Effect of Treatment with a Combination of Dichloroacetate and Valproic Acid on Adult Glioblastoma Patient-Derived Primary Cells Xenografts on the Chick Embryo Chorioallantoic Membrane

<b>Background/Objectives:</b> The ineffectiveness of current treatments for glioblastoma underscores the urgent need for effective alternatives. This study aimed to investigate the effectiveness of sodium dichloroacetate (NaDCA) and a sodium valproate NaDCA combination (NaVPA-NaDCA) on formed patients' primary cell tumors on the chick embryo chorioallantoic membrane (CAM). <b>Methods:</b> Glioblastoma tissue samples were obtained from three patients during tumor surgery. WHO grade IV, IDH wild-type, and a strong positive cytoplasmic GFAP reaction in tumor cells characterized the investigated glioblastoma cases. The tumor cells GBM2-2F, GBM2-3F, and GBM-4M from the patients were examined. Histological examination of tumor invasion into CAM, angiogenesis, and immunohistochemical expression of GFAP-, PCNA-, p53-, EZH2- and vimentin-positive cells were examined. <b>Results:</b> No difference in GFAP expression was observed between the patient's GBM tumor tissue and the tumor formed on CAM from the same patient's tumor cells. There were no significant differences in invasion or in the frequency of GFAP- and p53-positive cells among the study control groups. The expression of PCNA-, EZH2-, and vimentin-positive cells in control tumors varied significantly. Treatment significantly reduced the incidence of tumor invasion in GBM2-2F and GBM2-4M and did not affect GBM2-3F tumors; treatment also significantly reduced GFAP expression in GBM2-3F and GBM2-4M and did not affect GBM2-2F tumors. The treatment with NaVPA-NaDCA significantly reduced the expression of PCNA, p53, EZH2 and vimentin in the tested tumors. <b>Conclusions:</b> Data demonstrated an antitumor effect of NaVPA-NaDCA in an in vivo model of a patient's primary glioblastoma cells.

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Publication Details

Journal
Pharmaceutics
Published
2025-12-30
DOI
https://doi.org/10.3390/pharmaceutics18010052
Primary Topic
Glioma Diagnosis and Treatment
Type
article
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article

Effect of Treatment with a Combination of Dichloroacetate and Valproic Acid on Adult Glioblastoma Patient-Derived Primary Cells Xenografts on the Chick Embryo Chorioallantoic Membrane

Angelija Valančiūtė, Aidanas Preikšaitis, Ingrida Balnytė, Rūta Skredėnienė et al.
Pharmaceutics
Glioma Diagnosis and Treatment
article

Effect of Treatment with a Combination of Dichloroacetate and Valproic Acid on Adult Glioblastoma Patient-Derived Primary Cells Xenografts on the Chick Embryo Chorioallantoic Membrane

Angelija Valančiūtė, Aidanas Preikšaitis, Ingrida Balnytė, Rūta Skredėnienė, V Lesauskaite, Donatas Stakišaitis
article en

Abstract

<b>Background/Objectives:</b> The ineffectiveness of current treatments for glioblastoma underscores the urgent need for effective alternatives. This study aimed to investigate the effectiveness of sodium dichloroacetate (NaDCA) and a sodium valproate NaDCA combination (NaVPA-NaDCA) on formed patients' primary cell tumors on the chick embryo chorioallantoic membrane (CAM). <b>Methods:</b> Glioblastoma tissue samples were obtained from three patients during tumor surgery. WHO grade IV, IDH wild-type, and a strong positive cytoplasmic GFAP reaction in tumor cells characterized the investigated glioblastoma cases. The tumor cells GBM2-2F, GBM2-3F, and GBM-4M from the patients were examined. Histological examination of tumor invasion into CAM, angiogenesis, and immunohistochemical expression of GFAP-, PCNA-, p53-, EZH2- and vimentin-positive cells were examined. <b>Results:</b> No difference in GFAP expression was observed between the patient's GBM tumor tissue and the tumor formed on CAM from the same patient's tumor cells. There were no significant differences in invasion or in the frequency of GFAP- and p53-positive cells among the study control groups. The expression of PCNA-, EZH2-, and vimentin-positive cells in control tumors varied significantly. Treatment significantly reduced the incidence of tumor invasion in GBM2-2F and GBM2-4M and did not affect GBM2-3F tumors; treatment also significantly reduced GFAP expression in GBM2-3F and GBM2-4M and did not affect GBM2-2F tumors. The treatment with NaVPA-NaDCA significantly reduced the expression of PCNA, p53, EZH2 and vimentin in the tested tumors. <b>Conclusions:</b> Data demonstrated an antitumor effect of NaVPA-NaDCA in an in vivo model of a patient's primary glioblastoma cells.

PharmaceuticsVol. 18(1)
Lithuanian University of Health Sciences (LT), Vilnius University (LT), National Cancer Institute (LT)
Good health and well-being
Openalex Percentile: Top 25%
Glioma Diagnosis and Treatment
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