| 1. |
|
|
| 2. |
- Bryukhovetskiy, Igor, et al.
(författare)
-
Personalized therapy and stem cell transplantation for pro-inflammatory modulation of cancer stem cells microenvironment in glioblastoma : Review
- 2020
-
Ingår i: NOVEL THERAPEUTIC ADVANCES IN GLIOBLASTOMA. - LONDON ENGLAND : Elsevier. - 9780128211144 ; , s. 67-98
-
Bokkapitel (refereegranskat)abstract
- Glioblastoma multiforme (GBM) is one of the most aggressive types of brain tumor in humans. The prognosis for patients with GBM is unfavorable and treatment is largely ineffective, where modern treatment regimens typically increase survival by 15 months. GBM relapse and progression are associated with cancer stem cells (CSCs). The present review provides a critical analysis of the primary reasons underlying the lack of effectiveness of modern CSC management methods. An emphasis is placed on the role of the blood-brain barrier in the development of treatment resistance. The existing methods for increasing the efficiency of antitumor genotoxic therapy are also described, and a strategy for personalized regulation of CSC based on post-genome technologies is suggested. The hypothesis that GBM cells employ a special mechanism for DNA repair based on their interactions with normal stem cells, is presented and the function of the tumor microenvironment in fulfilling the antitumor potential of normal stem cells is explained. Additionally, the mechanisms by which cancer stem cells regulate glioblastoma progression and recurrence are described based on novel biomedical technologies.
|
|
| 3. |
- Bryukhovetskiy, Igor, et al.
(författare)
-
Transforming growth factor-beta mimics the key proteome properties of CD133- differentiated and CD133+ cancer stem cells in glioblastoma
- 2020
-
Ingår i: Novel therapeutic advances in glioblastoma. - : Elsevier BV. - 9780128211144 ; , s. 219-242
-
Bokkapitel (refereegranskat)abstract
- Glioblastoma multiforme is the most aggressive type of primary brain tumor in humans. Its invasive growth is associated with cluster of differentiation (CD)133 cancer stem cells (CSCs) and CD133(-) differentiated glioblastoma cells (DGCs) with aggressive phenotype, which are developed under the influence of transforming growth factor (TGF)-beta. The present study aimed to compare the proteomes of CD133 CSCs and CD133(-) DGCs stimulated by TGF-beta, as well as the expression levels of the main proteins responsible for activating the signaling pathway of receptor interactions with the extracellular matrix (ECM). The U87MG GBM cell line was used in this study. CSCs were extracted from gliomaspheres through magnetic-activated cell sorting based on the expression of CD133 (CD133); CD133(-) DCGs served as a control. CD133(-) DGCs of the U87-MG cell line were treated with 10ng/mL TGF-beta 1, and cell proliferation and migration were analyzed via real-time quantitative microscopy. High-performance liquid chromatography mass spectrometry was used for proteome analysis. The results revealed 589 proteins with significantly changes in expression among CD133 CSCs compared with those in CD133(-) DGCs (P < 0.05). Bioinformatics analysis allowed to attribute 134 differentially expressed proteins to 15 signaling pathways; among these proteins, 14 were involved in signaling cascades associated with the interaction between CSCs and the ECM, and were upregulated > twofold, while four proteins activated this signaling cascade. TGF-beta-stimulation increased the mobility, suppressed the proliferation and transformed the proteome profile of CD133(-) DGCs. Were identified 13 key proteins that activate the signaling pathway of receptor interaction with the ECM and three proteins activating this signaling pathway in CD133(-) DGCs which had the same values as those of CD133 CSCs. In conclusion, TGF-beta increased the expression of proteins that activate the signaling pathway of receptor interaction with the ECM in CD133(-) DGCs to the level of those in CD133 CSCs.
|
|
| 4. |
- Li, Cong, et al.
