P14.59 Rapid early progression of glioblastoma is not related to cortical/neural stem cells regions

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii49-ii49
Author(s):  
T Kazda ◽  
R Lakomy ◽  
I Selingerova ◽  
P Pospisil ◽  
L Hynkova ◽  
...  
Keyword(s):  
Stem Cells ◽  
Overall Survival ◽  
Neural Stem Cells ◽  
Spatial Relationship ◽  
Clinical Biomarkers ◽  
Increased Risk ◽  
Initial Location ◽  
Early Progression ◽  
Multifocal Tumor ◽  
Relationship Of

Abstract BACKGROUND Rapid early progression (REP) of glioblastoma after surgery observed on pre-radiotherapy MRI scan is common. Subventricular zone (SVZ) and hippocampal regions are supposed to harbor astrocyte-like neural stem cells (NSC) with tumors arising from these transformed stem cells threatening of higher risk of REP. REP is defined as a new enhancing tumor or >25% increase in enhancement before radiotherapy. Lim′s classification of initial glioblastoma location related to these NSC regions predicts invasive and multifocal tumor phenotype. Glioblastomas are classified preoperatively into four groups by the spatial relationship of the contrast-enhancing lesion with the SVZ and cortex. The aim of this retrospective single-institutional study is to evaluate the relations of this Lim classification on REP in unselected cohort of glioblastoma patients. MATERIAL AND METHODS Patients receiving radiotherapy between 2014–2017 were analyzed, 95 were evaluable. 47 patients (30.5%) were treated with the Stupp regimen. Lim1 classification (contact with cortex as well as SVZ) was presented in 74(48%) patients, Lim2 (contact with SVZ only) in 22(14.3%), Lim3 (contact with cortex only) in 50(32.5%) and Lim4 in 8(5.2%) patients. A total of 52% of patients developed REP. RESULTS Significantly better overall survival was with Stupp regimen (23.3 vs. 8.6 months, p<0.001) and without REP (18.5 vs. 10.2 months, p=0.001). There was no significant impact of time to start of radiotherapy. No significant relation between REP and Lim classification was observed. CONCLUSION The initial location is not predictive for REP. Patients experiencing REP have significantly worse overall survival and modification of their management represents an urgent unmet clinical need. Molecular and clinical biomarkers indicating an increased risk of REP are needed.Presented will also be an already published analysis of clinical factors associated with REP in glioblastoma and the effect of REP and treatment on survival outcomes. Newly, we will introduce the investigator-initiated prospective academic clinical trial (GlioMET) focused on optimization of glioblastoma radiotherapy by 11C-Methionine PET scan in patients with REP. Supported by Ministry of Health of the Czech Republic AZV, No.18-03-00469 and AZV NU20-03-00148.

scholarly journals P14.107 Rapid early progression of glioblastoma is not related to cortical/neural stem cells regions

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii93-iii93
Author(s):  
R Jancalek ◽  
T Kazda ◽  
R Belanova ◽  
P Pospisil ◽  
P Burkon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Overall Survival ◽  
Neural Stem Cells ◽  
Post Surgery ◽  
Clinical Biomarkers ◽  
Increased Risk ◽  
Initial Location ◽  
Early Progression ◽  
Multifocal Tumor ◽  
Tumor Phenotype

