ترغب بنشر مسار تعليمي؟ اضغط هنا

Mathematical model for the thermal enhancement of radiation response: Thermodynamic approach

53   0   0.0 ( 0 )
 نشر من قبل Adriana Maria De Mendoza
 تاريخ النشر 2020
  مجال البحث فيزياء علم الأحياء
والبحث باللغة English




اسأل ChatGPT حول البحث

Radiotherapy can effectively kill malignant cells, but the doses required to cure cancer patients may inflict severe collateral damage to adjacent healthy tissues. Hyperthermia (HT) is a promising option to improve the outcome of radiation treatment (RT) and is increasingly applied in hospital. However, the synergistic effect of simultaneous thermoradiotherapy is not well understood yet, while its mathematical modelling is essential for treatment planning. To better understand this synergy, we propose a theoretical model in which the thermal enhancement ratio (TER) is explained by the fraction of cells being radiosensitised by the infliction of sublethal damage through mild HT. Further damage finally kills the cell or inhibits its proliferation in a non-reversible process. We suggest the TER to be proportional to the energy invested in the sensitisation, which is modelled as a simple rate process. Assuming protein denaturation as the main driver of HT-induced sublethal damage and considering the temperature dependence of the heat capacity of cellular proteins, the sensitisation rates were found to depend exponentially on temperature; in agreement with previous empirical observations. Our predictions well reproduce experimental data from in-vitro and in-vivo studies, explaining the thermal modulation of cellular radioresponse for simultaneous thermoradiotherapy.

قيم البحث

اقرأ أيضاً

113 - Ankang Hu , Rui Qiu , Zhen Wu 2020
Background: Experiments have reported low normal tissue toxicities during FLASH radiation, but the mechanism has not been elaborated. Several hypotheses have been proposed to explain the mechanism. The oxygen depletion hypothesis has been introduced and mostly studied qualitatively. Methods: We present a computational model to describe the time-dependent change of oxygen concentration in the tissue. The kinetic equation of the model is solved numerically using the finite difference method. The model is used to analyze the FLASH effect with the oxygen depletion hypothesis, and the brain tissue is chosen as an example. Results: The oxygen distribution is determined by the oxygen consumption rate of the tissue and the distance between capillaries. The change of oxygen concentration with time after radiation has been found to follow a negative exponential function, and the time constant is determined by the distance between capillaries. When the dose rate is high enough, the same dose results in the same change of oxygen concentration regardless of dose rate. The analysis of FLASH effect in the brain tissue based on this model does not support the explanation of the oxygen depletion hypothesis. Conclusions: The oxygen depletion hypothesis remains controversial because oxygen in most normal tissues cannot be depleted by FLASH radiation according to the mathematical analysis with this model and experiments on the expression and distribution of the hypoxia-inducible factors.
98 - Robert D. Young 2018
A novel energy landscape model, ELM, for proteins recently explained a collection of incoherent, elastic neutron scattering data from proteins. The ELM of proteins considers the elastic response of the proton and its environment to the energy and mom entum exchanged with the neutron. In the ELM, the elastic potential energy is expressed as a sum of a temperature dependent term resulting from equipartition of potential energy among the active degrees of freedom and a wave vector transfer dependent term resulting from the elastic energy stored by the protein during the neutron scattering event. The elastic potential energy involves a new elastobaric coefficient that is proportional to the product of two factors: one factor depends on universal constants and the other on the incident neutron wave vector per degree of freedom. The ELM was tested for dry protein samples with an elastobaric coefficient corresponding to 3 degrees of freedom. A discussion of the data requirements for additional tests of ELM is presented resulting in a call for published data that have not been preprocessed by temperature and wave-vector dependent normalizations.
Proteins from the kinesin-8 family promote microtubule (MT) depolymerization, a process thought to be important for the control of microtubule length in living cells. In addition to this MT shortening activity, kinesin 8s are motors that show plus-en d directed motility on MTs. Here we describe a simple model that incorporates directional motion and destabilization of the MT plus end by kinesin 8. Our model quantitatively reproduces the key features of length-vs-time traces for stabilized MTs in the presence of purified kinesin 8, including length-dependent depolymerization. Comparison of model predictions with experiments suggests that kinesin 8 depolymerizes processively, i.e., one motor can remove multiple tubulin dimers from a stabilized MT. Fluctuations in MT length as a function of time are related to depolymerization processivity. We have also determined the parameter regime in which the rate of MT depolymerization is length dependent: length-dependent depolymerization occurs only when MTs are sufficiently short; this crossover is sensitive to the bulk motor concentration.
The human adaptive immune response is known to weaken in advanced age, resulting in increased severity of pathogen-born illness, poor vaccine efficacy, and a higher prevalence of cancer in the elderly. Age-related erosion of the T-cell compartment ha s been implicated as a likely cause, but the underlying mechanisms driving this immunosenescence have not been quantitatively modeled and systematically analyzed. T-cell receptor diversity, or the extent of pathogen-derived antigen responsiveness of the T-cell pool, is known to diminish with age, but inherent experimental difficulties preclude accurate analysis on the full organismal level. In this paper, we formulate a mechanistic mathematical model of T-cell population dynamics on the immunoclonal subpopulation level, which provides quantitative estimates of diversity. We define different estimates for diversity that depend on the individual number of cells in a specific immunoclone. We show that diversity decreases with age primarily due to diminished thymic output of new T-cells and the resulting overall loss of small immunoclones.
Osteocytes and their cell processes reside in a large, interconnected network of voids pervading the mineralized bone matrix of most vertebrates. This osteocyte lacuno-canalicular network (OLCN) is believed to play important roles in mechanosensing, mineral homeostasis, and for the mechanical properties of bone. While the extracellular matrix structure of bone is extensively studied on ultrastructural and macroscopic scales, there is a lack of quantitative knowledge on how the cellular network is organized. Using a recently introduced imaging and quantification approach, we analyze the OLCN in different bone types from mouse and sheep that exhibit different degrees of structural organization not only of the cell network but also of the fibrous matrix deposited by the cells. We define a number of robust, quantitative measures that are derived from the theory of complex networks. These measures enable us to gain insights into how efficient the network is organized with regard to intercellular transport and communication. Our analysis shows that the cell network in regularly organized, slow-growing bone tissue from sheep is less connected, but more efficiently organized compared to irregular and fast-growing bone tissue from mice. On the level of statistical topological properties (edges per node, edge length and degree distribution), both network types are indistinguishable, highlighting that despite pronounced differences at the tissue level, the topological architecture of the osteocyte canalicular network at the subcellular level may be independent of species and bone type. Our results suggest a universal mechanism underlying the self-organization of individual cells into a large, interconnected network during bone formation and mineralization.
التعليقات
جاري جلب التعليقات جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
mircosoft-partner

هل ترغب بارسال اشعارات عن اخر التحديثات في شمرا-اكاديميا