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- Alkasalias, Twana, et al.
(författare)
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RhoA knockout fibroblasts lose tumor-inhibitory capacity in vitro and promote tumor growth in vivo
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 114:8, s. E1413-E1421
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Tidskriftsartikel (refereegranskat)abstract
- Fibroblasts are a main player in the tumor-inhibitory microenvironment. Upon tumor initiation and progression, fibroblasts can lose their tumor-inhibitory capacity and promote tumor growth. The molecular mechanisms that underlie this switch have not been defined completely. Previously, we identified four proteins over-expressed in cancer-associated fibroblasts and linked to Rho GTPase signaling. Here, we show that knocking out the Ras homolog family member A (RhoA) gene in normal fibroblasts decreased their tumor-inhibitory capacity, as judged by neighbor suppression in vitro and accompanied by promotion of tumor growth in vivo. This also induced PC3 cancer cell motility and increased colony size in 2D cultures. RhoA knockout in fibroblasts induced vimentin intermediate filament reorganization, accompanied by reduced contractile force and increased stiffness of cells. There was also loss of wide F-actin stress fibers and large focal adhesions. In addition, we observed a significant loss of a-smooth muscle actin, which indicates a difference between RhoA knockout fibroblasts and classic cancer-associated fibroblasts. In 3D collagen matrix, RhoA knockout reduced fibroblast branching and meshwork formation and resulted in more compactly clustered tumor-cell colonies in coculture with PC3 cells, which might boost tumor stem-like properties. Coculturing RhoA knockout fibroblasts and PC3 cells induced expression of proinflammatory genes in both. Inflammatory mediators may induce tumor cell stemness. Network enrichment analysis of transcriptomic changes, however, revealed that the Rho signaling pathway per se was significantly triggered only after coculturing with tumor cells. Taken together, our findings in vivo and in vitro indicate that Rho signaling governs the inhibitory effects by fibroblasts on tumor-cell growth.
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| 2. |
- Danielsson, Tatiana
(författare)
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Further Investigations of Convergence Results for Homogenization Problems with Various Combinations of Scales
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is based on six papers. We study the homogenization of selected parabolic problems with one or more microscopic scales in space and time, respectively. The approaches are prepared by means of certain methods, like two-scale convergence, multiscale convergence and also the evolution setting of multiscale convergence and very weak multiscale convergence. Paper I treats a linear parabolic homogenization problem with rapid spatial and temporal oscillations in perforated domains. Suitable results of two-scale convergence type are established. Paper II deals with further development of compactness results which can be used in the homogenization procedure engaging a certain limit condition. The homogenization procedure deals with a parabolic problem with a certain matching between a fast spatial and a fast temporal scale and a coefficient passing to zero that the time derivative is multiplied with. Papers III and IV are further generalizations of Paper II and investigate homogenization problems with different types of matching between the microscopic scales. Papers III and IV deal with one and two rapid scales in both space and time respectively. Paper V treats the nonlinearity of monotone parabolic problems with an arbitrary number of spatial and temporal scales by applying the perturbed test functions method together with multiscale convergence and very weak multiscale convergence adapted to the evolution setting. In Paper VI we discuss the relation between two-scale convergence and the unfolding method and potential extensions of existing results. The papers above are summarized in Chapter 4. Chapter 1 gives a brief introduction to the topic and Chapters 2 and 3 are surveys over some important previous results.
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| 3. |
- Danielsson, Tatiana, et al.
(författare)
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Homogenization of linear parabolic equations with three spatial and three temporal scales for certain matching between the microscopic scales
- 2021
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Ingår i: Mathematica Bohemica. - 0862-7959 .- 2464-7136. ; 146:4, s. 483-511
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we establish compactness results of multiscale and very weak multiscale type for sequences bounded in L2 (0, T; H10 (Ω)), fulfilling a certain condition. We apply the results in the homogenization of the parabolic partial differential equation εp ∂t uε(x, t) − ∇ · (a(xε−1, xε−2, tε−q, tε−r)∇uε(x, t)) = f(x, t), where 0 < p < q < r. The homogenization result reveals two special phenomena, namely that the homogenized problem is elliptic and that the matching for which the local problem is parabolic is shifted by p, compared to the standard matching that gives rise to local parabolic problems.
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| 4. |
- Danielsson, Tatiana, et al.
(författare)
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Homogenization of monotone parabolic problems with an arbitrary number of spatial and temporal scales
- 2024
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Ingår i: Applications of Mathematics. - : Institute of Mathematics, Czech Academy of Sciences. - 0862-7940 .- 1572-9109. ; 69:1, s. 1-24
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we prove a general homogenization result for monotone parabolic problems with an arbitrary number of microscopic scales in space as well as in time, where the scale functions are not necessarily powers of epsilon. The main tools for the homogenization procedure are multiscale convergence and very weak multiscale convergence, both adapted to evolution problems. At the end of the paper an example is given to concretize the use of the main result.
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