scholarly journals In Silico Neuro-Oncology: Brownian Motion-Based Mathematical Treatment as a Potential Platform for Modeling the Infiltration of Glioma Cells into Normal Brain Tissue

2015 ◽  
Vol 14s4 ◽  
pp. CIN.S19341 ◽  
Author(s):  
Markos Antonopoulos ◽  
Georgios Stamatakos
Keyword(s):  
Brownian Motion ◽  
Brain Tissue ◽  
Diffusion Tensor ◽  
Glioma Cells ◽  
Tomographic Imaging ◽  
Mathematical Treatment ◽  
Normal Brain ◽  
Imaging Data ◽  
Clinical Observations ◽  
Anisotropic Character

Intensive glioma tumor infiltration into the surrounding normal brain tissues is one of the most critical causes of glioma treatment failure. To quantitatively understand and mathematically simulate this phenomenon, several diffusion-based mathematical models have appeared in the literature. The majority of them ignore the anisotropic character of diffusion of glioma cells since availability of pertinent truly exploitable tomographic imaging data is limited. Aiming at enriching the anisotropy-enhanced glioma model weaponry so as to increase the potential of exploiting available tomographic imaging data, we propose a Brownian motion-based mathematical analysis that could serve as the basis for a simulation model estimating the infiltration of glioblastoma cells into the surrounding brain tissue. The analysis is based on clinical observations and exploits diffusion tensor imaging (DTI) data. Numerical simulations and suggestions for further elaboration are provided.

scholarly journals Chronic pathophysiological changes in the normal brain parenchyma caused by radiotherapy accelerate glioma progression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuichiro Tsuji ◽  
Naosuke Nonoguchi ◽  
Daisuke Okuzaki ◽  
Yusuke Wada ◽  
Daisuke Motooka ◽  
...  
Keyword(s):  
Survival Time ◽  
Brain Tissue ◽  
Median Survival ◽  
Median Survival Time ◽  
Glioma Cell ◽  
Right Hemisphere ◽  
Glioma Cells ◽  
Chronic Phase ◽  
Normal Brain ◽  
X Ray

AbstractRadiation therapy is one of standard treatment for malignant glioma after surgery. The microenvironment after irradiation is considered not to be suitable for the survival of tumor cells (tumor bed effect). This study investigated whether the effect of changes in the microenvironment of parenchymal brain tissue caused by radiotherapy affect the recurrence and progression of glioma. 65-Gy irradiation had been applied to the right hemisphere of Fisher rats. After 3 months from irradiation, we extracted RNA and protein from the irradiated rat brain. To study effects of proteins extracted from the brains, we performed WST-8 assay and tube formation assay in vitro. Cytokine production were investigated for qPCR. Additionally, we transplanted glioma cell into the irradiated and sham animals and the median survival time of F98 transplanted rats was also examined in vivo. Immunohistochemical analyses and invasiveness of implanted tumor were evaluated. X-ray irradiation promoted the secretion of cytokines such as CXCL12, VEGF-A, TGF-β1 and TNFα from the irradiated brain. Proteins extracted from the irradiated brain promoted the proliferation and angiogenic activity of F98 glioma cells. Glioma cells implanted in the irradiated brains showed significantly high proliferation, angiogenesis and invasive ability, and the post-irradiation F98 tumor-implanted rats showed a shorter median survival time compared to the Sham-irradiation group. The current study suggests that the microenvironment around the brain tissue in the chronic phase after exposure to X-ray radiation becomes suitable for glioma cell growth and invasion.

scholarly journals Machine Learning for the Classification of Alzheimer’s Disease and Its Prodromal Stage Using Brain Diffusion Tensor Imaging Data: A Systematic Review

