Analysis of anticancer efficiency of combined fractionated radiotherapy and antiangiogenic therapy via mathematical modelling

2018 ◽  
Vol 33 (4) ◽  
pp. 225-242 ◽  
Author(s):  
Maxim B. Kuznetsov ◽  
Vladimir V. Gubernov ◽  
Andrey V. Kolobov
Keyword(s):  
Mathematical Model ◽  
Antiangiogenic Therapy ◽  
Combined Treatment ◽  
Palliative Therapy ◽  
Nutrient Deprivation ◽  
Curative Effect ◽  
Model Simulations ◽  
Fractionated Radiotherapy ◽  
Spatially Distributed ◽  
Preclinical And Clinical Studies

Abstract One of the relatively new modalities in treatment of cancer is antiangiogenic therapy (AAT), which stops the formation of new blood vessels, thus leading to nutrient deprivation of a tumor. It has been discovered that it can cause transient alleviation of intratumoral hypoxia, which has induced interest in investigation of its combination with radiotherapy (RT), since presence of oxygen stimulates efficiency of the latter. Preclinical and clinical studies have shown ambiguous results concerning such combined treatment, indicating a need for theoretical investigation. For that purpose, we have developed a spatially-distributed mathematical model of tumor growth and combined RT with AAT. Model simulations in a physiologically justified range of parameters suggest that outcome of addition of AAT to RT should depend on the tumor radiosensitivity: under its low values, when RT de facto serves as a palliative therapy, inclusion of AAT may prolong patient’s survival; however, under high tumor radiosensitivity, AAT may compromise curative effect of RT.

scholarly journals Algorithm of optimization of fractionated radiotherapy within its combination with antiangiogenic therapy by means of mathematical modeling

2020 ◽  
Vol 31 ◽  
pp. 02001
Author(s):  
Maxim Kuznetsov ◽  
Andrey Kolobov
Keyword(s):  
Mathematical Modeling ◽  
Antiangiogenic Therapy ◽  
Combined Treatment ◽  
Tumor Oxygenation ◽  
Nutrient Deprivation ◽  
Optimal Distribution ◽  
Tumor Treatment ◽  
Fractionated Radiotherapy ◽  
Transient Improvement ◽  
Ambiguous Effect

Antiangiogenic therapy is the anti-tumor treatment, that leads to the cessation of blood vessels formation and subsequent nutrient deprivation of the tumor. One of its frequently occurring effects is the transient improvement of tumor oxygenation, which lasts several days and leads to increased efficiency of successive exposure to radiation. It is followed by an escalation of hypoxia, and therefore the addition of antiangiogenic therapy to the whole course of fractionated radiotherapy has an ambiguous effect. Previously we have developed a mathematical model of such combined anti-tumor treatment. Herein we present an algorithm of optimization of radiotherapy fractionation, which aim is to find the most optimal distribution of irradiation doses in order to increase the efficiency of such combined treatment. We demonstrate an example of its work and discuss its further application.

The ancient Lake Albano tunnel: origins and considerations regarding the hydraulic regulation achieved

2007 ◽  
Vol 7 (1) ◽  
pp. 269-276
Author(s):  
R. Drusiani ◽  
P. Bersani ◽  
P. Penta
Keyword(s):  
Mathematical Model ◽  
Ancient Lake ◽  
Model Simulations ◽  
Volcanic Lakes ◽  
Colli Albani ◽  
Atmospheric Phenomena

A brief description of the geomorphological, historical, and archaeological aspects of the Colli Albani area, where the volcanic lakes of Albano and Nemi are situated, is followed by an examination on the problem of the policies of lake Albano regulation, by means of an ancient tunnel dating at least to the 5th century BC. In particular, it is investigated how, in the presence of even severe atmospheric phenomena, it was possible to control fluctuations in the level of the lake on the banks of which there were large settlements. Mathematical model simulations indicate the effectiveness of the ancient tunnel in achieving these objectives.

scholarly journals In Vivo Study of the Efficacy and Safety of 5-Aminolevulinic Radiodynamic Therapy for Glioblastoma Fractionated Radiotherapy

2021 ◽  
Vol 22 (18) ◽  
pp. 9762
Author(s):  
Junko Takahashi ◽  
Shinsuke Nagasawa ◽  
Motomichi Doi ◽  
Masamichi Takahashi ◽  
Yoshitaka Narita ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Aminolevulinic Acid ◽  
Combined Treatment ◽  
Reactive Oxygen Species Generation ◽  
Photodynamic Diagnosis ◽  
High Dose ◽  
Severe Toxicity ◽  
Fractionated Radiotherapy ◽  
Post Surgery

