scholarly journals Effects of the neurogenic cells supernatant on the tumor-inducing ability of glioma 101.8 in rats

2015 ◽  
Vol 3 (1) ◽  
pp. 57-61
Author(s):  
L. Lyubich ◽  
M. Lisyany
Keyword(s):  
Tumor Cells ◽  
Malignant Gliomas ◽  
Clinical Manifestations ◽  
Treatment Strategies ◽  
Glioma Cells ◽  
Intracerebral Injection ◽  
Migration Potential ◽  
The Central Nervous System ◽  
Antitumor Properties ◽  
Brain And Spinal Cord

The use of neurogenic stem cells (NSCs) and neurogenic progenitor cells (NPCs) is one of the areas of brain and spinal cord lesions cell therapy. Intensive research of NSCs biology has revealed their tumor-tropic properties. Great migration potential and integration of NSCs in places of pathology in the central nervous system allows to consider their application as a means of targeted therapy of tumors. Antitumor properties of NSCs substantiate the development of treatment strategies for malignant gliomas using NSCs.The aim was to study the effect of rat neurogenic cells supernatant (NCS) on the tumor-inducing ability of glioma 101.8 cells at the intracerebral implantation in rats.Brain glioma 101.8 was modeling by intracerebral injection of 101.8-glioma cells suspension. NCS was received from whole rat brain tissue on 14th (E14) day of gestation.Modification of 101.8-glioma cells suspension by means of incubation with NCS (0.02 and 0.1 mg/ml) reduced the tumor-inducing ability of tumor cells, postponing the time of tumor clinical manifestations debut and increasing the lifetime of experimental animals.Under conditions of glioma induction with tumor cells, previously modified by NCS, cytotoxic activity of immune cells of tumor-bearing animals in MTT-test with allogeneic 101.8-glioma cells was increased.

scholarly journals EXTH-70. ENHANCEMENT OF ANTITUMOR ACTIVITY BY USING 5-ALA–MEDIATED SONODYNAMIC THERAPY TO INDUCE APOPTOSIS AND NECROSIS IN A MOUSE GLIOMA MODEL

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi97-vi97
Author(s):  
Satoshi Suehiro ◽  
Takanori Ohnishi ◽  
Akihiro Inoue ◽  
Daisuke Yamashita ◽  
Masahiro Nishikawa ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
High Intensity Focused Ultrasound ◽  
Control Group ◽  
Normal Brain ◽  
Sonodynamic Therapy ◽  
Cytotoxic Effects

Abstract OBJECTIVE High invasiveness of malignant gliomas frequently causes local tumor recurrence. To control such recurrence, novel therapies targeted toward infiltrating glioma cells are required. Here, we examined cytotoxic effects of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas both in vitro and in vivo. METHODS In vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells. Treatment-related apoptosis was analyzed using flow cytometry. Intracellular reactive oxygen species (ROS) were measured and the role of ROS in treatment-related cytotoxicity was examined. Effects of 5-ALA-SDT with high-intensity focused ultrasound (HIFU) on tumor growth, survival of glioma-transplanted mice, and histological features of the mouse brains were investigated. RESULTS The 5-ALA-SDT inhibited cell growth and changed cell morphology. Flow cytometric analysis indicated that 5-ALA-SDT induced apoptotic cell death. The 5-ALA-SDT generated higher ROS than in the control group, and inhibition of ROS generation completely eliminated the cytotoxic effects of 5-ALA-SDT. In the in vivo study, 5-ALA-SDT with HIFU greatly prolonged survival of the tumor-bearing mice compared with that of the control group (p < 0.05). Histologically, 5-ALA-SDT produced mainly necrosis of the tumor tissue in the focus area and induced apoptosis of the tumor cells in the perifocus area around the target of the HIFU-irradiated field. Normal brain tissues around the ultrasonic irradiation field of HIFU remained intact. CONCLUSIONS The 5-ALA-SDT was cytotoxic toward malignant gliomas. Generation of ROS by the SDT was thought to promote apoptosis of glioma cells. The 5-ALA-SDT with HIFU induced tumor necrosis in the focus area and apoptosis in the perifocus area of the HIFU-irradiated field. These results suggest that 5-ALA-SDT with HIFU may present a less invasive and tumor-specific therapy, not only for a tumor mass but also for infiltrating tumor cells in malignant gliomas.

