Aim - a recently discovered enzyme, indoleamine 2,3-dioxygenase (IDO), is expressed in placenta, dendritic cells and also in many kinds of tumors and in tumor-infiltrating macrophages. By catabolizing tryptophan, IDO causes local depletion of this essential amino acid and excess of kinurenin, and suppresses in situ proliferation and functioning of T lymphocytes. Thus, immune resistance of tumors can be overcome by inhibiting IDO activity. C3HA mice immunized with non-syngeneic H-29 tumor were used to study the effect of the IDO inhibitor ethyl pyruvate, under systemic or local (at site of tumor cells localization) administration, on the occurrence and rate of rejection of the second transplants of this tumor. Both systemic and local administration of ethyl pyruvate increases the incidence of and substantially accelerates tumor regression as compared with control. Conclusion: IDO inhibitors impairing immune resistance of tumors may appear useful in leveraging the efficacy of antitumor therapy.

Aim - to study in vivo changes of lipid composition of plasma membranes of sensitive and resistant to cisplatin Guerin carcinoma cells under influence of free and liposomal cisplatin forms. The isolation of plasma membranes from parental (sensitive) and resistant to cisplatin Guerin carcinoma cells was by differential ultracentrifugation in sucrose density gradient. Lipids were detected by method of thin-layer chromatography. It was determined, that more effective action of cisplatin liposomal form on resistant cells is associated with essential abnormalities of conformation of plasma membrane due to change of lipid components and architectonics of rafts. It results in the increase of membrane fluidity. Conclusion: reconstructions in lipid composition of plasma membranes of cisplatin-resistant Guerin carcinoma cells provide more intensive delivery of drug into the cells, increase of its concentration and more effective interaction with cellular structural elements.

Aim - to investigate anticancer and immunologic effects of chicken embryonic proteins (CEP) in mice bearing Ehrlich solid carcinoma. The study was carried out on male Balb/c mice bearing Ehrlich solid carcinoma. The immunizations were performed after the tumor transplantation. The immune status was assessed on days 7, 14, 21 and 28 after the tumor challenge. Cytotoxic activity (CAT) of macrophages (Mph), natural killer cells (NK), cytotoxic T-lymphocytes (CTL) and blood serum, as well as the influence of the blood serum on immune cells activity was checked in MTT-assay; Mph's cytochemical activity was tested in NBT-assay; Ehrlich antigen-specific or CEP-specific antibodies were detected in ELISA-assay; medium size circulating immune complexes (CIC) were detected in reaction of 4,5 % polyethylene glycol precipitation. The immunization resulted in tumor growth suppression and significant 25,64 % prolongation of the survival time. In both control and immunized mice with transplanted tumors antibodies specific to Ehrlich carcinoma antigens and to CEP were detected, but antibody response was more balanced in the treatment group. In the treatment group both cytochemical and CAT of Mph was moderately activated and well preserved until late stages of tumor development; CAT of NK and CTL remained in the range of the intact mice until day 28 after the tumor transplantation. The immunized mice were well protected from accumulation of CIC and suppressive activity of autologous blood serum. Conclusion: collectively, our data indicate that CEP can elicit immunomodulating and immunoprotecting effects sufficient to provide tumor growth inhibition. The further elaboration of a xenogeneic anticancer vaccine based on CEP is warranted.

Aim - the aim of the presented article was investigation of anticancer efficacy of hydroxyethyithiamine diphosphate (HTD) in vivo. The study was carried out on 30 C57BL/6J mice subcutaneously transplanted with Ehrlich carcinoma. Animals were treated with intraperitoneal injections of the solution composed from pyruvic acid and thiamine bromide every other day during 10 days and thereafter, every day during 2 weeks. Treatment efficacy was evaluated by tumor growth inhibition. In experimental animals treated with HTD, significant tumor growth inhibition has been registered: 73 % at day 45<^>th compared to the control group (p << 0,001). Conclusion: treatment with HTD demonstrated high anticancer efficacy in vivo.