Processes ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 1071
Author(s):  
Lucia Billeci ◽  
Asia Badolato ◽  
Lorenzo Bachi ◽  
Alessandro Tonacci
Keyword(s):  
Machine Learning ◽  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Diffusion Tensor Imaging ◽  
Magnetic Resonance ◽  
Diffusion Tensor ◽  
Classification Problem ◽  
Computer Algorithms ◽  
Imaging Data

Alzheimer’s disease is notoriously the most common cause of dementia in the elderly, affecting an increasing number of people. Although widespread, its causes and progression modalities are complex and still not fully understood. Through neuroimaging techniques, such as diffusion Magnetic Resonance (MR), more sophisticated and specific studies of the disease can be performed, offering a valuable tool for both its diagnosis and early detection. However, processing large quantities of medical images is not an easy task, and researchers have turned their attention towards machine learning, a set of computer algorithms that automatically adapt their output towards the intended goal. In this paper, a systematic review of recent machine learning applications on diffusion tensor imaging studies of Alzheimer’s disease is presented, highlighting the fundamental aspects of each work and reporting their performance score. A few examined studies also include mild cognitive impairment in the classification problem, while others combine diffusion data with other sources, like structural magnetic resonance imaging (MRI) (multimodal analysis). The findings of the retrieved works suggest a promising role for machine learning in evaluating effective classification features, like fractional anisotropy, and in possibly performing on different image modalities with higher accuracy.

scholarly journals Protein Kinase A Distribution in Meningioma

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1686 ◽  
Author(s):  
Caretta ◽  
Denaro ◽  
D’Avella ◽  
Mucignat-Caretta
Keyword(s):  
Brain Tissue ◽  
Catalytic Subunit ◽  
Therapeutic Interventions ◽  
Normal Brain ◽  
Local Concentration ◽  
Correlation Pattern ◽  
Catalytic Subunits ◽  
Tissue Specimens ◽  
Pka Catalytic Subunit

Deregulation of intracellular signal transduction pathways is a hallmark of cancer cells, clearly differentiating them from healthy cells. Differential intracellular distribution of the cAMP-dependent protein kinases (PKA) was previously detected in cell cultures and in vivo in glioblastoma and medulloblastoma. Our goal is to extend this observation to meningioma, to explore possible differences among tumors of different origins and prospective outcomes. The distribution of regulatory and catalytic subunits of PKA has been examined in tissue specimens obtained during surgery from meningioma patients. PKA RI subunit appeared more evenly distributed throughout the cytoplasm, but it was clearly detectable only in some tumors. RII was present in discrete spots, presumably at high local concentration; these aggregates could also be visualized under equilibrium binding conditions with fluorescent 8-substituted cAMP analogues, at variance with normal brain tissue and other brain tumors. The PKA catalytic subunit showed exactly overlapping pattern to RII and in fixed sections could be visualized by fluorescent cAMP analogues. Gene expression analysis showed that the PKA catalytic subunit revealed a significant correlation pattern with genes involved in meningioma. Hence, meningioma patients show a distinctive distribution pattern of PKA regulatory and catalytic subunits, different from glioblastoma, medulloblastoma, and healthy brain tissue. These observations raise the possibility of exploiting the PKA intracellular pathway as a diagnostic tool and possible therapeutic interventions.

scholarly journals Neuroinflammatory changes of the normal brain tissue in cured mice following combined radiation and anti-PD-1 blockade therapy for glioma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mariano Guardia Clausi ◽  
Alexander M. Stessin ◽  
Zirun Zhao ◽  
Stella E. Tsirka ◽  
Samuel Ryu
Keyword(s):  
Brain Tissue ◽  
Cranial Irradiation ◽  
Subcortical White Matter ◽  
Glioma Cell Line ◽  
Hippocampal Neurogenesis ◽  
Normal Brain ◽  
Long Term Effects ◽  
Normal Brain Tissue ◽  
Molecule Inhibitor

