Natural and chemotherapy-induced clonal evolution of tumors

Evolution and natural selection of tumoral clones in the process of transformation and the following carcinogenesis can be called natural clonal evolution. Its main driving factors are internal: genetic instability initiated by driver mutations and microenvironment, which enables selective pressure while forming the environment for cell transformation and their survival. We present our overview of contemporary research dealing with mechanisms of carcinogenesis in different localizations from precancerous pathologies to metastasis and relapse. It shows that natural clonal evolution establishes intratumoral heterogeneity and enables tumor progression. Tumors of monoclonal origin are of low-level intratumoral heterogeneity in the initial stages, and this increases with the size of the tumor. Tumors of polyclonal origin are of extremely high-level intratumoral heterogeneity in the initial stages and become more homogeneous when larger due to clonal expansion. In cases of chemotherapy-induced clonal evolution of a tumor, chemotherapy becomes the leading factor in treatment. The latest research shows that the impact of chemotherapy can radically increase the speed of clonal evolution and lead to new malignant and resistant clones that cause tumor metastasis. Another option of chemotherapy-induced clonal evolution is formation of a new dominant clone from a clone that was minor in the initial tumor and obtained free space due to elimination of sensitive clones by chemotherapy. As a result, in ~20% of cases, chemotherapy can stimulate metastasis and relapse of tumors due to clonal evolution. The conclusion of the overview formulates approaches to tumor treatment based on clonal evolution: in particular, precision therapy, prediction of metastasis stimulation in patients treated with chemotherapy, methods of genetic evaluation of chemotherapy efficiency and clonal-oriented treatment, and approaches to manipulating the clonal evolution of tumors are presented

Copy number aberrations landscape of a breast tumor, connection with the efficiency of neoadjuvant chemotherapy

The research involved 80 patients diagnosed with breast cancer (BC). Each patient had their tumor biopsy material sampled before their treatment. We studied the tumor tissue using the CytoScan HD Array (Affymetrix, USA) microarray to evaluate the CNA landscape. We studied the frequency of segmental and numerical CNA occurrence, their association with the efficiency of neoadjuvant chemotherapy (NAC). We found that the biggest number of amplifications (with frequency over 60%) were found on in the following locuses; 1q32.1 1q32.3, 1q42.13, 1q42.2, 1q43. The biggest frequency of deletions (more than in 58% of the patients) was found in these locuses: 16q21, 16q23.2, 16q23.3, 17p12, 17p13.1. However, we found the locuses with full absence of segmental chromosome anomalies. We observed trisomy most frequently in the 7, 8, 12, and 17 chromosomes, and monosomy in the 3, 4, 9, 11, 18, and X-chromosomes. We demonstrated the connection between the high frequency of cytobands with CNA in the patients’ tumors and the efficiency of NAC. We also identified the cytobands, whose CNA are linked to the response to NAC

Microarray research of allelic imbalance in breast cancers during neoadjuvant chemotherapy

