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- Bryukhovetskiy, Igor, et al.
(författare)
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Glioblastoma : What can we do for these patients today and what will we be able to do in the future?
- 2021
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Ingår i: NANOMEDICINE AND NEUROPROTECTION IN BRAIN DISEASES. - : ELSEVIER ACADEMIC PRESS INC. - 9780323901628 ; , s. 99-118
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Bokkapitel (refereegranskat)abstract
- Glioblastoma multiforme (GBM) is an extremely aggressive primary human brain tumor. The median survival of GBM patients is 15 months in case of completing the modern complex treatment protocol. Chemotherapy can help to extend the life expectancy of patients. GBM treatment resistance is associated with cancer stem cells (CSCs). The present paper analyses the main reasons for ineffectiveness of the existing GBM treatment methods and suggests treating CSCs as a complex phenomenon, resulting from the coordinated interaction of normal stem cells and cancer cells (CCs) in immunosuppressive microsurroundings. The GBM treatment strategy is suggested not for only suppressing strategically important signaling pathways in CCs, but also for regulating interaction between normal stem cells and cancer cells. The paper considers the issue of controlling penetrability of the blood-brain barrier that is one of the main challenges in neuro-oncology. Also, the paper suggests the ways of extending life expectancy of GBM patients today and prospects for the near future.
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| 3. |
- Pak, Oleg, et al.
(författare)
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Effectiveness of bortezomib and temozolomide for eradication of recurrent human glioblastoma cells, resistant to radiation
- 2021
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Ingår i: Brain protection strategies and nanomedicine. - : Elsevier BV. - 9780323989275 ; , s. 195-209
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Bokkapitel (refereegranskat)abstract
- Background: Glioblastoma multiforme (GBM) is a primary human brain tumor with the highest mortality rate. The prognosis for such patients is unfavorable, since the tumor is highly resistant to treatment, and the median survival of patients is 13 months. Chemotherapy might extend patients' life, but a tumor, that reappears after chemoradiotherapy, is resistant to temozolomide (TMZ). Using postgenome technologies in clinical practice might have a positive effect on the treatment of a recurrent GBM.Methods: T98G cells of human GBM have been used. Radiation treatment was performed with Rokus-M gamma-therapeutic system, using Co-60 as a source of radionuclide emissions. High-performance liquid chromatography-mass spectrometry was used for proteome analysis. Mass spectrometry data were processed with MaxQuant (version 1.6.1.0) and Perseus (version 1.6.1) software, Max Planck Institute of Biochemistry (Germany). Biological processes, molecular functions, cells locations and protein pathways were annotated with a help of PubMed, PANTHER, Gene Ontology and KEGG and STRING v10 databases. Pharmaceutical testing was performed in vitro with a panel of traditional chemotherapeutic agents.Results: GBM cells proliferation speed is inversely proportional to the irradiation dose and recedes when the dosage is increased, as expected. Synthesis of ERC1, NARG1L, PLCD3, ROCK2, SARNP, TMSB4X and YTHDF2 in GBM cells, treated with 60Gy of radiation, shows more than a fourfold increase, while the synthesis level of PSMA2, PSMA3, PSMA4, PSMB2, PSMB3, PSMB7, PSMC3, PSMD1, PSMD3 proteins increases significantly. Traditional chemotherapeutic agents are not very effective against cancer cells of the recurrent GBM. Combination of TMZ and CCNU with a proteasome inhibitor-bortezomib-significantly increases their ability to eradicate cells of a radioresistant GBM.Conclusions: Bortezomib and temozolomide effectively destroy cells of a radioresistant recurrent human glioblastoma; proteome mapping of the recurrent GBM cancer cells allows to identify new targets for therapy to improve the treatment results.
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