scholarly journals Mathematical characterization of population dynamics in breast cancer cells treated with doxorubicin

2021 ◽  
Author(s):  
Emily Y. Yang ◽  
Grant R. Howard ◽  
Amy Brock ◽  
Thomas E. Yankeelov ◽  
Guillermo Lorenzo

AbstractThe development of chemoresistance remains a significant cause of treatment failure in breast cancer. We posit that a mathematical understanding of chemoresistance could assist in developing successful treatment strategies. Towards that end, we have developed a model that describes the effects of the standard chemotherapeutic drug doxorubicin on the MCF-7 breast cancer cell line. We assume that the tumor is composed of two subpopulations: drug-resistant cells, which continue proliferating after treatment, and drug-sensitive cells, which gradually transition from proliferating to treatment-induced death. The model is fit to experimental data including variations in drug concentration, inter-treatment interval, and number of doses. Our model recapitulates tumor growth dynamics in all these scenarios (as quantified by the concordance correlation coefficient, CCC > 0.95). In particular, superior tumor control is observed with higher doxorubicin concentrations, shorter inter-treatment intervals, and a higher number of doses (p < 0.05). Longer inter-treatment intervals require adapting the model parameterization after each doxorubicin dose, suggesting the promotion of chemoresistance. Additionally, we propose promising empirical formulas to describe the variation of model parameters as functions of doxorubicin concentration (CCC > 0.78). Thus, we conclude that our mathematical model could deepen our understanding of the effects of doxorubicin and could be used to explore practical drug regimens achieving optimal tumor control.

2002 ◽  
Vol 129 (1-2) ◽  
pp. 55-63 ◽  
Author(s):  
Christel M Olsen ◽  
Elise T.M Meussen-Elholm ◽  
Jørn A Holme ◽  
Jan K Hongslo

2013 ◽  
Vol 17 (2) ◽  
pp. 817-828 ◽  
Author(s):  
M. Stoelzle ◽  
K. Stahl ◽  
M. Weiler

Abstract. Streamflow recession has been investigated by a variety of methods, often involving the fit of a model to empirical recession plots to parameterize a non-linear storage–outflow relationship based on the dQ/dt−Q method. Such recession analysis methods (RAMs) are used to estimate hydraulic conductivity, storage capacity, or aquifer thickness and to model streamflow recession curves for regionalization and prediction at the catchment scale. Numerous RAMs have been published, but little is known about how comparably the resulting recession models distinguish characteristic catchment behavior. In this study we combined three established recession extraction methods with three different parameter-fitting methods to the power-law storage–outflow model to compare the range of recession characteristics that result from the application of these different RAMs. Resulting recession characteristics including recession time and corresponding storage depletion were evaluated for 20 meso-scale catchments in Germany. We found plausible ranges for model parameterization; however, calculated recession characteristics varied over two orders of magnitude. While recession characteristics of the 20 catchments derived with the different methods correlate strongly, particularly for the RAMs that use the same extraction method, not all rank the catchments consistently, and the differences among some of the methods are larger than among the catchments. To elucidate this variability we discuss the ambiguous roles of recession extraction procedures and the parameterization of the storage–outflow model and the limitations of the presented recession plots. The results suggest strong limitations to the comparability of recession characteristics derived with different methods, not only in the model parameters but also in the relative characterization of different catchments. A multiple-methods approach to investigating streamflow recession characteristics should be considered for applications whenever possible.


2017 ◽  
Vol 14 (4) ◽  
pp. 5039-5045 ◽  
Author(s):  
Sergei Boichuk ◽  
Aigul Galembikova ◽  
Alexandr Sitenkov ◽  
Ramil Khusnutdinov ◽  
Pavel Dunaev ◽  
...  

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4340 ◽  
Author(s):  
Manasi P. Jogalekar ◽  
Elba E. Serrano

Triple negative breast cancer (TNBC) is a belligerent carcinoma that is unresponsive to targeted receptor therapies. Development of new treatment strategies would benefit from an expanded repertoire of in vitro cell culture systems, such as those that support tridimensional growth in the presence of hydrogel scaffolds. To this end, we established protocols for maintenance of the TNBC cell line HCC70 in monolayer culture and in a commercially available basement membrane matrix hydrogel. We evaluated the general morphology of cells grown in both conditions with light microscopy, and examined their subcellular organization using transmission electron microscopy (TEM). Phase contrast and confocal microscopy showed the prevalence of irregularly shaped flattened cells in monolayer cultures, while cells maintained in hydrogel organized into multi-layered spheroids. A quantitative ultrastructural analysis comparing cells from the two culture conditions revealed that cells that formed spheroids comprised a greater number of mitochondria, autophagic vacuoles and intercellular junctions than their monolayer counterparts, within the equivalent area of sampled tissue. These observations suggest that triple negative breast cancer cells in culture can alter their organelle content, as well as their morphology, in response to their microenvironment. Methods presented here may be useful for those who intend to image cell cultures with TEM, and for investigators who seek to implement diverse in vitro models in the search for therapeutic molecular targets for TNBC.


Endocrinology ◽  
1987 ◽  
Vol 121 (5) ◽  
pp. 1759-1765 ◽  
Author(s):  
ANNE-MARIE NUNEZ ◽  
SONIA JAKOWLEV ◽  
JEAN-PAUL BRIAND ◽  
MIREILLE GAIRE ◽  
ANDRÉE KRUST ◽  
...  

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