In vitro modeling of tumor interclonal interactions using breast cancer cell lines.

AIM: To study the peculiarities of ecological relationships of breast cancer (BC) cell lines MCF-7, BT-474 and MDA-MD-231 under co-culturing conditions. MATERIALS AND METHODS: Three BC cell lines: luminal A - MCF-7, luminal B - BT-474 and triple-negative - MDA-MD-231 were co-cultured pairwise. Immunocytochemistry was used to differentiate the cell lines in the wells. The effect of the cell-free culture medium on the growth rate of the alternate cell line in the pair was also evaluated. RESULTS: It was shown that when BT-474 cells were co-cultured with MCF-7 and BT-474 cells were co-cultured with MDA-MD-231, two types of ecological interactions could be observed: commensalism and amensalism, respectively. While the cells do not interact with each other in contact, the supernatants of single cultures of MCF-7 and MDA-MD-231 exert the same effect on BT-474 as co-cultivation of BT-474 with these cells. CONCLUSIONS: The paracrine mechanism of intercellular interaction between different human BC cell lines has been demonstrated. The models used in population ecology can be applicable to identify the types of interaction between cell lines.

Breast tumour cell subpopulations with expression of the MYC and OCT4 proteins.

The MYC and OCT4 genes are known factors associated with maintaining pluripotency and are linked with a more aggressive course, progression, and resistance to therapy in cancer. Determining the subpopulations of tumour cells expressing the Myc and Oct4 proteins will provide an opportunity to understand which tumour cell subpopulations expressing MYC and OCT4 are associated with metastasis and resistance and which subpopulations can be targeted by anti-MYC and anti-OCT4 therapy. The study included paraffin-embedded tissue from tumours from 27 patients with luminal B breast cancer obtained after neoadjuvant chemotherapy (NACT). Immunofluorescence staining was used to identify subpopulations of tumour cells expressing Myc, Oct4 and Snai2 (Opal™ 7-Color Kit (PerkinElmer, Hopkinton, MA). The following tumour cell subpopulations were identified with the Myc and Oct4 proteins and the Snai2 EMT marker: stem/progenitor tumour cells with/without Myc, Oct4 or Snai2 expression; differentiated tumour cells with/without Myc, Oct4 or Snai2 expression; and other nontumour cells (CK7-EpCAM-CD44+/-Myc+/-(Oct4, Snai2)+/-) within the inflammatory infiltrate in the tumour parenchyma and stroma. The circulating tumour cell subpopulations with Oct4 protein expression in the bloodstream were studied by flow cytometry. It was found that in patients with partial regression (PR) in response to NACT, the frequency of tumour stem cells was 3.6-fold increased (p = 0.038) in the non-EMT state (CK7+EpCam+CD44+Snai2-). In patients with metastases, there was a statistically significant 2.5-fold increase in the frequency of differentiated tumour cells with Myc expression (CK7+EpCam+CD44-Myc+) and a 2.7-fold increase in the frequency of cells with Oct4 expression (CK7+EpCam+CD44-OCT4+). In the next stage, the frequencies of subpopulations with expression of the Oct4 protein and signs of EMT among circulating tumour cells (CTCs) were determined. In patients with metastases, the frequency of tumour stem cells in the EMT state (CD326+CD44+CD24-CD325+) (p = 0.015) was more than fourfold increased, and the frequency of progenitor tumour cells with expression of the Oct4 stem protein (CD326+CD44+CD24+Oct4+) (p = 0.016) was almost sixfold higher than that in patients without metastases. Nonstem (differentiated) tumour cells with expression of the stemness proteins Myc and Oct4 were present in the breast tumour. Their content was significantly higher in residual tumours after NACT in patients who subsequently developed metastases compared with that in patients without metastases. Such cells are a new in situ marker of metastasis.

[The chemical toxicological investigation of gamma-hydroxybutyric acid in biological objects and the interpretation of the results of the analysis]. / Khimiko-toksikologicheskoe issledovanie GOMK v bioob''ektakh i interpretatsiia rezul'tatov analiza.

