Treatment of Patients with Glioblastomas by Low Concentrations of Verapamil Hydrochloride in the Late Postoperative Period

Nina Gridina; Anatoliy Morozov; Yuriy Ushenin; Vladimir Rozumenko; Nataliya Draguntsova

doi:doi:10.11648/j.crj.20190703.14

| Peer-Reviewed

Treatment of Patients with Glioblastomas by Low Concentrations of Verapamil Hydrochloride in the Late Postoperative Period

Nina Gridina, Anatoliy Morozov, Yuriy Ushenin, Vladimir Rozumenko, Nataliya Draguntsova

Published in Cancer Research Journal (Volume 7, Issue 3)

Received: 5 July 2019 Accepted: 12 August 2019 Published: 23 August 2019

Views: Downloads:

Download PDF

Share This Article

Twitter
Linked In
Facebook

Abstract

Antitumor effect of calcium channel blockers low concentrations has been investigated on the example of verapamil hydrochloride in the combined treatment of patients with glioblastomas after operation. Patients, who underwent brain tumor surgery, postoperative radiotherapy and chemotherapy, were divided into two groups. The first group of 11 patients was taken by verapamil - hydrochloride in low concentrations, the second group (32 patients) served as a control. The concentration of the drug was selected individually by means of peripheral blood cells aggregation data on the “Plasmon-6” biosensor. The criterion for the drug concentration selecting was the lowest level of peripheral blood cells aggregation in vitro, reflecting the level of NMDA-dependent calcium channels blocking of the peripheral blood cells membranes. The optimal concentration of verapamil - hydrochloride for all patients was less than 10,000. The criteria of the antitumor activity of verapamil-hydrochloride in low concentrations was the length of the patients life in the postoperative period. When using the drug in patients there were no signs of toxic effects of verapamil - hydrochloride on the body, life expectancy was 10 months more compared to the group of patients not treated with verapamil – hydrochloride and the absence of the toxic and tumor-stimulating action of the drug.

Published in	Cancer Research Journal (Volume 7, Issue 3)
DOI	10.11648/j.crj.20190703.14
Page(s)	101-105
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2019. Published by Science Publishing Group

Keywords

Glioblastomas, Tumor-Associated Inflammation, Low Concentrations of Verapamil-Hydrochloride, Life Expectancy