(författare)
-
Advanced multimodal imaging in differentiating glioma recurrence from post-radiotherapy changes
- 2020
-
Ingår i: Novel therapeutic advances in glioblastoma. - LONDON ENGLAND : Elsevier. - 9780128211144 ; , s. 281-297
-
Bokkapitel (refereegranskat)abstract
- Gliomas are the most common malignant primary brain tumor, and their prognosis is extremely poor. Radiotherapy is an important treatment for glioma patients, but the changes caused by radiotherapy have brought difficulties in clinical image evaluation because differentiating glioma recurrence from post-radiotherapy changes including pseudo-progression (PD) and radiation necrosis (RN) remains a challenge. Therefore, accurate and reliable imaging evaluation is very important for making clinical decisions. In recent years, advanced multimodal imaging techniques have been applied to achieve the goal of better differentiating glioma recurrence from post-radiotherapy changes for minimizing errors associated with interpretation of treatment effects. In this review, we discuss the recent applications of advanced multimodal imaging such as diffusion MRI sequences, amide proton transfer MRI sequences, perfusion MRI sequences, MR spectroscopy and multinuclides PET/CT in the evaluation of post-radiotherapy treatment response in glioma patients and highlight their potential role in differentiating post-radiotherapy changes from glioma recurrence.
|
|
| 5. |
- Li, Cong, et al.
(författare)
-
Expression of Twist associated to microcirculation patterns of human glioma correlated with progression and survival of the patient
- 2020
-
Ingår i: NOVEL THERAPEUTIC ADVANCES IN GLIOBLASTOMA. - LONDON ENGLAND : Elsevier. - 9780128211144 ; , s. 201-217
-
Bokkapitel (refereegranskat)abstract
- Twist is a transcription factor involved in the process of epithelial to mesenchymal transition (EMT) of carcinoma cells, and the promotion of invasion of gliomas through the mesenchymal adjusting process. However, its clinical significance in human glioma has not yet to be understood. To delineate the clinical-pathological significance and prognostic value of Twist, the expression of Twist was evaluated by Immunohistochemistry for 187 glioma samples. We found that Twist demonstrated frequent nuclear expression in the glioma samples and its expression levels were associated with tumor grade (P < 0.001). Furthermore, high Twist expression was correlated with a poor outcome in patients with glioma (P = 0.001), particularly with high grade glioma (P = 0.026). Interestingly, Twist expression showed positive correlation with microvascular density (MVD) (r = 0.145, P = 0.048) as well as vasculogenic mimicry (VM) (r = 0.273, P < 0.001) in the tumors. These results suggest that Twist could be a predictor for poor prognosis in glioma patients. Additionally, Twist expression was associated with two major microcirculation patterns: endothelial-dependent vessels and VM in glioma, indicating that Twist could be a potential molecular target for anti-glioma therapy.
|
|
| 6. |
- Lyakhova, Irina, et al.
(författare)
-
3-Bromofascaplysin is a prospective chemical compound for developing new chemotherapy agents in glioblastoma treatment
- 2020
-
Ingår i: Novel therapeutic advances in glioblastoma. - : Elsevier BV. - 9780128211144 ; , s. 325-343
-
Bokkapitel (refereegranskat)abstract
- Glioblastoma (GB) is one of the most aggressive human brain tumors. The prognosis is unfavorable, its treatment is relatively ineffective, and the median survival is about 15months. Medication development with new chemical compounds is one of the ways to solve the problem of current treatment inefficiency. This study is focused on the group of chemical substances, based on pentacyclic system of 12H-pyrido[1,2-a:3,4-b] diindole, and the most well-known part of this group is fascaplysin, first extracted from the sponge Fascaplysinopsis spp. We have synthesized a series of the following fascaplysin derivatives: 7-phenylfascaplysin, 3-chlorofascaplysin, 3-bromofascaplysin, 9-bromofascaplysin. The paper is aimed at analyzing the cytotoxic effect of these compounds on GB cells. Materials and methods. The study used rat glioma C6 cell line (ATCC (R); cat no CCL-107), U-87MG cell line (ATCC; cat no. HTB-14T) and human glioblastoma T98-G cells (ATCC (R) CRL-1690T). Cell culture method, experimental pharmacological trials and.-radiation in vitro, as well as flow cytofluorometry were used in the study. Results: Cytotoxic effect of the tested compounds is stronger than the effect of unsubstituted fascaplysin, and appears to be dose-dependent and time-dependent. 3-bromofascaplysin is more efficient for cancer cells elimination, and by the end of the experiment the amount of living cancer cells in G(0) phase remained at its lowest. Cytotoxic effect of 3-bromofascaplysin on glioblastoma T98-G cells is inferior to that of TMZ, and in case of preliminary radiation treatment of cancer cells with 48Gy the effect of the compound matches the TMZ treatment results. Conclusion: 3-Bromofascaplysin is a prospective chemical compound for development of new anti-cancer chemotherapeutic agents.
|
|
| 7. |
- Lyakhova, Irina, et al.