The authors propose a method for the quantitative determination of gamma-hydroxybutyric acid (GHBA) in biological objects including biological fluids (blood, urine) and tissues with the use of gas chromatography with mass-selective detector. The samples for the analysis were prepared by liquid-liquid extraction by butyl acetate with subsequent derivatization using a N,O-Bis(trimethylsilyl)trifluoroacetamide/Trimethylchlorosilane mixture (BSTFA + 1%TMCS). The graded graphs were linear in the range of GHBA concentrations from 26.4 to 1321.6 mg/l. Coefficients of correlation for all the graphs were higher than 0.999. The threshold of detectability for GHBA in blood, urine, and internal organs was 10 mg/l, the quantification limit concentration 26 mg/l.

[Organization of quality control of the forensic medical investigations]. / Organizatsiia kontrolia kachestva sudebno-khimicheskikh issledovanii.

The article describes the system of quality control at all stages of forensic chemical investigations (including pre-analytical, analytical, and post-analytical ones) carried out by the Saint-Petersburg Bureau of Forensic Medical Expertise It is shown that standardization and control taken together make up a solid foundation for obtaining the reliable and reproducible results of forensic chemical investigations. Responsibility for the quality control at all stages of forensic chemical investigations lies on the heads of the respective departments. Special staff members are appointed to supervise performing each concrete form of control and keeping the relevant documentation.

HPV status and its genomic integration affect survival of patients with cervical cancer.

To evaluate the relapse-free and overall survival of HPV-positive patients with regard to the physical status of type 16 HPV and of HPV-negative patients with primary CC. As a main result of the study the predictive value of the physical status of type 16 HPV was determined for relapse-free and overall survival of patients with CC. Episomal form of the virus is a favorable predictive factor. Integrated form of the virus is a severely unfavorable predictive factor and survival of such patients is significantly lower, than for HPV- patients and patients with mixed form of the virus. The results of the research are data on survival of patients with CC depending on the physical status of the virus (for HPV+ patients) and of patients with HPV-negative cancer.

Constraints on Oscillation Parameters from ν_{e} Appearance and ν_{µ} Disappearance in NOvA.

Results are reported from an improved measurement of ν_{µ}→ν_{e} transitions by the NOvA experiment. Using an exposure equivalent to 6.05×10^{20} protons on target, 33 ν_{e} candidates are observed with a background of 8.2±0.8 (syst.). Combined with the latest NOvA ν_{µ} disappearance data and external constraints from reactor experiments on sin^{2}2θ_{13}, the hypothesis of inverted mass hierarchy with θ_{23} in the lower octant is disfavored at greater than 93% C.L. for all values of δ_{CP}.

Measurement of the Neutrino Mixing Angle θ_{23} in NOvA.

This Letter reports new results on muon neutrino disappearance from NOvA, using a 14 kton detector equivalent exposure of 6.05×10^{20} protons on target from the NuMI beam at the Fermi National Accelerator Laboratory. The measurement probes the muon-tau symmetry hypothesis that requires maximal θ_{23} mixing (θ_{23}=π/4). Assuming the normal mass hierarchy, we find Δm_{32}^{2}=(2.67±0.11)×10^{-3} eV^{2} and sin^{2}θ_{23} at the two statistically degenerate values 0.404_{-0.022}^{+0.030} and 0.624_{-0.030}^{+0.022}, both at the 68% confidence level. Our data disfavor the maximal mixing scenario with 2.6σ significance.

Comprehensive meta-analytical summary on human papillomavirus association with head and neck cancer.

An etiological role of high risk human papillomavirus (HPV) in the development of cervical cancer has been well established. Hence, attention of researchers has been focused on the role of HPV in pathogenesis of other malignancies, such as head and neck cancers. An analysis of epidemiological data on the prevalence of HPV infection among healthy people and patients with precancerous lesions and/or cancer is an important step in understanding the role of HPV in head and neck carcinogenesis. More and more data de-monstrate the impact of HPV infection on disease outcome. HPV-positive patients have been shown to have better responses to radiotherapy and better overall and disease-free survival than HPV-negative patients. This review presents data of the meta-analysis based on a large number of original studies on HPV prevalence in patients with precancerous lesions and in patients with oral, oropharyngeal and laryngeal cancers as well as findings on the impact of HPV infection on survival of these patients.

Integrative and episomal forms of genotype 16 of human papillomavirus in patients with cervical intraepithelial neoplasia and cervical cancer.