To treat malignant glioma, standard fractionated radiotherapy (RT; 60 Gy/30 fractions over 6 weeks) was performed post-surgery in combination with temozolomide to improve overall survival. Malignant glioblastoma recurrence rate is extremely high, and most recurrent tumors originate from the excision cavity in the high-dose irradiation region. In our previous study, protoporphyrin IX physicochemically enhanced reactive oxygen species generation by ionizing radiation and combined treatment with 5-aminolevulinic acid (5-ALA) and ionizing radiation, while radiodynamic therapy (RDT) improved tumor growth suppression in vivo in a melanoma mouse model. We examined the effect of 5-ALA RDT on the standard fractionated RT protocol using U251MG- or U87MG-bearing mice. 5-ALA was orally administered at 60 or 120 mg/kg, 4 h prior to irradiation. In both models, combined treatment with 5-ALA slowed tumor progression and promoted regression compared to treatment with ionizing radiation alone. The standard fractionated RT protocol of 60 Gy in 30 fractions with oral administration of 120 and 240 mg/kg 5-ALA, the human equivalent dose of photodynamic diagnosis, revealed no significant increase in toxicity to normal skin or brain tissue compared to ionizing radiation alone. Thus, RDT is expected to enhance RT treatment of glioblastoma without severe toxicity under clinically feasible conditions.

Mathematical model of fixed assets’ joint use by the machine-building enterprises

2021 ◽  
Vol 57 (4) ◽  
pp. 96
Author(s):  
Georgy Kolesnik
Keyword(s):  
Mathematical Model ◽  
Asset Management ◽  
Supply And Demand ◽  
Machine Building ◽  
Goods And Services ◽  
Operating Profit ◽  
Fixed Assets ◽  
Spatially Distributed ◽  
Distributed Production ◽  
Building Enterprises

High competition in the markets of goods and services makes it urgent to improve the efficiencyof the use of production assets by the enterprises. One of the possible ways to solve the problem is joint use of the assets by different subjects. The use of this mechanism in the various branches grows rapidly in the last decade due to the opportunities for aggregation of supply and demand and automated contracting provided by the modern digital technologies. The basis for production asset management systems based on sharing is a mathematical model that allows determining the optimal modes of asset use in terms of their utilization, reducing the total cost of ownership and obtaining additional operating profit. This article considers a mathematical model of a multi-product spatially distributed production system that reflects the features of the activities of machine-building enterprises and assumes the possibility of joint use of their fixed assets. Economic and social criteria for the efficiency of fixed assets sharing are formulated in terms of maximizing the profit of enterprises, minimizing logistics and downtime costs. The optimal modes of joint use of the fixed assets concerning these criteria are investigated. It is shown that the joint use of fixed assets under the certain conditions can significantly improve the efficiency of the operating activities of enterprises.

Ouabain modulation of cellular calcium stores and signaling

2007 ◽  
Vol 293 (5) ◽  
pp. F1518-F1532 ◽  
Author(s):  
Aurélie Edwards ◽  
Thomas L. Pallone
Keyword(s):  
Mathematical Model ◽  
Sarcoplasmic Reticulum ◽  
Active Transport ◽  
Intracellular Localization ◽  
Calcium Stores ◽  
Model Simulations ◽  
Store Depletion ◽  
Intracellular Ca ◽  
Atpase Inhibition ◽  
Predominant Effect

Ouabain-like factors modulate intracellular Ca2+ concentrations and Ca2+ stores. Recently, a role for Na+-K+-ATPase Na+ transport inhibition as a pivotal event in ouabain signaling was questioned (Kaunitz JD. Am J Physiol Renal Physiol 290: F995–F996, 2006). In the present study, we used a mathematical model of Ca2+ trafficking in cytoplasm and subplasmalemmal microdomains to simulate the pathways through which ouabain can affect Ca2+ signaling: inhibition of active transport by Na+-K+-ATPase α1- and α2-isoforms, activation of inositol trisphosphate (IP3) production, and increased IP3 receptor (IP3R) conductance. A fundamental prediction is that Na+-K+-ATPase inhibition favors sarcoplasmic reticulum Ca2+ store loading, whereas Src-mediated increases in IP3 production and IP3R sensitization favor store depletion. The model predicts that α2-isoform inhibition generates a peak-and-plateau pattern of cytosolic Ca2+ concentration ([Ca2+]cyt) elevation, whereas α1-isoform inhibition yields a monophasic rise. The effects of ouabain-mediated increases in IP3 production or IP3R conductance on [Ca2+]cyt depend on their relative distributions between cellular microdomains and the bulk cytoplasm. Simulations suggest that the intracellular localization of IP3 production is a pivotal determinant of the changes in compartmental Ca2+ concentrations that can be induced by ouabain. As a consequence of sequestration of the ouabain-sensitive α2-isoform into microdomains, inhibition of the α2-isoform in rodents is not predicted to significantly affect cytosolic Na+ concentration. Model simulations support the hypothesis that ouabain can enhance agonist-evoked [Ca2+]cyt transients when its predominant effect is to inhibit α2-isoform Na+ transport and, thereby, increase Ca2+ loading into sarcoplasmic reticulum stores.