Мета: вивчити вплив карвакролу на хімічний канцерогенез, проліферацію пухлинних клітин та на процес агрегації тромбоцитів (АТ), а також виявити можливі взаємозв'язки між цими процесами та антиоксидантними властивостями карвакролу. Матеріали та методи: використано модель хімічного канцерогенезу на щурах лінії Вістар та 3,4-бензо[а]пірену як хімічного індуктора канцерогенезу. Клітини лейоміосаркоми від щурів лінії Вістар було використано для вивчення антипроліферативної активності карвакролу in vitro. Антитромбоцитарні властивості карвакролу вивчено за допомогою методів АТ та проточної цитометрії. Продукцію тромбоксану В2, кінцевого продукту АТ, оцінено за допомогою радіоімунологічного методу. Результати: виявлено антиканцерогенну дію карвакролу: зниження канцерогенної активності 3,4-бензо[а]пірену становило 30 % в системі in vivo. Антипроліферативна активність карвакролу (IC50) становила 90 <$E mu roman M> та 67 <$E mu roman М> при 24 та 48 год інкубації клітин з агентом, відповідно. Карвакрол також мав слабкий антитромбоцитарний ефект, індукуючи зниження синтезу тромбоксану А2 в тромбоцитах та як результат - обмежену експресію тромбоцитарних рецепторів GPIIb/IIIa. Висновки: показано, що карвакрол має антиканцерогенні, антипроліферативні та антитромбоцитарні властивості.

Aim - to investigate the influence of exogenous lactoferrin (LF) on tumor growth, energy and lipid metabolism of Walker-256 carcinosarcoma and to assess genotoxic effects of LF. The study was performed on Walker-256 tumor-bearing rats. Total lipids and phospholipids were determined by thin-layer chromatography. Comet assay was used to investigate the genotoxic effects of LF. Daily i.p. administrations of exogenous LF at concentrations of 1 mg/kg and 10 mg/kg starting from the 4<^>th day after tumor transplantation suppressed growth of Walker-256 carcinosarcoma by almost 44 %. After treatment with recombinant LF in both doses, the phospholipid composition of Walker-256 carcinosarcoma cells was changed (3-fold increase of phosphatidylethanolamine, 3.4-fold increase of phosphatidylcholine, and 1.8-fold increase of sphingomyelin, while the cardiolipin content decreased by 67 %. Exogenous LF was not genotoxic for bone marrow cells (as assessed by the ratio of PCE/NCE, number of micronuclei) and peripheral blood lymphocytes (percentage of DNA in the tail of a comet) in Walker-256 carcinosarcoma-bearing rats. Conclusion: exogenous LF caused the inhibition of Walker-256 carcinosarcoma growth and a decrease in the microviscosity of plasma cell membranes, and exerted no genotoxicity toward bone marrow cells and peripheral blood of experimental animals.

Індекс рубрикатора НБУВ: Р56-52

Рубрики:

Онкологія

Шифр НБУВ: Ж21341/а Пошук видання у каталогах НБУВ 

Представлены данные относительно возможности использования теста на микроядра (МЯ) в эксфолитивных эпителиальных клетках онкологических больных, получающих противоопухолевую терапию, как биомаркера цитогенетического эффекта. Количество МЯ у больных, получавших химиотерапию, крайне противоречиво. Показано, что как в опухолевых, так и в нормальных эпителиальных клетках после радиотерапии число МЯ достоверно увеличивается. Оценка числа МЯ, индуцированных радиотерапией в эксфолитивных эпителиальных клетках, потенциально может выявить радиочувствительность опухоли и эффективность лечения уже после первых сеансов терапии. Этот метод практически неинвазивен и его можно применять для оценки лечения опухолей ротовой полости и шейки матки.

