a histone deacetylase inhibitor, and both have modest but synergistic anticancer activity in vitro. We conducted a phase I trial combining valproic acid and Hydralazine to determine the maximally tolerated dose (MTD) of Hydralazine in combination with a therapeutic dose of valproic acid in patients with advanced, unresectable, and previously treated solid cancers. Twenty females and nine males were enrolled, with a median age of 57 years and a median ECOG performance status of 0. Grade 1 lymphopenia and fatigue were the most common adverse effects. Three subjects withdrew for treatment-related toxicities occurring after the DLT observation period, including testicular edema, rash, and an increase in serum lipase accompanied by hyponatremia in one subject each. A true MTD of Hydralazine in combination with therapeutic doses of valproic acid was not reached in this trial, and the planned upper limit of Hydralazine investigated in this combination was 400 mg/day without grade 3 or 4 toxicities. A median number of two treatment cycles were delivered. One partial response by Response Evaluation Criteria In Solid Tumors criteria was observed, and five subjects experienced stable disease for 3 to 6 months. The combination of Hydralazine and valproic acid is simple, nontoxic, and might be appropriate for chemoprevention or combination with other cancer treatments. This trial supports further investigation of epigenetic modification as a new therapeutic strategy.
Laurent Loufrani - One of the best experts on this subject based on the ideXlab platform.
-
alteration in flow shear stress induced remodelling in rat resistance arteries with aging improvement by a treatment with Hydralazine
Cardiovascular Research, 2007Co-Authors: Odile Dumont, Frederic Pinaud, Annelaure Guihot, Christophe Baufreton, Laurent LoufraniAbstract:Aims The link between aging and vascular diseases remains unclear, especially in resistance arteries. As a decreased vasodilator capacity of the endothelium is usually described in aging, we hypothesized that arteriolar remodelling in response to a chronic increase in blood flow might be altered. In addition, we tested the capacity of a vasodilator treatment with Hydralazine to restore remodelling, as we have previously shown that Hydralazine has a potent effect on the process. Methods and results Mesenteric resistance arteries (350 µm diameter) from 3- and 24-month-old rats were exposed to high blood flow (HF) and normal blood flow (NF), for 2 weeks by sequential ligating second-order arteries in vivo . In HF arteries, diameter increased by 21% when intraluminal pressure was 100 mmHg, in association with a rise in superoxide production in young rats. On the other hand, both diameter and superoxide levels failed to increase in old rats. Hydralazine restored HF-induced remodelling in old rats in association with an increased superoxide production and a decreased superoxide dismutase (SOD) expression. The SOD-mimetic 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (TEMPOL) prevented the effect of Hydralazine on the arterial diameter. In old rats, Hydralazine increased the arterial diameter in HF arteries without increasing eNOS expression. Furthermore, Hydralazine also restored HF remodelling in eNOS knockout mice. Conclusion Thus, flow remodelling in resistance arteries failed to occur in aging but it could be restored by Hydralazine via a reactive oxygen species-dependent mechanism. These findings may have serious pathophysiological consequences in situations requiring flow-dependent remodelling such as ischaemic and metabolic diseases, more frequent in the elderly.
Odile Dumont - One of the best experts on this subject based on the ideXlab platform.
-
alteration in flow shear stress induced remodelling in rat resistance arteries with aging improvement by a treatment with Hydralazine
Cardiovascular Research, 2007Co-Authors: Odile Dumont, Frederic Pinaud, Annelaure Guihot, Christophe Baufreton, Laurent LoufraniAbstract:Aims The link between aging and vascular diseases remains unclear, especially in resistance arteries. As a decreased vasodilator capacity of the endothelium is usually described in aging, we hypothesized that arteriolar remodelling in response to a chronic increase in blood flow might be altered. In addition, we tested the capacity of a vasodilator treatment with Hydralazine to restore remodelling, as we have previously shown that Hydralazine has a potent effect on the process. Methods and results Mesenteric resistance arteries (350 µm diameter) from 3- and 24-month-old rats were exposed to high blood flow (HF) and normal blood flow (NF), for 2 weeks by sequential ligating second-order arteries in vivo . In HF arteries, diameter increased by 21% when intraluminal pressure was 100 mmHg, in association with a rise in superoxide production in young rats. On the other hand, both diameter and superoxide levels failed to increase in old rats. Hydralazine restored HF-induced remodelling in old rats in association with an increased superoxide production and a decreased superoxide dismutase (SOD) expression. The SOD-mimetic 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (TEMPOL) prevented the effect of Hydralazine on the arterial diameter. In old rats, Hydralazine increased the arterial diameter in HF arteries without increasing eNOS expression. Furthermore, Hydralazine also restored HF remodelling in eNOS knockout mice. Conclusion Thus, flow remodelling in resistance arteries failed to occur in aging but it could be restored by Hydralazine via a reactive oxygen species-dependent mechanism. These findings may have serious pathophysiological consequences in situations requiring flow-dependent remodelling such as ischaemic and metabolic diseases, more frequent in the elderly.
