Кабозантиниб при гепатоцеллюлярном раке: от предклинических экспериментов к наблюдательным исследованиям

Based on the results of registration studies, the drug cabozantinib, the mechanism of action of which is determined by the inhibition of tyrosine kinases on a relatively wide range of cellular receptors, is registered in the treatment of hepatocellular cancer, kidney cancer and thyroid cancer. This literature review collects data on the mechanism of action, the results of preclinical experiments and phases I–III studies. Emphasis is placed on the tolerability and efficacy of the drug in the population of hepatocellular cancer patients.По результатам регистрационных исследований препарат кабозантиниб, механизм действия которого определяется ингибированием тирозинкиназ относительно широкого спектра клеточных рецепторов, зарегистрирован в лечении гепатоцеллюлярного рака, рака почки и рака щитовидной железы. В данном обзоре литературы собраны данные по механизму действия, результаты предклинических экспериментов и исследований I–III фаз. Акцент сделан на особенностях переносимости и эффективности препарата в популяции пациентов с гепатоцеллюлярным раком

СПОРНЫЕ ВОПРОСЫ АДЪЮВАНТНОЙ ХИМИОТЕРАПИИ РАКА ПРЯМОЙ КИШКИ ВТОРОЙ СТАДИИ

At stage II and III colon cancer (cT3/PT 4 or cN +), in most cases, the standard approach in the treatment strategy is a combination of surgery and preoperative chemoradiotherapy. This approach allows to reduce significantly the frequency of relapses and, according some studies, it leads to improvement in overall survival. However 10 years after surgery from 30% patients with stage IIc to 70% patients with stage IIIc die from disease progression. This progression of the disease in the majority cases manifests with distant metastasis, which dictates the need of improving of systemic therapy. Adjuvant chemotherapy is the main method of preventing distant metastasis at the early stages of the disease. However, for today the data on the effectiveness of post-operative treatment of rectal cancer after preoperative chemoradiotherapy remains controversial. This literature review is devoted to the analysis of the results of studies evaluating the effectiveness of adjuvant chemotherapy in patients with rectal cancer after preoperative treatment for stage II disease.При II и III стадии рака прямой кишки (cT3/сТ 4 или cN+) в большинстве случаях стандартным подходом в лечебной тактике является сочетание хирургического и предоперационного  химиолучевого лечения. Такой подход позволяет значимо снизить частоту рецидивов болезни, а в некоторых исследованиях  приводит к улучшению общей выживаемости.  Однако в течение последующих 10 лет от 30% при  IIa до 70% больных  при IIIc стадии погибают от прогрессирования  болезни.  При этом прогрессирование  заболевания  у большинства реализуется  через отдаленное метастазирование,  что диктует необходимость совершенствования системной терапии. Основным методом профилактики отдаленного метастазирования  при ранних стадиях болезни является адъювантная химиотерапия. Однако к настоящему времени данные об эффективности  послеоперационного  лечения при раке прямой кишки после предоперационной  химиолучевой терапии остаются противоречивыми. Настоящий обзор литературы посвящен анализу результатов исследований, посвященных оценке эффективности адъювантной химиотерапии у больных раком прямой кишки после проведенного предоперационного  лечения при II стадии болезни

Contribution of the magnetic resonance to the third harmonic generation from a fishnet metamaterial

We investigate experimentally and theoretically the third harmonic generated by a double-layer fishnet metamaterial. To unambiguously disclose most notably the influence of the magnetic resonance, the generated third harmonic was measured as a function of the angle of incidence. It is shown experimentally and numerically that when the magnetic resonance is excited by pump beam, the angular dependence of the third harmonic signal has a local maximum at an incidence angle of {\theta} \simeq 20{\deg}. This maximum is shown to be a fingerprint of the antisymmetric distribution of currents in the gold layers. An analytical model based on the nonlinear dynamics of the electrons inside the gold shows excellent agreement with experimental and numerical results. This clearly indicates the difference in the third harmonic angular pattern at electric and magnetic resonances of the metamaterial.Comment: 7 pages, 5 figure