Abstract BACKGROUND Rapid early progression (REP) of glioblastoma after surgery is quite often observed on pre-radiotherapy MR scan. Clinical and molecular biomarkers indicating increased risk of this REP may be of high clinical need. Subventricular brain zone (SVZ) and hippocampal regions are supposed to harbor astrocyte-like neural stem cells with tumors arising from these transformed SVZ stem cells dreaded to be of higher risk of REP. Lim′s et al classification of initial glioblastoma location related to these neural stem cells regions was predictive for invasive and multifocal tumor phenotype. The aim of this retrospective single-institutional study is to evaluate the relations of this Lim classification on REP in unselected cohort of glioblastoma patients. MATERIAL AND METHODS Patients treated by radiotherapy between 2014–2017 were grouped as follows: Lim1 (SVZ+⋯SVZ/hippocampal involvement and Cortex+⋯cortex involvement), Lim2 (SVZ+ and Cortex-), Lim3 (SVZ- and Cortex+) and Lim4 (SVZ- and Cortex-). Some patients were indicated to Stupp regimen. REP was defined on pre-radiotherapy MR as new distant lesion, progression of residuum, or new enhancement in postsurgery cavity. RESULTS In total, 144 patients were analyzed (94 men, mean age 59 years). 47 patients (30.5%) were treated according to Stupp regimen. Lim1 classification was presented in 74 (48%) patients, Lim2 in 22 (14.3%), Lim3 in 50 (32.5%) and Lim4 in 8 (5.2%) patients. Cortical structures (Lim1 and Lim3) were involved in 124 (80.5%) patients. Median overall survival was significantly better in patients treated according to Stupp regimen (23.3 vs. 8.6 months, p<0.001) and in those without REP (18.5 vs. 10.2 months, p=0.001). REP was presented in 52% of 95 evaluable patients who underwent both post-surgery and pre-radiotherapy MR scans and there was no significant impact of time to start of radiotherapy. No significant relation between REP and Lim classification was observed (REP in 23/47 Lim1, in 8/13 Lim2, in 16/31 Lim3 and in 2/4 Lim4 patients). CONCLUSION Initial location of enhancing glioblastoma is not predictive for REP. Patients experiencing REP have significantly worse overall survival and modification of their management represents urgent unmet clinical need. Molecular and clinical biomarkers indicating increased risk of REP are needed. Supported by Ministry of Health of the Czech Republic, grant No. 18-03-00469.

scholarly journals P14.101 Glioblastoma survival outcomes related to cortical/neural stem cells regions

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii91-iii92
Author(s):  
T Kazda ◽  
R Jancalek ◽  
R Belanova ◽  
P Pospisil ◽  
P Burkon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Overall Survival ◽  
Neural Stem Cells ◽  
Median Overall Survival ◽  
Initial Location ◽  
Multifocal Tumor ◽  
Tumor Phenotype ◽  
Cortical Involvement ◽  
Plastic Transformation ◽  
Molecular Patterns

Abstract BACKGROUND Subventricular brain zone (SVZ) and hippocampal regions are supposed to harbor astrocyte-like neural stem cells. While some tumors may arise from transformed SVZ stem cells, other may be initiated by neo-plastic transformation of non-SVZ progenitor cells or mature glial cells. Lim′s et al classification (Neuro-Oncology 2007) of initial glioblastoma location, related to these neural stem cells regions, was predictive for invasive and multifocal tumor phenotype. The aim of this retrospective single-institutional study is to evaluate the relations of this Lim classification on survival parameters in unselected cohort of glioblastoma patients. MATERIAL AND METHODS Patients treated between 2014–2017 were grouped according to initial location of their contrast enhancing lesion as follows: Lim1 (SVZ+⋯SVZ/hippocampal involvement and Cortex+⋯cortex involvement), Lim2 (SVZ+ and Cortex-), Lim3 (SVZ- and Cortex+) and Lim4 (SVZ- and Cortex-). All patients underwent radiotherapy, some patients were indicated to full treatment according to Stupp regimen (at least 3 cycles of adjuvant chemotherapy after postsurgery chemoradiotherapy). RESULTS In total, 144 patients were analyzed (94 men, mean age 59 years). 47 patients (30.5%) were treated according to Stupp regimen. Lim1 classification was presented in 74 (48%) patients, Lim2 in 22 (14.3%), Lim3 in 50 (32.5%) and Lim4 in 8 (5.2%) patients. Cortical structures (Lim1 and Lim3) were involved in 124 (80.5%) patients. Median overall survival was significantly better in patients treated according to Stupp regimen (23.3 vs. 8.6 months, p<0.001). Median overall survival differs in respective Lim groups: 12.3, 5.6, 11.8 and 6.6 months (p=0.07). Better survival was in patients with cortical involvement (Lim1+Lim3): 12.3 vs. 6.4 months (p=0.02), especially in subgroup of patients who were not treated according to Stupp regimen (8.9 vs. 4.4 months, p=0.02) vs. those after Stupp regimen (23 vs. 23.4 months, p=0.7). CONCLUSION Initial location of enhancing glioblastoma was prognostic for overall survival, with better outcomes in patients presented by involvement of cortical structures comparing to subventricular/hippocampal zones. Molecular patterns may further clarify potential effects of neural stem cells in glioma genesis mirrored in different clinical behavior and location of initial tumor. Supported by Ministry of Health of the Czech Republic, grant No. 18-03-00469

