Malignant Brain Tumors: Death Sentence, No Mercy

The article presents critical analysis of current methodological approaches, the standard and the options of complex therapy of malignant brain tumors (MBT). Author defines the main reasons for low effectiveness of MBT therapy. Relying on post-genome innovations (mass-spectrometry proteome mapping and whole transcriptome profiling of gene expression of cancer cells (CCs), cancer stem cells (CSCs) and tissue-specific stem cells (TSSCs) of the cancer patient, and their comparative analysis) the author proposes systemic solution for the MBT complex therapy that consists in a new alternative paradigm of cytoregulatory anti-cancer treatment of the MBT that is aimed at rigid control, management and regulation of the number of CCs and CSCs in the body. The goal of a new treatment paradigm is to transfer acute, uncontrollable and mortal process into chronic and non-lethal disease, and, thus, to improve survival rates and life quality of the patients. The instrument to implement the new paradigm is a sparing algorithm of conventional therapeutic methods and immune therapy, supplemented with personalized anti-tumor proteome-based cell therapy. The therapy implies transfusions of transcriptome-modified autologous TSSCs with specified properties to regulate the reproductive functions of the CSCs. The author proposes the complex therapy of the MBT and shows its social and economic significance for the society and neuroscience

Personalized regulation of glioblastoma cancer stem cells based on biomedical technologies : From theory to experiment (Review)

Glioblastoma multiforme (GBM) is one of the most aggressive brain tumors. GBM represents >50% of primary tumors of the nervous system and similar to 20% of intracranial neoplasms. Standard treatment involves surgery, radiation and chemotherapy. However, the prognosis of GBM is usually poor, with a median survival of 15 months. Resistance of GBM to treatment can be explained by the presence of cancer stem cells (CSCs) among the GBM cell population. At present, there are no effective therapeutic strategies for the elimination of CSCs. The present review examined the nature of human GBM therapeutic resistance and attempted to systematize and put forward novel approaches for a personalized therapy of GBM that not only destroys tumor tissue, but also regulates cellular signaling and the morphogenetic properties of CSCs. The CSCs are considered to be an informationally accessible living system, and the CSC proteome should be used as a target for therapy directed at suppressing clonal selection mechanisms and CSC generation, destroying CSC hierarchy, and disrupting the interaction of CSCs with their microenvironment and extracellular matrix. These objectives can be achieved through the use of biomedical cellular products

Interaction of hematopoietic CD34(+) CD45(+) stem cells and cancer cells stimulated by TGF-beta 1 in a model of glioblastoma in vitro

The majority of modern treatment methods for malignant brain tumors are not sufficiently effective, with a median survival time varying between 9 and 14 months. Metastatic and invasive processes are the principal characteristics of malignant tumors. The most important pathogenic mechanism is epithelial-mesenchymal transition (EMT), which causes epithelial cells to become more mobile, and capable of invading the surrounding tissues and migrating to distant organs. Transforming growth factor-beta 1 (TGF-beta 1) serves a key role in EMT-inducing mechanisms. The current study presented the interaction between hematopoietic stem cells and glioblastoma cells stimulated by TGF-beta 1 in vitro. The materials for the study were hematopoietic progenitor cell antigen CD34(+) hematopoietic stem cells (HSCs) and U87 glioblastoma cells. Cell culture methods, automated monitoring of cell-cell interactions, confocal laser microscopy, flow cytometry and electron microscopy were used. It was demonstrated that U87 cells have a complex communication system, including adhesive intercellular contacts, areas of interdigitation with dissolution of the cytoplasm, cell fusion, communication microtubes and microvesicles. TGF-beta 1 affected glioblastoma cells by modifying the cell shape and intensifying their exocrine function. HSCs migrated to glioblastoma cells, interacted with them and exchanged fluorescent tags. Stimulation of cancer cells with TGF-beta 1 weakened the ability of glioblastoma cells to attract HSCs and exchange a fluorescent tag. This process stimulated cancer cell proliferation, which is an indication of the ability of HSCs to 'switch' the proliferation and invasion processes in glioblastoma cells