Clinical Experience of Luminescent Diagnostics of Precancerous Diseases and Cervical Cancer

The article summarizes the experience of using luminescent diagnostics with the use of ytterbium porphyrin complexes in gynecology and oncology. A pharmaceutical composition based on the Yb complex of 2,4-dimethoxyhematoporphyrin IX was used as the luminescent markers within the infrared range. The determination of luminescence characteristics (luminescence intensity) was carried out using a laserfiber fluorimeter in the range of 900-1100 nm. A new method for diagnosis of cervical disease has been proposed. The method of luminescent diagnostics allows to conduct a survey of a large number of patients in a short time. The method of luminescent diagnostics using the ytterbium complexes of porphyrins is not invasive. The method can be used as a screening. Differences between normal and pathologically altered cervical tissue have been identified and differences between pathological changes in the cervix HSIL (CIN II, CIN III) and cervical cancer are reliable. Keywords: Cervical cancer, squamous cell carcinoma, diagnosis of cervical cancer, squamous intraepithelial lesions of high grade – HSIL, luminescent diagnostics, luminescing in the near infrared (NIR) spectral region, porphyrins, ytterbium complexes of porphyrins

Diagnosis of Cervical Cancer Using Raman Spectroscopy

The aim of the study was to develop a method of detecting cervical cancer using Raman spectroscopy in the examination of biopsy and surgical material. Significant differences in the spectral characteristics between the tissues of the intact cervix and tissues with squamous cell carcinoma of the cervix have been revealed. Intensity of fluorescence in cervical cancer was higher than in intact cervical tissue.     Keywords: cervical cancer, squamous cell carcinoma, diagnosis of cervical cancer, fluorescence in cervical cancer, Raman spectroscopy for the diagnosis of cervical cance

СВЕРХБЫСТРАЯ ПРОСВЕЧИВАЮЩАЯ ЭЛЕКТРОННАЯ МИКРОСКОПИЯ

Ultrafast laser spectral and electron diffraction methods complement each other and open up new possibilities in chemistry and physics to light up atomic and molecular motions involved in the primary processes governing structural transitions. Since the 1980s, scientific laboratories in the world have begun to develop a new field of research aimed at this goal. “Atomic-molecular movies” will allow visualizing coherent dynamics of nuclei in molecules and fast processes in chemical reactions in real time. Modern femtosecond and picosecond laser sources have made it possible to significantly change the traditional approaches using continuous electron beams, to create ultrabright pulsed photoelectron sources, to catch ultrafast processes in the matter initiated by ultrashort laser pulses and to achieve high spatio-temporal resolution in research. There are several research laboratories all over the world experimenting or planning to experiment with ultrafast electron diffraction and possessing electron microscopes adapted to operate with ultrashort electron beams. It should be emphasized that creating a new-generation electron microscope is of crucial importance, because successful realization of this project demonstrates the potential of leading national research centers and their ability to work at the forefront of modern science.Методы сверхбыстрой электронной дифракции, лазерной спектроскопии и квантовой химии, дополняя друг друга, открывают новые возможности изучения внутримолекулярной динамики веществ, участвующих в процессах химических реакций. Переходное состояние химических реакций определяет направление этих процессов. Начиная от первых работ 1980-х годов, выполненных в России и показавших принципиальную возможность исследования когерентной динамики ядер молекулярных систем, многие научные лаборатории в мире начали интенсивную разработку новой области исследований, направленную на экспериментальное исследование переходного состояния методом сверхбыстрой дифракции электронов. Последовательное развитие этого направления привело к созданию так называемого “атомно-молекулярного кино”, позволяющего визуализировать когерентную динамику ядер в молекулах и сверхбыстрые процессы в химических реакциях в режиме реального времени. В настоящее время ряд научно-исследовательских лабораторий в мире разрабатывают методы сверхбыстрой дифракции электронов и рентгеновского излучения, которые открыли возможность исследования переходного состояния химических реакций. Создание электронных микроскопов с высоким пространственно-временным разрешением является новым направлением в электронной микроскопии, близко примыкающим к этому новому направлению науки. Успешная реализация этого направления исследований демонстрирует потенциал ведущих национальных научно-исследовательских центров и их способность работать на переднем крае современной науки

МОРФОМЕТРИЧЕСКОЕ ИССЛЕДОВАНИЕ ПЕЧЕНИ КРЫС ВИСТАР С МОДЕЛЬЮ АЛИМЕНТАРНОГО ОЖИРЕНИЯ

Experimental alimentary obesity leads to significant structural changes in the liver of rats. Structural changes in the parenchymal cells are accompanied by functional strain in the capillary-connective tissue structures, and by disorders in the blood circulation and lymph drainage in the liver.Экспериментальное алиментарное ожирение приводит к значительным структурным изменениям в печени крыс. Структурные изменения в паренхиматозных клетках сопровождаются функциональным напряжением капилляросоединительнотканных структур, нарушением кровообращения и лимфотока в печени