scholarly journals The Üstikuddus sherbiti in the treatment of abnormal cold and dry-type depression patients with comorbid anxiety: A randomized and controlled clinical trial

2019 ◽  
Vol 02 (03) ◽  
pp. 127-133 ◽  
Author(s):  
Aman Gul ◽  
Nassirhadjy Memtily ◽  
Pirdun Mijit ◽  
Mihriban Imin ◽  
Hua Rui ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Combined Treatment ◽  
Modern Medicine ◽  
Controlled Clinical Trial ◽  
Curative Effect ◽  
Comorbid Anxiety ◽  
Potential Target ◽  
Treatment Of Depression ◽  
The Us ◽  
Hamilton Anxiety Scale

Objective: To evaluate the clinical effect of Üstikuddus sherbiti (US), a traditional herbal prescription of Uyghur medicine, in the treatment of cold and dry-type major depression disorder (MDD) patients with comorbid anxiety. Methods: A total of 150 cold and dry-type depressive patients with comorbid anxiety were randomly divided into three groups of 50 patients; then they were, respectively, treated with US, modern medicine Fluoxetine, and the combination of Fluoxetine and US. The depression degrees of patients were evaluated zero and six weeks after the treatment based on the Hamilton Anxiety Scale (HAMA), in the clinical study. Analysis of variance (ANOVA) was used to detect significant differences at various time points or among the three groups. Statistical analysis was performed by SPSS version 21.0. Results: The main results are as follows: After taking the medicine, the depressive condition of patients with comorbid anxiety in the three groups was getting better with the passage of time; particularly, the clinical efficacy of US combined with Fluoxetine was significantly improved, indicating that the effect of combined treatment is better than treatment with pure Fluoxetine or pure US treatment. Statistical difference exists between the end time point within groups, but not among the three groups. Moreover, in the detection process of the patient’s physical indicators, no obvious side effects were found. These results together suggested that US can strengthen the curative effect of modern medicine in the treatment of depression, which would lay a foundation for studying the molecular mechanism and potential target of US. Conclusion: Fluoxetine and US combination therapy played a significant role in the treatment of depressive symptoms, suggesting that it can improve the curative effect of depression. The study provided a new way of thinking to clarify the US molecular mechanism for the treatment of depression and potential target.

scholarly journals Spatially distributed GIS-realized mathematical model of rainstorm erosion losses of soil

2019 ◽  
Vol 28 (3) ◽  
pp. 562-571
Author(s):  
А. A. Svetlitchnyi ◽  
A. V. Piatkova
Keyword(s):  
Mathematical Model ◽  
Soil Erosion ◽  
Water Balance ◽  
Water Erosion ◽  
Physical Geography ◽  
Forest Steppe ◽  
Spatially Distributed ◽  
Soil Losses ◽  
Slope Runoff ◽  
Distributed Gis

In connection with the wide and ever increasing spread of erosion degradation of agricultural lands in Ukraine, the task of developing mathematical models and methods for calculating water erosion of soils corresponding to the current level of erosion study and the demands of soil protection practices is becoming increasingly important. The article is devoted to the development of a spatially distributed GIS-implemented mathematical model of rainstorm soil erosion, which accounts for most of the annual soil losses (in the Steppe zone, for example, about 90 %). The development of the model is based on the most theoretically and informationally grounded model for the Steppe and Forest-Steppe of Ukraine , “the logical-mathematical model of rainstorm soil outwash” developed by H. I. Shvebs (1974, 1981), as well as the results of theoretical and field studies and mathematical modeling of the slope runoff and water erosion of soil, carried out at the Department of Physical Geography and Environmental Management of Odessa I. I. Mechnikov National University in the 1990s - 2010s, and also the possibilities of modern geoinformation technologies. For the spatial implementation of the model, a raster model of spatial data and operators of the PCRaster GIS-package (University of Utrecht, the Netherlands) were used, integrated with the Basic programming language into a single system that provides an implementation of the computational algorithm. The developed physical-statistical model of soil erosion-sedimentation takes into account the peculiarities of the formation of slope runoff and soil outwash in conditions of excessive nonstationarity of heavy rainfall, as well as spatial heterogeneity of all major natural and economic factors of water erosion on a slope, including slope steepness, exposure, longitudinal and transverse forms of slopes, soil erodibility, structure of sown areas and anti-erosion measures. Checking the adequacy of the mathematical model was performed using observational data of four experimental catchments ; two runoff plots of the Moldavan water-balance station with total area of 0.08 ha, the Ploska catchment with area of 8.5 ha (Boguslav field experimental base of Ukrainian Hydrometeorological Institute) and the Sukha catchment with area of 63 ha (Veliko-Anadol water-balance station) with observation periods of 17-31 years. Comparison of the calculated average over the catchment area of mean annual values of rainstorm soil losses, with the corresponding values obtained from measurements on these catchments, made on the basis of Nash-Sutcliff efficiency criterion (NS), allowed us to evaluate the quality of the model as good (NS = 0.72).

