Место иммуноонкологии в лечении немелкоклеточного рака легкого

Non–small cell lung cancer (NSCLC) is the leading cause of cancer related mortality worldwide. Many patients present with metastatic disease and traditional CT treatment fails to provide long- term benefit for most patients. Patients with driver mutations demonstrate substantially better response rate and progressionfree survival when the appropriate targeted agents are used, but only approximately 25%-30% of patients with NSCLC have actionable mutations. Novel treatment options are clearly needed for patients with lung cancer. Immuno-oncology recently has been identified as effective second line therapy of NCSLC. Almost all of this progress has been due to the development of PD‑1 and PD-L1 inhibitors. In this review, we explore the data currently available for these agents.Немелкоклеточный рак легкого (НМРЛ) является ведущей причиной смертности от онкологических заболеваний во всем мире. При применении стандартной химиотерапии не удалось достигнуть хороших результатов долгосрочной выживаемости у пациентов с метастатическим НМРЛ. При наличии драйверных мутаций назначение таргетной терапии позволяет добиться хорошего ответа и значительного увеличения показателя выживаемости без прогрессирования. Однако только около у 25%-30% пациентов с НМРЛ выявляются эти мутации. Таким образом, для лечения рака легкого актуальна разработка новых подходов терапии. Недавно было показано, что иммуноонкология является эффективным подходом во второй линии терапии НМРЛ. Этот прогресс был достигнут благодаря разработке препаратов ингибиторов рецептора PD‑1 и лиганда PD-L1. В этом обзоре мы рассмотрим данные исследований, доступные для этих препаратов в настоящее время

ИММУНООПОСРЕДОВАННЫЕ НЕЖЕЛАТЕЛЬНЫЕ ЯВЛЕНИЯ, СВЯЗАННЫЕ С ЛЕЧЕНИЕМ ПРЕПАРАТАМИ, БЛОКИРУЮЩИМИ КОНТРОЛЬНЫЕ ТОЧКИ Т-ЛИМФОЦИТОВ

In recent years, immunotherapy is the main emphasis approach for malignant tumors treatment due to the development and registration of a new class of drugs –immune checkpoint inhibitors. Results of the randomized clinical trials, which showed a benefit in overall survival in comparison with standard therapy, was the basis for registration of this class of medicines [1–3]. Their toxicity profile is more favorable. However, the adverse reactions, which accrues during immunotherapy, are essentially new and different from standard chemotherapy. The standard management algorithm compensates the variety of immunemediated adverse reactions [4]. Early detection and timely treatment is necessary for the successful management of these adverse reactions. В последние годы основной акцент в лекарственном лечении злокачественных опухолей делается на иммунотерапию.Это обусловлено разработкой и регистрацией нового класса препаратов – блокаторов контрольных точек иммунного пути. Основанием для регистрации этого класса препаратов послужили результаты рандомизированных клинических исследований, показавших преимущество этих препаратов по сравнению со стандартной терапией в общей выживаемости [1–3]. Более благоприятным оказался их токсический профиль. Однако те осложнения, с которыми пришлось столкнуться клиницистам, имели принципиально новый, отличный от обусловленных стандартными цитостатиками характер. Многообразие побочных иммуноопосредованных реакций компенсируется стандартным алгоритмом их коррекции [4]. Раннее выявление и своевременное лечение необходимо для успешного купирования этих осложнений

The role of molecular methods in diagnosis of opportunistic diseases in HIV-infected patients

Objective: to assess the diagnostic significance ot opportunistic diseases pathogens detection in biological samples from HIV- infected patients. Methods: in 2007-2013,4133 adult hospital patients were examined (76% had AIDS; CD4 blood count < 200 cells/mcL - 75%). 6847 biological samples (blood samples, BAL, CSF, etc.) were examined for M. tuberculosis, Cytomegalovirus, C. albicans, C. glabrata, C. cruzei, C. neoformins, T. gondii, H. Simplex l-ll, HerpesVI, Epstein-Barr virus (EBV) and JC-virus DNAs, and HIV RNA presence and concentration (PCR-test in Federal Budget Institution of Science 'Central Research Institute of Epldemiol-ogy* was used). Results: The role of the main opportunistic diseases pathogens DNA presence and concentrations in biological fluids and tissues in diagnosis was established; the central role of molecular methods in prompt diagnosis of opportunistic diseases in HIV-infected people was proven.С целью определения диагностического значения выявления ДНК возбудителей вторичных заболеваний в биологических материалах у больных ВИЧ-инфекцией в 2007-2013 гг. обследовано 4133 стационарных взрослых пациентов (в стадии 4Б (СПИД) - 4В (СПИД) - 76%, количеством С04-лимфоцитов в крови <200 кл/мкл - 75%). Исследовано 6847 биоматериалов (образцов крови, БАЛЖ, СМЖ и др.) на наличие и количественное определение ДНК М. Tuberculosis, Cytomegal-ovirus, С. albicans, С. glabrata, С. cruzei, С. neoformins, Т. gondii, Н. Simplexl-ll, HerpesVI, ВЭБ, JC-вируса, РНК ВИЧ молекулярными методами (ПЦР-тест-системы ФБУН «Центральный НИИ эпидемиологии» Роспотребнадзора). Установлено диагностическое значение качественного и количественного содержания ДНК возбудителей основных оппортунистических заболеваний в биологических жидкостях и тканях; обоснована центральная роль молекулярных методов в своевременной постановке этиологического диагноза вторичных патологий у больных ВИЧ-инфекцией

