bluuebunny/crossref_metadata_2025 huggingface dataset:
The usage possibilities of entomopathogenic fungi in the control of western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae)
Authors: KIRIŞIK Musa , ERLER Fedai
Published: November 2018

The western flower
thrips, Frankliniella occidentalis
(Pergande) (Thysanoptera: Thripidae), one of the main pests of agricultural
areas, causing occurrence of significant economic losses if no control measure
is taken. In recent years, the use of entomopathogenic fungi (EPF), an
alternative method of control, has come into the prominence. EPF have a
different place among insect pathogens in terms of direct infection of hosts
through the integument. The most common fungal pathogens of F. occidentalis are Verticillium lecanii, Beauveria
bassiana, Entomophtholares spp.
and Metarhizium anisopliae. In
Turkey, only V. lecanii and B. bassiana are commercially licensed
against F. occidentalis. In this
review, the usage possibilities of these two fungi, as well as the use of other
species in controlling the pest will be discussed.
Filling the Frame: Photography of May Day Crowds during the Early Nazi Era
Authors: Conze Linda
Published: November 2018

Filling the Frame: Photography of May Day Crowds during the Early Nazi Era

When one thinks of festive crowds under National Socialism, the state-orchestrated events at Berlin's Tempelhofer Feld, the Bückeberg or at the Reichsparteitagsgelände in Nuremberg are what first come to mind. But apart from the huge festival grounds, festive crowds also came together on sports fields and town squares all over Germany. They were certainly smaller in number, yet the presence of the many was clearly also of great ritual importance in small towns and rural communities. Whenever they came together, a camera was there to document. It is especially in forms of representation that the crowd becomes negotiable. Stories of crowds unfold along images. The article examines the role of photographs of crowd scenes in the process of community-formation during the early Nazi era when the idea of a racially defined Volksgemeinschaft was ubiquitous throughout the German Reich. It focuses primarily on the particular importance of photography as a means of negotiating, adapting and transforming social affiliation. Also addressed is the overall relationship between photography and the masses. Inspired by Elias Canetti's typology of crowds, a comparison of state-controlled and local depictions of May Day festivities reveals a variety and ambivalence of photographic representations of crowds during the early 1930s, which has been overlooked by historic research so far. A surprising visual openness made the crowd images adaptable to traditional ideas of community as well as able to respond to the need to position oneself in the new social framework.
National in Front of the Camera, Soviet Behind It: Central Asia in Press Photography, 1925–1937
Authors: Holzberger Helena
Published: November 2018

National in front of the Camera, Soviet behind it: Central Asia in Press Photography, 1925–1937

While photography in early Soviet Union is a well-researched field, researchers addressed hitherto mostly Soviet Russia. The history of photography in the Central Asian Soviet Republics, though, lacks research. This article focuses on the means of production and distribution of photographs taken in Uzbekistan 1926–1937. With Roland Barthes theory of «connotation», it interprets the visual invention of the Soviet Orient. Photographs by Georgij Zel'ma and Maks Penson of Uzbekistan that were published in Soviet mass media are analyzed, determining style, content and function. Through additional textual analysis, I discuss the network of photographers on the periphery and image agents on the centre. Socialist connotations are derived from appropriations of pre-revolutionary photographs accompanied by false textual framing, innovative compositions of ethnographic images and combinations of local cultural symbols with Soviet modernity. As photographers, primarily from Moscow, travelled to Central Asia, they greatly dominated its visual depiction. Although they emphasized Soviet modernity, they also reproduced older stereotypes about the Orient. Besides offering a history on photography, this article also discusses the establishment of Soviet cultural structures between the centre and the periphery as well as the subordinated agency of local actors at the periphery.
The Dictator's Photo Albums: Photography under the Metaxas Dictatorship
Authors: Soursos Nathalie Patricia
Published: November 2018

The Dictator's Photo Albums: Private and Public Photographs in the Metaxas-Dictatorship

