scholarly journals Modeling invasion patterns in the glioblastoma battlefield

2021 ◽  
Vol 17 (1) ◽  
pp. e1008632
Author(s):  
Martina Conte ◽  
Sergio Casas-Tintò ◽  
Juan Soler
Keyword(s):  
Evolution Equations ◽  
Dynamical Evolution ◽  
Brain Regions ◽  
Infiltration Capacity ◽  
Invasion Front ◽  
In Vivo Experiments ◽  
Tissue Resistance ◽  
Tissue Porosity ◽  
Non Linear System

Glioblastoma is the most aggressive tumor of the central nervous system, due to its great infiltration capacity. Understanding the mechanisms that regulate the Glioblastoma invasion front is a major challenge with preeminent potential clinical relevances. In the infiltration front, the key features of tumor dynamics relate to biochemical and biomechanical aspects, which result in the extension of cellular protrusions known as tumor microtubes. The coordination of metalloproteases expression, extracellular matrix degradation, and integrin activity emerges as a leading mechanism that facilitates Glioblastoma expansion and infiltration in uncontaminated brain regions. We propose a novel multidisciplinary approach, based on in vivo experiments in Drosophila and mathematical models, that describes the dynamics of active and inactive integrins in relation to matrix metalloprotease concentration and tumor density at the Glioblastoma invasion front. The mathematical model is based on a non-linear system of evolution equations in which the mechanisms leading chemotaxis, haptotaxis, and front dynamics compete with the movement induced by the saturated flux in porous media. This approach is able to capture the relative influences of the involved agents and reproduce the formation of patterns, which drive tumor front evolution. These patterns have the value of providing biomarker information that is related to the direction of the dynamical evolution of the front and based on static measures of proteins in several tumor samples. Furthermore, we consider in our model biomechanical elements, like the tissue porosity, as indicators of the healthy tissue resistance to tumor progression.

scholarly journals Modeling invasion patterns in the glioblastoma battlefield

2020 ◽  
Author(s):  
Martina Conte ◽  
Sergio Casas-Tinto ◽  
Juan Soler
Keyword(s):  
Multidisciplinary Approach ◽  
Brain Regions ◽  
Matrix Degradation ◽  
Infiltration Capacity ◽  
In Vivo Experiments ◽  
The Central Nervous System ◽  
Aggressive Tumor ◽  
Key Features ◽  
Invasion Patterns

Glioblastoma is the most aggressive tumor of the central nervous system, due to its great infiltration capacity. Understanding the mechanisms that regulate the Glioblastoma invasion front is a major challenge with preeminent potential clinical relevance. In the in1ltration front, the key features of its dynamics relate to biochemical and biomechanical aspects, which result in extended cellular protrusions, known as tumor microtubes. The coordination of metalloproteinase expression, extracellular matrix degradation, and integrin activity emerges as leading mechanism that facilitates Glioblastoma expansion and in1ltration in uncontaminated brain regions. We propose a novel multidisciplinary approach, based on in vivo experiments in Drosophila and mathematical models, for the proteins dynamics at the front of Glioblastoma, with a predictive value of the tumor progression.

Mechanics of Microtubule Buckling Supported by Cytoplasm

2008 ◽  
Vol 75 (6) ◽  
Author(s):  
Hanqing Jiang ◽  
Jiaping Zhang
Keyword(s):  
Evolution Equations ◽  
Compressive Force ◽  
Cylindrical Tube ◽  
Long Wavelength ◽  
Euler Buckling ◽  
In Vivo Experiments ◽  
Critical Wavelength ◽  
A Cell

The cytoskeleton provides the mechanical scaffold and maintains the integrity of cells. It is usually believed that one type of cytoskeleton biopolymer, microtubules, bears compressive force. In vitro experiments found that isolated microtubules may form an Euler buckling pattern with a long-wavelength for very small compressive force. This, however, does not agree with in vivo experiments where microtubules buckle with a short-wavelength. In order to understand the structural role of microtubules in vivo, we developed mechanics models that study microtubule buckling supported by cytoplasm. The microtubule is modeled as a linearly elastic cylindrical tube while the cytoplasm is characterized by different types of materials, namely, viscous, elastic, or viscoelastic. The dynamic evolution equations, the fastest growth rate, the critical wavelength, and compressive force, as well as equilibrium buckling configurations are obtained. The ability for a cell to sustain compressive force does not solely rely on microtubules but is also supported by the elasticity of cytoplasm. With the support of the cytoplasm, an individual microtubule can sustain a compressive force on the order of 100pN. The relatively stiff microtubules and compliant cytoplasm are combined to provide a scaffold for compressive force.

