Research Article
Volume 12 Issue 4 - 2020
Some Aspects of the Systemic Mechanism of Brain Malignant Gliomas Progression and Methodological Approaches to its Correction
N Ya Gridina1*, AN Morozov1, VD Rozumenko1, YuV Ushenin2, LP Shvachko3, VN Klyuchka1 and AD Beloysova1
1Institute of Neurosurgery, A.P. Romodanova, Kiev, Ukraine
2Institute of Semiconductor Physics, V. E. Lashkaryova, Kiev, Ukraine
3Institude of Molecular Biology and Genetic, Kiev, Ukraine
*Corresponding Author:N Ya Gridina, Institute of Neurosurgery, A. P. Romodanova, Kiev, Ukraine.
Received: February 17, 2020; Published: March 27, 2020


The growth of malignant gliomas was considered at a systemic level, which allows us to understand the basic shifts in the protective-compensatory reactions of the body, leading to the progression of brain tumors. It was shown that activation of NMDA-receptors affects the transmembrane potential, the indices of which are mediated through the level of aggregation of blood cells of patients with malignant gliomas. An increase in the level of aggregation of blood cells corresponds to stage II of the in vivo inflammatory process, which is a protective-compensatory reaction of the body. Verapamil is an NMDA- receptor dependent blocker of slow calcium L- channels, because they localized in the structure of NMDA- receptors. Using a highly sensitive Plasmon biosensor, the level of aggregation of blood cells was studied before surgery and on the 7th day after surgery. The effect of low concentrations of verapamil-hydrochloride on the indicators of blood cell aggregation in in vitro experiments made it possible to determine the differences between non-tumor inflammation and tumor-associated inflammation in glioblastomas. Tumor-associated inflammation is aseptic microinflammation, which is rarely detected by traditional laboratory tests and requires the use of biosensor equipment. Further, the use of verapamil-hydrochloride in dilutions with distillate water 10,000 times allowed to reveal the mechanism of “non-healing wounds” in malignant tumors. The oxidation enzymes of the polyamines DAO and PAO, which carry out repair processes in the III stage of inflammation, at low concentrations of verapamil- hydrochloride were characterized by a sharp decrease in activity in glioblastomas compared with identical indices in spinal hernias. These results are one of the experimental confirmations of the incompleteness of stage III of inflammation in malignant gliomas of the brain. This leads to the transition of reparative processes during inflammation to the processes of regeneration by mesenchymal stem cells through the epithelial - mesenchymal transition (EMT) and the subsequent progression of the tumor. It was shown that verapamil - hydrochloride in low concentrations reduces the expression of Snail, one of the main EMT genes, by 50%. The existing relationship between the development of glioma progression and the activity of ionotropic receptors that affect the transmembrane potential, defines a new methodology for therapeutic measures in the postoperative period. It consists in the suppression of tumor-associated inflammation by inhibitors of ionotropic receptors and ion channel blockers, stabilization of cell membranes, and inhibition of EMT. These therapeutic effects should be carried out after completing courses of any types of traditional therapy for malignant tumors.

Keywords: Glioblastoma; Systemic Mechanism of Progression; Tumor-Associated Inflammation; Blood Cells Aggregation; Surface Plasmon Resonance; Low Concentrations of Verapamil


