Topical Review Article: Brainstem and Other Malignant Gliomas: II. Possible Mechanisms of Brain Infiltration by Tumor Cells

1993 ◽  
Vol 8 (4) ◽  
pp. 292-305 ◽  
Author(s):  
Bernard L. Maria ◽  
Thomas A. Eskin ◽  
Ronald G. Quisling
Keyword(s):  
Tumor Cells ◽  
Malignant Gliomas ◽  
Review Article ◽  
Topical Review

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 Sonodynamic Therapy for the Treatment of Intracranial Gliomas

2021 ◽  
Vol 10 (5) ◽  
pp. 1101
Author(s):  
Antonio D’Ammando ◽  
Luca Raspagliesi ◽  
Matteo Gionso ◽  
Andrea Franzini ◽  
Edoardo Porto ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Therapeutic Option ◽  
Malignant Gliomas ◽  
Progression Free Survival ◽  
High Grade ◽  
Sonodynamic Therapy ◽  
Treatment Protocols ◽  
Ultrasound Waves ◽  
High Grade Gliomas ◽  
Preclinical And Clinical Studies

High-grade gliomas are the most common and aggressive malignant primary brain tumors. Current therapeutic schemes include a combination of surgical resection, radiotherapy and chemotherapy; even if major advances have been achieved in Progression Free Survival and Overall Survival for patients harboring high-grade gliomas, prognosis still remains poor; hence, new therapeutic options for malignant gliomas are currently researched. Sonodynamic Therapy (SDT) has proven to be a promising treatment combining the effects of low-intensity ultrasound waves with various sound-sensitive compounds, whose activation leads to increased immunogenicity of tumor cells, increased apoptotic rates and decreased angiogenetic potential. In addition, this therapeutic technique only exerts its cytotoxic effects on tumor cells, while both ultrasound waves and sensitizing compound are non-toxic per se. This review summarizes the present knowledge regarding mechanisms of action of SDT and currently available sonosensitizers and focuses on the preclinical and clinical studies that have investigated its efficacy on malignant gliomas. To date, preclinical studies implying various sonosensitizers and different treatment protocols all seem to confirm the anti-tumoral properties of SDT, while first clinical trials will soon start recruiting patients. Accordingly, it is crucial to conduct further investigations regarding the clinical applications of SDT as a therapeutic option in the management of intracranial gliomas.

Thymidine kinase activation of ganciclovir in recurrent malignant gliomas: a gene-marking and neuropathological study

2000 ◽  
Vol 92 (5) ◽  
pp. 804-811 ◽  
Author(s):  
Griffith R. Harsh ◽  
Thomas S. Deisboeck ◽  
David N. Louis ◽  
John Hilton ◽  
Michael Colvin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enzymatic Activity ◽  
Thymidine Kinase ◽  
Tumor Cells ◽  
Malignant Gliomas ◽  
Retroviral Vectors ◽  
Content Type ◽  
Tumor Bed ◽  
Immunohistochemical Evidence ◽  
Fine Print

Object. The gene therapy paradigm of intratumoral activation of ganciclovir (GCV) following transduction of tumor cells by retroviral vectors bearing the thymidine kinase (tk) gene has produced dramatic remissions of malignant gliomas in animal models. In human trials, although the technique has been deemed safe, little antitumor effect has been demonstrated. To evaluate the basis of this inefficacy in human gliomas, the authors conducted a gene-marking trial involving neuropathological and biochemical studies of treated tumor specimens.Methods. Five patients with malignant recurrent gliomas underwent stereotactic biopsy sampling and intratumoral implantation procedures with three aliquots of 106 vector-producing cells (VPCs) in columns. After 5 days, the tumor was resected and the tumor bed reimplanted with VPCs, and a course of GCV was given. Patients received clinical and radiological follow up for 6 months. Tumor specimens were analyzed neuropathologically and for tk gene expression by anti-TK immunohistochemistry and TK enzymatic activity.Four patients tolerated the treatment well but experienced tumor progression. The other developed an abscess after the second operation and died. Increased TK enzymatic activity was demonstrated in the one tumor specimen analyzed. Immunohistochemical evidence of tk gene expression was limited to VPCs. Transduction of tumor cells was not seen. Viable tumor cells were seen near VPCs containing TK. The lymphocytic immune response was mild.Conclusions. Except for the risk of infection inherent in reoperation, this tk—GCV paradigm was both feasible and safe. Pathological studies indicated that limited dissemination of VPCs and vector from the infusion site and failure to transduce tumor cells with the tk gene are major barriers to efficacy.