(författare)
-
Alkaloids of fascaplysin are promising chemotherapeutic agents for the treatment of glioblastoma : Review
- 2020
-
Ingår i: NOVEL THERAPEUTIC ADVANCES IN GLIOBLASTOMA. - LONDON ENGLAND : Elsevier. - 9780128211144 ; , s. 299-324
-
Bokkapitel (refereegranskat)abstract
- Glioblastoma is one of the most aggressive human brain tumors. Even following all the modern protocols of complex treatment, the median patient survival typically does not exceed 15 months. This review analyzes the main reasons for glioblastoma resistance to therapy, as well as attempts at categorizing the main approaches to increasing chemotherapy efficiency. Special emphasis is placed on the specific group of compounds, known as marine alkaloids and their synthetic derivatives exerting a general antitumor effect on glioblastoma cells. The unique mechanisms of marine alkaloid influence on the tumor cells prompt considering them as a promising basis for creating new chemotherapeutic agents for glioblastoma treatment.
|
|
| 8. |
- Sharma, Hari Shanker, et al.
(författare)
-
Pathophysiology of blood-brain barrier in brain tumor. : Novel therapeutic advances using nanomedicine
- 2020
-
Ingår i: Novel Therapeutic Advances In Glioblastoma. - LONDON ENGLAND : Elsevier. - 9780128211144 ; , s. 1-66
-
Bokkapitel (refereegranskat)abstract
- Glioblastoma Multiforme (GBM) is one the most common intracranial tumors discovered by Burns (1800) and Abernethy (1804) based on gross morphology of the autopsied material and referred to as "medullary sarcoma" and later "fungus medullare" (Abernethy, 1804; Burns, 1800). Virchow in 1863 was the first German pathologist using histomorphological techniques discovered that GBM is a tumor of glial origin. Virchow (1863/65) also then used the term Glioma for the first time and classified as low-grade glioma and high-grade glioma very similar to that of today according to World health organization (WHO) classification (Jellinger, 1978; Virchow, 1863/65). After almost >50 years of this discovery, Baily and Cushing (1926) based on modern neuropathological tools provide the classification of gliomas that is still valid today (Baily & Cushing, 1926). Although, our knowledge about development of gliomas has advanced through development of modern cellular and molecular biological tools (Gately, McLachlan, Dowling, & Philip, 2017; Omuro & DeAngelis, 2013), therapeutic advancement of GBM still requires lot of efforts for the benefit of patients. This review summarizes new developments on pathophysiological aspects of GBM and novel therapeutic strategies to enhance quality of life of patients. These novel therapeutic approaches rely on enhanced penetration of drug therapy into the tumor tissues by use of nanomedicine for both the diagnostic and therapeutic purposes, referred to as "theranostic nanomedicine" (Alphandery, 2020; Zhao, van Straten, Broekman, Preat, & Schiffelers, 2020). Although, the blood-brain barrier (BBB) is fenestrated around the periphery of the tumor tissues, the BBB is still tight within the deeper tissues of the tumor. Thus, drug delivery is a challenge for gliomas and requires new therapeutic advances (Zhao et al., 2020). Associated edema development around tumor tissues is another factor hindering therapeutic effects (Liu, Mei, & Lin, 2013). These factors are discussed in details using novel therapeutic advances in gliomas.
|
|
| 9. |
- Shevchenko, Valeriy, et al.