Modeling Avascular Tumor Growth: Approach with an Adaptive Grid Numerical Technique

2018 ◽  
Vol 09 (03) ◽  
pp. 1840002
Author(s):  
Antonino Amoddeo
Keyword(s):  
Numerical Technique ◽  
Nonlinear Partial Differential Equations ◽  
Dynamical Evolution ◽  
Short Review ◽  
Model Parameters ◽  
Cancer Evolution ◽  
Cancer Proliferation ◽  
In Vivo Experiments ◽  
Spatio Temporal

The mathematical modeling of complex biological systems leads to system of coupled nonlinear partial differential equations (PDEs). In this paper, we present a short review on the interaction of the urokinase plasminogen activator (uPA) system with a model for cancer cell in the avascular phase, faced using the moving mesh PDE/(MMPDE) numerical technique. The dynamical evolution of the system as a function of the diffusion properties of cancer cells has been considered, as well as the effect of hypoxia to the cancer evolution, introducing a model equation for the nutrient oxygen. The model parameters have been taken from the data existing in the literature, in particular to gauge the oxygen supply, data determined from in vivo experiments on human tumors have been used. The numerical results obtained simulating a one-dimensional portion of the biological tissue are consistent with the data existing in the literature. Our high-resolution computations show that cancer proliferation begins through highly irregular spatio-temporal pattern, which depends on cancer motility characteristics. In presence of hypoxia, the cancer proliferation patterns are still characterized by an inhomogeneous pattern, but other effects are present which depend on the model parameters, triggered by the oxygen.

scholarly journals SU-8 Based Waveguide for Optrodes

Proceedings ◽  
2018 ◽  
Vol 2 (13) ◽  
pp. 814
Author(s):  
Sara Pimenta ◽  
João F. Ribeiro ◽  
Sandra B. Goncalves ◽  
Marino J. Maciel ◽  
Rosana A. Dias ◽  
...  
Keyword(s):  
Optical Fiber ◽  
Optical Power ◽  
Brain Regions ◽  
Neural Probes ◽  
Tissue Penetration ◽  
In Vivo Experiments ◽  
Small Probe ◽  
Promising Solution ◽  
Neural Probe

Neural probes can be equipped with light for optogenetics applications. Different approaches are used for delivering light to the tissue: an optical fiber coupled to the probe, a µLED or a waveguide integrated on the probe. Small probe dimensions, adequate optical power for photostimulation and good tissue penetration for in-vivo experiments are critical requirements. Thus, integrating a waveguide is a promising solution. This work shows the design and simulation of a SU-8 based waveguide for integration in a neural probe. The waveguide contains 3 apertures, spaced by 0.5 mm, which will allow the photostimulation of different brain regions simultaneously.

Stem Cell Cure for Kidney Injury: Therapy to Solve Most Complex Issues in Renal System

2020 ◽  
Author(s):  
Prithiv K R Kumar
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Kidney Injury ◽  
Cell Types ◽  
Tissue Remodelling ◽  
Major Health Problem ◽  
In Vivo Experiments ◽  
Renal Regeneration ◽  
Induced Pluripotent

Renal failure is a major health problem. The mortality rate remain high despite of several therapies. The most complex of the renal issues are solved through stem cells. In this review, different mechanism for cure of chronic kidney injury along with cell engraftment incorporated into renal structures will be analysed. Paracrine activities of embryonic or induced Pluripotent stem cells are explored on the basis of stem cell-induced kidney regeneration. Several experiments have been conducted to advance stem cells to ensure the restoration of renal functions. More vigour and organised protocols for delivering stem cells is a possibility for advancement in treatment of renal disease. Also there is a need for pressing therapies to replicate the tissue remodelling and cellular repair processes suitable for renal organs. Stem cells are the undifferentiated cells that have the ability to multiply into several cell types. In vivo experiments on animal’s stem cells have shown significant improvements in the renal regeneration and functions of organs. Nevertheless more studies show several improvements in the kidney repair due to stem cell regeneration.