Cellular FLICE (FADD-like IL-1beta-converting enzyme)-inhibitory protein (c-FLIP) is a master anti-apoptotic regulator and resistance factor that suppresses tumor necrosis factor-alpha (TNF-alpha), Fas-L, and TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, as well as apoptosis triggered by chemotherapy agents in malignant cells. c-FLIP is expressed as long (c-FLIP_L), short (c-FLIP_S), and c-FLIPR splice variants in human cells. c-FLIP binds to FADD and/or caspase-8 or -10 and TRAIL receptor 5 (DR5) in a ligand dependent and -independent fashion and forms an apoptosis inhibitory complex (AIC). This interaction in turn prevents death-inducing signaling complex (DISC) formation and subsequent activation of the caspase cascade. c-FLIP_L and c-FLIP_S are also known to have multifunctional roles in various signaling pathways, as well as activating and/or upregulating several cytoprotective and prosurvival signaling proteins including Akt, ERK, and NF-kB. Upregulation of c-FLIP has been found in various tumor types, and its silencing has been shown to restore apoptosis triggered by cytokines and various chemotherapeutic agents. Hence, c-FLIP is an important target for cancer therapy. For example, small interfering RNAs (siRNAs) that specifically knockdown the expression of c-FLIP_L in diverse human cancer cell lines augmented TRAIL-induced DISC recruitment and increased the efficacy of chemotherapeutic agents, thereby enhancing effector caspase stimulation and apoptosis. Moreover, small molecules causing degradation of c-FLIP as well as decreasing mRNA and protein levels of c-FLIPL and c-FLIPS splice variants have been found, and much effort is focused on developing other c-FLIP-targeted cancer therapies. This review focuses on (1) the anti-apoptotic role of c-FLIP splice variants in preventing apoptosis and inducing cytokine and chemotherapy drug resistance, (2) the molecular mechanisms and factors that regulate c-FLIP expression, and (3) modulation of c-FLIP expression and function to eliminate cancer cells or increase the efficacy of anticancer agents. This article is part of a Special Issue entitled "Apoptosis: Four Decades Later".

The results of own investigations and literature data are summarized to determine the place of the main methods of adsorption therapy in complex treatment of the patients with malignant tumors. New possibilities for the usage of new generation of carbon adsorbents and modern adsorptive technologies in cancer treatment are discussed.

Aim - to synthesize and to study for photodynamic activity a composite photosensitizer consisting of chlorin e6 and human serum albumin nanoparticles (HSA NPs). Starting from sorption-purified HSA, the albumin nanoparticles with a different degree of lysine residues cross-linking (10; 20; 40, and 100 %) were obtained by the coacervation method. The HSA NPs were used for synthesis of nanocomposites with chlorin e6 and fluorescein isothiocyanate (FITC)-labled preparations. Malignant lymphocytes of the MT-4 (human T-cell leukemia) line and normal lymphocytes of healthy donors served as cell targets. For photodynamic treatment, a semiconductor laser was exploited as a light source, and cell viability was assessed by MTT or trypan blue dye exclusion tests. For cell imaging and HSA NPs visualization, the fluorescence microscopy and transmission electron microscopy were applied, respectively. C57BI/6 mice were used in animal experiments. The absorption and fluorescence spectra of chlorin e6-HSA NPs composites were characterized, and by the electron microscopy investigation the size of NPs (nanospheres) was estimated: 100 - 120 nm. FITC-labled albumin preparations allowed to establish that HSA NPs have much higher exposition and concentration dependent affinity to malignant cell surface than initial HSA. In experiments with MT-4 cells on PDT activity of chlorin e6-HSA NPs, the nanocomposite effectiveness elevated along with increasing percentage of cross-linked aminoacid residues, and for the nanocomposite with 100 % of albumin cross-linking it exceeded the activity of free chlorin e6. In contrast to malignant cells, the complexation of chlorin e6 with HSA NPs decreased its photodynamic effect on normal human lymphocytes. Intravenous introduction of the chlorin e6-HSA NPs composite to mice showed prolonged circulation of the nanocomposite in blood in comparison with free PS. Conclusion: promising results obtained with chlorin e6-HSA NPs composites warrant conduction of full-fledged PDT studies in vivo using the nanocomposites as photosensitizers.

