Spin Texture in a Cold Exciton Gas

We report on the observation of a spin texture in a cold exciton gas in a GaAs/AlGaAs coupled quantum well structure. The spin texture is observed around the exciton rings. The observed phenomena include: a ring of linear polarization, a vortex of linear polarization with polarization perpendicular to the radial direction, an anisotropy in the exciton flux, a skew of the exciton fluxes in orthogonal circular polarizations and a corresponding four-leaf pattern of circular polarization, a periodic spin texture, and extended exciton coherence in the region of the polarization vortex. The data indicate a transport regime where the spin polarization is locked to the direction of particle propagation and scattering is suppressed.Comment: version 2 contains updated supplementary materia

On selection of foxes for enhanced aggressiveness and its correlated implications

The results of a 35-year selection of foxes for aggressive response to humans are reported. Averaged estimates of the phenotypic manifestation of aggressiveness in all selection generations are presented. The dynamics of these estimates shows that the phenotypic response to the selection was obvious only in the first 12 generations. Subsequent selection did not alter the mean aggressiveness score. Analysis of variance was performed for the intergroup variability (among descendants of different mothers) and intragroup variability (among the offspring within a family). The intragroup variability was constantly low. Most likely, the trait is stabilized by maternal prenatal and early neonatal factors. The general tendency in the dynamics of intergroup variability is that it does not decrease over time during selection, no matter how long the population has been under it. It follows from the statistical indices of the phenotypic similarity between parents and offspring that additive interactions are insufficient for the explanation of the persisting variability. The contribution of epistatic interactions is not ruled out, though. Emphasis is laid on the correlated consequences of the selection for aggressiveness and their coordination with the consequences of the selection in the opposite direction, for elimination of aggressive response to humans, or for tameness. The parallelism of correlated changes in the selection in contrasting directions is illustrated by the examples of some physiological and morphological traits. The phenomenon is discussed in the light of classical notions of the resource of cryptic genetic variation and the role of selection in its phenotypic manifestation. Its interpretation also invokes molecular data pointing that some genetic pathways may regulate parameters of both aggression and tameness and that the selection processes in both directions may have some genetic targets in common

РЕЗУЛЬТАТЫ ЛЕЧЕНИЯ БОЛЬНЫХ МЕСТНОРАСПРОСТРАНЕННЫМ И МЕТАСТАТИЧЕСКИМ НЕПЛОСКОКЛЕТОЧНЫМ НЕМЕЛКОКЛЕТОЧНЫМ РАКОМ ЛЕГКОГО ПРЕПАРАТОМ ПЕМЕТРЕКСЕД (СОБСТВЕННЫЙ ОПЫТ)

Lung cancer is one of the most common malignant tumors. As over 70 % of patients at diagnosis have locally advanced or generalized process, the majority of patients receive drug treatment only. We evaluated effectiveness and toxicity of pemetrexed (Alimta) in 24 patients with locally advanced and metastatic non-squamous cell non-small-cell lung carcinoma with the known EGFR mutation status. Pemetrexed 500 mg/m2 was administered as monotherapy (8 patients) or in combination with platinum-based drugs (15 patients). Three (12.5 %) patients showed complete regression, 7 (29.2 %) – partial regression, 10 (41.7 %) – stabilization, 4 (16.6 %) – progression. The median survival was 14.8 months. Non-hematological complications were registered, usually concerning the digestive system. Hematological complications included first-degree leukopenia – 27 (21.3 %), second- and third-degree thrombocytopenia – 1 case of each (0.8%). The complications did not require administration of drugs or were corrected medicamentally. We observed a high effectiveness of pemetrexed in patients with non-squamous NSCLC, as well as a low rate of complications and controlled toxicity

Checkpoint inhibitors in non-small cell lung carcinoma therapy for progression to the brain (clinical observation)