scholarly journals Preliminary Report: Rapid Intraoperative Detection of Residual Glioma Cell in Resection Cavity Walls Using a Compact Fluorescence Microscope

2021 ◽  
Vol 10 (22) ◽  
pp. 5375
Author(s):  
Jiro Akimoto ◽  
Shinjiro Fukami ◽  
Megumi Ichikawa ◽  
Kenta Nagai ◽  
Michihiro Kohno
Keyword(s):  
Tumor Cell ◽  
Malignant Glioma ◽  
Tumor Cells ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
Fluorescence Microscope ◽  
Talaporfin Sodium ◽  
Surgical Microscope ◽  
Resection Cavity ◽  
Intraoperative Detection

Objective: The surgical eradication of malignant glioma cells is theoretically impossible. Therefore, reducing the number of remaining tumor cells around the brain–tumor interface (BTI) is crucial for achieving satisfactory clinical results. The usefulness of fluorescence–guided resection for the treatment of malignant glioma was recently reported, but the detection of infiltrating tumor cells in the BTI using a surgical microscope is not realistic. Therefore, we have developed an intraoperative rapid fluorescence cytology system, and exploratorily evaluated its clinical feasibility for the management of malignant glioma. Materials and methods: A total of 25 selected patients with malignant glioma (newly diagnosed: 17; recurrent: 8) underwent surgical resection under photodiagnosis using photosensitizer Talaporfin sodium and a semiconductor laser. Intraoperatively, a crush smear preparation was made from a tiny amount of tumor tissue, and the fluorescence emitted upon 620/660 nm excitation was evaluated rapidly using a compact fluorescence microscope in the operating theater. Results: Fluorescence intensities of tumor tissues measured using a surgical microscope correlated with the tumor cell densities of tissues evaluated by measuring the red fluorescence emitted from the cytoplasm of tumor cells using a fluorescence microscope. A “weak fluorescence” indicated a reduction in the tumor cell density, whereas “no fluorescence” did not indicate the complete eradication of the tumor cells, but indicated that few tumor cells were emitting fluorescence. Conclusion: The rapid intraoperative detection of fluorescence from glioma cells using a compact fluorescence microscope was probably useful to evaluate the presence of tumor cells in the resection cavity walls, and could provide surgical implications for the more complete resection of malignant gliomas.

scholarly journals Enhancement of antitumor activity by using 5-ALA–mediated sonodynamic therapy to induce apoptosis in malignant gliomas: significance of high-intensity focused ultrasound on 5-ALA-SDT in a mouse glioma model

2018 ◽  
Vol 129 (6) ◽  
pp. 1416-1428 ◽  
Author(s):  
Satoshi Suehiro ◽  
Takanori Ohnishi ◽  
Daisuke Yamashita ◽  
Shohei Kohno ◽  
Akihiro Inoue ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Cells ◽  
High Intensity ◽  
Focused Ultrasound ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
High Intensity Focused Ultrasound ◽  
Control Group ◽  
Tunel Staining ◽  
Sonodynamic Therapy