In vivo Experiments of Natural Products Protection of Antagonistic Effects of Lead on Iron

2018 ◽  
Vol 68 (12) ◽  
pp. 2747-2751
Author(s):  
Marioara Nicula ◽  
Nicolae Pacala ◽  
Lavinia Stef ◽  
Ioan Pet ◽  
Dorel Dronca ◽  
...  
Keyword(s):  
Aquatic Environment ◽  
Iron Homeostasis ◽  
Iron Concentration ◽  
Antagonistic Effect ◽  
Tissue Samples ◽  
Antagonistic Effects ◽  
In Vivo Experiments ◽  
Living Organisms ◽  
Toxic Potential

Living organisms take nutrients from the environment, and together with them, substances with toxic potential � such as heavy metals. Lead is one common metal pollutant especially in aquatic environment, from where the fish can be intoxicated very easily. Bioavailability, distribution, toxic action, synergistic and antagonistic effects are characteristics which can alter the fish health. Our experimental study followed the effects of lead overload in water on iron distribution, in different tissues sample Carassius gibelio Bloch fish. We performed the experiment in four different fish groups: control C; lead � Pb (administration of lead in water 0.075mg/mL of water, as Pb(NO3)2 x � H2O); lead (the same dose) and 2% of freeze-dry garlic incorporated into fishes� food � Pb+garlic; lead (the same dose) and 2% chlorella incorporated into fishes� food � Pb+chlorella, for 21 consecutive days. The iron concentration was analysed with AAS (Atomic Absorption Spectroscopy) from gills, muscle, skin (and scales), intestine, liver, heart, brain, ovary, testicles, and kidney. The obtained data presented a significantly decrease of iron content in all tested tissue samples that demonstrated, alteration of iron homeostasis, explained by a strong antagonistic effect of lead on iron. Our experiment showed that biologic active principles from garlic and chlorella act like natural protectors, and potentiate the iron deficiency even in the case of lead overload in aquatic environment, for fish.

ANTITUMOR EFFECT OF COLLOIDAL SILVER BISILICATE IN EXPERIMENTAL IN VITRO AND IN VIVO STUDIES

2019 ◽  
Vol 65 (5) ◽  
pp. 760-765
Author(s):  
Margarita Tyndyk ◽  
Irina Popovich ◽  
A. Malek ◽  
R. Samsonov ◽  
N. Germanov ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Human Tumor ◽  
Significant Inhibition ◽  
In Vivo Studies ◽  
Ehrlich Carcinoma ◽  
In Vivo Experiments

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.

Human Fibronectin Extra-Domain B (EDB)-Specific Aptide (APTEDB) Radiolabelling with Technetium-99m as a Potent Targeted Tumour-Imaging Agent

2018 ◽  
Vol 18 (2) ◽  
pp. 277-285 ◽  
Author(s):  
Mohsen Mohammadgholi ◽  
Nourollah Sadeghzadeh ◽  
Mostafa Erfani ◽  
Saeid Abediankenari ◽  
Seyed Mohammad Abedi ◽  
...  
Keyword(s):  
Radioligand Binding ◽  
Specific Binding ◽  
Specific Protein ◽  
Tumour Imaging ◽  
Specific Binding Ratio ◽  
Tumour Uptake ◽  
Technetium 99M ◽  
In Vivo Experiments ◽  
Human Fibronectin

Background: Human fibronectin extra-domain B (EDB) is particularly expressed during angiogenesis progression. It is, thus, a promising marker of tumour growth. Aptides are a novel class of peptides with high-affinity binding to specific protein targets. APTEDB is an antagonist-like ligand that especially interacts with human fibronectin EDB. Objective: This study was the first attempt in which the hydrazinonicotinamide (HYNIC)-conjugated APTEDB was labelled with technetium-99m (99mTc) as an appropriate radiotracer and tricine/EDDA exchange labeling. Methods: Radiochemical purity, normal saline, and serum stability were evaluated by HPLC and radio-isotope TLC scanner. Other examinations, such as protein-binding calculation, dissociation radioligand binding assay, and partition coefficient constant determination, were also carried out. The cellular-specific binding of 99mTc- HYNIC-conjugated APTEDB was assessed in two EDB-positive (U87MG) and EDB-negative (U373MG) cell lines. Bio-distribution was investigated in normal mice as well as in U87MG and U373MG tumour-bearing mice. Eventually, the radiolabelled APTEDB was used for tumour imaging using planar SPECT. Results: Radiolabelling was achieved with high purity (up to 97%) and accompanied by high solution (over 90% after overnight) and serum (80% after 2 hours) stability. The obtained cellular-specific binding ratio was greater than nine-fold. In-vivo experiments showed rapid blood clearance with mainly renal excretion and tumour uptake specificity (0.48±0.03% ID/g after 1h). The results of the imaging also confirmed considerable tumour uptake for EDB-positive cell line compared with the EDB-negative one. Conclusion: Aptides are considered to be a potent candidate for biopharmaceutical applications. They can be modified with imaging or therapeutic agents. This report shows the capability of 99mTc-HYNIC-APTEDB for human EDB-expressing tumours detection.

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