Star-shaped D–π–A oligothiophenes with a tris(2-methoxyphenyl)amine core and alkyldicyanovinyl groups: synthesis and physical and photovoltaic properties

Synthesis of a series of star-shaped oligomers having a novel electron donating tris(2-methoxyphenyl)amine (m-TPA) core, which is linked through a bithiophene or terthiophene π-bridge with electron-deficient alkyldicyanovinyl (alkyl-DCV) groups, is described. A comprehensive study of the oligomers revealed significant dependence of their physical properties, including absorption, molecular frontier energy levels, crystal packing, and melting and glass transition temperatures, upon the chemical structure. A comparison of their photophysical properties to the nearest analog having the common dicyanovinyl (DCV) groups demonstrated a number of benefits to use alkyl-DCV units for the design of donor–acceptor small molecules: higher solubility, increased electrochemical stability, better photovoltaic performance, and possibility to control the relative physical and photovoltaic properties by a simple adjustment of alkyl and π-bridge lengths. Modification of the well-known triphenylamine (TPA) core in the star-shaped oligomers by methoxy groups increases not only solubility, but also crystallinity of the oligomers, whereas their photovoltaic performance stays on a similar level as their analogs with a TPA core. The study demonstrates that these design strategies represent interesting and simple tools for the effective modulation of properties of star-shaped molecules

Effects of oligothiophene π-bridge length on physical and photovoltaic properties of star-shaped molecules for bulk heterojunction solar cells

The preparation of four different star-shaped donor (D)–π–acceptor (A) small molecules (N(Ph-1T-DCN-Me)3, N(Ph-2T-DCN-Me)3, N(Ph-2T-DCN-Hex)3 and N(Ph-3T-DCN-Hex)3) possessing various oligothiophene π-bridge lengths and their use in solution-processed bulk heterojunction small molecule solar cells is reported. Optical and electrochemical data show that increasing oligothiophene π-bridge length leads to a decrease of the optical band gap due to a parallel increase of the highest occupied molecular orbital (HOMO) level. Furthermore, subtle modifications of a molecular π-bridge length strongly affect the thermal behavior, solubility, crystallization, film morphology and charge carrier mobility, which in turn significantly change the device performance. Although the moderately increasing oligothiophene π-bridge length uplifts the HOMO level, it nevertheless induces an increase of the efficiency of the resulting solar cells due to a simultaneous improvement of the short circuit current (Jsc) and fill factor (FF). The study demonstrates that such an approach can represent an interesting tool for the effective modulation of the photovoltaic properties of the organic solar cells (OSCs) at a moderate cost

Effects of electron-withdrawing group and electron-donating core combinations on physical properties and photovoltaic performance in D-pi-A star-shaped small molecules

The first representatives of star-shaped molecules having 3-alkylrhodanine (alkyl-Rh) electron-withdrawing groups, linked through bithiophene pi-spacer with electron-donating either triphenylamine (TPA) or tris(2-methoxyphenyl)amine (m-TPA) core were synthesized. The physical properties and photovoltaic performance of these novel molecules with 3-ethylrhodanine groups were comprehensively studied and compared to their full analogs having dicyanovinyl (DCV) units as the other type of well-known and frequently used acceptor groups. On one hand, the former demonstrate several advantages such as higher solubility and better photovoltaic performance in bulk-heterojunction (BHJ) organics solar cells (OSCs) as compared to the latter. Nevertheless, the former have slightly lower optical/electrochemical bandgaps and higher thermooxidation stability. On the other hand, molecules of both series based on m-TPA core along with higher solubility and higher position of HOMO energy levels have more pronounced tendency to crystalize as compared to the TPA-based molecules. Detailed investigation of the structure-property relationships for these series of molecules revealed that donor and acceptor unit combinations influence both charge generation and charge transport/recombination properties, as demonstrated by the ultrafast photoinduced absorption spectroscopy, space charge limited current measurements and transient photovoltage technique. These results give more insight how to fine-tune and predict physical properties and photovoltaic performance of small molecules having either alkyl-Rh or DCV units in their chemical structures and thus providing a molecular design guideline for the next generation of high-performance photovoltaic materials. (C) 2016 Elsevier B.V. All rights reserved

Effect of oligothiophene π-bridge length in D-π-A star-shaped small molecules on properties and photovoltaic performance in single-component and bulk heterojunction organic solar cells and photodetectors

Donor-acceptor molecules with thiophene fragments as the π-bridge represent a promising class of materials for organic photovoltaics especially in single-component (SC) organic solar cells (OSCs) and other related applications. However, the effect of the oligothiophene π-bridge length on physicochemical properties, photophysics, charge transport, and photovoltaic performance of these materials has not been thoroughly addressed. Here, we report on the synthesis and comprehensive investigation of the series of star-shaped donor-acceptor molecules (0T–4T) with triphenylamine as a donor core linked through an oligothiophene π-bridge of variable length to the terminal hexyl-dicyanovinyl electron-withdrawing groups. We found that variation of the π-bridge length from 0 to 4 thiophene units strongly impacts their properties such as the solubility, highest occupied molecular orbital energy, optical absorption and photophysics, film morphology, phase behavior, and molecular packing as well as the charge carrier mobility. The performance of the SC and bulk heterojunction OSCs and photodetectors is comprehensively studied and compared. The results obtained provide insight into how to fine-tune and predict properties and photovoltaic performance of small molecules for organic solar cells and photodetectors