References

[1]	Matsko DE. Neyrokhirurgicheskaya patologiya. SPb.: FGBU «RNKHI im. prof. A. L. Polenova» MZ Rossii; 2015. 424 p., Russian.
[2]	Zozulya YuA, Vasil'yeva IG, Glavatskiy AYa, Rozumenko VD, Lisyaniy NI, Gridina NY. Sovremenniye tekhnologii konservativnogo lecheniya gliom. V: Zozulya YUA, red. Gliomy golovnogo mozga. Kiyev: UIPK “YeksOb”; 2007. pp. 383-509. Russian.
[3]	Rozumenko AV., Kliuchka VM., Rozumenko VD., Fedorenko ZP. Survival rates in patients with the newly diagnosed glioblastoma: Data from National Cancer Registry of Ukraine, 2008-2016. Ukrainian Neurosurgical Journal. 2018; (2): 33-39. DOI: https://doi.org/10.25305/unj.124878.
[4]	Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002; 2 (6): 442-454. PMID: 12189386. DOI: 10.1038/nrc822.
[5]	[5 Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009; 9 (4): 265-273. PMID: 19262571. DOI: 10.1038/nrc2620.
[6]	Luchnik AN. А common link in the mechanism of self-maintenance of malignant growth: the syndrome of the nonhealing wound. Ontogenesis 2000; 31 (3): 227-231. English.
[7]	Schwarzburd PM. Chronic inflammation increases risk of epithelial neoplasia by inducing precancerous microenvironment: an evaluation of pathways of disregulation. Problems in Оncology. 2006; 52 (2): 137-144. Russian.
[8]	Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008 Jul; 454 (7203): 436-44. doi: 10. 1038/nature07205. Review. PubMed PMID: 18650914.
[9]	Whiteside TL. The tumor microenvironment and its role in promoting tumor growth. Oncogene. 2008; 27 (45): 5904-5912. PMID: 18836471; PMCID: PMC3689267. DOI: 10. 1038/onc. 2008. 271.
[10]	Gridina N, Maslov V, Ushenin Yu. Tumor-Associated Inflammation and Brain Glyomas. Saarbrücken, Lambert Academic Publishing; 2013. 186 p. Russian.
[11]	Takano T, Lin JH, Arcuino G, Gao Q, Yang J, Nedergaard M. Glutamate release promotes growth of malignant gliomas. Nat Med. 2001 Sep; 7 (9): 1010-5. PubMed PMID: 11533703. DOI: 10. 1038/nm0901-1010.
[12]	Fu YS, Lin YY, Chou SC, Tsai TH, Kao LS, Hsu SY, Cheng FC, Shih YH, Cheng H, Fu YY, Wang JY. Tetramethylpyrazine inhibits activities of glioma cells and glutamate neuro-excitotoxicity: potential therapeutic application for treatment of gliomas. Neuro Oncol. 2008 Apr; 10 (2): 139-52. doi: 10. 1215/15228517-2007-051. Epub 2008 Feb 26. PubMed PMID: 18314418; PubMed Central PMCID: PMC2613816.
[13]	Gridina NYa. Utilizing SPR as a novel technique to measure cell aggregation for ketamine treated brain gliomas. Cancer Oncol. Res. 2013; 1 (1): 1-5. DOI: 10.13189/cor.2013.010101.
[14]	Clements JD, Lester RA, Tong G, Jahr CE, Westbrook GL. The time course of glutamate in the synaptic cleft. Science. 1992 Nov; 258 (5087): 1498-501. PubMed PMID: 1359647. DOI: 10. 1126/science. 1359647.
[15]	Davydova ON, Boldyrev AA. Glutamatniye retseptory v kletkakh nervnoy i immunnoy systems. Annaly klinicheskoy i eksperimental'noy nevrologii. 2007; 1 (4): 28-34. Russian.
[16]	Gridina NYa, Shvachko LP, Draguntsova NG. Tumor-Associated Inflammation Mechanisms Correction by Verapamil at Brain Gliomas Progression. [Internet]. Eur J Pharmaceutic Med Res (EJPMR). 2016; 3 (8): 73-78 Available from: https://www.ejpmr.com/admin/assets/article_issue/1469854979.pdf
[17]	Gridina NYa, Maslov VP, Kotovsky VY, Draguntsova NG. Peculiarities of the Spectrum of Chromosome Aberrations in the Peripheral Blood Lymphocytes in Cases of Brain Gliomas and their Correction with Verapamil and Ketamine. [Internet]. Scholar Journal of Applied Medical Sciences (SJAMS). 2015 Sep; 3 (6A): 2156-2160. Available from: http://saspublishercom/wp-content/uploads/2015/09/SJAMS-36A-2156-2160.pdf.
[18]	`Medyanik IA. New approaches to early diagnosis and treatment tactics for malignant brain tumors (wedge. - experimental. Studies): author. dis. for nauch. degree doctor Sciences: specialist. 01/14/18 - Neurosurgery / AND. A. Medyanik; Federal State Institution "Volga Federal Medical Research Center" of the Ministry of Health of the Russian Federation. - Nizhny Novgorod, 2016. - 40 p.
[19]	Karpov YuA, Soboleva GN. Calcium antagonists – first-line drugs in modern cardiology (2 part). Terapevt. arkhiv. 1997; 69 (1): 74-78. Russian.
[20]	Mokhort NA, Seredinskaya NN, Bobkova LS. Calcium antagonists: prospects for new medical preparations development (review of literature). Journal AMS of Ukraine. 2003; 9 (1): 15-27. Russian.
[21]	Soybir G, Köksoy F, Koyuncu H, Yalçin O, Köse H, Topuzlu C. Chemoprevention of DMBA-induced mammary gland carcinogenesis - preventive effects of free oxygen radical scavengers. Breast Cancer Res Treat. 1998 Jul; 50 (2): 193-9. PubMed PMID: 9822224. DOI: 10. 1023/A:1005701116297.
[22]	Dunn AJ, Faust J, Krowech G. Evidence on the carcinogenicity of verapamil. [Internet]. California: OEHHA; 2004. 45 p. Available from: https://oehha.ca.gov/media/downloads/proposition-65/chemicals/hidverapamil.pdf
[23]	Helson L. Calcium channel blocker enhancement of anticancer drug cytotoxicity - a review. Cancer Drug Deliv. 1984; 1 (4): 353-61. Review. PubMed PMID: 6100477.