The Greek authoritarian «Fourth of August Regime» (1936–1941) focussed in its propaganda on promoting the dictator Ioannis Metaxas as father, grandfather and «First peasant» and while in foreign policy the close ties to the Balkan Entente was advertised, the transfer of ideas from the European fascist regimes was negated. By examining 57 photo albums preserved today in the Hellenic Parliament Archives the article discusses photo albums as a source for the interpretation of the Metaxas dictatorship and as a source for the history of photography in Greece. It examines the private photo album aesthetics and its use in three official brochures with an exceptional high amount of photographs: Fourth of August 1936–1938, Fourth of August 1938–1939 and Four Years of Government by I. Metaxas, 1936–1940. The article's main argument is, that due to their photo album aesthetic the propaganda brochures were invoking the intimacy of a family album.
Re-Reading the Photographic Archive: The Propagandistic Staging of the Portuguese Estado Novo in the Braga District
Authors: Ferreira Fatima Moura , Leal Patricia
Published: November 2018

Re-reading the Photographic Archive: The Propagandistic Staging of the Portuguese Estado Novo in the Braga District

The article focuses on visual representations of political propaganda in a local context in the early years of the Estado Novo. Braga, the city of the military coup of 28 May 1926, became nationally famous because of its symbolic value, profusely exploited by the government and the local elites. By means of thick description of iconographic material, this study analyses the use of photography in terms of symbolic materialisation, within the processes of circulation and reception of aesthetic and artistic codes fostered and spread by the «politics of spirit».
ERİTROSİT DAĞILIM HACMİ ACİL SERVİSTE BURUN KANAMASININ CİDDİYETİNİ ÖN GÖREBİLİR Mİ?
Authors: KARAMAN Kivanç , ENHOŞ Şerafettin , OSKAY Alten , ARMAĞAN Hamit Hakan
Published: November 2018

Amaç:
Bu çalışmada burun kanaması için risk faktörlerinin sıklıkları ortaya konulmaya
çalışılırken aynı zamanda bu risk faktörlerinin acil serviste burun kanaması yönetimi
üzerine etkisi olup olmadığı sorgulandı.Gereç
ve Yöntem: Erişkin acil servisde 01/01/2017-01/01/2018 tarihleri arasında burun
kanaması (R04.0) tanı kodu girilen hastaların dosyaları tarandı ve hastaların
isim, yaş, cinsiyet, başvuru tarihi, tıbbi özgeçmiş, kullandığı ilaç, vital
bulguları, konsultasyon bilgileri ve laboratuar bulguları kaydedildi. Travma
hastaları ve 18 yaş altı hastalar çalışma dışı bırakıldı. Konsultasyon istenen
hastalar ciddi burun kanaması olarak değerlendirildi.Bulgular:
Çalışmaya 68 erkek, 40 kadın olmak üzere toplam 108 hasta dahil edildi.
%70.4  (n:76) hasta 50 yaş üzeri olduğu
en sık başvurunun sırasıyla %30.6 (n:33) ve %29.6 (n:32) ile kış ve ilkbahar
aylarında olduğu görüldü. %46.3 (n:50) hastada hipertansiyon, %31.5 (n:34)
hastada ilaçlara bağlı kanama saptandı. %19.4 (n:21) hastaya konsultasyon
istendiği görüldü. Konsultasyon istenen ve istenmeyen hastaların birbiri ile
karşılaştırılması sonucunda erkek cinsiyet ve yüksek Eritrosit Dağılım Genişliği
(RDW) açısından anlamlı farklılık saptandı (P değerleri sırasıyla 0.016 ve
0.029).

            Sonuç: Acil servise başvuran burun kanamalı hastalarda
yüksek RDW ve erkek cinsiyet kanamanın ciddiyetini gösteren parametreler olarak
ortaya çıkmaktadır. Acil serviste burun kanamalı hasta yaklaşımında bu
parametreler de göz önünde bulundurulmalıdır.
COMPARATIVE EFFICACY OF TEMOBEL AND TEMODAL DRUGS IN MULTIMODALITY TREATMENT OF HIGH-GRADE (III-IV)
Authors: Sinaiko V. V. , Artemova N. A. , Yurkshtovich T. L. , Bychkovsky P. M. , Frolenkov K. A.
Published: November 2018