Effect of vibrostimulation of foot and supporting afferentation on functional state of shin muscles in rats during hindlimb unloading

© 2014, Pleiades Publishing, Inc. The goal of this work was to study the influence of daily 3-hr vibrostimulation of the supporting zones of the foot and 3-hr of usual locomotion on the functional state of the soleus, gastrocnemius, and tibial anterior muscles in rats after 7 and 14 days of hindlimb unloading. After 7 days of unloading the soleus weight decreased, while the weight of gastrocnemius and tibial anterior remained unchanged. After 14 days of hindlimb unloading a weight reduction was observed in all studied muscles. Vibrostimulation of the foot and supporting afferentation prevented the loss of weight in gastrocnemius and tibial anterior during the first week of unloading and reduced the negative effect of hindlimb unloading in 14 days. Our results demonstrate that the amplitude of the M-response after 7 days of hindlimb unloading was decreased predominantly in soleus as compared to gastrocnemius and tibial anterior. By the 14 day we observed restoration of the amplitude of the M-response in gastrocnemius and tibial anterior, and the increased amplitude of the M-response in soleus. Different techniques for foot stimulation in rats during hindlimb unloading demonstrated the positive effect in regard to M-response restoration — the amplitude of the M-response was increased in all studied muscles. Thus, our results demonstrate that foot vibrostimulation or supporting afferentation can completely prevent atrophy caused by hindlimb unloading in gastrocnemius and tibial anterior and decrease atrophy in soleus in rats

Role of microsatellite instability in colon cancer

Coloncancer is among leading causes of cancer morbidity and mortality both inRussiaand worldwide. Development of molecular biology lead to decoding of carcinogenesis and tumor progression mechanisms. These processes require accumulation of genetic and epigenetic alterations in a tumor cell.Coloncancer carcinogenesis is characterized by mutations cumulation in genes controlling growth and differentiation of epithelial cells, which leads to their genetic instability. Microsatellite instability is a type of genetic instability characterized by deterioration of mismatch DNA repair. This leads to faster accumulation of mutations in DNA. Loss of mismatch repair mechanism can easily be diagnosed by length of DNA microsatellites. These alterations are termed microsatellite instability. They can be found both in hereditary and sporadic colon cancers. This review covers the questions of microsatellite instability, its prognostic and predictive value in colon cancer

Enhancing second harmonic generation by Q-boosting lossless cavities beyond the time bandwidth limit

Nanostructures proved to be versatile platforms to control the electromagnetic field at subwavelength scale. Indeed, high-quality-factors nanocavities have been used to boost and control nonlinear frequency generation by increasing the light-matter interaction. However, nonlinear processes are triggered by high-intensities, which are provided by ultrashort laser pulses with large bandwidth, that cannot be fully exploited in such devices. Time-varying optical systems allow one to overcome the time-bandwidth limit by modulating the cavity external coupling. Here we present a general treatment, based on coupled mode theory, to describe second harmonic generation in a doubly resonant cavity for which the quality-factor at the fundamental frequency is modulated in time. We identify the initial quality factor maximizing second harmonic efficiency when performing Q-boosting and we predict a theoretical conversion efficiency close to unity. Our results have direct impact on the design of next generation time-dependent metasurfaces to boost nonlinear frequency conversion of ultrashort laser pulses

The Influence of Hindlimb Unloading on the Bone Tissue’s Structure

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The results of numerous studies indicate interactions between antiortostatic support and bone’s tissue. It is known that mechanical, genetic, endocrine, and age-related factors can influence the bones at the same time. Nevertheless, the physiological and pathological mechanisms of interconnection between unloading hindlimb and bones are largely unclear. The purpose of this study is to evaluate the correlation between unloading hindlimb and changes in bone’s tissue. After unloading of the hindlimb during 14 days, femoral bones were collected in order to evaluate the weight, density, and geometrical bone parameters. Additionally, a test with a three-point bending and computed tomography scanning was carried out. Using computed tomography data, fabric tensor was built. From the assumption that the bone tissue is orthotropic (exists a maximum of three mutually orthogonal axes with different material properties), we performed this analysis. Orthotropic properties of the bone tissue were analyzed in assumption that the principal direction of the fabric tensor is coaxial with the axes of orthotropy of the material. It was found that the axes of orthotropy of the bone tissue in the cross section are mostly directed in tangent direction, and after hindlimb unloading, axes of orthotropy rotate 90° (became directed in radial direction). Anisotropy ratio in the cross section changes significantly. Meanwhile, Young’s modulus and ultimate strength decrease. It shows that unloading of the hindlimb aggravates quality of the bone tissue

