scholarly journals Lung Cancer Radiotherapy: Simulation and Analysis Based on a Multicomponent Mathematical Model

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Wen-song Hong ◽  
Shun-guan Wang ◽  
Gang-qing Zhang
Keyword(s):  
Lung Cancer ◽  
Mathematical Model ◽  
Optimization Methods ◽  
Model Parameters ◽  
Analysis And Evaluation ◽  
Basic Work ◽  
Near Future ◽  
Radiotherapy Treatment ◽  
Accelerated Hypofractionated Radiotherapy

Background. Lung cancer has been one of the most deadly illnesses all over the world, and radiotherapy can be an effective approach for treating lung cancer. Now, mathematical model has been extended to many biomedical fields to give a hand for analysis, evaluation, prediction, and optimization. Methods. In this paper, we propose a multicomponent mathematical model for simulating the lung cancer growth as well as radiotherapy treatment for lung cancer. The model is digitalized and coded for computer simulation, and the model parameters are fitted with many research and clinical data to provide accordant results along with the growth of lung cancer cells in vitro. Results. Some typical radiotherapy plans such as stereotactic body radiotherapy, conventional fractional radiotherapy, and accelerated hypofractionated radiotherapy are simulated, analyzed, and discussed. The results show that our mathematical model can perform the basic work for analysis and evaluation of the radiotherapy plan. Conclusion. It will be expected that in the near future, mathematical model will be a valuable tool for optimization in personalized medical treatment.

scholarly journals Lung Cancer Radiotherapy: Simulation and Analysis Based on a Multi-component Mathematical Model

2020 ◽  
Author(s):  
Wen-song Hong ◽  
Shun-guan Wang ◽  
Gang-qing Zhang
Keyword(s):  
Lung Cancer ◽  
Mathematical Model ◽  
Cancer Growth ◽  
Model Parameters ◽  
Fractionated Radiotherapy ◽  
Analysis And Evaluation ◽  
Basic Work ◽  
Near Future ◽  
Radiotherapy Treatment

Abstract Background: Lung cancer has been one of the most deadly illnesses all over the world and radiotherapy can be an effective approach for treating lung cancer. Now, mathematical model has been extended to many biomedical fields to give a hand for analysis, evaluation, prediction and optimization. Methods: In this paper, we propose a multi-component mathematical model for simulating the lung cancer growth as well as radiotherapy treatment for lung cancer. The model is digitalized and coded for computer simulation and the model parameters are fitted with many research and clinical data to provide accordant results along with the growth of lung cancer cells in vitro. Results: Some typical radiotherapy plans such as stereotactic body radiotherapy, conventional fractional radiotherapy and accelerated hypo-fractionated radiotherapy are simulated, analyzed and discussed. The results show that our mathematical model can perform the basic work for analysis and evaluation of the radiotherapy plan. Conclusion: It will be expected that in the near future, mathematical model will be a valuable tool for optimization in personalized medical treatment.

scholarly journals Mathematical modeling quantifies ERK-activity in response to inhibition of the BRAFV600E-MEK-ERK cascade

2021 ◽  
Author(s):  
Sara Hamis ◽  
Yury Kapelyukh ◽  
Aileen McLaren ◽  
Colin J. Henderson ◽  
C. Roland Wolf ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Drug Resistance ◽  
Chemical Reactions ◽  
Molecular Mechanisms ◽  
Braf Inhibitor ◽  
Mass Action ◽  
Model Parameters ◽  
Mass Action Kinetics ◽  
Erk Activity

AbstractSimultaneous inhibition of multiple components of the BRAF-MEK-ERK cascade (vertical inhibition) has become a standard of care for treating BRAF-mutant melanoma. However, the molecular mechanisms of how vertical inhibition synergistically suppress intracellular ERK activity, and as a consequence cell proliferation, are yet to be fully elucidated.In this study, we develop a mechanistic mathematical model that describes how the mutant BRAF-inhibitor, dabrafenib, and the MEK-inhibitor, trametinib, affect signaling through the BRAFV600E-MEK-ERK cascade. We formulate a system of chemical reactions that describes cascade signaling dynamics and, using mass action kinetics, the chemical reactions are re-expressed as ordinary differential equations. Using model parameters obtained from in vitro data available in the literature, these equations are solved numerically to obtain the temporal evolution of the concentrations of the components in the signaling cascade.Our mathematical model provides a quantitative method to compute how dabrafenib and trametinib can be used in combination to synergistically inhibit ERK activity in BRAFV600E mutant melanoma cells. This work elucidates molecular mechanisms of vertical inhibition of the BRAFV600E-MEK-ERK cascade and delineates how elevated cellular BRAF concentrations generate drug resistance to dabrafenib and trametinib. In addition, the computational simulations suggest that elevated ATP levels could be a factor in drug resistance to dabrafenib. The mathematical model that is developed in this study will have generic application in the improved design of anticancer combination therapies that target BRAF-MEK-ERK pathways.