An open-label, retrospective comparative clinical trial evaluated the efficacy of Temobel (RUP Belmedpreparaty) and Temodal (Schering-Plough, the Office of the Joint-Stock Company «Schering-Plough Central East AG») in 90 patients with high-grade (III-IV) glial brain tumors within a postoperative chemoradiotherapy course (a total target dose of 50-60 Gy). The compared groups, 45 patients in each, were fully matchable in prognostic factors affecting treatment outcomes. Median survival, 1- and 3-year overall survivals with Temobel in the combination treatment scheme were 20 months, 72.7±6.7% and 23.7±9.5%, whereas with Temodal they were 17 months, 77.8±6.2% and 30.3±7.0% respectively (P=0.935). Meanwhile, progressive-free median survival and progressive-free 1- and 3-year survival with Temobel and Temodal were 12 months, 51.0±7.5%, 21.3±6.4% and 11 months, 49.3±7.6%, 15.5±5,7% respectively (P=0.814). No statistically significant differences were found in the survival of patients in the compared groups.
SUPPRESSION OF GLIOBLASTOMA CELLULAR TRANSPORTERS SENSITIZES TARGET CELLS TO INFECTION WITH ONCOLYTIC VIRUS IN THE PRESENCE OF IONIZING RADIATION
Authors: Ulasov I. V. , Kaverina N. V. , Kadagidze Z. G. , Baryshnikov A. Yu.
Published: November 2018

It is already established that verapamil inhibits Pgp expression in the brain tumor cancer cells such as medulloblastoma. The aim of this study is to investigate the sensitivity of glioblastoma cancer cells to verapamil and its combination with oncolytic adenoviral victor CRAd-S-pK7. In vitro using U87 and U251 human glioblastoma cell lines, we obtained experimental data suggesting a therapeutic effect of verapamil and CRAd-S-pK7. Moreover, we established that verapamil improves anti-glioma effect of oncolytic adenoviral vector in the presence of ionizing radiation, which results into more suppression of U251 cancer cells via inhibition of their proliferation.
PRODUCTION OF PURIFIED HUMAN RECOMBINANT ANTIGEN PRAME AND SPECIFIC MONOCLONAL ANTIBODIES
Authors: Finashutina Yu. P. , Misyurin A. V. , Akhlynina T. V. , Lyzhko N. A. , Krutov A. A. , Aksenova E. V. , Misyurin V. A. , Baryshnikov A. Yu.
Published: November 2018

Tumor antigens recognized by CTLs have been identified several years ago and are major targets for creating anticancer vaccines. PRAME is an antigen which is highly expressed in various malignant tumors including melanomas and hematopoietic malignancies such as acute and chronic leukemias (AML, CML). Technology for producing recombinant antigen PRAME is based on creating a bacterial producer strain containing cDNA of human PRAME gene. We have obtained two producers of recombinant PRAME protein and its N-half, the synthesis of the target protein in the producers occurs in the inclusion bodies. The schemes of isolation and purification of soluble proteins have been developed. The protein purity was approximately 95-96%. The monoclonal antibodies raised against truncated recombinant PRAME were used for PRAME protein analysis by Western blot on the various tumor cells. Specific monoclonal antibodies recognized the native PRAME protein in tumor cell lines as well as in tumor samples from patients. Our findings support the suggestion that this recombinant antigen may be further used as a target for diagnostic and therapeutic approaches. The monoclonal antibodies can be used for immunoassays of tumor samples from patients with hematologic malignancies to reveal clinical features and to monitor tumor progression.
BIOMARKERS OF DRUG NEPHROTOXICITY
Authors: Osipova T. V. , Bukhman V. M.
Published: November 2018

Antineoplastic drugs, especially those on the basis of platinum, used for chemotherapy of cancer can also affect various normal tissues and organs including kidneys. Cisplatin occupies one of the leading places and possesses the greatest nephrotoxisity. For many years nephrotoxicity has been evaluated at the level of serum creatinine and of blood urea nitrogen. However these markers have a number of essential shortcomings and do not provide early detection of AKI. To identify early AKI stages new more informative markers are needed, which could make evidence of emerging initial signs of disorders at the earliest and irrespective of filtrational function of kidneys. Characteristics of modern perspective markers of early disoeders of kidneys are presented in the review. Special attention is paid to the panel of markers of potential nephrotoxicity of drugs - candidates for clinical trials, which are recommended for preclinical study. The review presents data of investigations of the role of biomarkers in early diagnostics of AKI caused by cisplatin and its analogues. Use of the ROC analysis in these studies showed that new markers are more sensitive and specific than serum creatinine and blood urea nitrogen and can be used for diagnostics and monitoring of kidney disorders caused by chemotherapeutic drugs.
STUDY OF THE «ACUTE» TOXICITY OF LIPOSOMAL DRUG FORM OF ANTINEOPLASTIC PHOTOSENSITIZER THIOSENS
Authors: Kulbachevskay N. Yu. , Sanarova E. V. , Konyeva O. I. , Ermakova N. P. , Buchman V. M. , Lantsova A. V. , Polozkova A. P. , Orlova O. L. , Oborotova N. A.
Published: November 2018