The development of a new area of antitumor drug therapy, immunotherapy using immune checkpoint inhibitors targeting PD-1/PD-L1, has significantly changed approaches to the treatment of advanced non-small cell lung cancer (NSCLC). Many clinical trials have demonstrated the clinical benefit as well as the long-term effect of these drugs. Currently, the problem of treatment of patients after disease progression against the background of the use of checkpoint inhibitors is relevant. Equally relevant is the issue of choosing the correct and most effective treatment tactics for NSCLC patients with oligoprogression, as well as with abscopal effect. This paper describes a clinical case of a patient with lung adenocarcinoma without driver mutations with PD-L1-positive status, who was treated with nivolumab after second-line chemotherapy for disease progression, and after oligoprogression of the disease into the brain was given stereotactic radiotherapy of metastatic lesion and continued therapy with nivolumab. Partial regression of metastases was achieved with a prolonged effect on the background of continued treatment with nivolumab for 24 months. Tolerability of therapy was satisfactory: no adverse events were observed. The patient retained the result for 1.5 years

Опыт применения трансартериальной химиоэмболизации печеночной артерии в комплексном лечении больных метастатическим раком молочной железы

Local therapy can complement traditional systemic drug therapy for metastatic breast cancer. The objective of the study was to assess toxicity, immediate results of the treatment and to determine the overall survival rate in patients with breast cancer with metastases to the liver, who underwent transarterial chemoembolization (TACE) of the hepatic artery in combination with traditional chemotherapy with taxanes. Sixty patients were divided into 2 groups: 34 patients received combined treatment (systemic chemotherapy with the following TACE (1–2 procedures) with HepaSphere microspheres, lipiodol, doxorubicin 30 mg/m² and 5‑fluorouracil 600 mg/m²), while 26 patients received chemotherapy only. The groups were comparable in terms of their main clinical parameters: age, initial stage, biological subtype, and previous treatment (p>0.05). Median follow‑up period was 17 months. The immediate response to the therapy according to the RECIST criteria in the chemotherapy+TACE group was the following: partial response — 7 (20.6 %), stabilization — 23 (67.6 %), disease progression — 4 (11.8 %). Adverse effects of TACE were manageable. Kaplan‑Meier 3‑year‑survival rate was 63.2 % in the chemotherapy+TACE group versus 43.8 % in the control group (p=0.039). Thus, TACE method can be included to the treatment protocol for the patients with metastatic breast cancer with partial response to chemotherapy or stabilization of the disease progression after chemotherapy for consolidation of the result.Локальные методы лечения могут дополнять традиционную системную лекарственную терапию метастатического рака молочной железы. Целью исследования была оценка токсичности, непосредственных результатов лечения и определение общей выживаемости у больных раком молочной железы с метастазами в печень, которым выполнялась трансартериальная химиоэмболизация печеночной артерии (ТАХЭ) в сочетании с традиционной химиотерапией таксанами. Шестьдесят пациенток были разделены на 2 группы: 34 пациентки получили комбинированное лечение в виде системной полихимиотерапии с последующим выполнением 1–2 процедур ТАХЭ с использованием микросфер HepaSphere, липиодола, доксорубицина 30 мг/м² и 5-фторурацила 600 мг/м², тогда как 26 пациенток получали только химиотерапию. Группы были сопоставимы по основным клиническим характеристикам: возраст, начальная стадия, биологический подтип и предшествующее лечение (р> 0,05). Медиана наблюдения составила 17 месяцев. Непосредственный ответ на терапию по критериям RECIST в группе химиотерапия + ТАХЭ был следующим: частичный ответ — 7 (20,6 %), стабилизация — 23 (67,6%), прогрессирование — 4 (11,8 %). Побочные эффекты ТАХЭ были контролируемыми. 3-летняя общая выживаемость по Каплану — Мейеру в группе химиотерапия + ТАХЭ составила 63,2 %, в группе контроля — 43,8 % (р = 0,039). Таким образом, метод ТАХЭ может быть включен в протокол лечения пациентов с метастазами рака молочной железы с частичным ответом или стабилизацией после химиотерапии для консолидации полученного эффекта