scholarly journals Mathematical Multiobjective Optimization for Metal Hip Arthroplasty with Medical Physics Applications

2021 ◽  
Keyword(s):  
Experimental Testing ◽  
Medical Physics ◽  
Optimization Methods ◽  
Model Parameters ◽  
Model Parameter ◽  
Erosion Prediction ◽  
Model Match ◽  
Acceptable Model ◽  
Parameter Values

Total hip metal arthroplasty (THA) model-parameters for a group of commonly used ones is optimized and numerically studied. Based on previous ceramic THA optimization software contributions, an improved multiobjective programming method/algorithm is implemented in wear modeling for THA. This computational nonlinear multifunctional optimization is performed with a number of THA metals with different hardnesses and erosion in vitro experimental rates. The new software was created/designed with two types of Sytems, Matlab and GNU Octave. Numerical results show be improved/acceptable for in vitro simulations. These findings are verified with 2D Graphical Optimization and 3D Interior Optimization methods, giving low residual-norms. The solutions for the model match mostly the literature in vitro standards for experimental simulations. Numerical figures for multifunctional optimization give acceptable model-parameter values with low residual-norms. Useful mathematical consequences/calculations are obtained for wear predictions, model advancements and simulation methodology. The wear magnitude for in vitro determinations with these model parameter data constitutes the advance of the method. In consequence, the erosion prediction for laboratory experimental testing in THA add up to the literature an efficacious usage-improvement. Results, additionally, are extrapolated to efficient Medical Physics applications and metal-THA Bioengineering designs.

scholarly journals Quantification of the effects of antibodies on the extra- and intracellular dynamics of Salmonella enterica

2013 ◽  
Vol 10 (79) ◽  
pp. 20120866 ◽  
Author(s):  
Olivier Restif ◽  
Yun S. Goh ◽  
Matthieu Palayret ◽  
Andrew J. Grant ◽  
Trevelyan J. McKinley ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Maximum Likelihood ◽  
Fluorescence Microscopy ◽  
Relative Efficiency ◽  
Igg Subclasses ◽  
Model Parameters ◽  
Exact Role ◽  
Factors Affecting ◽  
Potential Factors

Antibodies are known to be essential in controlling Salmonella infection, but their exact role remains elusive. We recently developed an in vitro model to investigate the relative efficiency of four different human immunoglobulin G (IgG) subclasses in modulating the interaction of the bacteria with human phagocytes. Our results indicated that different IgG subclasses affect the efficacy of Salmonella uptake by human phagocytes. In this study, we aim to quantify the effects of IgG on intracellular dynamics of infection by combining distributions of bacterial numbers per phagocyte observed by fluorescence microscopy with a mathematical model that simulates the in vitro dynamics. We then use maximum likelihood to estimate the model parameters and compare them across IgG subclasses. The analysis reveals heterogeneity in the division rates of the bacteria, strongly suggesting that a subpopulation of intracellular Salmonella , while visible under the microscope, is not dividing. Clear differences in the observed distributions among the four IgG subclasses are best explained by variations in phagocytosis and intracellular dynamics. We propose and compare potential factors affecting the replication and death of bacteria within phagocytes, and we discuss these results in the light of recent findings on dormancy of Salmonella .

Dwindling status of Epimedium Elatum (Morren & Decne) and its geographical distribution in Kashmir Himalaya, India

2018 ◽  
pp. 47-52
Keyword(s):  
Medicinal Plant ◽  
Biological Activities ◽  
Conservation Status ◽  
Natural Populations ◽  
Culture Techniques ◽  
Kashmir Himalayas ◽  
Near Future ◽  
First Time ◽  
Tissue Culture Techniques

Epimedium elatum (Morren & Decne) of family Berberidaceace is a rare perennial medicinal plant, endemic to high altitude forests of Northwestern Himalayas in India. Ethnobotanically, it has been used as an ingredient for treatment of bone-joint disorders, impotence and kidney disorders in Kashmir Himalayas. Phytochemically, it is rich in Epimedin ABC and Icariin; all of these have been demonstrated to possess remarkable biological activities like PDE-5 inhibition (treatment of erectile dysfunction), anticancer, antiosteoporosis antioxidant and antiviral properties. The present investigation reports its traditional usage, comprehensive distribution and conservation status from twenty ecogeographical regions in Kashmir Himalayas, India. The species was reported from Gurez valley for the first time. Numerous threats like excessive grazing, deforestration, habitat fragmentation, tourism encroachment, landslides and excessive exploitation have decreased its natural populations in most of the surveyed habitats. Consequently, its existence may become threatened in near future if timely conservation steps are not taken immediately by concerned stakeholders involved in medicinal plant research. Moreover, use of plant tissue culture techniques is recommended for development of its in vitro propagation protocols. Therefore, introduction of this medicinal plant in botanical gardens, protected sites and development of monitoring programmes are needed for its immediate conservation in Northwestern Himalayas, India.