The laboratory for development of drug forms, N.N. Blokhin Russian Cancer Research Center developed a lyophilized liposomal dosage form (LLDF) of a new infrared photosensitizer phthalocyanine derivative - Thiosens. Previous studies determined optimal composition of the dosage form, technology of its production and methods of analysis; a number of biological experiments were performed. The next step of preclinical research is studying "acute" toxicity of LLDF, which is presented in this paper. The study of "acute" toxicity of LLDF Thiosens was carried out in the laboratory of Pharmacology and Toxicology. "Acute" toxicity of LLDF Thiosens was studied in the experiments on mice hybrids F1 (CBA » C57Bl / 6J) male and female and weinbrener outbred male rats. In the first series of experiments LLDF Thiosens was administered to male mice in the dose range of 5; 10; 20 and 30 mg/kg. In the second series of experiments, male and female mice were injected with LLDF Thiosens in the dosage range 6; 12 and 24 mg/kg. Male mice were treated by LLDF Thiosens intravenously; no symptoms of toxicity were registered at the doses of 5 and 10 mg/kg; death was observed in all experimental animals after administration at the doses of 20 and 30 mg/kg on the first day in the result of inactivity and piloerection. In the second series of experiments no sex differences were found in single intravenous injection of LLDF Thiosens. The results of the studies of "acute" toxicity in rats demon strated that when LLDF Thiosens was administered in doses 3, 6 and 9 mg/kg animal deaths were reported. A single intravenous LLDF Thiosens administration in rats in the excess of the expected dose for human in 1.5-4.5 times was well tolerated by the animals: animal mortality, clinical signs of toxicity and changes in behavioral responses were absent.
MORPHOLOGICAL CHARACTERISTIC AND CLINICAL VALUE OF DIFFERENT TYPES OF TUMOR VESSELS IN BREAST CANCER
Authors: Nikitenko N. V. , Senchukova M. A. , Tomchuk O. N. , Zaitsev N. V. , Stadnikov A. A. , Mitriakov S. O. , Degtiarev A. M. , Kirtbaia D. V.
Published: November 2018

Цель исследования - изучение морфологии опухолевых сосудов и ее связи с клинико-морфологическими характеристиками и рецепторным статусом новообразования при раке молочной железы (РМЖ). Материалы и методы. Образцы опухолей 66 пациенток с T1-2 стадиями инвазивного РМЖ неспецифического типа окрашивали гематоксилином Майера и эозином, а также иммуногистохимическим методом с использованием антител к CD34. Результаты. Проведенное исследование позволило выделить следующие типы опухолевых сосудов: обычные капилляры, диля-тированные капилляры (ДК) перитуморальной стромы и атипичные дилятированные капилляры (АДК) интратуморальной стромы, характеризующиеся хаотичным расположением клеток эндотелиальной выстилки. Количество ДК в перитуморальной строме коррелировало с выраженностью лимфоидной инфильтрации стромы опухоли (р = 0,0001), количеством АДК (р = 0,0001) и наличием опухолевых эмболов в сосудах (р = 0,02); количество АДК - с отрицательным статусом рецепторов эстрогенов (р = 0,008) и прогестерона (р = 0,043) и наличием опухолевых эмболов в сосудах (р = 0,001). Выводы. Полученные результаты свидетельствуют о неоднородности сосудов по морфологии и клинической значимости при РМЖ.
DEVELOPMENT AND VALIDATION OF CYPHETRYLIN ASSAY IN TABLETS
Authors: Shprakh Z. S. , Ignatieva E. V. , Yartseva I. V. , Dmitricheva N. A. , Smirnova L. I.
Published: November 2018