Методом Western blotting досліджено рівень експресії білка p53 під впливом протипухлинних препаратів у клітинах лінії A549 (карцинома легені людини) та лінії MCF7 (карцинома молочної залози людини), чутливих (WT) та резистентних (DOX/R) до доксорубіцину. Після обробки клітин ліній A549 і MCF7 (WT) протипухлинними препаратами виявлено збільшення рівня експресії білка p53 у порівнянні з контролем, тоді як у клітинах лінії MCF7 (DOX/R) рівень цього білка змінюється незначно. Рівень експресії цього білка у клітинах лінії MCF7 (DOX/R), необроблених протипухлинними препаратами, істотно нижчий, ніж у клітинах лінії MCF7, чутливих до доксорубіцину. Одержані дані свідчать про те, що білок p53 може бути залучений у процес виникнення резистентності пухлинних клітин до доксорубіцину.

Зазначено, що алкілувальні сполуки часто застосовують у хіміотерапії раку. Вони алкілують геномну ДНК по багатьох сайтах. Алкілування гуаніну в позиції O<^>6 цитотоксичне, має найсильніший мутагенний потенціал, а також може спричиняти розвиток вторинних пухлин. Алкільні групи у позиції O<^>6 гуаніну видаляються за допомогою репаративного ферменту O<^>6-метилгуанін-ДНК метилтрансферази (MGMT). Ефективність хіміотерапії з використанням O<^>6-алкілувальних сполук обмежена експресією MGMT у ракових клітинах і шкідливим побічним токсичним впливом у нормальних клітинах. Наразі для покращання хіміотерапії раку розробляють різні підходи до модуляції експресії та активності MGMT. До них належать два головних напрямки, а саме - підвищення хіміочутливості ракових клітин до алкілувальних ліків і захист нормальних клітин від токсичної дії хіміотерапії. Розглянуто існуючі спроби покращити хіміотерапію злоякісних пухлин за допомогою алкілувальних сполук як у світі, так і в Україні.

Індекс рубрикатора НБУВ: Р56-52

Рубрики:

Онкологія

Шифр НБУВ: Ж21341/а Пошук видання у каталогах НБУВ 

Впервые показано, что туберозно-склерозный комплекс 2 (TSC2) специфически взаимодействует с протеинфосфатазой 5 (РР5) в клетках млекопитающих. Данное взаимодействие является характерным для клеток, находящихся в фазе экспоненциального роста, а также в стимулированных сывороткой клетках. Установлено, что РР5 дефосфорилирует TSC2 по сайтам, специфичным для AMP киназы, и соответственно может играть негативную роль в регуляции активности TSC1/2 комплекса.

Aim - the research was aimed to analyze a level of triglycerides in blood serum as a possible new marker of toxicity, particularly in patients with excess body weight, receiving cisplatin. Study involved 20 oncological patients with stage III lung cancer, who received palliative treatment with cisplatin. High-performance liquid chromatography was used for quantitative determination of pure cisplatin in urine and blood samples. Cisplatin concentration of the test samples was determined based on the data obtained from the calibration graph. Quantitative determination of pure cisplatin is quite complicated. The elimination half-time for one of the groups was observed higher almost by half than for other patients. Higher dose of cisplatin showed a significant association with increase in triglyceride levels. We found a close correlation between body mass index and triglyceride changes during chemotherapy (p = 0,001; r = 0,67). The results indicate that a higher body mass index gives higher fluctuations of triglyceride levels in blood serum. Analyses of correlation between level of triglycerides and elimination half-time show that by an increase in the level of triglycerides in the blood serum cisplatin elimination half-time is prolonged (R<^>2 Linear = 0,596). Cisplatin concentration in urine is higher and elimination takes longer time at elevated levels of triglycerides, where close correlation between fraction of excreted substance in urine and concentration parameters was seen (p << 0,01). Also good correlation for body mass index with fraction of excreted substance in urine and concentration parameters was observed (p << 0,05). Conclusion - clearance of cisplatin, which was determined by the chromatographic method, is reduced in individuals with increased adipose tissue mass. Research data suggest that overweight affects cisplatin elimination from the body. The greater body fat mass can contribute to a greater rise of triglyceride level in blood serum. Triglycerides in blood plasma may serve as an additional indicator of higher cisplatin toxicity as a cardiotoxicity marker.

Індекс рубрикатора НБУВ: Р56-52

Рубрики:

Онкологія

Шифр НБУВ: Ж21341/а Пошук видання у каталогах НБУВ