The content of cancer stem cells and CD3+CD8+ T cells in the blood of a patient with small cell lung cancer (SCLC) and chronic obstructive pulmonary disease (COPD) was evaluated. In vitro analysis of tumorospheres allowed us to characterize circulating tumor stem cells in the blood of patients at risk. The fundamental possibility of reprogramming exhausted CD3+CD8+ T cells (rCD3CD8T) of a patient with SCLC and COPD using a mitogen-activated protein kinase inhibitor (iMEK) and human monoclonal antibody nivolumab was demonstrated. Target cell elimination by rCD3CD8T was achieved by treatment with autologous cancer cell and stem cancer cell lysate in vitro. Thus, blockade of the MAPK/ERK signaling pathway and the PD-1/PD-L1 checkpoints may be used to overcome exhaustion and enhance cytotoxicity of CD3+CD8+ T cells in patients with SCLC and COPD.

We propose a model of combination treatment of Lewis lung carcinoma (LLC) in C57BL/6 mice that includes tumor resection and chemotherapy. A single injection of 5×106 LLC cells into the right lateral subcostal region caused the growth of the primary tumor and its metastasis to the lung. For reducing metastasis and mortality after resection, the primary tumor should be removed with subcutaneous fat on day 8 after inoculation. Antitumor and antimetastatic effects and reduced mortality were achieved by intraperitoneal injection of carboplatin (63.3 mg/kg) and paclitaxel (13.3 mg/kg); chemotherapy was administered twice. The combination of the two approaches increased the survival: the antitumor and antimetastatic effects were observed in 60

We studied the effect of reprogrammed CD8+ T cells (rT cells) from the bone marrow of intact mice on tumor cells and neovasculogenesis in mice with orthotopic Lewis lung carcinoma (LLC). Reprogramming of T cells was carried out using a MEK inhibitor and a PD-1 blocker; the targeting of rT cells to tumor cells was achieved by preincubation with LLC cell lysate. It was shown that the antitumor effect of rT cells was based on apoptosis of tumor cells. In addition, cell therapy reduced the number of endothelial cells (CD45—CD309+) and angiogenic cell precursors (CD45—CD117+CD309+), mesenchymal stem cells (CD45—CD31—CD34—CD44+), myeloid (CD45+CD34+CD31—) and non-myeloid (CD45+CD34—CD31—) fibrocytes, and leukocytes (CD45+) in the lungs and increased their number in the blood. Thus, rT cells impaired the recruitment of neovasculogenic cells to the lung. The antitumor effects of rT cells are superior to those of naive CD8+ T cells. The proposed reprogramming method can be useful in developing effective approaches to the therapy of lung cancer, as it allows obtaining cytotoxic rT cells capable of reducing the activity of neovasculogenesis.

The antitumor and antimetastatic activity of dopamine D2 receptor antagonists spiperone was studied in C57BL/6 mice in a model of combined pathology (emphysema and lung cancer). Emphysema was induced by administration of LPS and cigarette smoke extract. Lung cancer was induced by injection of Lewis lung carcinoma cells into the lung. It has been shown that under conditions of combined lung pathology, spiperone prevents inflammatory infiltration and emphysematous expansion of the lungs and reduces the size of the primary tumor node, the number of metastases, and the area of the lungs affected by metastases. Spiperone reduces the number of cancer stem cells (CSCs) in the lungs and blood of mice with combined pathology. CSCs isolated from the lungs and blood of mice with combined pathology treated with spiperone had a significantly lower potential to form a tumorosphere in vitro than CSCs from untreated mice with emphysema and lung carcinoma. Thus, blockade of dopamine D2 receptors is a promising approach for correcting combined lung pathology and can be used in the development of a method for treating lung cancer in patients with emphysema.

We studied the effects of the extract of the terrestrial part of Aconitum baicalense in BALB/c female mice at the early stages after the injection of N-methyl-N-nitrosourea (MNU). The extract reduced inflammatory activity and tumor growth in the mammary gland. The antitumor and anti-inflammatory effects of the extract are based on the inhibition of cancer stem cells, hematopoietic stem cells, and hematopoietic progenitor cells that promote inflammation. The extract of A. baicalense disrupted the recruitment of epithelial progenitor cells and angiogenesis precursors to the mammary gland preventing neovascularization and transformation of epithelial cells into tumor cells.

The effects of platinum nanoparticles on the morphological structures of the solid phase of blood serum and the tone of cerebral microvessels as indicators of the dynamics of homeostasis were studied on outbred albino male rats (n=40) weighing 300-350 g. Platinum nanoparticles were injected to experimental animals in 1 ml of physiological saline. For systemic BP measurements and blood sampling, the femoral artery was isolated and catheterized. The study of solid phase structures of blood serum was conducted by the method of cuneiform dehydration. The results showed that injection of platinum nanoparticles significantly affected the body of experimental animals.