ОСОБЕННОСТИ МЕТАБОЛИЧЕСКИХ НАРУШЕНИЙ У БОЛЬНЫХ С ЗАБОЛЕВАНИЯМИ, АССОЦИИРОВАННЫМИ С АТЕРОСКЛЕРОЗОМ, НА ФОНЕ ФУНКЦИОНАЛЬНЫХ РАССТРОЙСТВ СИСТЕМЫ ЖЕЛЧЕОТТОКА

The paper presents the results of evaluation of the pathogenetic relationship between atherosclerosis and functional abnormalities of the bile outflow. The main group included 54 patients with cardiovascular pathology and biliary dyskinesia. The group of comparison consisted of 20 patients with chronic coronary artery disease. The results suggest that the functional bile outflow abnormality is a risk factor of atherosclerosis progression leading to hypercholesterolemia and dyslipidemia, and should be considered in the development of integrated approaches to prevention and treatment of the diseases caused by atherosclerosis.Приведены результаты оценки патогенетических взаимосвязей атеросклероза и функциональных нарушений системы желчеоттока. Основную группу составили 54 пациента с сердечно-сосудистыми заболеваниями и с установленной дискинезией желчевыводящих путей. В сравнительную группу вошли 20 больных с хроническими формами ИБС. Полученные результаты позволяют считать, что функциональные нарушения системы желчеоттока являются фактором риска прогрессирования атеросклероза, способствуя гиперхолестеринемии и дислипидемии, и должны учитываться в разработке комплексных подходов к профилактике и лечению заболеваний, обусловленных атеросклерозом

SYNTHESIS OF NEW PHOSPHORS BASED ON Tm3+, Nd3+ OR Ho3+ DOPED GERMANATES BY “WET” CHEMICAL ROUTES

Various “wet” synthetic chemical techniques are widely used for the production of multifunctional inorganic materials. In contrast to the standard high-temperature solid state route, methods based on the dissolution of starting reagents allow one to obtain phases with given particle morphology and particle size distribution. Besides, with this approach, the defect structure can be efficiently controlled by varying the synthesis conditions and solution preparation. These advantages are important for producing luminescent materials.This work was supported by the Russian Science Foundation, project № 16-13-10111

МОЛЕКУЛЯРНЫЕ ОСНОВЫ СОВРЕМЕННОЙ ТАРГЕТНОЙ ТЕРАПИИ ПЛОСКОКЛЕТОЧНОГО РАКА ЯЗЫКА И СЛИЗИСТОЙ ДНА ПОЛОСТИ РТА МОНОКЛОНАЛЬНЫМИ АНТИТЕЛАМИ

The review presents an analysis of current data on the molecular mechanisms of targeted drugs action based on monoclonal antibodies aimed at main signaling pathways that change their activity in squamous cell carcinoma of the tongue and mucosa of the oral cavity. The main cellular signaling pathways and disturbances in their functioning, involved in the pathogenesis of this group of diseases, as well as the mechanisms of action of monoclonal antibodies on the ERBB 1 and 2 receptors (cetuximab, matuzumab, trastuzumab), VEGF ligands (bevacizumab, aflibercept), IGF- receptors (fizitumumab) and MET-receptor ligands (AV299 and AMG102) described in detail. The literature analysis showed that the therapeutic potential of monoclonal antibodies to ERBB-, VEGF-, IGF and MET receptors is far from exhausted, and the effectiveness of such therapy can be improved by the combined action of several antibodies.В обзоре представлен анализ современных данных о молекулярных механизмах действия таргетных препаратов на основе моноклональных антител, нацеленных на основные сигнальные пути, изменяющие свою активность при плоскоклеточном раке языка и слизистой дна полости рта. Подробно описаны основные клеточные сигнальные пути и нарушения в их функционировании, вовлеченные в патогенез данной группы заболеваний, а также механизмы действия моноклональных антител на рецепторы ERBB 1 и 2 (цетуксимаб, матузумаб, трастузумаб), VEGF-лиганды (бевацизумаб, афлиберцепт), IGF-рецепторы (фижитумумаб) и лиганды MET-рецепторов (AV299 и AMG102). Анализ литературы показал, что терапевтический потенциал моноклональных антител к ERBB-, VEGF-, IGF- и MET-рецепторам еще далеко не исчерпан, а эффективность подобной терапии может быть повышена при комбинированном воздействии нескольких антител