AbstractThe efficacy of combining radiation therapy with immune checkpoint inhibitor blockade to treat brain tumors is currently the subject of multiple investigations and holds significant therapeutic promise. However, the long-term effects of this combination therapy on the normal brain tissue are unknown. Here, we examined mice that were intracranially implanted with murine glioma cell line and became long-term survivors after treatment with a combination of 10 Gy cranial irradiation (RT) and anti-PD-1 checkpoint blockade (aPD-1). Post-mortem analysis of the cerebral hemisphere contralateral to tumor implantation showed complete abolishment of hippocampal neurogenesis, but neural stem cells were well preserved in subventricular zone. In addition, we observed a drastic reduction in the number of mature oligodendrocytes in the subcortical white matter. Importantly, this observation was evident specifically in the combined (RT + aPD-1) treatment group but not in the single treatment arm of either RT alone or aPD-1 alone. Elimination of microglia with a small molecule inhibitor of colony stimulated factor-1 receptor (PLX5622) prevented the loss of mature oligodendrocytes. These results identify for the first time a unique pattern of normal tissue changes in the brain secondary to combination treatment with radiotherapy and immunotherapy. The results also suggest a role for microglia as key mediators of the adverse treatment effect.

scholarly journals CSIG-13. TRPM7 INDUCES TUMORIGENESIS AND STEMNESS THROUGH NOTCH ACTIVATION IN GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii30-ii30
Author(s):  
Jingwei Wan ◽  
Alyssa Guo ◽  
Mingli Liu
Keyword(s):  
Notch Signaling ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Inhibitory Effect ◽  
Notch Signaling Pathway ◽  
Normal Brain ◽  
Diffuse Astrocytoma ◽  
Notch1 Signaling ◽  
Signaling Activation ◽  
Proliferation And Invasion

Abstract Our group found that the inhibitory effect of TRPM7 on proliferation and invasion of human glioma cell is mediated by multiple mechanisms. TRPM7 regulates miR-28-5p expression, which suppresses cell proliferation and invasion in glioma cells by targeting Ras-related protein Rap1b. In particular, our group found that TRPM7 channels regulate glioma stem cell (GSC) growth/proliferation through STAT3 and Notch signaling. However, which Notch component(s) is crucial for its activity regulated by TRPM7, and its relationship with other GSC markers, such as CD133 and ALDH1, remain unclear. In the current project, we elucidate the mechanisms of TRMP7’s regulation of Notch signaling pathway that contribute to the development and progression of glioma and maintenance of self-renewal and tumorigenicity of GSC using multiple glioma cell lines (GC) with different molecular subtypes and GSCs derived from the GC lines. 1) We first analyzed TRPM7 expression using the Oncomine database (https://www.oncomine.org) and found that the TRPM7 mRNA expression is significantly increased in anaplastic astrocytoma, diffuse astrocytoma, and GBM patients compared to that in normal brain tissue controls. 2) TRPM7 is expressed in GBM, and its channel activity is correlated with Notch1 activation. Inhibition of TRPM7 downregulates Notch1 signaling, while upregulation of TRPM7 upregulates Notch1 signaling. 3) GSC markers, CD133 and ALDH1, are correlated with TRPM7 in GBM. 4) Targeting TRPM7 suppresses the growth and proliferation of glioma cells through G1/S arrests and apoptosis of glioma cells. 5) Targeting Notch1 suppresses the TRPM7-induced growth and proliferation of glioma cells, as well as the expression of GSC markers CD133 and ALDH1. In summary, TRPM7 is responsible for sustained Notch signaling activation, enhanced expression of GSC markers, and regulation of glioma stemness, which contribute to malignant glioma cell growth and invasion. Notch1 and ligand DII4 are key components that contribute GSC stemness.

scholarly journals MS-2 Minimally invasive glioma surgery with navigation system and tubular retractor

