The influence of sodium dichloroacetate on the oxidative processes in sarcoma 37

Aim: to study the activity of antioxidant enzymes and to evaluate an intensity of prooxidant processes in sarcoma 37 (S37) cells during tumor development and under influence of sodium dichloroacetate (SDA). Methods: Activity of total superoxide dismutase (SOD), SOD isoforms, catalase (Cat), glutathione peroxidase (GP), and glutathione reductase (GR), as well as content of reduced glutathione (GSH) and lipid peroxidation (LP) secondary byproducts were determined in S37 homogenated tissues of untreated mice and animals treated with SDA at daily dose of 86 mg/kg. Results: SDA treatment of S37-bearing mice resulted in the reduced activities of total SOD, SOD isoforms (especially Mn-SOD), Cat, GP and significantly decreased GSH content on the background of LP intensification in tumor tissue. Conclusion: The observed changes of oxidative homeostasis in S37-bearing animals treated with SDA could be considered as an element of antitumor action of SDA

Toxic effect of C₆₀ fullerene-doxorubicin complex towards tumor and normal cells in vitro

Creation of new nanostructures possessing high antitumor activity is an important problem of modern biotechnology. Aim. To evaluate cytotoxicity of created complex of pristine C₆₀ fullerene with the anthracycline antibiotic doxorubicin (Dox), as well as of free C₆₀ fullerene and Dox, towards different cell types – tumor, normal immunocompetent and hepatocytes. Methods. Measurement of size distribution for particles in C₆₀ + Dox mixture was performed by a dynamic light scattering (DLS) technique. Toxic effect of C₆₀+ Dox complex in vitro towards tumor and normal cells was studied using the MTT assay. Results. DLS experiment demonstrated that the main fraction of the particles in C₆₀+ Dox mixture had a diameter in the range of about 132 nm. The toxic effect of C₆₀ + Dox complex towards normal (lymphocytes, macrophages, hepatocytes) and tumor (Ehrlich ascites carcinoma, leukemia L1210, Lewis lung carcinoma) cells was decreased by ~10–16 % and ~7–9 %, accordingly, compared with the same effect of free Dox. Conclusions. The created C₆₀ + Dox composite may be considered as a new pharmacological agent that kills effectively tumor cells in vitro and simultaneously prevents a toxic effect of the free form of Dox on normal cells.Створення нових наноструктур з високою протипухлинною активністю є важливою проблемою сучасної біотехнології. Мета. Оцінити цитотоксичність створеного комплексу фулерену C₆₀ з антибіотиком антрациклінового ряду доксорубіцином (Докс) на різні типи клітин (пухлинні, імунокомпетентнi і гепатоцити) та порівняти одержані результати з токсичною дією вільного фулерену C₆₀ і Докс за умов in vitro. Методи. Розподіл за розміром частинок у C₆₀+ Докс суміші вимірювали методом динамічного розсіювання світла (ДРС). Токсичний ефект комплексу C₆₀+ Докс щодо нормальних і пухлинних клітин вивчали in vitro з використанням МТТ-тесту. Результати. Встановлено, що в суміші C₆₀+ Докс в основному реєструються частинки з діаметром 132 нм. Токсична дія комплексу C₆₀+ Докс щодо нормальних (лімфоцити, макрофаги, гепатоцити) і пухлинних (асцитна карцинома Ерліха, лейкоз L1210, карцинома легені Льюїс) клітин виявилася меншою приблизно на 10–16 і 7–9 % відповідно порівняно із впливом вільного Докс. Висновки. Розроблений комплекс C₆₀ + Докс можна розглядати як новий фармакологічний препарат, що за умов in vitro здатний ефективно знищувати пухлинні клітини і одночасно запобігати побічним токсичним ефектам, притаманним традиційному протипухлинному препарату Докс щодо нормальних клітин.Создание новых наноструктур с высокой противоопухолевой активностью является важной проблемой современной биотехнологии. Цель. Оценить цитотоксичность созданного комплекса фуллерена C₆₀ с антибиотиком антрациклинового ряда доксорубицином (Докс) на разные типы клеток (опухолевые, иммунокомпетентные, гепатоциты) и сравнить полученные результаты с токсическим действием свободного фуллерена C₆₀и Докс в условиях in vitro. Методы. Распределение по размеру частиц в смеси C₆₀ + Докс измеряли методом динамического рассеивания света (ДРС). Токсический эффект комплекса C₆₀ + Докс на нормальные и опухолевые клетки in vitro изучали с использованием МТТ-теста. Результаты. Установлено, что в смеси C₆₀ + Докс регистрируются в основном частицы с диаметром 132 нм. Токсическое действие комплекса C₆₀+ Докс по отношению к нормальным (лимфоциты, макрофаги, гепатоциты) и опухолевым (асцитная карцинома Эрлиха, лейкоз L1210, карцинома легкого Льюис) клеткам оказалось меньшим на ~ 10–16 и 7–9 % соответственно по сравнению с действием свободного Докс. Выводы. Разработанный комплекс C₆₀ + Докс можно рассматривать как новый фармакологический препарат, способный в условиях in vitro эффективно уничтожать опухолевые клетки и одновременно предотвращать побочные токсические эффекты, присущие традиционному противоопухолевому препарату Докс относительно нормальных клеток