For single nucleotide polymorphism – SNP (SNP – Single Nucleotide Polymorphism) is characterized by phenomenon of allelic imbalance (AI). The phenomenon of allelic imbalanced (AI) is typical of many genes in different malignancies. Allelic imbalanced may result allelic deletions (loss of one copy of the locus) or amplification of one allele, resulting in only a single allelic variant of SNP is determined in the tumor in the PCR. Phenomenon of AI in tumors of breast cancer (BC) is considered in one or more genes. The phenomenon of AI during chemotherapy (CT) and especially in the longer format of the gene had not previously been studied. Thus, the aim of this work was to study microarray imbalanced allele in mammary tumors during neoadjuvant chemotherapy (NCT). Materials and methods: The study included 26 breast cancer patients with stage IIA – IIIC. The patients in the neoadjuvant mode received 2–4 courses of chemotherapy regimens FAC or CAX. DNA from 26 paired samples before treatment and operational samples were isolated by dialing QIAampDNA miniKit (Qiagen, Germany). Microarray analysis was performed on DNA chips of high density company Affymetrix (USA) CytoScanTM HD Array, which contains more than 750 thousand SNP. Microarray analysis was performed on SNP genotypes DNA tumor tissue before and after treatment for each patient and recorded as change occurring allelic imbalanced tumor tissue genotype (AA > AB > AB AA BB > AB > AB BB) during therapy. Results: The frequency of the AI in breast tumor during NCT was highly variable (within 0.9–66.5%) of the studied SNP (6850 – 497,979 SNP). For each patient, frequency shift genotype (homozygous in heterozygous genotype, and vice versa) was calculated as a percentage of all the shifts. Changes in the wild or mutant heterozygous genotypes (AA or BB > AB) were combined into one group; the second group was the sum of the change in the heterozygous genotype homozygous wild genotype or the mutant (AB > AA or BB). We have found that the direction of the AI was significantly associated effect of NCT. In the group of patients with partial regression, the direction of AI change from homozygous to heterozygous genotype often occurs (AA or BB > AB) (9/14, 64%), whereas patients with no response to the NCT (with stabilization or progression) have the opposite effect. All these patients (12/12 cases) have the direction of the change of AI from heterozygous genotype to homozygous (AA or AB > BB) (p = 0.00071). AI during chemotherapy at the level of the marked tendency (Log-rank test, p = 0.062) is associated with 5-year metastasis-free survival. Low metastasis-free survival rate is observed in patients with AI in the direction of the change from the heterozygous to homozygous genotype, while 100% survival is noted in patients with change from homozygous to heterozygous genotypes, and this imbalanced t allele is a favorable prognostic factor. Conclusion: Allelic imbalanced in breast tumor during NCT phenomenon is massive and may affect up to 67% of SNP. AI may occur in the direction of change from homozygous to heterozygous genotype, and it is associated with a good response to treatment and 100% metastasis-free survival. Apparently, this can be explained by the fact that the change from homozygous genotypes to heterozygous occur due to partial destruction of tumor cells by chemotherapy, resulting in the increase of stromal elements. In contrast, AI in the direction change from heterozygous to homozygous genotype during NCT is associated with no response to chemotherapy due to metastasis and occurring of new mutant clones in the tumor

Evaluation of the Efficiency of Detection and Capture of Manganese in Aqueous Solutions of FeCeOx Nanocomposites Doped with Nb2O5

: The main purpose of this work is to study the effectiveness of using FeCeOx nanocomposites doped with Nb2O5 for the purification of aqueous solutions from manganese. X-ray diffraction, energy-dispersive analysis, scanning electron microscopy, vibrational magnetic spectroscopy, and mössbauer spectroscopy were used as research methods. It is shown that an increase in the dopant concentration leads to the transformation of the shape of nanoparticles from spherical to cubic and rhombic, followed by an increase in the size of the nanoparticles. The spherical shape of the nanoparticles is characteristic of a structure consisting of a mixture of two phases of hematite (Fe2O3) and cerium oxide CeO2. The cubic shape of nanoparticles is typical for spinel-type FeNbO4 structures, the phase contribution of which increases with increasing dopant concentration. It is shown that doping leads not only to a decrease in the concentration of manganese in model solutions, but also to an increase in the efficiency of adsorption from 11% to 75%

Examination of Lower Secondary Mathematics Teachers’ Content Knowledge and Its Connection to Students’ Performance