Актуальность. Проблема гипоксии представляет важный аспект в медицине. При этом вопросы глубинного влияния гипоксии на организм остаются во многом не изученными. Цель исследования состояла в оценке патофизиологических изменений организма экспериментальных животных в условиях острой гипобарической гипоксии (ОГГ) с разных позиций: с позиций базового (молекулярного) уровня - по твёрдофазным структурам сыворотки крови, и с позиций центрального управления жизнедеятельностью организма - по показателям мозгового кровотока. Методы. Для опосредованной оценки данных о трансформации структурно-энергетических параметров белковых молекул сыворотки крови (СК) в условиях гипоксии использован метод клиновидной дегидратации биологических жидкостей. Для оценки мозгового кровотока в условиях гипоксии использован вейвлет-анализ колебаний церебрального кровотока. Результаты. Исследование действия ОГГ на крыс методом структурного анализа твёрдой фазы СК и методом регистрации локального мозгового кровотока показало разделение животных по уровню устойчивости к гипоксии на две группы. Первая группа при гипобарии равной высоте 11,5 км быстро входила в агональное состояние, однако при этом сохраняла значительную часть энергетических ресурсов белковых молекул, что устанавливалось по системной организации и локальным структурам твёрдой фазы сыворотки крови, а также подтверждалось достаточно высоким уровнем активности мозгового кровотока. Вторая группа животных, при тех же условиях гипоксии, входила в агональное состояние значительно позднее, при этом отмечалось значительные изменения структуры и почти полное истощение энергетических ресурсов белковых молекул, и выраженное падение показателей мозгового кровотока. Однако у животных второй группы после перевода их в условия нормобарической оксигенации наблюдалось более быстрое восстановление активности микроциркуляции. Заключение. В основе патофизиологических изменений организма экспериментальных животных при ОГГ лежит трансформация структур молекулярного уровня, наблюдаемых как по системной организации, так и локальным структурам твёрдой фазы СК. Экспериментальные животные имеют различный порог устойчивости по отношению к ОГГ. Background. The issue of hypoxia is an important aspect of medicine. However, the profound effect of hypoxia on the body remains largely unexplored. The aim of the study was to evaluate pathophysiological changes in experimental animals under the conditions of acute hypobaric hypoxia (AH) from different aspects: from the aspect of basic (molecular) level - by solid-phase structures of the blood serum (BS), and from the aspect of the central management of the body - by cerebral blood flow. Methods. Cuneiform dehydration of biological fluids was used for an indirect assessment of the transformation of structural and energy parameters of BS protein molecules in the hypoxic conditions. The wavelet analysis of cerebral blood flow oscillations was used to evaluate cerebral blood flow in hypoxia. Results. As a result of the study, the rats were divided into two groups based on their resistance to hypoxia. The first group faster developed the agonal state at a simulated altitude of 11.5 km. At the same time, these rats retained a significant part of the energy resources of protein molecules, which was established by the systemic organization and local structures of the BS solid phase and confirmed by a sufficiently high rate of cerebral blood flow. The second group of animals exposed to the same hypoxic conditions developed the agonal state much later and showed significant changes in the structure and almost complete depletion of energy resources of protein molecules associated with a marked drop of cerebral blood flow. However, the animals of the second group showed a faster recovery of microcirculation after return to the normobaric conditions. Conclusion. Pathophysiological changes in the rat body exposed to AH are based on transformation of molecular structures evident from both the systemic organization and local structures of the BS solid phase. The experimental animals have different thresholds of resistance to AH.

Reversible cerebral ischemia of medium severity was reproduced in male Wistar rats by bilateral occlusion of the common carotid arteries. Solid-phase structures (anisomorphons) were obtained by marginal dehydration of the serum. Small focal isotropic defects in the serum anisomorphon texture were found in 100% cases during occlusion of the carotid arteries. Similar signs were detected in all patients with chronic cerebral ischemia, which proved specificity of this morphological marker of the disease.

The purpose. To reveal solid-phase structures of blood serum during and after experimental cerebral ischemia. Methods. Integrated estimation pathophysiological changes at brain ischemia received on solid-phase structures of blood serum (BS) at 27 rats-male Vistar in weight of 300‒390 g. Reversible brain ischemia of moderate severity was reproduced imposing surgical clips on both common carotids for 15 minutes then clips removed and provided bloodstream restoration on carotids. Blood took away in Eppendorf´s test tube in volume on 1 ml before imposing clips, directly ahead of their removal and in 30 minutes after bloodstream restoration. By the Method cuneiform dehydration received BS facia (dry a film) which structures analyzed by means of stereomicroscope MZ12 firm Leica. Results of researches fixed on structural parameters BS before imposing clips, after removal clips and in 30 minutes after bloodstream restoration. Results.Before ischemia the integrated picture facias BS rats had the harmonious system organisation: the radial or partially-radial arrangement of the cracks, accurately generated konkrecias that testified to normal physiological condition of experimental animals. During the period occlusions carotids there were markers of a ischemia, activation of a capillary blood-groove, inflammatory reaction and stress. Partially these signs remained at reperfusion. Conclusion. The conducted researches of structures BS on experimental animals have allowed to reveal marker structures BS similar revealed at inspection of people with an ischemia of a brain.