Cite This Article

Plain Text BibTeX RIS

APA Style

Nina Gridina, Anatoliy Morozov, Yuriy Ushenin, Vladimir Rozumenko, Nataliya Draguntsova. (2019). Treatment of Patients with Glioblastomas by Low Concentrations of Verapamil Hydrochloride in the Late Postoperative Period. Cancer Research Journal, 7(3), 101-105. https://doi.org/10.11648/j.crj.20190703.14

Copy | Download

ACS Style

Nina Gridina; Anatoliy Morozov; Yuriy Ushenin; Vladimir Rozumenko; Nataliya Draguntsova. Treatment of Patients with Glioblastomas by Low Concentrations of Verapamil Hydrochloride in the Late Postoperative Period. Cancer Res. J. 2019, 7(3), 101-105. doi: 10.11648/j.crj.20190703.14

Copy | Download

AMA Style

Nina Gridina, Anatoliy Morozov, Yuriy Ushenin, Vladimir Rozumenko, Nataliya Draguntsova. Treatment of Patients with Glioblastomas by Low Concentrations of Verapamil Hydrochloride in the Late Postoperative Period. Cancer Res J. 2019;7(3):101-105. doi: 10.11648/j.crj.20190703.14

Copy | Download

@article{10.11648/j.crj.20190703.14,
  author = {Nina Gridina and Anatoliy Morozov and Yuriy Ushenin and Vladimir Rozumenko and Nataliya Draguntsova},
  title = {Treatment of Patients with Glioblastomas by Low Concentrations of Verapamil Hydrochloride in the Late Postoperative Period},
  journal = {Cancer Research Journal},
  volume = {7},
  number = {3},
  pages = {101-105},
  doi = {10.11648/j.crj.20190703.14},
  url = {https://doi.org/10.11648/j.crj.20190703.14},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.20190703.14},
  abstract = {Antitumor effect of calcium channel blockers low concentrations has been investigated on the example of verapamil hydrochloride in the combined treatment of patients with glioblastomas after operation. Patients, who underwent brain tumor surgery, postoperative radiotherapy and chemotherapy, were divided into two groups. The first group of 11 patients was taken by verapamil - hydrochloride in low concentrations, the second group (32 patients) served as a control. The concentration of the drug was selected individually by means of peripheral blood cells aggregation data on the “Plasmon-6” biosensor. The criterion for the drug concentration selecting was the lowest level of peripheral blood cells aggregation in vitro, reflecting the level of NMDA-dependent calcium channels blocking of the peripheral blood cells membranes. The optimal concentration of verapamil - hydrochloride for all patients was less than 10,000. The criteria of the antitumor activity of verapamil-hydrochloride in low concentrations was the length of the patients life in the postoperative period. When using the drug in patients there were no signs of toxic effects of verapamil - hydrochloride on the body, life expectancy was 10 months more compared to the group of patients not treated with verapamil – hydrochloride and the absence of the toxic and tumor-stimulating action of the drug.},
 year = {2019}
}