OBJECTIVEHigh invasiveness of malignant gliomas frequently causes early local recurrence of the tumor, resulting in extremely poor outcome. To control such recurrence, novel therapies targeted toward infiltrating glioma cells around the tumor border are required. Here, the authors investigated the antitumor activity of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas to explore the possibility for clinical use of 5-ALA–mediated SDT (5-ALA-SDT).METHODSIn vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells. Treatment-related apoptosis was analyzed using flow cytometry and TUNEL staining. Intracellular reactive oxygen species (ROS) were measured and the role of ROS in treatment-related cytotoxicity was examined by analysis of the effect of pretreatment with the radical scavenger edaravone. Effects of 5-ALA-SDT with high-intensity focused ultrasound (HIFU) on tumor growth, survival of glioma-transplanted mice, and histological features of the mouse brains were investigated.RESULTSThe 5-ALA-SDT inhibited cell growth and changed cell morphology, inducing cell shrinkage, vacuolization, and swelling. Flow cytometric analysis and TUNEL staining indicated that 5-ALA-SDT induced apoptotic cell death in all gliomas. The 5-ALA-SDT generated significantly higher ROS than in the control group, and inhibition of ROS generation by edaravone completely eliminated the cytotoxic effects of 5-ALA-SDT. In the in vivo study, 5-ALA-SDT with HIFU greatly prolonged survival of the tumor-bearing mice compared with that of the control group (p < 0.05). Histologically, 5-ALA-SDT produced mainly necrosis of the tumor tissue in the focus area and induced apoptosis of the tumor cells in the perifocus area around the target of the HIFU-irradiated field. The proliferative activity of the entire tumor was markedly decreased. Normal brain tissues around the ultrasonic irradiation field of HIFU remained intact.CONCLUSIONSThe 5-ALA-SDT was cytotoxic toward malignant gliomas. Generation of ROS by the SDT was thought to promote apoptosis of glioma cells. The 5-ALA-SDT with HIFU induced tumor necrosis in the focus area and apoptosis in the perifocus area of the HIFU-irradiated field, whereas the surrounding brain tissue remained normal, resulting in longer survival of the HIFU-treated mice compared with that of untreated mice. These results suggest that 5-ALA-SDT with HIFU may present a less invasive and tumor-specific therapy, not only for a tumor mass but also for infiltrating tumor cells in malignant gliomas.

scholarly journals Rapid Intraoperative Detection of Residual Glioma Cell in Resection Cavity Walls Using a Compact Fluorescence Microscope

2021 ◽  
Author(s):  
Jiro Akimoto ◽  
shinjiro Fukami ◽  
Megumi Ichikawa ◽  
Kenta nagai ◽  
Michihiro Kohno
Keyword(s):  
Tumor Cell ◽  
Malignant Glioma ◽  
Tumor Cells ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
Fluorescence Microscope ◽  
Talaporfin Sodium ◽  
Surgical Microscope ◽  
Resection Cavity ◽  
Intraoperative Detection

Objective: Surgical eradication of malignant glioma cells is theoretically impossible. Therefore, reducing the number of remaining tumor cells around the brain-tumor interface (BTI) is crucial for achieving satisfactory clinical results. The usefulness of fluorescence-guided resection for the treatment of malignant glioma was recently reported, but the detection of infiltrating tumor cells in the BTI using a surgical microscope is not realistic. Therefore, we developed an intraoperative rapid fluorescence cytology system, and evaluated its clinical feasibility for the management of malignant glioma. Materials and methods: Twenty-five selected patients with malignant glioma (newly diagnosed: 17; recurrent: 8) underwent surgical resection under photodiagnosis using photosensitizer Talaporfin sodium and a semiconductor laser. Intraoperatively, a crush smear preparation was made from a tiny amount of tumor tissue, and the fluorescence emitted upon 620/660 nm excitation was evaluated rapidly using a compact fluorescence microscope in the operating theater. Results: Fluorescence intensities of tumor tissues measured using a surgical microscope correlated with the tumor cell densities of tissues evaluated by measuring the red fluorescence emitted from the cytoplasm of tumor cells using a fluorescence microscope. A &ldquo;weak fluorescence&rdquo; indicated a reduction in the tumor cell density, whereas &ldquo;no fluorescence&rdquo; did not indicate the complete eradication of the tumor cells, but indicated that few tumor cells were emitting fluorescence.Conclusion: The rapid intraoperative detection of fluorescence from glioma cells using a compact fluorescence microscope was a useful to evaluate the presence of tumor cells in the resection cavity walls, and provides surgical implications for the more complete resection of malignant gliomas.

scholarly journals Immune response in glioma’s microenvironment

2021 ◽  
Vol 5 (3-4) ◽  
pp. 115-125
Author(s):  
Houminji Chen ◽  
Ming Li ◽  
Yanwu Guo ◽  
Yongsheng Zhong ◽  
Zhuoyi He ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Escape ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
Suppressor Cells ◽  
Future Research ◽  
Myeloid Derived Suppressor Cells ◽  
Local Production ◽  
Glioma Growth ◽  
The Central Nervous System

