scholarly journals A Computational Model for Investigating Tumor Apoptosis Induced by Mesenchymal Stem Cell-Derived Secretome

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Melisa Hendrata ◽  
Janti Sudiono
Keyword(s):  
Differential Equations ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Multiscale Model ◽  
Cellular Migration ◽  
Phenotypic Switching ◽  
Tumor Growth Rate ◽  
Discrete Equations ◽  
Pathological Conditions ◽  
Avascular Tumor

Apoptosis is a programmed cell death that occurs naturally in physiological and pathological conditions. Defective apoptosis can trigger the development and progression of cancer. Experiments suggest the ability of secretome derived from mesenchymal stem cells (MSC) to induce apoptosis in cancer cells. We develop a hybrid discrete-continuous multiscale model to further investigate the effect of MSC-derived secretome in tumor growth. The model encompasses three biological scales. At the molecular scale, a system of ordinary differential equations regulate the expression of proteins involved in apoptosis signaling pathways. At the cellular scale, discrete equations control cellular migration, phenotypic switching, and proliferation. At the extracellular scale, a system of partial differential equations are employed to describe the dynamics of microenvironmental chemicals concentrations. The simulation is able to produce both avascular tumor growth rate and phenotypic patterns as observed in the experiments. In addition, we obtain good quantitative agreements with the experimental data on the apoptosis of HeLa cancer cells treated with MSC-derived secretome. We use this model to predict the growth of avascular tumor under various secretome concentrations over time.

scholarly journals A Multiscale Model for Avascular Tumor Growth

2005 ◽  
Vol 89 (6) ◽  
pp. 3884-3894 ◽  
Author(s):  
Yi Jiang ◽  
Jelena Pjesivac-Grbovic ◽  
Charles Cantrell ◽  
James P. Freyer
Keyword(s):  
Tumor Growth ◽  
Multiscale Model ◽  
Avascular Tumor

scholarly journals Hsp70-containing Extracellular Vesicles are Capable of Activating of Adaptive Immunity in Models of Mouse Melanoma and Colon Carcinoma

2021 ◽  
Author(s):  
Elena Y. Komarova ◽  
Roman V. Suezov ◽  
Alina D. Nikotina ◽  
Nikolay D. Aksenov ◽  
Luiza А. Garaeva ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Full Scale ◽  
Tumor Growth Rate ◽  
Strong Increase ◽  
Rab Proteins ◽  
Arginase 1 ◽  
Recombinant Hsp70 ◽  
Anti Cancer

Abstract BackgroundThe release of Hsp70 chaperone from tumor cells is found to trigger the full-scale anti-cancer immune response. Such release and the proper immune reaction can be induced by the delivery of recombinant Hsp70 to a tumor and we sought to explore how the endogenous Hsp70 can be transported to extracellular space leading to the burst of anti-cancer activity. MethodsHsp70 transport mechanisms were studied by analyzing its intracellular tracks with Rab proteins as well as by using specific inhibitors of membrane domains. To study Hsp70 forms released from cells we employed the assay consisting of two affinity chromatography methods. Hsp70 content in culture medium and extracellular vesicles (EV) was measured with the aid of ELISA. The properties and composition of EVs were assessed using nanoparticle tracking analysis and immunoblotting. The activity of immune cells was studied using an assay of cytotoxic lymphocytes, and for in vivo studies we employed methods of affinity separation of lymphocyte fractions.Results Analyzing B16 melanoma cells treated with recombinant Hsp70 we found that the chaperone triggered extracellular transport of its endogenous analog in soluble and enclosed in EVs forms; both species efficiently penetrated adjacent cells and this secondary transport was corroborated with the strong increase of Natural Killer (NK) cell toxicity towards melanoma. When B16 and CT-26 colon cancer cells before their injection in animals were treated with Hsp70-enriched EVs, a powerful anti-cancer effect was observed as shown by a two-fold reduction in tumor growth rate and elevation of life span. We found that the immunomodulatory effect was due to the enhancement of the CD8-positive response and anti-tumor cytokine accumulation; supporting this there was no delay in CT-26 tumor growth when Hsp70-enriched EVs were grafted in nude mice. Importantly, pre-treatment of B16 cells with Hsp70-bearing EVs resulted in a decline of arginase-1-positive macrophages, showing no generation of tumor-associated macrophages. Conclusion In conclusion, Hsp70-containing EVs generated by specifically treated cancer cells give a full-scale and effective pattern of anti-tumor immune responses.

scholarly journals The radiation response of hormone-resistant prostate cancer induced by long-term hormone therapy