© 2015, Ministry of Science and Technology, Taiwan.This mixed methods study examined an association between cognitive types of teachers’ mathematical content knowledge and students’ performance in lower secondary schools (grades 5 through 9). Teachers (N = 90) completed the Teacher Content Knowledge Survey (TCKS), which consisted of items measuring different cognitive types of teacher knowledge. The first cognitive type (T1) assessed participants’ knowledge of basic facts and procedures. The second cognitive type (T2) measured teachers’ understanding of concepts and connections. The third cognitive type (T3) gauged teachers’ knowledge of mathematical models and generalizations. The study comprised two levels of quantitative data analysis. First, we explored each cognitive type of teachers’ content knowledge and the overall TCKS score as they related to student performance. Second, we studied the correlation between each cognitive type of teacher content knowledge to deepen the understanding of content associations. Results of the study show a statistically significant correlation between cognitive types T1 and T2 of teacher content knowledge and student performance (p < .05). The correlation between cognitive type T3 and student performance was not significant (p = .0678). The most substantial finding was the correlation between teachers’ total score on the TCKS and student performance (Pearson’s r = .2903, p = .0055 < .01). These results suggest that teachers’ content knowledge plays an important role in student performance at the lower secondary school. The qualitative phase included structured interviews with two of the teacher participants in order to further elaborate on the nature of the quantitative results of the study

Examination of Lower Secondary Mathematics Teachers’ Content Knowledge and Its Connection to Students’ Performance

© 2015 Ministry of Science and Technology, Taiwan This mixed methods study examined an association between cognitive types of teachers’ mathematical content knowledge and students’ performance in lower secondary schools (grades 5 through 9). Teachers (N = 90) completed the Teacher Content Knowledge Survey (TCKS), which consisted of items measuring different cognitive types of teacher knowledge. The first cognitive type (T1) assessed participants’ knowledge of basic facts and procedures. The second cognitive type (T2) measured teachers’ understanding of concepts and connections. The third cognitive type (T3) gauged teachers’ knowledge of mathematical models and generalizations. The study comprised two levels of quantitative data analysis. First, we explored each cognitive type of teachers’ content knowledge and the overall TCKS score as they related to student performance. Second, we studied the correlation between each cognitive type of teacher content knowledge to deepen the understanding of content associations. Results of the study show a statistically significant correlation between cognitive types T1 and T2 of teacher content knowledge and student performance (p < .05). The correlation between cognitive type T3 and student performance was not significant (p = .0678). The most substantial finding was the correlation between teachers’ total score on the TCKS and student performance (Pearson’s r = .2903, p = .0055 < .01). These results suggest that teachers’ content knowledge plays an important role in student performance at the lower secondary school. The qualitative phase included structured interviews with two of the teacher participants in order to further elaborate on the nature of the quantitative results of the study

HPV-associated cervical cancer: Current status and prospects

Every year, 570,000 new cases of cervical cancer (CC) are diagnosed in the world, and 311,000 people die from this disease. CC is the fourth most common type of cancer and therefore the fourth leading cause of cancer death in women worldwide. Numerous data on the occurrence and development of cervical cancer indicate an association in most cases (up to 90 %) with human papillomaviruses (HPV) of high carcinogenic risk (HCR).CC prevention strategies are based on screening, and deaths from this oncopathology can be prevented through vaccination and treatment with early detection of the disease.In this review, much attention is paid to current issues of detection and prevention of HPV-associated pathologies, and cervical cancer in particular, aiming to summarize and analyze the latest international literature data on this issue. As a result of this study, it was shown that for countries implementing the National program of vaccination against HPV of high carcinogenic risk, a decrease in the incidence of both cervical pathologies of varying severity and other cancers associated with the HPV carriage was registered.While effective implementation of actual experience and future advances in human papillomavirus vaccine prophylaxis may make it possible for all countries to move to the high levels of vaccination coverage required to eliminate HPV-associated pathologies, the results also suggest that the path to complete cervical cancer elimination as a global public health problem can be extremely difficult due to a number of existing limitations

HPV-negative cervical cancer: a distinct type of the uterine cervix with poor prognosis

The real-time PCR method was used to study cervical scrapings from 116 patients with stag

Template synthesis and magnetic characterization of FeNi nanotubes

Iron-nickel nanotubes consisting of 20% Ni and 80% Fe with an aspect ratio of about 100 were synthesized by electrochemical deposition in the pores of polyethylene terephthalate ion-track membranes. The main morphological parameters such as composition, wall thickness and structural characteristics were defined. Macro- and micromagnetic parameters of FeNi nanotubes were determined. © 2017, Electromagnetics Academy. All rights reserved