Background: Today, genomic changes are an important cause of the occurrence, growth and progression of cancer. Technological advances in cancer genomic analysis platforms have made it possible to identify genomic alterations that may influence response to lung cancer treatment. Methods: The study examined tumor growth-inhibiting oncogenes and genes responsible for cell growth and division to identify mutations characteristic of malignant lung tumors. The mutations were studied in 400 postoperative samples after amplifying p53 and HRAS fragments and p53, p21Waf1, MDM2 mRNA. p53 or p21Waf1 were expressed in 50% of squamous cell carcinomas and adenocarcinomas of the lung. Results:The study examined tumor growth-inhibiting oncogenes and genes responsible for cell growth and division to identify mutations characteristic of malignant lung tumors. The mutations were studied in 400 postoperative samples after amplifying p53 and HRAS fragments and p53, p21Waf1, MDM2 mRNA. p53 or p21Waf1 were expressed in 50% of squamous cell carcinomas and adenocarcinomas of the lung. HRAS mutations were present in most squamous cell carcinomas and adenocarcinomas of the lung. EcoR1-and Pst1-restriction enzymes destroyed the RT-PCR product of the p53 and p21Waf1 mRNA and increased the level of detected mutations in lung adenocarcinoma to 75% and 50 %, respectively. EGFR mutations were more frequent in lung adenocarcinoma than in lung squamous cell carcinoma. Mutations in EGFR exons 19 and 21 found in 65 of 263 lung tumor samples indicated the tumor sensitivity to EGFR tyrosine kinase inhibitors. EGFR deletions in exon 19 occurred mainly in adenocarcinoma, L858R mutations in EGFR exon 21 were quite common in lung adenocarcinoma. Conclusion: The mutations detected in most squamous cell carcinomas and adenocarcinomas of the lung could be used to diagnose and predict the disease severity and targeted therapy efficacy.
Relevance: According to the International Agency for Research on Cancer (IARC), lung cancer (LC) currently ranks first in cancer incidence and mortality worldwide. The gold standard of LC diagnostics is the histological verification, the determination of the degree of invasion and tumor phenotype. At first glance, epigenetic methods seem to be secondary after determining the patient’s genetic profile. However, standard genetic analysis reveals only the DNA nucleotide sequence. Thus, epigenetic analysis is the only method that allows detecting potential abnormalities in cells. An important difference between genetic and epigenetic changes is that drugs are efficient against epigenetic changes but absolutely powerless against genetic mutations. The purpose of the study was to review and analyze the available molecular genetic methods for DNA methylation profiling in lung cancer. Results: All these observations support the hypothesis that methylation profiling in body fluids can help determine the people predisposed to or affected by LC. Circulating acellular DNA in the blood plasma contains tumor-specific mutations and disease-related DNA methylation patterns. Identifying new biomarkers-precursors of a potential cancer susceptibility or aggressiveness in such DNA would be a considerable advancement in prognostic medicine for patients at high risk of developing LC. Conclusion: A low level of LC detection might limit the number of DNA samples of patients with LC included in the studies. This is also the reason why specific methylation biomarkers have not yet been confirmed for clinical use. Future research on a larger number of blood samples, combined with the entire epigenome studies, may contribute to finding a group of LC biomarkers to improve LC detection.
-It is well known that somatic mutations are induced by ionizing irradiation. We have previously reported the measurement of mutant frequency (MF) on the T-cell receptor (TCR) gene in mouse T-lymphocytes after irradiation by flow cytomery. In this study, we developed an in vitro system using murine EL-4 lymphoma cells and observed frequency of cells defective in TCR gene expression after exposure to ionizing irradiation. EL-4 cells were stained with fluorescein-labeled anti-CD4 and phycoerythrin-labeled anti-CD3 antibodies. They were analyzed with a flow cytometer to detect mutant EL-4 cells lacking surface expression of TCR/CD3 complexes which showed CD3− , CD4 + due to a somatic mutation at the TCR genes. Mutant cells could be observed at 2 days after 3 Gy irradiation. MF of EL-4 cells was 6.7 × 10 −4 for 0 Gy and the value increased to the maximum level of 39 × 10 −4 between 4 and 8 days after 3 Gy irradiation and these data were found to be best fitted by a linear-quadratic doseresponse model. After the peak value the TCR MF gradually decreased with a half-life of approximately 3.2 days. We also examined the hprt mutant frequencies at seven days after irradiation and the cytokinesisblocked micronucleus frequency at 20 hrs after irradiation. The frequencies of hprt mutation and micronuclei were found to be best fitted by a linear-quadratic dose-response model and a linear dose-response model, respectively. The method to detect mutation on TCR gene is quick and easy in comparison with other methods and is considered useful for the mutagenicity test.
In the scientific problem of design and calculation of thin elastic shells in the modern world, certain advances have already been made in mathematical and technical theory, based on hypotheses, experimental data, calculation equations and engineering calculations. Only such shells, which are designed based on calculation and used in building and technical constructions, can be referred to a small number of geometric surfaces. When designing thin shells, surfaces of rotation (sphere, torus, paraboloid, ellipsoid of rotation) and transfer surfaces (hyperbolic and elliptic paraboloid, circular transfer surface) are used. Trends in construction and engineering seek to apply complex mathematical models in harmony with environmental policy and the environment. This leads to the necessity of studying the influence of parameters when modeling an object on the parameters and properties of the created construction. Possessing a more complex shape the shells are realized as a result of experiment. As a result of active introduction of information technologies it became possible to introduce cardinally new methods in the application of geometric thin-walled spatial structures for the design of building and technical constructions, a number of machine-building parts. Modern analytical calculation programs and computer-aided design systems (Compass, Autocad, Archicad, etc.) make it possible to create a geometric projection model of a structure on the basis of primitives, to perform structural and static calculations of a project in an elementary manner. The solution of such layout problems is made possible with the support of computer geometry based on descriptive and analytical geometry, linear and vector algebra, mathematical analysis, and differential geometry. Modern bionics and environmental policy relies on the latest methods of mathematical modeling of architectural projects with a wide choice of computational and graphical software for calculation and 3d visualization.
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