Cytotoxic activity of immune cells following administration of xenogeneic cancer vaccine in mice with melanoma B-16

Aim: To study the effects of xenogeneic cancer vaccine (XCV) developed on the basis of nervous tissue antigen from rat embryo of late gestation period and protein-containing metabolite of Bacillus subtilis with molecular weight of 70 kDa, on specific and unspecific antitumor reactions of cellular and humoral chains of immune system, and to analyze possible mechanisms of its antimetastatic action. Materials and Methods: XCV was administered triply with 3-day intervals after surgical removal of experimental melanoma В-16 in C57Bl/6 mice. Cytotoxic activity (CTA) of splenocytes against target cells К-562 as well as CTA of splenocytes, peritoneal macrophages (PM) and blood serum against melanoma В-16 target cells were determined using МТТ test. The content of circulating immune complexes (CIC) in blood serum was evaluated by precipitation reaction. Results: Immunologic effects of XCV vaccination in experimental animals with surgically removed melanoma B-16 in comparison with similarly treated unvaccinated mice were as follows: prevention of medium molecular weight CIC accumulation in blood serum during all observation period, significant increase (р < 0.05) of CTA of effectors of unspecific antitumor immunity (natural killer cells — NK — by 25.5 ± 1.7 vs 12.5 ± 5.4%, and PM — by 37.3 ± 0.6 vs 32.0 ± 0.9%, respectively) at 37th day after the surgery, and also preservation of functional activity of specific cytotoxic lymphocytes at the level of intact control. Conclusion: The results of the study allow propose that antimetastatic effect of XCV vaccination could be based on increased CTA of NK and PM, and preservation of CTL functional activity at late terms after surgical removal of B-16 primary tumors. Key Words: xenogeneic cancer vaccine, melanoma В-16, natural killer cells, macrophages, cytotoxic lymphocytes, cytotoxic activity, antimetastatic activity

Use of xenogeneic vaccine modified with embryonal nervous tissue antigens in the treatment of B16‑melanoma-bearing mice

The aim of the work was experimental study of anticancer efficacy of xenogeneic cancer vaccine (XCV) developed on the basis of rat embryonic nervous tissue and protein-containing metabolite of Bacillus subtilis В-7015 (70 kDa), in В-16 melanoma-bearing С57Bl/6 mice. Methods: Immunological methods and methods of experimental oncology were used. Effects of XCV on primary and secondary organs of immune system of experimental animals, its anticancer and antimetastatic efficacy were evaluated. Results: It has been shown that XCV did not induced toxic effects on organism, and did not caused inflammatory reactions. The relation between the degree of XCV anticancer efficacy with the regimen of its use and the presence of primary tumor has been analyzed. It has been demonstrated that the developed XCV possesses significant antimetastatic activity if it is used after surgical removal of the primary tumor: in this case lung metastasis inhibition index reached 97.4%. Conclusion: High immunogenecity of new XCV creates perspectives for detailed study of its mechanisms of action. Key Words: oncofetal antigens, xenogeneic cancer vaccine, В-16 melanoma, immunotoxicity, effectors of anticancer defence

Search for heavy resonances decaying into a Z or W boson and a Higgs boson in final states with leptons and b-jets in 139 fb−1 of pp collisions at s√ = 13 TeV with the ATLAS detector

This article presents a search for new resonances decaying into a Z or W boson and a 125 GeV Higgs boson h, and it targets the νν¯¯¯bb¯¯, ℓ+ℓ−bb¯¯, or ℓ±νbb¯¯ final states, where ℓ = e or μ, in proton-proton collisions at s√ = 13 TeV. The data used correspond to a total integrated luminosity of 139 fb−1 collected by the ATLAS detector during Run 2 of the LHC at CERN. The search is conducted by examining the reconstructed invariant or transverse mass distributions of Zh or Wh candidates for evidence of a localised excess in the mass range from 220 GeV to 5 TeV. No significant excess is observed and 95% confidence-level upper limits between 1.3 pb and 0.3 fb are placed on the production cross section times branching fraction of neutral and charged spin-1 resonances and CP-odd scalar bosons. These limits are converted into constraints on the parameter space of the Heavy Vector Triplet model and the two-Higgs-doublet model