scholarly journals Adult Neural Stem Cells: Basic Research and Production Strategies for Neurorestorative Therapy

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
E. M. Samoilova ◽  
V. A. Kalsin ◽  
N. M. Kushnir ◽  
D. A. Chistyakov ◽  
A. V. Troitskiy ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Nervous Tissue ◽  
Molecular Mechanisms ◽  
Somatic Cells ◽  
Basic Research ◽  
Neural Cells ◽  
Pluripotent State ◽  
Increased Risk ◽  
Object Of Study

Over many decades, constructing genetically and phenotypically stable lines of neural stem cells (NSC) for clinical purposes with the aim of restoring irreversibly lost functions of nervous tissue has been one of the major goals for multiple research groups. The unique ability of stem cells to maintain their own pluripotent state even in the adult body has made them into the choice object of study. With the development of the technology for induced pluripotent stem cells (iPSCs) and direct transdifferentiation of somatic cells into the desired cell type, the initial research approaches based on the use of allogeneic NSCs from embryonic or fetal nervous tissue are gradually becoming a thing of the past. This review deals with basic molecular mechanisms for maintaining the pluripotent state of embryonic/induced stem and reprogrammed somatic cells, as well as with currently existing reprogramming strategies. The focus is on performing direct reprogramming while bypassing the stage of iPSCs which is known for genetic instability and an increased risk of tumorigenesis. A detailed description of various protocols for obtaining reprogrammed neural cells used in the therapy of the nervous system pathology is also provided.

Ultrastructural evidence for mast cell-macrophage interrelationships in the dura mater of the rat: Infrequent mast cell-nerve associations

1990 ◽  
Vol 48 (3) ◽  
pp. 352-353
Author(s):  
Ruth V.W. Dimlich
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Dura Mater ◽  
Spatial Relationship ◽  
Potassium Phosphate ◽  
Plasma Extravasation ◽  
Close Spatial Relationship ◽  
Male Wistar Rats ◽  
Headache Pain ◽  
Relationship Of

Mast cells in the dura mater of the rat may play a role in cerebral pathologies including neurogenic inflammation (vasodilation; plasma extravasation) and headache pain . As has been suggested for other tissues, dural mast cells may exhibit a close spatial relationship to nerves. There has been no detailed ultrastructural description of mast cells in this tissue; therefore, the goals of this study were to provide this analysis and to determine the spatial relationship of mast cells to nerves and other components of the dura mater in the rat.Four adult anesthetized male Wistar rats (290-400 g) were fixed by perfusion through the heart with 2% glutaraldehyde and 2.8% paraformaldehyde in a potassium phosphate buffer (pH 7.4) for 30 min. The head of each rat was removed and stored in fixative for a minimum of 24 h at which time the dural coverings were removed and dissected into samples that included the middle meningeal vasculature. Samples were routinely processed and flat embedded in LX 112. Thick (1 um) sections from a minimum of 3 blocks per rat were stained with toluidine blue (0.5% aqueous).

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