Common variable immunodeficiency disorder: a clinical case

Primary immunodeficiency is a rare congenital pathology associated with failure of immune system, manifested by disturbances of its functions. These defects lead to increased susceptibility of patients to various infectious agents, as well as the development of autoimmune, malignant and other diseases. Primary immunodeficiency is classified as a rare disease, which was previously associated with a poor prognosis with a high risk of mortality in childhood. To date, the emergence of highly effective treatment methods has changed the course and prognosis of these diseases. Clinicians of various specialties increasingly meet with this pathology in everyday practice, including adult age cohorts. In this regard, early diagnosis of primary immunodeficiency in adults becomes relevant, being associated with choosing optimal therapy, prevention of severe internal organ damage, determination of management strategy for the patient, as well as the need to identify inherited disorders and provide information to the patient’s family. Delayed verification of the diagnosis may cause disability of the patient and development of irreversible, often fatal complications. This article presents our own clinical case with a newly diagnosed clinical condition: Common variable immunodeficiency disorder (CVID), the most common form of primary immunodeficiency in adults. The symptoms of common variable immunodeficiency disorder appear in these patients in adulthood, but a high-quality collected history of the disease will allow you to trace symptoms in the patients even since early childhood. There is a common gap for several years between the onset of the disease and clinical diagnosis, since erroneous diagnosis is often made due to non-specific clinical symptoms that resemble other, more frequent diseases. The prognosis of patients with CVID depends on several factors: frequency of infections, structural disorders in the lungs, the occurrence of autoimmune diseases and the success of infection prevention. Thus, a variety of clinical forms of primary immunodeficiency, lack of awareness of doctors about this pathology, complexity of immunological examination in the general medical network lead to the fact that CVID is not diagnosed for long terms, and patients do not receive the necessary pathogenetic therapy. There is a need for drawing attention of doctors of various disciplines to the fact that the recurrent inflammatory processes of various localization, which are difficult to respond to adequate traditional therapy, may be caused by changes in the immune system, including congenital, genetically determined immunodeficiency

Influence of VEGF deprivation upon vascular formation by endothelium in the presence of macrophages

Development of angiogenesis depends on the functional state of endothelial cells, as well as on the balanced secretion of cytokines, growth factors and chemokines by endothelial cells and cells of microenvironment. Macrophages represent an essential component of the microenvironment and take part in the formation of blood vessels both due to the production of cytokines and due to contact interactions with endothelial cells. VEGF is among the most important cytokines that control angiogenesis at all its stages. Currently, the role of VEGF in the intercellular interactions of endothelial cells and macrophages is not well described. The aim of our study was to investigate the effect of VEGF deprivation using monoclonal antibodies on angiogenesis under conditions of co-cultivation of endothelium and macrophages. Materials and methods: monoclonal antibodies to VEGF-A were used for VEGF deprivation in monoculture of endothelial cells and in co-culture of endothelial cells with macrophages. The IL-1β, IL-6 and TNFα cytokines were used as inducers. When VEGF-A was removed from the medium, endothelial cells show plasticity and form longer vessels, they modify the expression of VEGF receptors. Macrophages regulate endothelial cell activity through the secretion of cytokines, including VEGF, and through contact interactions with endothelial cells. THP-1 cells increase the sensitivity of endothelial cells to VEGF by stimulating the VEGFR1 and VEGFR3 expression, this effect is VEGF-A-independent. The IL-1β, IL-6, TNFa cytokines independently stimulate non-branching angiogenesis, increasing the length of the vessels. At the same time, IL-ip increases the VEGFR1 expression on the surface of endothelial cells. In contrast, IL-6 and TNFα decrease it, thereby regulating the sensitivity of endothelial cells to VEGF. The effects of these cytokines are not dependent on VEGF-A. The IL-1β, IL-6, TNFα cytokines promote acquisition of anti-angiogenic properties by THP-1 cells that is independent on VEGF-A, as well as on expression of its receptors by endothelial cells. Thus, VEGF is an important, but not the sole factor controlling angiogenesis. Under conditions of VEGF-A deficiency, either endothelial cells or microenvironment cells are able to compensate for its functional load due to the production of other growth factors

DNA repair: the culprit for tumor-initiating cell survival?

The existence of “tumor-initiating cells” (TICs) has been a topic of heated debate for the last few years within the field of cancer biology. Their continuous characterization in a variety of solid tumors has led to an abundance of evidence supporting their existence. TICs are believed to be responsible for resistance against conventional treatment regimes of chemotherapy and radiation, ultimately leading to metastasis and patient demise. This review summarizes DNA repair mechanism(s) and their role in the maintenance and regulation of stem cells. There is evidence supporting the hypothesis that TICs, similar to embryonic stem (ES) cells and hematopoietic stem cells (HSCs), display an increase in their ability to survive genotoxic stress and injury. Mechanistically, the ability of ES cells, HSCs and TICs to survive under stressful conditions can be attributed to an increase in the efficiency at which these cells undergo DNA repair. Furthermore, the data presented in this review summarize the results found by our lab and others demonstrating that TICs have an increase in their genomic stability, which can allow for TIC survival under conditions such as anticancer treatments, while the bulk population of tumor cells dies. We believe that these data will greatly impact the development and design of future therapies being engineered to target and eradicate this highly aggressive cancer cell population