Anaplasia and Heterogeneity of Gfap Expression in Gliomas

1986 ◽  
Vol 72 (2) ◽  
pp. 163-170 ◽  
Author(s):  
Davide Schiffer ◽  
Maria Teresa Giordana ◽  
Isabella Germano ◽  
Alessandro Mauro
Keyword(s):  
Glial Fibrillary Acidic Protein ◽  
Tumor Cells ◽  
Cell Population ◽  
Malignant Gliomas ◽  
Reactive Astrocytes ◽  
Mutation Rates ◽  
Protein Distribution ◽  
Gfap Expression ◽  
Proliferating Cell ◽  
Negative Population

GFAP (glial fibrillary acidic protein) distribution was investigated in selected areas of glioblastomas and astrocytomas. The proliferating cell population of glioblastomas was GFAP negative and contained many mitoses which were also negative. The old, deeply located areas were composed of cells with visible cytoplasm, intensely GFAP-positive; mitoses in these areas were both GFAP-positive and negative. GFAP-positive reactive astrocytes, once trapped in the tumor, were no longer distinguishable from positive tumor cells. They sometimes contained mitoses. In astrocytoma, anaplasia was due to the development of a GFAP-negative population with negative mitoses. The problem of dedifferentiation and differentiation of malignant gliomas in discussed taking into account the possiblity that malignancy may be due to increasing mutation rates of tumors. The problem of redifferentiation of already dedifferentiated cells is also discussed.

Topical Review Article: Organic Acidurias: A Review. Part 1

1991 ◽  
Vol 6 (3) ◽  
pp. 196-219 ◽  
Author(s):  
Pinar T. Ozand ◽  
Generoso G. Gascon
Keyword(s):  
Review Article ◽  
Organic Acidurias ◽  
Topical Review

HER-2/neu expression in glioblastoma multiforme (GBM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13035-e13035
Author(s):  
S. Gupta ◽  
H. Sheikh ◽  
C. Schneider ◽  
X. Zhang ◽  
A. Padmanabhan ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Tumor Cells ◽  
Blood Brain Barrier ◽  
Malignant Gliomas ◽  
Human Tumor ◽  
Brain Barrier ◽  
Breast Cancer Patients ◽  
Over Expression ◽  
Blood Brain ◽  
Her 2

e13035 Background: Glioblastoma multiforme (GBM) is a disease in which very few cytotoxic chemotherapy agents have been shown to have activity. This is partly due to their inability to cross the blood brain barrier. Trials with bevacizumab, a VEGF inhibitor that disrupts tumor angiogenesis, have demonstrated activity against this otherwise chemotherapy resistant disease. This has led to interest in other biologic agents that target angiogenic pathways for the treatment of GBM. Over-expression of HER-2/neu by human tumor cells is closely associated with increased angiogenesis and expression of VEGF. Lapatinib is a recently available low molecular weight immunotherapeutic agent that targets HER-2/neu proteins. In a recent study, breast cancer patients treated with lapatinib and capcitabine had decreased brain metastases indicating that lapatinib may cross the blood brain barrier and thus have potential in the treatment of malignant gliomas. Limited studies have evaluated HER-2/neu gene expression in GBM and the results are inconsistent. We evaluated the expression of Her-2/neu protein in 41 consecutive GBM cases to explore the potential utility of targeting this pathway. Methods: Archival histopathologic sections from 41 patients (age 26–89 years) with a diagnosis of GBM from 2004–2008 were reviewed. The diagnosis was confirmed and optimal sections were selected. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections using the primary antibody against HER-2/neu (clone 4B5, Ventana). The results were evaluated by three independent investigators. Interpretation was performed using the semi-quantitative criteria (Score 0 to 3+) currently used for primary breast carcinomas. Results: 38 out of 41 cases showed no immunohistochemical staining with HER-2/neu antibody (score 0). Three cases demonstrated weak, incomplete membrane staining of rare tumor cells (score 1+) and were interpreted as negative. The positive and negative controls worked properly. Conclusions: Our study indicates that there is no significant immunohistochemical over-expression of HER-2/neu protein in GBM. This suggests that HER-2/neu over-expression is not a significant oncogenic pathway in GBM, and therefore may not be a potential therapeutic target in this disease. No significant financial relationships to disclose.

Topical Review Article: Organic Acidurias: A Review Part 2

1991 ◽  
Vol 6 (4) ◽  
pp. 288-303 ◽  
Author(s):  
Pinar T. Ozand ◽  
Generoso G. Gascon
Keyword(s):  
Review Article ◽  
Organic Acidurias ◽  
Topical Review

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.

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