Effects of X-Ray Radiation Exposure toward Lymphocytes of Radiographers in Abcd Hospital of Mataram Town 2014

Abstract:-X-ray radiation sources in ABC

Quantitative Analysis of the Effect of Cancer Invasiveness and Collagen Concentration on 3D Matrix Remodeling

Extracellular matrix (ECM) remodeling is a key component of cell migration and tumor metastasis, and has been associated with cancer progression. Despite the importance of matrix remodeling, systematic and quantitative studies on the process have largely been lacking. Furthermore, it remains unclear if the disrupted tensional homeostasis characteristic of malignancy is due to initially altered ECM and tissue properties, or to the alteration of the tissue by tumor cells. To explore these questions, we studied matrix remodeling by two different prostate cancer cell lines in a three-dimensional collagen system. Over one week, we monitored structural changes in gels of varying collagen content using confocal reflection microscopy and quantitative image analysis, tracking metrics of fibril fraction, pore size, and fiber length and diameter. Gels that were seeded with no cells (control), LNCaP cells, and DU-145 cells were quantitatively compared. Gels with higher collagen content initially had smaller pore sizes and higher fibril fractions, as expected. However, over time, LNCaP- and DU-145-populated matrices showed different structural properties compared both to each other and to the control gels, with LNCaP cells appearing to favor microenvironments with lower collagen fiber fractions and larger pores than DU-145 cells. We posit that the DU-145 cells' preference for denser matrices is due to their higher invasiveness and proteolytic capabilities. Inhibition of matrix proteases resulted in reduced fibril fractions for high concentration gels seeded with either cell type, supporting our hypothesis. Our novel quantitative results probe the dynamics of gel remodeling in three dimensions and suggest that prostate cancer cells remodel their ECM in a synergistic manner that is dependent on both initial matrix properties as well as their invasiveness

Effects of three-dimensional extracellular matrix properties on tumor cell behavior

Thesis ()--Boston UniversityPLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at [email protected]. Thank you.Cancer is a devastating disease that claims millions of lives each year. It has long been recognized that solid tumors are usually much stiffer than normal tissues. While it is well-established that extracellular matrix (ECM) properties affect many aspects of cell behaviour, the implications of altered matrix properties in cancer progression has not been investigated in a systematic, quantitative fashion. The question of how cell-ECM interactions drive cancer, especially in in vivo -like 3D conditions, is of great interest since tumor cells are closely interfacing with the ECM during metastasis. The central hypothesis of this work is that 3D ECM properties affect motility and matrix remodeling, two key components of invasion. This was explored in four studies. First, we developed a force-based simulation of the effect of proteolytic matrix degradation on 3D cell migration and found that peak motility is achieved at intermediate ECM ligand and matrix metalloproteinase (MMP) concentrations, with a linear relationship between ligand and MMPs yielding physiologically compelling results. Second, we used confocal reflectance microscopy to monitor remodeling behavior of two prostate cancer cell lines, LNCaP and DU-145, seeded in 3D matrices of varying collagen content. While both cell types increased the fraction of fibrils in the lowest density collagen gels, in higher density gels, the more invasive cells modified gels to achieve much higher fibril fractions. This difference was found to be due in part to higher MMP production in the more invasive DU-145 cell line. A 3D lattice-based Monte Carlo model was also developed that recreated this matrix remodeling experiment, explicitly accounting for both cellular and matrix properties, and confirmed the finding that more invasive cells more aggressively increase fibril fractions of their substrates. Finally, the dispersal of multicellular tumoroids was found to be dependent on matrix properties. Clusters of DU-145 cells dispersed most readily on 2D substrates and at intermediate collagen concentration in 3D. In summary, we found that 3D ECM properties can dictate how cancer cells migrate and reorganize their microenvironment. This work has major implications for understanding the clinically significant process of metastasis.2031-01-0

Modeling extracellular matrix reorganization in 3D environments.

Extracellular matrix (ECM) remodeling is a key physiological process that occurs in a number of contexts, including cell migration, and is especially important for cellular form and function in three-dimensional (3D) matrices. However, there have been few attempts to computationally model how cells modify their environment in a manner that accounts for both cellular properties and the architecture of the surrounding ECM. To this end, we have developed and validated a novel model to simulate matrix remodeling that explicitly defines cells in a 3D collagenous matrix. In our simulation, cells can degrade, deposit, or pull on local fibers, depending on the fiber density around each cell. The cells can also move within the 3D matrix. Different cell phenotypes can be modeled by varying key cellular parameters. Using the model we have studied how two model cancer cell lines, of differing invasiveness, modify matrices with varying fiber density in their vicinity by tracking the metric of fraction of matrix occupied by fibers. Our results quantitatively demonstrate that in low density environments, cells deposit more collagen to uniformly increase fibril fraction. On the other hand, in higher density environments, the less invasive model cell line reduced the fibril fraction as compared to the highly invasive phenotype. These results show good qualitative and quantitative agreement with existing experimental literature. Our simulation is therefore able to function as a novel platform to provide new insights into the clinically relevant and physiologically critical process of matrix remodeling by helping identify critical parameters that dictate cellular behavior in complex native-like environments

Cells are allowed to remodel and move through the environment.

<p>Three types of remodeling behavior are possible in the model: (<i>A</i>) Deposition of new ECM fibers; (<i>B</i>) degradation of fibers; and (<i>C</i>) fiber realignment. (<i>D</i>) Cells are also allowed to move through the matrix.</p

Comparison of experimental and simulated matrices.

<p>(<i>A</i>) CRM images of 2, 3, and 4 mg/mL collagen gels, from top to bottom (originally shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052509#pone.0052509-Harjanto1" target="_blank">[17]</a>); and (<i>B</i>) cross-sections of simulated matrices containing 1200, 2000, and 3000 fibers per lattice, from top to bottom. The CRM images show a view of a whole stack of acquired images from above, while the images from the model depict cross-sections of the matrices, which may give the appearance of there being a significant difference in fiber density between the two.</p

Comparison of results from experiments and simulations across all collagen concentrations.

<p>Fibril fractions shown from day 7 for matrices seeded with low invasive and high invasive cells.</p

Simulation captures remodeling dynamics.

<p>Fibril fractions over time from simulations for (<i>A</i>) LNCaP (low invasive) cells and (<i>B</i>) DU-145 (high invasive) cells, compared with experimental results, for 3 mg/mL collagen condition. Experimental data was originally reported in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052509#pone.0052509-Harjanto1" target="_blank">[17]</a>.</p