Role of 4-O Galloylchlorogenic Acid in Lung Cancer- An Insilico Approach

2017 ◽  
Vol 9 (5) ◽  
Author(s):  
Jaynthy C. ◽  
N. Premjanu ◽  
Abhinav Srivastava
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
In Silico ◽  
Computational Study ◽  
Regulation Mechanism ◽  
Down Regulation ◽  
Fruit Extract ◽  
In Vitro Techniques ◽  
Discovery Studio

Cancer is a major disease with millions of patients diagnosed each year with high mortality around the world. Various studies are still going on to study the further mechanisms and pathways of the cancer cell proliferation. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and inflammation. In cancer development increased core fucosylation by FUT8 play an important role in cell proliferation. Down regulation of FUT8 expression may help cure lung cancer. Therefore the computational study based on the down regulation mechanism of FUT8 was mechanised. Sapota fruit extract, containing 4-Ogalloylchlorogenic acid was used as the inhibitor against FUT-8 as target and docking was performed using in-silico tool, Accelrys Discovery Studio. There were several conformations of the docked result, and conformation 1 showed 80% dock score between the ligand and the target. Further the amino acids of the inhibitor involved in docking were studied using another tool, Ligplot. Thus, in-silico analysis based on drug designing parameters shows that the fruit extract can be studied further using in-vitro techniques to know its pharmacokinetics.

Neural Stem Cells to Glial Cells an Important Factor for Brain Injury

2020 ◽  
Author(s):  
Prithiv K R Kumar
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Neural Stem Cells ◽  
Glial Cells ◽  
Brain Injuries ◽  
The Body ◽  
The Central Nervous System ◽  
Near Future

Stem cells have the capacity to differentiate into any type of cell or organ. Stems cell originate from any part of the body, including the brain. Brain cells or rather neural stem cells have the capacitive advantage of differentiating into the central nervous system leading to the formation of neurons and glial cells. Neural stem cells should have a source by editing DNA, or by mixings chemical enzymes of iPSCs. By this method, a limitless number of neuron stem cells can be obtained. Increase in supply of NSCs help in repairing glial cells which in-turn heal the central nervous system. Generally, brain injuries cause motor and sensory deficits leading to stroke. With all trials from novel therapeutic methods to enhanced rehabilitation time, the economy and quality of life is suppressed. Only PSCs have proven effective for grafting cells into NSCs. Neurons derived from stem cells is the only challenge that limits in-vitro usage in the near future.

scholarly journals USP9X-mediated KDM4C deubiquitination promotes lung cancer radioresistance by epigenetically inducing TGF-β2 transcription

2021 ◽  
Author(s):  
Xiaohua Jie ◽  
William Pat Fong ◽  
Rui Zhou ◽  
Ye Zhao ◽  
Yingchao Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Affinity Purification ◽  
Smad Signaling ◽  
Lung Cancer Patients ◽  
Lysine Specific Demethylase ◽  
Underlying Mechanisms ◽  
H3k9me3 Level ◽  
Critical Binding

AbstractRadioresistance is regarded as the main barrier to effective radiotherapy in lung cancer. However, the underlying mechanisms of radioresistance remain elusive. Here, we show that lysine-specific demethylase 4C (KDM4C) is overexpressed and correlated with poor prognosis in lung cancer patients. We provide evidence that genetical or pharmacological inhibition of KDM4C impairs tumorigenesis and radioresistance in lung cancer in vitro and in vivo. Moreover, we uncover that KDM4C upregulates TGF-β2 expression by directly reducing H3K9me3 level at the TGF-β2 promoter and then activates Smad/ATM/Chk2 signaling to confer radioresistance in lung cancer. Using tandem affinity purification technology, we further identify deubiquitinase USP9X as a critical binding partner that deubiquitinates and stabilizes KDM4C. More importantly, depletion of USP9X impairs TGF-β2/Smad signaling and radioresistance by destabilizing KDM4C in lung cancer cells. Thus, our findings demonstrate that USP9X-mediated KDM4C deubiquitination activates TGF-β2/Smad signaling to promote radioresistance, suggesting that targeting KDM4C may be a promising radiosensitization strategy in the treatment of lung cancer.

