Data-driven modeling and characterization of anti-angiogenic molecule effects on tumoral vascular density

Tylcz, Jean-Baptiste; Alaoui‐Lasmaili, Karima El; Djermoune, El‐Hadi; Thomas, Noémie; Faivre, B.; Bastogne, Thierry

doi:10.1016/j.bspc.2015.04.008

Cited by 11 publications

(7 citation statements)

References 30 publications

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“…For a good model of vasculature dynamics and the effect of inhibition on the tumor vasculature, see [42]. Nevertheless, the results have shown that the extended model can describe the tumor growth dynamics efficiently even without modeling the vasculature; thus we have neglected the vasculature dynamics (note that modeling vasculature dynamics would increase the order of the system; thus the model would be more complicated).…”

Section: Discussionmentioning

confidence: 99%

Modeling of Tumor Growth Incorporating the Effects of Necrosis and the Effect of Bevacizumab

2017

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Tumor growth models are important to create an engineering background for cancer treatment either by using the models for simulations and evaluation of treatment protocols or, if combined with control engineering, by designing treatment protocols. A well-defined tumor growth model must describe the physiological processes and the measurements as well. Growing tumors are composed of dead tumor cells (forming the necrotic part) and living, proliferating tumor cells (forming the proliferating part); when tumor volume is measured, these parts are measured together. Most of the known tumor growth models do not consider the modeling of the necrotic part. Starting from a minimal model of the tumor growth under bevacizumab treatment, the aim of the current research is to extend it incorporating the volume and dynamics of the necrotic part and the pharmacodynamics and mixed-order pharmacokinetics of the applied drug. The extended model is validated using measurements with mice as hosts, colon adenocarcinoma as tumor, and bevacizumab as the drug used for treatment. The results show that the extended model can describe the important physiological phenomena and shows a good fit to the average of the measurements.

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Section: Discussionmentioning

confidence: 99%

Modeling of Tumor Growth Incorporating the Effects of Necrosis and the Effect of Bevacizumab

2017

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“…The whole mounts were prepared by spreading the mammary glands onto glass slides and stained as described by Vandenberg et al ( 20 ). A dedicated Matlab program for analysis of the mammary network, adapted from Tylcz et al ( 21 , 22 ), was previously described ( 16 ). The mammary network was quantified in terms of tree extension, branching, and amount of sprouts.…”

Section: Methodsmentioning

confidence: 99%

Low-Dose Alkylphenol Exposure Promotes Mammary Epithelium Alterations and Transgenerational Developmental Defects, But Does Not Enhance Tumorigenic Behavior of Breast Cancer Cells

et al. 2017

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Fetal and neonatal exposure to long-chain alkylphenols has been suspected to promote breast developmental disorders and consequently to increase breast cancer risk. However, disease predisposition from developmental exposures remains unclear. In this work, human MCF-10A mammary epithelial cells were exposed in vitro to a low dose of a realistic (4-nonylphenol + 4-tert-octylphenol) mixture. Transcriptome and cell-phenotype analyses combined to functional and signaling network modeling indicated that long-chain alkylphenols triggered enhanced proliferation, migration ability, and apoptosis resistance and shed light on the underlying molecular mechanisms which involved the human estrogen receptor alpha 36 (ERα36) variant. A male mouse-inherited transgenerational model of exposure to three environmentally relevant doses of the alkylphenol mix was set up in order to determine whether and how it would impact on mammary gland architecture. Mammary glands from F3 progeny obtained after intrabuccal chronic exposure of C57BL/6J P0 pregnant mice followed by F1–F3 male inheritance displayed an altered histology which correlated with the phenotypes observed in vitro in human mammary epithelial cells. Since cellular phenotypes are similar in vivo and in vitro and involve the unique ERα36 human variant, such consequences of alkylphenol exposure could be extrapolated from mouse model to human. However, transient alkylphenol treatments combined to ERα36 overexpression in mammary epithelial cells were not sufficient to trigger tumorigenesis in xenografted Nude mice. Therefore, it remains to be determined if low-dose alkylphenol transgenerational exposure and subsequent abnormal mammary gland development could account for an increased breast cancer susceptibility.

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“…A dedicated Matlab program, adapted from Tylcz et al [31] was used to quantify mammary tree extension and branching. First, the ducts in all the images are enhanced using the multiscale filtering method of Frangi et al [32] (S2A Fig).…”

Section: Methodsmentioning

confidence: 99%

Mammary epithelial cell phenotype disruption in vitro and in vivo through ERalpha36 overexpression

Thiébaut¹,

Chamard-Jovenin²,

Chesnel³

et al. 2017

PLoS ONE

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Estrogen receptor alpha 36 (ERα36) is a variant of the canonical estrogen receptor alpha (ERα66), widely expressed in hormone sensitive cancer cells and whose high expression level correlates with a poor survival prognosis for breast cancer patients. While ERα36 activity have been related to breast cancer progression or acquired resistance to treatment, expression level and location of ERα36 are poorly documented in the normal mammary gland. Therefore, we explored the consequences of a ERα36 overexpression in vitro in MCF-10A normal mammary epithelial cells and in vivo in a unique model of MMTV-ERα36 transgenic mouse strain wherein ERα36 mRNA was specifically expressed in the mammary gland. By a combination of bioinformatics and computational analyses of microarray data, we identified hierarchical gene networks, downstream of ERα36 and modulated by the JAK2/STAT3 signaling pathway. Concomitantly, ERα36 overexpression lowered proliferation rate but enhanced migration potential and resistance to staurosporin-induced apoptosis of the MCF-10A cell line. In vivo, ERα36 expression led to duct epithelium thinning and disruption in adult but not in prepubescent mouse mammary gland. These phenotypes correlated with a loss of E-cadherin expression. Here, we show that an enhanced expression of ERα36 is sufficient, by itself, to disrupt normal breast epithelial phenotype in vivo and in vitro through a dominant-positive effect on nongenomic estrogen signaling pathways. These results also suggest that, in the presence of adult endogenous steroid levels, ERα36 overexpression in vivo contributes to alter mammary gland architecture which may support pre-neoplastic lesion and augment breast cancer risk.

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Data-driven modeling and characterization of anti-angiogenic molecule effects on tumoral vascular density

Cited by 11 publications

References 30 publications

Modeling of Tumor Growth Incorporating the Effects of Necrosis and the Effect of Bevacizumab

Modeling of Tumor Growth Incorporating the Effects of Necrosis and the Effect of Bevacizumab

Low-Dose Alkylphenol Exposure Promotes Mammary Epithelium Alterations and Transgenerational Developmental Defects, But Does Not Enhance Tumorigenic Behavior of Breast Cancer Cells

Mammary epithelial cell phenotype disruption in vitro and in vivo through ERalpha36 overexpression

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