The study involved 500 patients with LSIL (low grade squamous intraepithelial lesion), HSIL (high grade squamous intraepithelial lesion), stage I-IV cervical cancer, infected with human papillomavirus (HPV), as well as 235 women without pathological changes in cervical mucosa. The comprehensive survey included colposcopy, cytological and histological analysis, detection and genotyping of high-risk human papillomavirus. Viral load and physical status of HPV16 DNA was evaluated in cases of mono-infection (n = 148). The prevalence of virus-positive cases among the patients with LSIL/NSIL, cervical cancer patients and healthy women was 69.2%, 76.7% and 51.9%, respectively. An association between the severity of disease and high viral load was revealed. The frequency of integrated DNA was strongly increased in patients with a high viral load. The frequency of episomal forms was either reduced or not detecteable in patients with high viral load as compared to patients with low viral load. It is reasonable to suggest that a high HPV16 viral load may cause an increase in the frequency of integration of virus DNA into the cellular/host genome. This suggests that a high HPV16 viral load may be considered as a risk factor for prognosis of cervical intraepithelial neoplasia and cervical cancer.

Genetic aspects of HPV infection detection in tumor and adjacent tissues of patients with laryngeal squamous cell carcinoma.

The article describes methods for the human papillomavirus (HPV) detection in tumor and adjacent (morphologically intact) tissues of patients with laryngeal squamous cell carcinoma (LSSC) in terms of viral pathogenesis. Comparative evaluation of the principles and techniques for HPV detection was performed. Advantages and disadvantages of the HPV detection methods are described. Approaches for DNA and HPV oncoproteins E6-E7 identification are substantiated. The results of our research into the qualitative and quantitative detection of HPV in the tumor and adjacent tissues of patients with Lssc are described. The research was conducted using commercial test systems Amplisens HPV HR screen-titre-FL and Amplisens HPV HR genotype-FL. Based on these results we developed the algorithm of HPV detection in samples of tumor tissue of patients with Lssc. The need for typing HPV-positive tissue samples with low concentration of HPV DNA was discussed.

[OPISTHORCHIASIS AS A PROMOTER OF GASTRIC CARCINOGENESIS].

The paper presents an experimental model of gastric cancer in the presence of chronic opisthorchiasis, which has been created to study its possible role in gastric carcinogenesis. The performed investigation has supported the hypothesis that opisthorchiasis plays a promoting role in the development of experimental gastric cancer. A larger number of experimental hamsters receiving the carcinogen methylnitronitrosoguanidine (MNNG) developed earlier gastric tumors in. the presence of chronic opisthorchiasis than the control animals in the experiment.

Multidimensional instability and dynamics of spin avalanches in crystals of nanomagnets.

We obtain a fundamental instability of the magnetization-switching fronts in superparamagnetic and ferromagnetic materials such as crystals of nanomagnets, ferromagnetic nanowires, and systems of quantum dots with large spin. We develop the instability theory for both linear and nonlinear stages. By using numerical simulations we investigate the instability properties focusing on spin avalanches in crystals of nanomagnets. The instability distorts spontaneously the fronts and leads to a complex multidimensional front dynamics. We show that the instability has a universal physical nature, with a deep relationship to a wide variety of physical systems, such as the Darrieus-Landau instability of deflagration fronts in combustion, inertial confinement fusion, and thermonuclear supernovae, and the instability of doping fronts in organic semiconductors.

[Justification for the study screening newborn hearing screening in terms of regionalization of perinatal care in Ukraine].

Conducting research screening newborn hearing screening in terms of regional perinatal centers in Ukraine and further rehabilitation of children with hearing impairment is a key step in their integration into society. Universal newborn hearing screening should be mandatory, especially in perinatal centers, because it has significant medical, social and economic effects. It is also necessary to reorganize the existing regional offices surdologichesky and create on their bases and methodological Regional Medical Center hearing and speech problems, which will provide high-quality diagnosis, epidemiological data form, will hold the register of children diagnosed with hearing defects, organize them continuously active surveillance, hearing aids and effective rehabilitation, to ensure the quality of screening. Creating a distributed database for these patients, by far. Will achieve success in the integration of children with special needs in society.