(författare)
-
Molecular determinants of the interaction between glioblastoma CD133(+) cancer stem cells and the extracellular matrix
- 2020
-
Ingår i: NOVEL THERAPEUTIC ADVANCES IN GLIOBLASTOMA. - LONDON ENGLAND : Elsevier. - 9780128211144 ; , s. 155-169
-
Bokkapitel (refereegranskat)abstract
- Glioblastoma multiforme (GBM) is the most common primary tumor of the human brain. It is characterized by invasive growth and strong resistance to treatment, and the median survival time of patients is 15 months. The invasive growth of this tumor type is associated with tumor cells with an aggressive phenotype, while its treatment resistance is attributed to cancer stem cells (CSCs). It remains unclear if CSCs have a more invasive nature than differentiated glioblastoma cells (DGCs), and what contribution CSCs make to the aggressive phenotype of GBM. Interaction with the extracellular matrix (ECM) is a key factor in the development of invasion. The aim of the present study was to compare the expression levels of signaling pathway proteins involved in interaction of receptors with the ECM in CSCs and DGCs. The U-87MG GBM cell line was used in the present study CSCs were extracted from gliomaspheres through magnetic-activated cell sorting based on the expression of cluster of differentiation 133 (CD133); CD133-negative DCGs were used as a control. HPLC and mass spectrometry were also used, and biological and molecular functions, signaling pathways and protein-protein interactions were analyzed using publicly available databases. Increased expression levels of the following 10 proteins involved in interaction with the ECM were identified in CSCs, compared with expression levels in DGCs: COL6A1, COL6A3, FN1, ITGA2, ITGA5, ITGAV, ITGB1, ITGB3, LAMB1 and LAMC1. The proteome of CSCs was observed to have >2-fold higher expression of these key proteins, when compared with the DGC proteome. Increased expression levels of four proteins (FERMT2, LOXL2, HDAC2 and FBN1) involved in activating signaling in response to receptor interaction with the ECM was also observed, indicating that CSCs may have highly invasive nature. LOXL2 expression level was >9-fold higher in CSCs compared to DGCs, suggesting that this protein may have potential as an marker for CSCs and as a target for this cell type in GBM.
|
|
| 10. |
- Shevchenko, Valeriy, et al.
(författare)
-
Proteins of Wnt signaling pathway in cancer stem cells of human glioblastoma
- 2020
-
Ingår i: NOVEL THERAPEUTIC ADVANCES IN GLIOBLASTOMA. - LONDON ENGLAND : Elsevier. - 9780128211144 ; , s. 185-200
-
Bokkapitel (refereegranskat)abstract
- Rationale: Glioblastoma multiforme (GBM) is the most aggressive primary glial brain tumor. The prognosis for GBM patients is not favorable, with the median survival time being 15 months. Its treatment resistance is associated with GBM cell population having cancer stem cells (CSCs). Wnt/beta-catenin signaling pathway is a strategically important molecular mechanism, providing proliferation of stem cells of all types. This study compares the expression levels of signaling pathway proteins in CD133(+) CSCs and CD133 (-) differentiated glioblastoma cells (DGCs). Materials and methods: the present study used U-87MG cells of human glioblastoma, the material was tested for mycoplasma contamination. High-performance liquid chromatography (HPLC) mass spectrometry was used for proteome analysis. Biological and molecular functions, signaling pathways and protein-protein interactions were analyzed using free-access databases: PubMed, PANTHER, Gene Ontology, Swiss-Prot and KEGG. Protein-protein interactions (PPIs) were analyzed using the STRING database (version 10). Results: There were identified 589 proteins with significantly changed expression in CD133+ CSCs, as compared with CD133-DGCs (P < 0.05). Bioinformatics analysis allowed to attribute 134 differentially expressed proteins to 16 signaling pathways. A significant increase in expression of eight Wnt signaling pathway proteins (APC, CSNK1E, CSNK1A, CSNK2A2, CSNK2B, CTNNB1, DVL1, RUVBL) was detected, as well as four proteins of the non-canonical Wnt pathway-RHOA, ROCK2, RAC2, DAAM1. Special attention should be paid to beta-catenin (CTNNB1) with more than 13.98-fold increase of expression in CSCs and Disheveled-associated activator of morphogenesis 1 (DAAM1) with 6.15-fold higher upregulation level. Conclusion: proteins of Wnt/beta-catenin signaling cascade are a prospective target for regulating CSCs activity.
|
|