2007 ◽  
Vol 14 (3) ◽  
pp. 633-643 ◽  
Author(s):  
Chun-Te Wu ◽  
Wen-Cheng Chen ◽  
Shuen-Kuei Liao ◽  
Cheng-Lung Hsu ◽  
Kuan-Der Lee ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Growth ◽  
Hormone Therapy ◽  
Cancer Cells ◽  
Radiation Treatment ◽  
Radiation Response ◽  
Tumor Growth Rate ◽  
Prostate Cancer Cells ◽  
Underlying Mechanisms

Hormone therapy for prostate cancer eventually fails leading to a stage called hormone-resistant (HR) disease. To investigate the issue about the characteristics and the radiation response in HR prostate cancer, we established HR cell sub-lines, 22RV1-F and 22RV1-DF, from 22RV1 cells with androgen deprivation for 16 weeks, and obtained LNCaP-HR from LNCaP with long-term bicalutamide treatment. We examined their sensitivities to radiation therapy and the underlying mechanisms. In vitro and in vivo faster tumor growth rate was noted in the HR prostate cancer cells when compared with control. Moreover, HR prostate cancer cells had greater capacity to scavenge reactive oxygen species, and suffered less apoptosis and senescence, and subsequently were more likely to survive from irradiation as measured by clonogenic assay invitro and growth delay invivo. The decreased p53 and increased mouse double minute 2 oncogene (MDM2) might be the potential underlying mechanisms for the more aggressive growth and more radioresistance in HR prostate cancer cells. In conclusion, HR prostate cancer cells appeared to be more aggressive in tumor growth and in resistance to radiation treatment. Regulation of the expressions of p53 and MDM2 should be the promising treatment strategies for relative radioresistant prostate cancer.

Finite Element Modeling of Avascular Tumor Growth Using a Stress-Driven Model

2017 ◽  
Vol 139 (8) ◽  
Author(s):  
Faezeh Iranmanesh ◽  
Mohammad Ali Nazari
Keyword(s):  
Growth Rate ◽  
Finite Element ◽  
Tumor Growth ◽  
Finite Element Modeling ◽  
Solid Phase ◽  
Collagen Fibers ◽  
Tumor Growth Rate ◽  
Fiber Distribution ◽  
Element Modeling ◽  
Avascular Tumor

Tumor growth being a multistage process has been investigated from different aspects. In the present study, an attempt is made to represent a constitutive-structure-based model of avascular tumor growth in which the effects of tensile stresses caused by collagen fibers are considered. Collagen fibers as a source of anisotropy in the structure of tissue are taken into account using a continuous fiber distribution formulation. To this end, a finite element modeling is implemented in which a neo-Hookean hyperelastic material is assigned to the tumor and its surrounding host. The tumor is supplied with a growth term. The growth term includes the effect of parameters such as nutrient concentration on the tumor growth and the tumor's solid phase content in the formulation. Results of the study revealed that decrease of solid phase is indicative of decrease in growth rate and the final steady-state value of tumor's radius. Moreover, fiber distribution affects the final shape of the tumor, and it could be used to control the shape and geometry of the tumor in complex morphologies. Finally, the findings demonstrated that the exerted stresses on the tumor increase as time passes. Compression of tumor cells leads to the reduction of tumor growth rate until it gradually reaches an equilibrium radius. This finding is in accordance with experimental data. Hence, this formulation can be deployed to evaluate both the residual stresses induced by growth and the mechanical interactions with the host tissue.

scholarly journals Hypoxia-Induced MALAT1 Promotes the Proliferation and Migration of Breast Cancer Cells by Sponging MiR-3064-5p

2021 ◽  
Vol 11 ◽  
Author(s):  
Chung-Hsien Shih ◽  
Li-Ling Chuang ◽  
Mong-Hsun Tsai ◽  
Li-Han Chen ◽  
Eric Y. Chuang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Cellular Migration ◽  
Expression Levels ◽  
Promote Tumor Growth ◽  
Rna Immunoprecipitation ◽  
And Migration

Hypoxia, a common process during tumor growth, can lead to tumor aggressiveness and is tightly associated with poor prognosis. Long noncoding RNAs (lncRNAs) are long ribonucleotides (>200 bases) with limited ability to translate proteins, and are known to affect many aspects of cellular function. One of their regulatory mechanisms is to function as a sponge for microRNA (miRNA) to modulate its biological functions. Previously, MALAT1 was identified as a hypoxia-induced lncRNA. However, the regulatory mechanism and functions of MALAT1 in breast cancer are still unclear. Therefore, we explored whether MALAT1 can regulate the functions of breast cancer cells through miRNAs. Our results showed the expression levels of MALAT1 were significantly up-regulated under hypoxia and regulated by HIF-1α and HIF-2α. Next, in contrast to previous reports, nuclear and cytoplasmic fractionation assays and fluorescence in situ hybridization indicated that MALAT1 was mainly located in the cytoplasm. Therefore, the labeling of MALAT1 as a nuclear marker should be done with the caveat. Furthermore, expression levels of miRNAs and RNA immunoprecipitation using antibody against AGO2 showed that MALAT1 functioned as a sponge of miRNA miR-3064-5p. Lastly, functional assays revealed that MALAT1 could promote cellular migration and proliferation of breast cancer cells. Our findings provide evidence that hypoxia-responsive long non-coding MALAT1 could be transcriptionally activated by HIF-1α and HIF-2α, act as a miRNA sponge of miR-3064-5p, and promote tumor growth and migration in breast cancer cells. These data suggest that MALAT1 may be a candidate for therapeutic targeting of breast cancer progression.