Background. In N.N. Blokhin Russian Cancer Research Center have been synthesized a number of hypothalamic hormone somatostatin analogues, including pentapeptide cyphetrylin, and drug Cyphetrylin tablets 6 mg has been created. One of the drug standardization step is development of assay technique for acting substance in the final preparation. Objective. Development and validation of cyphetrylin assay in tablets. Materials and methods. The study used cyphetrylin, tablets 6 mg, сyphetrylin powder substance (FSBI “N.N. Blokhin Russian Cancer Research Center”, branch “Naukaprofi”), lactose monohydrate, cellulose microcrystalline, potato starch, povidone, talc, magnesium stearate (European Pharmacopoeia current edition), 95 % ethyl alcohol. Method of assay - spectrophotometry. Results. The technique for assay of сyphetrylin in drug “Cyphetrylin, tablets 6 mg” has been developed. Validation was performed to confirm test validity and accuracy. The technique was estimated by validation characteristics: specificity, linearity, accuracy, precision (repeatability and intermediate precision). Conclusion. The developed technique has the required characteristics: specificity, accuracy, repeatability, intermediate precision, linearity and can be used in the range of 70-130 % of nominal сyphetrylin content in preparation.
QUANTITATIVE ASSESSMENT OF BETA-III TUBULIN EXPRESSION IN LUNG ADENOCARCINOMA AND SQUAMOUS CELL CARCINOMA
Authors: Davydov M. M. , Mamichev I. A. , Dudko E. A. , Bogush E. A. , Kirsanov V. Yu. , Polotsky B. E. , Davydov M. I. , Bogush T. A.
Published: November 2018

Background. Beta-III tubulin (TUBB3) is a tumor-specific isoform of the microtubule protein beta-tubulin. TUBB3 is considered to be a marker of adverse prognosis and tumor resistance to therapy with taxanes and Vinka alkaloids. Association between TUBB3 expression and histological type of the tumor has not been studied properly yet. Objective. The expression level of TUBB3 in non-small cell lung cancer biopsy specimens has been measured on 2 groups of patients with adenocarcinoma and squamous cell carcinoma. Materials and methods. The samples with adenocarcinoma (n = 43) and squamous cell carcinoma (n = 39) were converted to suspension, filtered, fixed with 4 % formaldehyde, stained with monoclonal antibodies for TUBB3 and DyLight 650-conjugated secondary antibodies to mouse IgG and analyzed by flow-cytometry. The method was developed in N.N. Blokhin Russian Cancer Research Center. Results. The average level of TUBB3 expression in the adenocarcinoma group is higher than in the squamous cell carcinoma group (33.1 ± 12.4 % of cells expressing the marker in adenocarcinoma vs. 26.0 ± 13.6 % in squamous cell carcinoma; differences were statistically significant). The average level of TUBB3 expression in adenocarcinoma is 29.7 ± 8.1 % in female and is 34.9 ± 13.9 % in male (differences statistically insignificant). Since the group of patients with adenocarcinoma was presented by both men and women, while the group of patients with squamous cell carcinoma was only men, from the analysis was excluded all female patients. Differences between the groups remained statistically significant. Conclusion. TUBB3 expression in tumor tissue does not depend on the gender, at least among patients with adenocarcinoma of the lung, and at the same time, the level of TUBB3 in adenocarcinoma tissue is higher in comparison with squamous cell carcinoma tissue.
PATHOPHYSIOLOGY OF DENDRITIC CELLS IN CANCER
Authors: Keskinov A. A. , Shurin M. R. , Bukhman V. M. , Shprakh Z. S.
Published: November 2018

Immune system plays a crucial role in tumor growth process. It exerts cancer surveillance function via innate and adaptive immune mechanisms, nonetheless tumor may exploit various immune cells to escape specific immune response. Dendritic cells are the primary antigen presenting cells, which mediate immune response against cancer cells. Dendritic cells are capable of processing and presenting tumor antigens to T cells, which results in tumor-specific T cell- mediated response. However, adoptive therapy with dendritic cells demonstrates poor clinical outcomes. Among a variety of factors, the impact of tumor microenvironment on dendritic cells may be the primary one. Therefore, tumor-derived factors, which lead to dendritic cells malfunction, may be the key target for improving dendritic cell - based therapy. Meanwhile, recovery of dendritic cell functions in cancer patients remains one of primary aims for cancer immunotherapy. This review outlines main types of tumor-induced dendritic cells dysfunctions in cancer.
EXPRESSION LEVEL OF ESTROGEN RECEPTOR ß IN NON-SMALL CELL LUNG CANCER AND LUNG METASTSIS
Authors: Polotsky B. E. , Akhmedov B. B. , Dudko E. A. , Bogush E. A. , Bogush T. A. , Davydov M. M.
Published: November 2018