Неоадъювантная терапия при местно-распространенном раке прямой кишки

By the beginning of the 2000s, oncologists have developed a standard algorithm for the management of patients with locally advanced rectal cancer. It includes preoperative chemoradiotherapy followed by surgery 6–8 weeks after chemoradiotherapy completion. However, there was no clear evidence indicating the efficacy of adjuvant chemotherapy in this clinical situation. In recent decades, the concept of neoadjuvant treatment for locally advanced colon cancer changed due to an opportunity to perform hypofractionated radiotherapy and conduct chemotherapy in the preoperative stage. This literature review aims to summarize the results of studies analyzing neoadjuvant therapy for locally advanced colon cancer, as well as to compare the efficacy and tolerability of various therapeutic options currently available for this group of patients.К началу 2000‑х годов сформировался определенный стандарт ведения пациентов с местно-распространенным раком прямой кишки – проведение предоперационной химиолучевой терапии с последующим, через 6–8 нед. с момента окончания лучевой терапии, хирургическим лечением. При этом четких данных, указывающих на эффективность адъювантной химиотерапии в данной клинической ситуации, получено не было. Однако за последние десятилетия концепция неоадъювантного лечения больных местно-распространенным раком толстой кишки поменялась за счет как более широкого применения гипофракционирования в лучевой терапии, так и переноса химиотерапевтического лечения с послеоперационного на предоперационный этап. Целью данного обзора литературы является изучение результатов исследований, посвященных неоадъювантному лечению при местно-распространенном раке толстой кишки, и сравнение эффективности и переносимости различных опций, которые имеются в настоящее время у онколога в лечении данной группы пациентов

Неоадъювантная химиотерапия при раке ободочной кишки

Promising results of neoadjuvant therapy have encouraged changes in treatment standards for many types of cancer, including triple negative and HER-positive breast cancer, gastric cancer, rectal cancer, etc. Preoperative chemotherapy can decrease the tumor burden, which might reduce the volume of surgery; it also improves the disease prognosis by reducing the number of viable tumor cells and micrometastases in regional lymph nodes; it increases the proportion of patients receiving systemic treatment, which often leads to an improved overall survival of patients; it enables the evaluation of tumor sensitivity to therapy, which also allows the investigation of tumor sensitivity to new pharmacological agents. However, colon cancer seems to stay away from these trends. This literature review focuses on studies analyzing neoadjuvant therapy for resectable colon cancer and analyzes the role of preoperative therapy in this disorder.Обнадеживающие результаты неоадъювантной терапии определили изменение стандартов лечения большого числа нозологий в онкологии (тройной негативный и HER-положительный подтипы рака молочной железы, рак желудка, прямой кишки и т. д.). Проведение предоперационного лечения приводит к снижению стадии болезни, что должно уменьшать объем хирургического вмешательства; улучшает прогноз течения заболевания, уменьшая число жизнеспособных опухолевых клеток и микрометастазов в регионарных лимфатических узлах; увеличивает долю больных, которые получают системное лечение, что зачастую приводит и к улучшению общей выживаемости пациентов; позволяет оценивать чувствительность опухоли к проводимому лечению, что также открывает возможности изучения чувствительности опухоли к новым фармакологическим агентам. При этом рак ободочной кишки находится в стороне от общих тенденций. Целью данного обзора литературы являются изучение результатов исследований, посвященных неоадъювантному лечению при резектабельных стадиях рака ободочной кишки, и попытка найти место предоперационной терапии при данной патологии