scholarly journals Hsp70-containing extracellular vesicles are capable of activating of adaptive immunity in models of mouse melanoma and colon carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elena Y. Komarova ◽  
Roman V. Suezov ◽  
Alina D. Nikotina ◽  
Nikolay D. Aksenov ◽  
Luiza A. Garaeva ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Full Scale ◽  
Tumor Growth Rate ◽  
Strong Increase ◽  
Rab Proteins ◽  
Arginase 1 ◽  
Recombinant Hsp70 ◽  
Anti Cancer

AbstractThe release of Hsp70 chaperone from tumor cells is found to trigger the full-scale anti-cancer immune response. Such release and the proper immune reaction can be induced by the delivery of recombinant Hsp70 to a tumor and we sought to explore how the endogenous Hsp70 can be transported to extracellular space leading to the burst of anti-cancer activity. Hsp70 transport mechanisms were studied by analyzing its intracellular tracks with Rab proteins as well as by using specific inhibitors of membrane domains. To study Hsp70 forms released from cells we employed the assay consisting of two affinity chromatography methods. Hsp70 content in culture medium and extracellular vesicles (EVs) was measured with the aid of ELISA. The properties and composition of EVs were assessed using nanoparticle tracking analysis and immunoblotting. The activity of immune cells was studied using an assay of cytotoxic lymphocytes, and for in vivo studies we employed methods of affinity separation of lymphocyte fractions. Analyzing B16 melanoma cells treated with recombinant Hsp70 we found that the chaperone triggered extracellular transport of its endogenous analog in soluble and enclosed in EVs forms; both species efficiently penetrated adjacent cells and this secondary transport was corroborated with the strong increase of Natural Killer (NK) cell toxicity towards melanoma. When B16 and CT-26 colon cancer cells before their injection in animals were treated with Hsp70-enriched EVs, a powerful anti-cancer effect was observed as shown by a two-fold reduction in tumor growth rate and elevation of life span. We found that the immunomodulatory effect was due to the enhancement of the CD8-positive response and anti-tumor cytokine accumulation; supporting this there was no delay in CT-26 tumor growth when Hsp70-enriched EVs were grafted in nude mice. Importantly, pre-treatment of B16 cells with Hsp70-bearing EVs resulted in a decline of arginase-1-positive macrophages, showing no generation of tumor-associated macrophages. In conclusion, Hsp70-containing EVs generated by specifically treated cancer cells give a full-scale and effective pattern of anti-tumor immune responses.

scholarly journals A Mathematical Model for the Onset of Avascular Tumor Growth in Response to the Loss of P53 Function

2006 ◽  
Vol 2 ◽  
pp. 117693510600200 ◽  
Author(s):  
Howard A. Levine ◽  
Michael W. Smiley ◽  
Anna L. Tucker ◽  
Marit Nilsen-Hamilton
Keyword(s):  
Mathematical Model ◽  
Differential Equations ◽  
Tumor Growth ◽  
Solid Tumor ◽  
Tumor Size ◽  
P53 Protein ◽  
Cell Movement ◽  
Inhomogeneous Solution ◽  
Cell Expression ◽  
Avascular Tumor

We present a mathematical model for the formation of an avascular tumor based on the loss by gene mutation of the tumor suppressor function of p53. The wild type p53 protein regulates apoptosis, cell expression of growth factor and matrix metalloproteinase, which are regulatory functions that many mutant p53 proteins do not possess. The focus is on a description of cell movement as the transport of cell population density rather than as the movement of individual cells. In contrast to earlier works on solid tumor growth, a model is proposed for the initiation of tumor growth. The central idea, taken from the mathematical theory of dynamical systems, is to view the loss of p53 function in a few cells as a small instability in a rest state for an appropriate system of differential equations describing cell movement. This instability is shown (numerically) to lead to a second, spatially inhomogeneous, solution that can be thought of as a solid tumor whose growth is nutrient diffusion limited. In this formulation, one is led to a system of nine partial differential equations. We show computationally that there can be tumor states that coexist with benign states and that are highly unstable in the sense that a slight increase in tumor size results in the tumor occupying the sample region while a slight decrease in tumor size results in its ultimate disappearance.

Sign in / Sign up

Export Citation Format

Share Document