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      Nanoscale structural alterations in cancer cells to assess anti-cancerous drug effectiveness in cancer treatment using TEM imaging

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          Abstract

          Understanding the nanoscale structural changes can provide the physical state of cells/tissues. It has been now shown that increases in nanoscale structural alterations are associated with the progress of carcinogenesis in most of the cancer cases, including early carcinogenesis. Anti-cancerous therapies are intended for the growth inhibition of cancer cells; however, it is challenging to detect the efficacy of such drugs in early stages of treatment. A unique method to assess the impact of anti-cancerous drugs on cancerous cells/tissues is to probe the nanoscale structural alterations. In this paper, we study the effect of different anti-cancerous drugs on ovarian tumorigenic cells, using their nanoscale structural alterations as a biomarker. Transmission electron microscopy (TEM) imaging on thin cell sections is performed to obtain their nanoscale structures. The degree of nanoscale structural alterations of tumorigenic cells and anti-cancerous drug treated tumorigenic cells are quantified by using the recently developed inverse participation ratio (IPR) technique. Results show an increase in the degree of nanoscale fluctuations in tumorigenic cells relative to non-tumorigenic cells; then a nearly reverse of the degree of fluctuation of tumorigenic cells to that of non-tumorigenic cells, after the anti-cancerous drugs treatment. These results support that the effect of anti-cancerous drugs in cancer treatment can be quantified by using the degree of nanoscale fluctuations of the cells via TEM imaging. Potential applications of the technique for cancer treatment are also discussed.

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          p53 mutations associated with aging-related rise in cancer incidence rates

          TP53’s role as guardian of the genome diminishes with age, as the probability of mutation increases. Previous studies have shown an association between p53 gene mutations and cancer. However, the role of somatic TP53 mutations in the steep rise in cancer rates with aging has not been investigated at a population level. This relationship was quantified using the International Agency for Research on Cancer (IARC) TP53 and GLOBOCAN cancer databases. The power function exponent of the cancer rate was calculated for 5-y age-standardized incidence or mortality rates for up to 25 cancer sites occurring in adults of median age 42 to 72 y. Linear regression analysis of the mean percentage of a cancer’s TP53 mutations and the corresponding cancer exponent was conducted for four populations: worldwide, Japan, Western Europe, and the United States. Significant associations (P ≤ 0.05) were found for incidence rates but not mortality rates. Regardless of the population studied, positive associations were found for all cancer sites, with more significant associations for solid tumors, excluding the outlier prostate cancer or sex-related tumors. Worldwide and Japanese populations yielded P values as low as 0.002 and 0.005, respectively. For the United States, a significant association was apparent only when analysis utilized the Surveillance, Epidemiology, and End Results (SEER) database. This study found that TP53 mutations accounts for approximately one-quarter and one-third of the aging-related rise in the worldwide and Japanese incidence of all cancers, respectively. These significant associations between TP53 mutations and the rapid rise in cancer incidence with aging, considered with previously published literature, support a causal role for TP53 according to the Bradford-Hill criteria. However, questions remain concerning the contribution of TP53 mutations to neoplastic development and the role of factors such as genetic instability, obesity, and gene deficiencies other than TP53 that reduce p53 activity.
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            Correlations due to localization in quantum eigenfunctions of disordered microwave cavities

            Statistical properties of experimental eigenfunctions of quantum chaotic and disordered microwave cavities are shown to demonstrate nonuniversal correlations due to localization. Varying energy E and mean free path l enable us to experimentally tune from localized to delocalized states. Large level-to-level inverse participation ratio ( I2) fluctuations are observed for the disordered billiards, whose distribution is strongly asymmetric about . The spatial density autocorrelations of eigenfunctions are shown to spatially decay exponentially and the decay lengths are experimentally determined. All the results are quantitatively consistent with calculations based upon nonlinear sigma models.
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              Light localization properties of weakly disordered optical media using confocal microscopy: application to cancer detection

              We have developed a novel technique to quantify submicron scale mass density fluctuations in weakly disordered heterogeneous optical media using confocal fluorescence microscopy. Our method is based on the numerical evaluation of the light localization properties of an ‘optical lattice’ constructed from the pixel intensity distributions of images obtained with confocal fluorescence microscopy. Here we demonstrate that the technique reveals differences in the mass density fluctuations of the fluorescently labeled molecules between normal and cancer cells, and that it has the potential to quantify the degree of malignancy of cancer cells. Potential applications of the technique to other disease situations or characterizing disordered samples are also discussed.
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                Author and article information

                Journal
                05 September 2019
                Article
                1909.02665
                36fee82a-617d-47fa-aeca-9caec5967f38

                http://arxiv.org/licenses/nonexclusive-distrib/1.0/

                History
                Custom metadata
                11 pages, 3 figures
                physics.bio-ph physics.med-ph

                Biophysics,Medical physics
                Biophysics, Medical physics

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