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii2-ii3
Author(s):  
Kazuhiko Kurozumi
Keyword(s):  
Navigation System ◽  
Diffusion Tensor ◽  
Therapeutic Option ◽  
Normal Brain ◽  
Navigation Systems ◽  
Glioma Surgery ◽  
Tubular Retractor ◽  
Neuronavigation System ◽  
Magnetic Resonance Imaging Mri ◽  
Neurological Surgery

Abstract Navigation systems are reliable and safe for neurological surgery. Navigation is an attractive and innovative therapeutic option. Recently, endo and exoscopic surgeries have been gradually increasing in neurosurgery. We are currently trialing to use 4K and 8K systems to improve the accuracy and safety of our surgical procedures. Surgeries for deep-seated tumors are challenging because of the difficulty in creating a corridor and observing the interface between lesions and the normal area. In total, 315 patients underwent surgery at Okayama University between 2017 and 2019. Among them, we experienced 92 glioma surgeries using navigation systems. Preoperatively, we performed computed tomography imaging and contrast-enhanced magnetic resonance imaging (MRI) for the neuronavigation system. We experienced Curve(TM) Image Guided Surgery (BrainLab, Munich, Germany). The surgical trajectory was planned with functional MRI and diffusion tensor imaging to protect the eloquent area and critical vasculature of the brain. We used a clear plastic tubular retractor system, the ViewSite Brain Access System, for surgery of deep seated gliomas. We gently inserted and placed the ViewSite using the neuronavigation. The tumor was observed and resected through the ViewSite tubular retractor under a microscope and endoscope. If the tumor was large, we switched the ViewSite tubular retractor to brain spatulas to identify the boundary between the normal brain and lesion. We are currently using the combination of the tubular retractor and brain spatulas using navigation system. Here, we present and analyze our preoperative simulation, surgical procedure, and outcomes.

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.

Quantitative Measurements of Regional Glucose Utilization and Rate of Valine Incorporation into Proteins by Double-Tracer Autoradiography in the Rat Brain Tumor Model

1989 ◽  
Vol 9 (1) ◽  
pp. 87-95 ◽  
Author(s):  
Michihiro Kirikae ◽  
Mirko Diksic ◽  
Y. Lucas Yamamoto
Keyword(s):  
Protein Synthesis ◽  
Brain Tumor ◽  
Rat Brain ◽  
Brain Tissue ◽  
Glucose Utilization ◽  
Tumor Model ◽  
Normal Brain ◽  
Normal Brain Tissue ◽  
Rat Brain Tumor ◽  
Brain Tumor Model

We examined the rate of glucose utilization and the rate of valine incorporation into proteins using 2-[18F]fluoro-2-deoxyglucose and L-[1-14C]-valine in a rat brain tumor model by quantitative double-tracer autoradiography. We found that in the implanted tumor the rate of valine incorporation into proteins was about 22 times and the rate of glucose utilization was about 1.5 times that in the contralateral cortex. (In the ipsilateral cortex, the tumor had a profound effect on glucose utilization but no effect on the rate of valine incorporation into proteins.) Our findings suggest that it is more useful to measure protein synthesis than glucose utilization to assess the effectiveness of antitumor agents and their toxicity to normal brain tissue. We compared two methods to estimate the rate of valine incorporation: “kinetic” (quantitation done using an operational equation and the average brain rate coefficients) and “washed slices” (unbound labeled valine removed by washing brain slices in 10% thrichloroacetic acid). The results were the same using either method. It would seem that the kinetic method can thus be used for quantitative measurement of protein synthesis in brain tumors and normal brain tissue using [11C]-valine with positron emission tomography.

PET Study of Methionine Accumulation in Glioma and Normal Brain Tissue

1987 ◽  
Vol 11 (2) ◽  
pp. 208-213 ◽  
Author(s):  
Mats Bergström ◽  
Kaj Ericson ◽  
Lars Hagenfeldt ◽  
Mikael Mosskin ◽  
Hans von Holst ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Normal Brain ◽  
Normal Brain Tissue
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