AbstractObjectivesGlioma is the most common tumor of the central nervous system. In this review, we outline the immunobiological factors that interact with glioma cells and tumor microenvironment (TME), providing more potential targets for clinical inhibition of glioma development and more directions for glioma treatment.ContentRecent studies have shown that glioma cells secrete a variety of immune regulatory factors and interact with immune cells such as microglial cells, peripheral macrophages, myeloid-derived suppressor cells (MDSCs), and T lymphocytes in the TME. In particular, microglia plays a key role in promoting glioma growth. Infiltrating immune cells induce local production of cytokines, chemokines and growth factors. Further leads to immune escape of malignant gliomas.Summary and OutlookThe complex interaction of tumor cells with the TME has largely contributed to tumor heterogeneity and poor prognosis. We review the immunobiological factors, immune cells and current immunotherapy of gliomas, provide experimental evidence for future research and treatment of gliomas.

Combined cimetidine and temozolomide, compared with temozolomide alone: significant increases in survival in nude mice bearing U373 human glioblastoma multiforme orthotopic xenografts

2005 ◽  
Vol 102 (4) ◽  
pp. 706-714 ◽  
Author(s):  
Florence Lefranc ◽  
Syril James ◽  
Isabelle Camby ◽  
Jean-François Gaussin ◽  
Francis Darro ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Tumor Cells ◽  
Nude Mice ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
Computer Assisted ◽  
Human Glioblastoma ◽  
Content Type ◽  
Human Glioblastoma Multiforme ◽  
Fine Print

Object. Malignant gliomas consist of both heterogeneous proliferating and migrating cell subpopulations, with migrating glioma cells exhibiting less sensitivity to antiproliferative or proapoptotic drugs than proliferative cells. Therefore, the authors combined cimetidine, an antiinflammatory agent already proven to act against migrating epithelial cancer cells, with temozolomide to determine whether the combination induces antitumor activities in experimental orthotopic human gliomas compared with the effects of temozolomide alone. Methods. Cimetidine added to temozolomide compared with temozolomide alone induced survival benefits in nude mice with U373 human glioblastoma multiforme (GBM) cells orthotopically xenografted in the brain. Computer-assisted phase-contrast microscopy analyses of 9L rat and U373 human GBM cells showed that cimetidine significantly decreased the migration levels of these tumor cells in vitro at concentrations at which tumor growth levels were not modified (as revealed on monotetrazolium colorimetric assay). Computer-assisted microscope analyses of neoglycoconjugate-based glycohistochemical staining profiles of 9L gliosarcomas grown in vivo revealed that cimetidine significantly decreased expression levels of endogenous receptors for fucose and, to a lesser extent, for N-acetyl-lactosamine moieties. Endogenous receptors of this specificity are known to play important roles in adhesion and migration processes of brain tumor cells. Conclusions. Cimetidine, acting as an antiadhesive and therefore an antimigratory agent for glioma cells, could be added in complement to the cytotoxic temozolomide compound to combat both migrating and proliferating cells in GBM.

Capillary permeability factor secreted by malignant brain tumor

1990 ◽  
Vol 72 (2) ◽  
pp. 245-251 ◽  
Author(s):  
Takanori Ohnishi ◽  
Peter B. Sher ◽  
Jerome B. Posner ◽  
William R. Shapiro
Keyword(s):  
Tumor Cells ◽  
Capillary Permeability ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
Lipoxygenase Inhibitor ◽  
Brain Capillary ◽  
Content Type ◽  
Rat Glioma ◽  
Permeability Factor ◽  
Capillary Endothelial Cells

✓ Conditioned media from two human malignant gliomas, C6 rat glioma, Walker 256 carcinosarcoma, and normal human glia were concentrated 50-fold to create a culture supernatant (SUP-C). The effect of SUP-C on rat brain capillary permeability was investigated by measuring the entry of 14C-aminoisobutyric acid (14C-AIB) by means of quantitative autoradiography. The SUP-C contained proteins with a molecular weight of 10 kD or greater. The SUP-C from all tumor cells markedly increased brain capillary permeability, indicating the presence of a permeability factor, whereas that from normal glial cells did not. Glioma cells produced more factor after incubation for 20 hours than 4 hours. The activity of capillary permeability factor in the SUP-C was inhibited by pretreatment of animals with BW755C (lipoxygenase inhibitor), but not with indomethacin (cyclo-oxygenase inhibitor). Pretreatment of animals with dexamethasone prior to intracerebral infusion of tumor SUP-C significantly reduced the factor-induced increase in capillary permeability. On the other hand, coincubating glioma cells with dexamethasone produced SUP-C with a permeability activity that was about one and a half times greater than that without dexamethasone. These results indicate that glucocorticoids produce their anti-edema effects by directly acting on capillary endothelial cells, possibly through the inhibition of phospholipase A2 activity, resulting in a decrease of lipoxygenase rather than cyclo-oxygenase products. The production of capillary permeability factor by tumor cells was not inhibited, but rather enhanced, by administration of glucocorticoids.