Copy | Download

TY  - JOUR
T1  - Treatment of Patients with Glioblastomas by Low Concentrations of Verapamil Hydrochloride in the Late Postoperative Period
AU  - Nina Gridina
AU  - Anatoliy Morozov
AU  - Yuriy Ushenin
AU  - Vladimir Rozumenko
AU  - Nataliya Draguntsova
Y1  - 2019/08/23
PY  - 2019
N1  - https://doi.org/10.11648/j.crj.20190703.14
DO  - 10.11648/j.crj.20190703.14
T2  - Cancer Research Journal
JF  - Cancer Research Journal
JO  - Cancer Research Journal
SP  - 101
EP  - 105
PB  - Science Publishing Group
SN  - 2330-8214
UR  - https://doi.org/10.11648/j.crj.20190703.14
AB  - Antitumor effect of calcium channel blockers low concentrations has been investigated on the example of verapamil hydrochloride in the combined treatment of patients with glioblastomas after operation. Patients, who underwent brain tumor surgery, postoperative radiotherapy and chemotherapy, were divided into two groups. The first group of 11 patients was taken by verapamil - hydrochloride in low concentrations, the second group (32 patients) served as a control. The concentration of the drug was selected individually by means of peripheral blood cells aggregation data on the “Plasmon-6” biosensor. The criterion for the drug concentration selecting was the lowest level of peripheral blood cells aggregation in vitro, reflecting the level of NMDA-dependent calcium channels blocking of the peripheral blood cells membranes. The optimal concentration of verapamil - hydrochloride for all patients was less than 10,000. The criteria of the antitumor activity of verapamil-hydrochloride in low concentrations was the length of the patients life in the postoperative period. When using the drug in patients there were no signs of toxic effects of verapamil - hydrochloride on the body, life expectancy was 10 months more compared to the group of patients not treated with verapamil – hydrochloride and the absence of the toxic and tumor-stimulating action of the drug.
VL  - 7
IS  - 3
ER  -

Copy | Download

Author Information

Nina Gridina

Experimental Department, Romodanov Neurosurgery Institute of the National Academy of Medical Science of Ukraine, Kiev, Ukraine
Anatoliy Morozov

Romodanov Neurosurgery Institute of the National Academy of Medical Science of Ukraine, Kiev, Ukraine
Yuriy Ushenin

Department of Physical and Technological Bases of Sensor Material Science, V. Ye. Lashkaryov Institute of Semiconductor of National Science Academy of Ukraine, Kiev, Ukraine
Vladimir Rozumenko

Clinical Department, Romodanov Neurosurgery Institute of the National Academy of Medical Science of Ukraine, Kiev, Ukraine
Nataliya Draguntsova

Experimental Department, Romodanov Neurosurgery Institute of the National Academy of Medical Science of Ukraine, Kiev, Ukraine

Download PDF

Sections

Plain Text BibTeX RIS

APA Style

Nina Gridina, Anatoliy Morozov, Yuriy Ushenin, Vladimir Rozumenko, Nataliya Draguntsova. (2019). Treatment of Patients with Glioblastomas by Low Concentrations of Verapamil Hydrochloride in the Late Postoperative Period. Cancer Research Journal, 7(3), 101-105. https://doi.org/10.11648/j.crj.20190703.14

Copy | Download

ACS Style

Nina Gridina; Anatoliy Morozov; Yuriy Ushenin; Vladimir Rozumenko; Nataliya Draguntsova. Treatment of Patients with Glioblastomas by Low Concentrations of Verapamil Hydrochloride in the Late Postoperative Period. Cancer Res. J. 2019, 7(3), 101-105. doi: 10.11648/j.crj.20190703.14

Copy | Download

AMA Style

Nina Gridina, Anatoliy Morozov, Yuriy Ushenin, Vladimir Rozumenko, Nataliya Draguntsova. Treatment of Patients with Glioblastomas by Low Concentrations of Verapamil Hydrochloride in the Late Postoperative Period. Cancer Res J. 2019;7(3):101-105. doi: 10.11648/j.crj.20190703.14

