Notch signaling defects in NK cells in patients with cancer.

Altered expressions of proto-oncogenes have been reported during normal lymphocytes mitogenesis and in T and B lymphocytes in patients with autoimmune diseases. We have recently demonstrated a significantly decreased expression of c-kit and c-Myc in NK cells isolated from patients with cancer, which might be related to the functional deficiency of NK cells in the tumor environment. Here, focusing on the regulatory mechanisms of this new clinical phenomenon, we determined expression of c-Myc, Notch1, Notch2, p-53, Cdk6, Rb and phosphorylated Rb in NK cells isolated from the healthy donors and cancer patients. The results of our study revealed a significant down-regulation of expression of Notch receptors and up-regulation of Cdk6 expression in NK cells in cancer, while no significant changes in the expression of p53 and Rb proteins were seen. These data revealed novel signaling pathways altered in NK cells in the tumor environment and support further investigation of the origin of deregulated expression of proto-oncogenes in NK cells patients with different types of cancer.

Molecular genetic tests in survival factors in patients with NSCLC in the clinical practice of Kazakhstan.

Background: Recent changes in understanding of the nature of cancer allow us, in some cases, to consider it a chronic process that requires constant or periodic treatment. The purpose of this study was to assess the efficacy of the methods for diagnosis and treatment of non-small cell lung cancer (NSCLC) in the Republic of Kazakhstan and present scientifically proven methods for the improvement of existing diagnostic algorithms and treatment programs. Methods: This work was a retrospective study. A retrospective study using descriptive and analytical statistics was used as the main method. Reported data and medical records of the patients with NSCLC who were treated from 2015 to 2017 in 6 oncology clinics in the Republic of Kazakhstan were used as study materials. The methods used for histological studies and influence of the patient's sex on the frequency of various histological forms of NSCLC were studied. Polymerase chain reaction (PCR) studies to determine the epidermal growth factor receptor (EGFR) gene status as well as surgical methods were also studied. Results: A comparative analysis of the compliance of oncologists from various regions of the republic with molecular genetic testing as an essential component of the diagnosis of NSCLC showed that the coverage of patients with immunohistochemical (IHC) and PCR studies in this country is low, 50.9% and 21.2%, respectively. The study included data on 423 patients. At the same time, the majority of studies, 64.2% (IHC) and 100% (PCR), were performed in patients in Almaty and only 35.8% of IHC studies were performed in other 5 regions included in this study. Conclusion: The morphological verification of malignant neoplasms in the lungs was based on histological studies. IHC and PCR coverage of the patients in the country was low. Most of the patients received pharmacotherapy. Surgical interventions were rarely performed. Also, the lack of IHC status data were a risk factor for the patients with NSCLC.

Theoretical considerations and supporting evidence for the primary role of source geometry on field potential amplitude and spatial extent.

Field potential (FP) recording is an accessible means to capture the shifts in the activity of neuron populations. However, the spatial and composite nature of these signals has largely been ignored, at least until it became technically possible to separate activities from co-activated sources in different structures or those that overlap in a volume. The pathway-specificity of mesoscopic sources has provided an anatomical reference that facilitates transcending from theoretical analysis to the exploration of real brain structures. We review computational and experimental findings that indicate how prioritizing the spatial geometry and density of sources, as opposed to the distance to the recording site, better defines the amplitudes and spatial reach of FPs. The role of geometry is enhanced by considering that zones of the active populations that act as sources or sinks of current may arrange differently with respect to each other, and have different geometry and densities. Thus, observations that seem counterintuitive in the scheme of distance-based logic alone can now be explained. For example, geometric factors explain why some structures produce FPs and others do not, why different FP motifs generated in the same structure extend far while others remain local, why factors like the size of an active population or the strong synchronicity of its neurons may fail to affect FPs, or why the rate of FP decay varies in different directions. These considerations are exemplified in large structures like the cortex and hippocampus, in which the role of geometrical elements and regional activation in shaping well-known FP oscillations generally go unnoticed. Discovering the geometry of the sources in play will decrease the risk of population or pathway misassignments based solely on the FP amplitude or temporal pattern.