scholarly journals SYVN1-MTR4-MAT2A Signaling Axis Regulates Methionine Metabolism in Glioma Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Lude Wang ◽  
Bin Hu ◽  
Kailing Pan ◽  
Jie Chang ◽  
Xiaoya Zhao ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Nuclear Export ◽  
Treatment Strategies ◽  
Glioma Cells ◽  
Essential Amino Acids ◽  
High Expression ◽  
World Health ◽  
Methionine Restriction ◽  
Restricted Environment ◽  
Health Organization

Methionine is one of the essential amino acids. How tumor cells adapt and adjust their signal transduction networks to avoid apoptosis in a methionine-restricted environment is worthy of further exploration. In this study, we investigated the molecular mechanism of glioma response to methionine restriction, providing a theoretical basis for new treatment strategies for glioma.MethodsWe constructed methionine-restriction-tolerant cells in order to study the response of glioma to a methionine-restricted environment. The transcriptome analysis of the tolerant cells showed significant changes in MAT2A. Western blotting, immunohistochemistry, quantitative real-time PCR, colony formation assays, and other experiments were used to verify the role of MAT2A in glioma genesis. In addition, the regulatory mechanism of MAT2A mRNA nuclear export was investigated by transfection, plasma nucleation separation, and co-immunoprecipitation.ResultsUnder methionine restriction, glioma cells showed high expression of MAT2A, and an inhibitor of MAT2A reduced the proliferation of tumor cells. The expression of MAT2A was positively correlated with World Health Organization-grade glioma. High expression of MAT2A was related to increased transfer of its mRNA out of the nucleus. The expression of nuclear export regulatory molecule MTR4 could affect the export of MAT2A mRNA. In a methionine-restricted environment, ubiquitination of MTR4 was enhanced, and thus its protein level was reduced. The E3 ubiquitin ligase was verified to be SYVN1.ConclusionIn summary, methionine restriction leads to increased ubiquitination of MTR4, which promotes the transfer of MAT2A mRNA out of the nucleus and MAT2A protein expression. MAT2A promotes histone methylation, prompting cells to proliferate in a methionine-restricted environment.

Emigration of neutrophils in the central nervous system

1983 ◽  
Vol 41 ◽  
pp. 788-789
Author(s):  
John L.Beggs ◽  
John D. Waggener ◽  
Wanda Miller ◽  
Jane Watkins
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Osmium Tetroxide ◽  
White Blood Cells ◽  
Arterial Perfusion ◽  
E Coli ◽  
Intracisternal Injection ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
Interendothelial Junctions

Studies using mesenteric and ear chamber preparations have shown that interendothelial junctions provide the route for neutrophil emigration during inflammation. The term emigration refers to the passage of white blood cells across the endothelium from the vascular lumen. Although the precise pathway of transendo- thelial emigration in the central nervous system (CNS) has not been resolved, the presence of different physiological and morphological (tight junctions) properties of CNS endothelium may dictate alternate emigration pathways.To study neutrophil emigration in the CNS, we induced meningitis in guinea pigs by intracisternal injection of E. coli bacteria.In this model, leptomeningeal inflammation is well developed by 3 hr. After 3 1/2 hr, animals were sacrificed by arterial perfusion with 3% phosphate buffered glutaraldehyde. Tissues from brain and spinal cord were post-fixed in 1% osmium tetroxide, dehydrated in alcohols and propylene oxide, and embedded in Epon. Thin serial sections were cut with diamond knives and examined in a Philips 300 electron microscope.

Sign in / Sign up

Export Citation Format

Share Document