scholarly journals Design and Decomposition of Waste Prognostic Model with Hierarchical Structures

MENDEL ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 85-92
Author(s):  
Veronika Smejkalova ◽  
Radovan Somplak ◽  
Vlastimir Nevrly ◽  
Martin Pavlas
Keyword(s):  
Mathematical Model ◽  
Waste Management ◽  
Current Trend ◽  
Hierarchical Structures ◽  
Regression Function ◽  
Distributed Data ◽  
Aggregated Data ◽  
Waste Production ◽  
Spatially Distributed ◽  
The Individual

The waste management is a dynamically progressive area, with the current trend leading to circular economy scheme. The development in this area requires quality prognosis reflecting the analysed timeframe. The forecast of the waste production and composition of waste is an important aspect with regards to the planning in waste management. However, the regular prognostic methods are not appropriate for these purposes due to short time series of historical data and unavailability of socio-economic data. The paper proposes a general approach via mathematical model for forecasting of future waste-related parameters based on spatially distributed data with hierarchical structure. The approach is based on principles of regression analysis with final balance to ensure the compliance of aggregated data values. The selection of the regression function is a part of mathematical model for high-quality description of data trend. In addition, outlier values are cleared, which occur abundantly in the database. The decomposition of the model into subtasks is performed in order to simpler implementation and reasonable time solvability. The individual algorithm steps are applied to municipal waste production data in the Czech Republic.

scholarly journals Evaluation of clinical efficacy of Chemotherapy for Rhabdomyosarcoma in children

2020 ◽  
Vol 36 (5) ◽  
Author(s):  
Zhaohui Ning ◽  
Xiping Liu ◽  
Guang Qin ◽  
Lei Wei ◽  
Xia Li ◽  
...  
Keyword(s):  
High Risk ◽  
Clinical Efficacy ◽  
Clinical Characteristics ◽  
Risk Group ◽  
Clinical Stage ◽  
Combined Treatment ◽  
Low Risk ◽  
Alveolar Type ◽  
Urogenital System ◽  
Curative Effect

Objective: To investigate the clinical characteristics and treatment methods of rhabdomyosarcoma in children and the efficacy of the methods. Methods: The clinical data of 30 children with rhabdomyosarcoma who were admitted to our hospital from August 2013 to August 2017 were retrospectively analyzed. The clinical characteristics were summarized, and the curative effect and prognosis were evaluated. Results: Among all the children (N=30), there were 20 males and 10 females, with a median age of 3.5 years. As to the primary site, there were 13 cases of head and neck, 11 cases of trunk, three cases of urogenital system and three cases of limbs. There were 25 cases of embryonic type, 4 cases of alveolar type and one case of polymorphic type. As to the clinical stage, there were one case of stage I, 9 cases of stage II, 13 cases of stage III and 7 cases of stage IV. There were one case of low risk, 19 cases of medium risk and 10 cases of high risk. Eight cases received surgery alone, 22 cases received combined treatment of surgery and chemotherapy (the chemotherapeutics followed three schemes, low-risk group (VAC+VA), moderate risk group (VAC) and high risk group (alternating use of VDC and IE). Among all the cases (N=30), there were 14 cases of complete remission (CR), five cases of partial remission (PR), four cases of stable disease (SD), and 7 cases of progressive disease (PD). The CR rate was (N=14, 46.7%). The three-year overall survival (OS) rate was (N=19, 63.3%). The clinical efficacy and prognosis of children receiving surgery and chemotherapy were better than those of children receiving surgery alone, and the difference was statistically significant (P<0.05). Conclusion: Rhabdomyosarcoma in children frequently happens in the head, neck and trunk. Embryonic type is the main pathological type of rhabdomyosarcoma. Comprehensive and standardized treatment based on surgery and chemotherapy is an important way to improve the curative effect in the treatment of rhabdomyosarcoma in children. doi: https://doi.org/10.12669/pjms.36.5.1829 How to cite this:Ning Z, Liu X, Qin G, Wei L, Li X, Shen J. Evaluation of clinical efficacy of Chemotherapy for Rhabdomyosarcoma in children. Pak J Med Sci. 2020;36(5):1069-1074. doi: https://doi.org/10.12669/pjms.36.5.1829 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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