Usefulness of collaboration between mathematical models and cell engineering for elucidating complex disease mechanisms and discover effective drugs

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Kohjitani ◽  
A Kashiwa ◽  
T Makiyama ◽  
F Toyoda ◽  
Y Yamamoto ◽  
...  
Keyword(s):  
Mathematical Model ◽  
In Silico ◽  
Complex Disease ◽  
Ion Selectivity ◽  
Public Institution ◽  
Cell Engineering ◽  
Funding Source ◽  
Patch Clamp Technique ◽  
In Silico Model

Abstract Background A missense mutation, CACNA1C-E1115K, located in the cardiac L-type calcium channel (LTCC), was recently reported to be associated with diverse arrhythmias. Several studies reported in-vivo and in-vitro modeling of this mutation, but actual mechanism and target drug of this disease has not been clarified due to its complex ion-mechanisms. Objective To reveal the mechanism of this diverse arrhythmogenic phenotype using combination of in-vitro and in-silico model. Methods and results Cell-Engineering Phase: We generated human induced pluripotent stem cell (hiPSC) from a patient carrying heterozygous CACNA1C-E1115K and differentiated into cardiomyocytes. Spontaneous APs were recorded from spontaneously beating single cardiomyocytes by using the perforated patch-clamp technique. Mathematical-Modeling Phase: We newly developed ICaL-mutation mathematical model, fitted into experimental data, including its impaired ion selectivity. Furthermore, we installed this mathematical model into hiPSC-CM simulation model. Collaboration Phase: Mutant in-silico model showed APD prolongation and frequent early afterdepolarization (EAD), which are same as in-vitro model. In-silico model revealed this EAD was mostly related to robust late-mode of sodium current occurred by Na+ overload and suggested that mexiletine is capable of reducing arrhythmia. Afterward, we applicated mexiletine onto hiPSC-CMs mutant model and found mexiletine suppress EADs. Conclusions Precise in-silico disease model can elucidate complicated ion currents and contribute predicting result of drug-testing. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists

scholarly journals MSCs-engineered biomimetic PMAA nanomedicines for multiple bioimaging-guided and photothermal-enhanced radiotherapy of NSCLC

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yipengchen Yin ◽  
Yongjing Li ◽  
Sheng Wang ◽  
Ziliang Dong ◽  
Chao Liang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Membranes ◽  
Imaging System ◽  
Fluorescence Signal ◽  
Bimodal Imaging ◽  
Red Blood Cell Membranes ◽  
Magnetic Resonance Imaging Mri ◽  
Tumor Accumulation

Abstract Background The recently developed biomimetic strategy is one of the mostly effective strategies for improving the theranostic efficacy of diverse nanomedicines, because nanoparticles coated with cell membranes can disguise as “self”, evade the surveillance of the immune system, and accumulate to the tumor sites actively. Results Herein, we utilized mesenchymal stem cell memabranes (MSCs) to coat polymethacrylic acid (PMAA) nanoparticles loaded with Fe(III) and cypate—an derivative of indocyanine green to fabricate Cyp-PMAA-Fe@MSCs, which featured high stability, desirable tumor-accumulation and intriguing photothermal conversion efficiency both in vitro and in vivo for the treatment of lung cancer. After intravenous administration of Cyp-PMAA-Fe@MSCs and Cyp-PMAA-Fe@RBCs (RBCs, red blood cell membranes) separately into tumor-bearing mice, the fluorescence signal in the MSCs group was 21% stronger than that in the RBCs group at the tumor sites in an in vivo fluorescence imaging system. Correspondingly, the T1-weighted magnetic resonance imaging (MRI) signal at the tumor site decreased 30% after intravenous injection of Cyp-PMAA-Fe@MSCs. Importantly, the constructed Cyp-PMAA-Fe@MSCs exhibited strong photothermal hyperthermia effect both in vitro and in vivo when exposed to 808 nm laser irradiation, thus it could be used for photothermal therapy. Furthermore, tumors on mice treated with phototermal therapy and radiotherapy shrank 32% more than those treated with only radiotherapy. Conclusions These results proved that Cyp-PMAA-Fe@MSCs could realize fluorescence/MRI bimodal imaging, while be used in phototermal-therapy-enhanced radiotherapy, providing desirable nanoplatforms for tumor diagnosis and precise treatment of non-small cell lung cancer.

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