[STATE OF DEVELOPMENT OF HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THE EUROPE AND WORLD].

In this review, we summarize information about the current trends in hematopoietic stem cells transplantation (HSCT) in Europe and world. HSCT has represented one of the most innovative and highly expensive method of treatment for a set of malignant and non-malignant disorders. Differences in the number of HSCT and transplant rates (number of HSCT per 10 million inhabitants), indications and types of transplantations between countries have been reported. They were attributed mainly to differences in the economic situation of the countries and differences in prevalence of certain types of diseases. The gross national income per capita, health care expenditures per capita, number of transplant teams per 1 million inhabitants and team experience are the main impact factors influencing on transplant activity. These data provide a basis for health care planning, preparation of normative acts and future research in Ukraine for rapid expansion HSCT

[Morphological changes of testicular tissues in rats of different age groups, depending on the time of being in the abdominal cavity].

Pathological changes in the testes of animals of different age groups with the experimentally simulated cryptorchidism were evaluated. Animals were divided into 3 groups according to the time of fixation of testes into the abdominal cavity for a term of 2, 3 and 4 weeks. The changes were recorded at the time of bringing down the testes into the scrotum and at 14th and 28th day after bringing down. An assessment of pathological changes and the dynamics of the reparative capacity of testicular tissue in animals of different age groups at different stages of the study was performed. Experimental cryptorchidism leads to marked degenerative changes in the testes, up to the destruction of the elements of the testicular tissue in both groups. Comparative analysis of reparative capabilities revealed that potential of recovery of testicular tissue in young group of animals is much higher than that of mature animals.

[The strategy of a parasite is to preserve and continue its species; some trends for achieving the goal].

The authors show that the strategy of parasites, which is to preserve and continue its species is accomplished mainly by providing of a trophic substrate. Opisthorichiasis is used as an example to show that the nutriceutic biomass of cholangiocytes may be increased due to gene mutations, induced proliferation of liver stem cells, their differentiation to committed ones and cholangiocellular differon elements; moreover, the proliferative processes of mesenchymal components become active in other organs of a host. During their ontogenesis in the intermediate and final hosts, the parasites work out the mechanisms for prolonging their life span to complete a full development cycle (Margaritifera margaritifera glochidia); however, predominantly the parasite-host symbiosis is attended by the latter's lameness. Predation is one of the types of symbiotic relations.

Ultrafast spin avalanches in crystals of nanomagnets in terms of magnetic detonation.

Recent experiments [W. Decelle et al., Phys. Rev. Lett. 102, 027203 (2009)] have discovered ultrafast propagation of spin avalanches in crystals of nanomagnets, which is 3 orders of magnitude faster than the traditionally studied magnetic deflagration. The new regime has been hypothetically identified as magnetic detonation. Here we demonstrate unequivocally the possibility of magnetic detonation in the crystals, as a front consisting of a leading shock and a zone of Zeeman energy release. We study the key features of the process and find that the magnetic detonation speed only slightly exceeds the sound speed in agreement with the experimental observations. For combustion science, our results provide a unique physical example of extremely weak detonation.

[Complicated forms of superinvasion opisthorchiasis: pathogenetic aspects].

Superinvasion opisthorchiasis is characterized by host growth retardation and weight reduction, which are due to the cleptoeffect of Opisthorchis felineus; metabolic disturbances, proliferative processes, accelerated collagen biosynthesis and biodegradation in the organs reflect parasite-host interactions as components of the system. The productive reactions of visceral pathology are initiated by the parasite's metabolites located in the liver, lung, heart, and testes.

Speedup of doping fronts in organic semiconductors through plasma instability.

The dynamics of doping transformation fronts in organic semiconductor plasma is studied for application in light-emitting electrochemical cells. We show that new fundamental effects of the plasma dynamics can significantly improve the device performance. We obtain an electrodynamic instability, which distorts the doping fronts and increases the transformation rate considerably. We explain the physical mechanism of the instability, develop theory, provide experimental evidence, perform numerical simulations, and demonstrate how the instability strength may be amplified technologically. The electrodynamic plasma instability obtained also shows interesting similarity to the hydrodynamic Darrieus-Landau instability in combustion, laser ablation, and astrophysics.