Copy | Download

@article{10.11648/j.crj.20190703.14,
  author = {Nina Gridina and Anatoliy Morozov and Yuriy Ushenin and Vladimir Rozumenko and Nataliya Draguntsova},
  title = {Treatment of Patients with Glioblastomas by Low Concentrations of Verapamil Hydrochloride in the Late Postoperative Period},
  journal = {Cancer Research Journal},
  volume = {7},
  number = {3},
  pages = {101-105},
  doi = {10.11648/j.crj.20190703.14},
  url = {https://doi.org/10.11648/j.crj.20190703.14},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.20190703.14},
  abstract = {Antitumor effect of calcium channel blockers low concentrations has been investigated on the example of verapamil hydrochloride in the combined treatment of patients with glioblastomas after operation. Patients, who underwent brain tumor surgery, postoperative radiotherapy and chemotherapy, were divided into two groups. The first group of 11 patients was taken by verapamil - hydrochloride in low concentrations, the second group (32 patients) served as a control. The concentration of the drug was selected individually by means of peripheral blood cells aggregation data on the “Plasmon-6” biosensor. The criterion for the drug concentration selecting was the lowest level of peripheral blood cells aggregation in vitro, reflecting the level of NMDA-dependent calcium channels blocking of the peripheral blood cells membranes. The optimal concentration of verapamil - hydrochloride for all patients was less than 10,000. The criteria of the antitumor activity of verapamil-hydrochloride in low concentrations was the length of the patients life in the postoperative period. When using the drug in patients there were no signs of toxic effects of verapamil - hydrochloride on the body, life expectancy was 10 months more compared to the group of patients not treated with verapamil – hydrochloride and the absence of the toxic and tumor-stimulating action of the drug.},
 year = {2019}
}

Copy | Download

TY  - JOUR
T1  - Treatment of Patients with Glioblastomas by Low Concentrations of Verapamil Hydrochloride in the Late Postoperative Period
AU  - Nina Gridina
AU  - Anatoliy Morozov
AU  - Yuriy Ushenin
AU  - Vladimir Rozumenko
AU  - Nataliya Draguntsova
Y1  - 2019/08/23
PY  - 2019
N1  - https://doi.org/10.11648/j.crj.20190703.14
DO  - 10.11648/j.crj.20190703.14
T2  - Cancer Research Journal
JF  - Cancer Research Journal
JO  - Cancer Research Journal
SP  - 101
EP  - 105
PB  - Science Publishing Group
SN  - 2330-8214
UR  - https://doi.org/10.11648/j.crj.20190703.14
AB  - Antitumor effect of calcium channel blockers low concentrations has been investigated on the example of verapamil hydrochloride in the combined treatment of patients with glioblastomas after operation. Patients, who underwent brain tumor surgery, postoperative radiotherapy and chemotherapy, were divided into two groups. The first group of 11 patients was taken by verapamil - hydrochloride in low concentrations, the second group (32 patients) served as a control. The concentration of the drug was selected individually by means of peripheral blood cells aggregation data on the “Plasmon-6” biosensor. The criterion for the drug concentration selecting was the lowest level of peripheral blood cells aggregation in vitro, reflecting the level of NMDA-dependent calcium channels blocking of the peripheral blood cells membranes. The optimal concentration of verapamil - hydrochloride for all patients was less than 10,000. The criteria of the antitumor activity of verapamil-hydrochloride in low concentrations was the length of the patients life in the postoperative period. When using the drug in patients there were no signs of toxic effects of verapamil - hydrochloride on the body, life expectancy was 10 months more compared to the group of patients not treated with verapamil – hydrochloride and the absence of the toxic and tumor-stimulating action of the drug.
VL  - 7
IS  - 3
ER  -

Copy | Download