The ATLAS trigger system for LHC Run 3 and trigger performance in 2022

The ATLAS trigger system is a crucial component of the ATLAS experiment at the LHC. It is responsible for selecting events in line with the ATLAS physics programme. This paper presents an overview of the changes to the trigger and data acquisition system during the second long shutdown of the LHC, and shows the performance of the trigger system and its components in the proton-proton collisions during the 2022 commissioning period as well as its expected performance in proton-proton and heavy-ion collisions for the remainder of the third LHC data-taking period (2022–2025)

Search for boosted diphoton resonances in the 10 to 70 GeV mass range using 138 fb−1 of 13 TeV pp collisions with the ATLAS detector

A search for diphoton resonances in the mass range between 10 and 70 GeV with the ATLAS experiment at the Large Hadron Collider (LHC) is presented. The analysis is based on pp collision data corresponding to an integrated luminosity of 138 fb−1 at a centre-of-mass energy of 13 TeV recorded from 2015 to 2018. Previous searches for diphoton resonances at the LHC have explored masses down to 65 GeV, finding no evidence of new particles. This search exploits the particular kinematics of events with pairs of closely spaced photons reconstructed in the detector, allowing examination of invariant masses down to 10 GeV. The presented strategy covers a region previously unexplored at hadron colliders because of the experimental challenges of recording low-energy photons and estimating the backgrounds. No significant excess is observed and the reported limits provide the strongest bound on promptly decaying axion-like particles coupling to gluons and photons for masses between 10 and 70 GeV

Evidence for the charge asymmetry in pp → tt¯ production at s√ = 13 TeV with the ATLAS detector

Inclusive and differential measurements of the top–antitop (tt¯) charge asymmetry Att¯C and the leptonic asymmetry Aℓℓ¯C are presented in proton–proton collisions at s√ = 13 TeV recorded by the ATLAS experiment at the CERN Large Hadron Collider. The measurement uses the complete Run 2 dataset, corresponding to an integrated luminosity of 139 fb−1, combines data in the single-lepton and dilepton channels, and employs reconstruction techniques adapted to both the resolved and boosted topologies. A Bayesian unfolding procedure is performed to correct for detector resolution and acceptance effects. The combined inclusive tt¯ charge asymmetry is measured to be Att¯C = 0.0068 ± 0.0015, which differs from zero by 4.7 standard deviations. Differential measurements are performed as a function of the invariant mass, transverse momentum and longitudinal boost of the tt¯ system. Both the inclusive and differential measurements are found to be compatible with the Standard Model predictions, at next-to-next-to-leading order in quantum chromodynamics perturbation theory with next-to-leading-order electroweak corrections. The measurements are interpreted in the framework of the Standard Model effective field theory, placing competitive bounds on several Wilson coefficients

Search for the Zγ decay mode of new high-mass resonances in pp collisions at √s = 13 TeV with the ATLAS detector

This letter presents a search for narrow, high-mass resonances in the Zγ final state with the Z boson decaying into a pair of electrons or muons. The √s = 13 TeV pp collision data were recorded by the ATLAS detector at the CERN Large Hadron Collider and have an integrated luminosity of 140 fb−1. The data are found to be in agreement with the Standard Model background expectation. Upper limits are set on the resonance production cross section times the decay branching ratio into Zγ. For spin-0 resonances produced via gluon–gluon fusion, the observed limits at 95% confidence level vary between 65.5 fb and 0.6 fb, while for spin-2 resonances produced via gluon–gluon fusion (or quark–antiquark initial states) limits vary between 77.4 (76.1) fb and 0.6 (0.5) fb, for the mass range from 220 GeV to 3400 GeV

Search for single production of vector-like T quarks decaying into Ht or Zt in pp collisions at s√ = 13 TeV with the ATLAS detector

This paper describes a search for the single production of an up-type vector-like quark (T) decaying as T → Ht or T → Zt. The search utilises a dataset of pp collisions at s√ = 13 TeV collected with the ATLAS detector during the 2015–2018 data-taking period of the Large Hadron Collider, corresponding to an integrated luminosity of 139 fb−1. Data are analysed in final states containing a single lepton with multiple jets and b-jets. The presence of boosted heavy resonances in the event is exploited to discriminate the signal from the Standard Model background. No significant excess above the Standard Model expectation is observed, and 95% CL upper limits are set on the production cross section of T quarks in different decay channels. The results are interpreted in several benchmark scenarios to set limits on the mass and universal coupling strength (κ) of the vector-like quark. For singlet T quarks, κ values above 0.53 are excluded for all masses below 2.3 TeV. At a mass of 1.6 TeV, κ values as low as 0.35 are excluded. For T quarks in the doublet scenario, where the production cross section is much lower, κ values above 0.72 are excluded for all masses below 1.7 TeV, and this exclusion is extended to κ above 0.55 for low masses around 1.0 TeV