  1. Coussens LM and Werb Z. “Inflammation and cancer”. Nature 420 (2002): 860-867.
  2. Hussain SP and Harris CC. “Inflammation and cancer: an ancient link with novel potentials”. The International Journal of Cancer 121.11 (2007): 2373-2380.
  3. Mantovani A., et al. “Cancer-related inflammation”. Nature 454 (2008): 436-444.
  4. Kundu JK and Surh YJ. “Inflammation: gearing the journey to cancer”. Mutation Research 659.1-2 (2008): 15-30.
  5. Fernandes JV., et al. “The role of the mediators of inflammation in cancer development”. Pathology and Oncology Research 21.3 (2015): 527-34.
  6. BalkwillF and Mantovani A. “Inflammation and cancer: back to Virchow”. Lancet 357.9255 (2001): 539-545. 
  7. Luchnik AN. “А common link in the mechanism of self-maintenance of malignant growth: the syndrome of the nonhealing wound”. Ontogenesis 31.3 (2000): 227-231.
  8. Schwarzburd PM. “Chronic inflammation increases risk of epithelial neoplasia by inducing precancerous microenvironment: an evaluation of pathways of dysregulation”. Problems in Оncology 52.2 (2006): 137-144. 
  9. Colotta F., et al. “Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability”. Carcinogenesis 30 (2009): 1073-1081.
  10. Allavena P., et al. “Pathways Connecting Inflammation and Cancer”. Current Opinion in Genetics and Development 18.1 (2008): 3-10.
  11. Bunt SK., et al. “Reduced inflammation in the tumor microenvironment delays the accumulation of myeloid-derived suppressor cells and limits tumor progression”. Cancer 67 (2007): 10019-10026.
  12. Lobo NA., et al. “The biology of cancer stem cells”. The Annual Review of Cell and Developmental Biology 23 (2007): 675-699.
  13. Manzo G. “Similarities Between Embryo Development and Cancer Process Suggest New Strategies for Research and Therapy of Tumors: A New Point of View”. Cell and Developmental Biology 7.20 (2019).
  14. Quail DF., et al. “Microenvironmental regulation of cancer stem cell phenotypes”. Current Stem Cell Research and Therapy 7 (2012): 197-216. 
  15. Tanno T and Matsui W. “Development and Maintenance of Cancer Stem Cells under Chronic Inflammation”. Journal of Nippon Medical School 78.3 (2011): 138-145. 
  16. Thiery JP. “Epithelial-mesenchymal transitions in tumour progression”. Nature Reviews Cancer 2 (2002): 442-454.
  17. Gavert N and Ben-Ze’ev A. “Epithelial-mesenchymal transition and the invasive potential of tumors”. Trends in Molecular Medicine 14 (2008): 199-209.
  18. Mani SA., et al. “The epithelial-mesenchymal transition generates cells with properties of stem cells”. Cell 133 (2008): 704-715.
  19. Gridina NYa., et al. “Tumor-Associated Inflammation Mechanisms Correction by Verapamil at Brain Gliomas Progression”. European Journal of Pharmaceutical and Medical Research 3.8 (2016): 73-78.  
  20. Petroff OA. “GABA and glutamate in the human brain”. Neuroscientist 8.6 (2002): 562-573. 
  21. Shirshov Yu., et al. “Analysis and numerical simulation of PPR spectrometers with mechanical scanning by angle: algorithm for determining the minimum angular position”. Registration, storage and processing of data 6.3 (2004): 3-18.
  22. Bondeson K., et al. “Lactose Repressor-Operator DNA Interactions: Kinetic Analysis by a Surface Plasmon Resonance Biosensor”. Analytical Biochemistry 214 (1993): 245 - 251. 
  23. Gridina N., et al. “Surface Plasmon Resonance Biosensor”. Sensors and Transducers 149.2 (2013): 60 - 68.
  24. Gridina N., et al. “Tumor-associated inflammation and brain gliomas”. Lambert Academic Publishing (2013): 196. 
  25. Gridina NYa. “Utilizing SPR as a Novel Technique to Measure Cell Aggregation for Ketamine Treated Brain Gliomas”. Cancer and Oncology Research 1 (2013): 1-5.
  26. Syatkin SP and Berezov TT. “Oxidative deaminization of polyamines in hepatomas with different rate of growth”. Voprosy Medit͡sinskoĭ Khimii 25 (1979): 611- 617. 
  27. Lowry OH., et al. “Protein measurement with the Folin phenol reagent”. The Journal of Biological Chemistry 193 (1951): 265-275.
  28. Chomczynski P and Sacchi N. “Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction”. Analytical Biochemistry 162 (1987): 156-159.
  29. Clements JD., et al. “The time course of glutamate in the synaptic cleft”. Science 258.5087 (1992): 1498-1501. 
  30. Spaeth EL., et al. “Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression”. Plos One 4 (2009): e4992.
  31. Gkountela S and Aceto N. “Stem-like features of cancer cells on their way to metastasis”. Biology Direct 11 (2016): 33.
  32. Zhao Sun., et al. “The roles of mesenchymal stem cells in tumor inflammatory microenvironment”. Journal of Hematology and Oncology 7.1 (2014): 2-21.
  33. Bjorson Ch., et al. “Turning Brain into Blood: A Hematopoietic Fate Adopted by Adult Neural Stem Cells in Vivo”. Science 283 (1999): 534 - 536.
  34. Polyak K and Weinberg RA. “Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits”. Nature Reviews Cancer 9 (2009): 265-273.
  35. Nishimura., et al. “Mesenchymal stem cells provide an advantageous tumor microenvironment for the restoration of cancer stem cells”. Pathobiology 79 (2012): 290-306. 
  36. Kleihues P and Cavenee WK. “Pathology and Genetics Tumours of the Nervous System”. Lyon. 84.1 (2000): 9-71.
  37. Gridina N.Ya., et al. “Peculiarities of the Spectrum of Chromosome Aberrations in the Peripheral Blood Lymphocytes in Cases of Brain Gliomas and their Correction with Verapamil and Ketamine”. Scholar Journal of Applied Medical Sciences 3.6A (2015): 2156-2160.
Citation: N Ya Gridina., et al. “Some Aspects of the Systemic Mechanism of Brain Malignant Gliomas Progression and Methodological Approaches to its Correction”. EC Neurology 12.4 (2020): 80-90.

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