Bioinformatics Profiling of Missense Mutations

The ability to distinguish missense nucleotide substitutions that contribute to harmful effect from those that do not is a difficult problem usually accomplished through functional in vivo analyses. In this study, instead current biochemical methods, the effects of missense mutations upon protein structure and function were assayed by means of computational methods and information from the databases. For this order, the effects of new missense mutations in exon 5 of PTEN gene upon protein structure and function were examined. The gene coding for PTEN was identified and localized on chromosome region 10q23.3 as the tumor suppressor gene. The utilization of these methods were shown that c.319G>A and c.341T>G missense mutations that were recognized in patients with breast cancer and Cowden disease, could be pathogenic. This method could be use for analysis of missense mutation in others genes.

Rigorous Electromagnetic Model of Fourier Transform Infrared (FT-IR) Spectroscopic Imaging Applied to Automated Histology of Prostate Tissue Specimens

Fourier transform infrared (FT-IR) spectroscopic imaging is an emerging technique that provides both chemically and spatially resolved information. The rich chemical content of data may be utilized for computer-aided determinations of structure and pathologic state (cancer diagnosis) in histological tissue sections for prostate cancer. FT-IR spectroscopic imaging of prostate tissue has shown that tissue type (histological) classification can be performed to a high degree of accuracy [1] and cancer diagnosis can be performed with an accuracy of about 80% [2] on a microscopic (≈ 6μm) length scale. In performing these analyses, it has been observed that there is large variability (more than 60%) between spectra from different points on tissue that is expected to consist of the same essential chemical constituents. Spectra at the edges of tissues are characteristically and consistently different from chemically similar tissue in the middle of the same sample. Here, we explain these differences using a rigorous electromagnetic model for light-sample interaction. Spectra from FT-IR spectroscopic imaging of chemically heterogeneous samples are different from bulk spectra of individual chemical constituents of the sample. This is because spectra not only depend on chemistry, but also on the shape of the sample. Using coupled wave analysis, we characterize and quantify the nature of spectral distortions at the edges of tissues. Furthermore, we present a method of performing histological classification of tissue samples. Since the mid-infrared spectrum is typically assumed to be a quantitative measure of chemical composition, classification results can vary widely due to spectral distortions. However, we demonstrate that the selection of localized metrics based on chemical information can make our data robust to the spectral distortions caused by scattering at the tissue boundary.

Evolutionary of Prostate Cancer Stem Cells in Prostate Duct

A systems approach model for prostate cancer in prostate duct, as a sub-system of the organism is developed. It is accomplished in two steps. First this research work starts with a nonlinear system of coupled Fokker-Plank equations which models continuous process of the system like motion of cells. Then extended to PDEs that include discontinuous processes like cell mutations, proliferation and deaths. The discontinuous processes is modeled by using intensity poisson processes. The model incorporates the features of the prostate duct. The system of PDEs spatial coordinate is along the proximal distal axis. Its parameters depend on features of the prostate duct. The movement of cells is biased towards distal region and mutations of prostate cancer cells is localized in the proximal region. Numerical solutions of the full system of equations are provided, and are exhibit traveling wave fronts phenomena. This motivates the use of the standard transformation to derive a canonically related system of ODEs for traveling wave solutions. The results obtained show persistence of prostate cancer by showing that the non-negative cone for the traveling wave system is time invariant. The traveling waves have a unique global attractor is proved also. Biologically, the global attractor verifies that evolution of prostate cancer stem cells exhibit the avascular tumor growth. These numerical solutions show that altering prostate stem cell movement or mutation of prostate cancer cells lead to avascular tumor. Conclusion with comments on clinical implications of the model is discussed.