Молекулярные механизмы резистентности к терапии моноклональными антителами у больных плоскоклеточным раком языка и слизистой дна полости рта

The review analyzes current data on the molecular mechanisms of resistance to monoclonal antibodies in patients withsquamous cell carcinoma of the tongue and mucosa of the oral cavity. The mechanisms of resistance to monoclonal anti-ERBBand anti-PD1 antibodies and ways to overcome it are described in detail. The analysis made it possible to identify a number of factorsthat should be taken into account when assigning therapy with monoclonal antibodies: activation of alternative receptor tyrosinekinases, increased expression of receptor ligand genes, mutations in effectors and the receptor tyrosine kinases themselves, disruptionof the formation of functional receptor dimers, changes in proteins and coding for them genes responsible for the regulation ofcascades of apoptosis, mitosis, epithelial-mesenchymal transition, secretion of anti-inflammatory cytokines and immunosuppressivemetabolites.В обзоре проведен анализ современных данных о молекулярных механизмах резистентности к терапии моноклональными антителами у больных плоскоклеточным раком языка и слизистой дна полости рта. Подробно описаны механизмы резистентности к моноклональным анти-ERBB-антителам и анти-PD1‑антителам и пути ее преодоления. Проведенный анализ позволил выделить ряд факторов, которые необходимо учитывать при назначении терапии моноклональными антителами: активацию альтернативных рецептрорных тирозин киназ; повышение экспрессии генов лигандов рецепторов; мутации в эффекторах и самих рецептрорных тирозин-киназах; нарушение образования функциональных димеров рецепторов; изменения в белках и кодирующих их генах, ответственных за регуляцию каскадов апоптоза, митоза, эпителиально-мезенхимального перехода; секрецию противовоспалительных цитокинов и иммуносупрессорных метаболитов

Resolution on the results of Advisory Board “Searching the effective methods of testing and treating patients with NSCLC caused by <i>NTRK</i> gene fusions“

The Advisory Board was held on December 24, 2021. The molecular genetic research lead specialists and national lead oncologists discussed issues of diagnosis of NTRK gene translocations in patients with non-small cell lung cancer (NSCLC), as well as current opportunities for the treatment of patients with NSCLC caused by NTRK gene fusions. The experts reaffirmed the necessity to identify timely patients with NSCLC caused by NTRK gene fusions, as the correct diagnosis of the disease, including the use of modern diagnostic methods of NTRK gene fusion (NGS is the most sensitive and specific method) determines the success of patient treatment. In this regard, it is critical that physicians know the advantages and disadvantages of each molecular diagnostic method used to have the opportunity to choose the best approach in each clinical case. In order to have a clear, well-functioning strategy for managing patients with suspected NSCLC caused by NTRK gene fusion, it is necessary to use molecular genetic tests, as well as include TRK inhibitors (in particular, the drug larotrectinib; at the time publication of the Resolution, the drug larotrectinib is not registered in the territory of the Russian Federation) in the clinical guidelines for the treatment of lung cancer. Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor. The clinical studies on larotrectinib have demonstrated high response rates and durable responses in adults and children with tumours associated with NTRK gene fusions, including primary CNS tumours and brain metastases. The objective response rate observed with larotrectinib was 79%, with 16% achieving a complete response and 64% achieving a partial response. At the same time, the median progression-free survival on larotrectinib was 28.3 months, and the median overall survival was 44.4 months