Background. A search for pathogenetically grounded approaches to the treatment of non-small cell lung cancer is undoubtedly one of the top priorities, because of the results of its treatment cannot be regarded as satisfactory. Discovery of a new type of receptors, estrogen receptors ß, that expressed in non-small cell lung cancer, created the preconditions for the development of a new treatment strategy for non-small cell lung cancer, namely antiestrogen therapy. Objective was to answer to the clinically significant question of how many patients with non-small cell lung cancer and lung metastases are potential candidates for antiestrogen treatment. Materials and methods. A comparative quantitative estimation of the level and frequency of the estrogen receptors ß expression in non-small cell lung cancer tissues and also in lung metastases (74 in total) was carried out by flow cytometry. Results. The estrogen receptors ß expression was detected in the majority of the investigated tumors and lung metastases, in 92 and 86 % of patients, respectively. The average level of estrogen receptors ß expression in non-small cell lung cancer tissue was higher then in metastases (42 % and 34.6 % respectively). The differences was statistically significant (p = 0.03). Primary tumors with a high and low+moderate estrogen receptors ß expression levels were detected in 35 % and 65 % of cases respectively and metastases with such expression levels - in 14 % and 86 % of cases respectively. Conclusion. 1. The estrogen receptors ß expression in the tumor predicts a more favorable course of the disease. One of the reasons for this may be a greater metastatic potential of tumor cells with low estrogen receptors ß expression. 2. The group of potential candidates for carrying out the adjuvant antiestrogen therapy comprises about 70 % of patients with primary lung tumors and with metastatic lesions of lung.
CYPHETRYLIN CYTOTOXIC ANALOGUES (REPORT I)
Authors: Osipov V. N. , Sushinina L. P. , Ustinkina S. V. , Smirnova L. I. , Shprakh Z. S.
Published: November 2018

Background. The drug cyphetrylin, hypothalamic hormone somatostatin analogue, was developed in N.N. Blokhin Russian Cancer Research Center at the Ministry of Health of Russia. The basis of this work is the idea of using cyphetrylin as a specific carrier of cytotoxic groups. Objective. Synthesis of cytotoxic cyphetrylin analogues in order to study the effect of the presence of cytotoxic agents on its antitumor activity. Results. The classical methods of peptide chemistry were used for 5 the new cyphetrylin analogues synthesis. The compounds have been obtained by the addition to the cyphetrylin Na-group of the cysteine or lysine Ns-group chlorophenacyl or hydrolyzed сyphelin (cytotoxic agent). Purification of the peptides was performed by column chromatography on silica gel. The purity of the obtained compounds was confirmed by elemental analysis, TLC, optical rotation angle data and HPLC. Preliminary studies of anti-tumor activity were performed in mice transplanted tumors: adenocarcinoma Ca755 breast and melanoma B16. Conclusions. New peptides - analogues cyphetrylin containing cytotoxic fragment have been synthesized, their structure and purity have been confirmed.
POTENTIAL ANTITUMOR ACTIVITY STUDIES ON SOME COORDINATION COMPOUNDS OF RARE EARTH ELEMENTS WITH ANTIPYRINE
Authors: Golubeva I. S. , Yavorskaya N. P. , Baryshnikova M. A. , Afanasieva D. A. , Rudakova A. A. , Apryshko G. N. , Rukk N. S. , Skraybina A. Yu.
Published: November 2018

The aim of this study was to examine the anticancer activity of rare earth elements complexes with antipirin. Materials and methods. We have studied the cytotixic activity of in vitro and antineoplastic activity in vivo of 28 iodides and perchlorates containing as a ligand antipirine. Results. Here we show, that non of tested compounds exert cytotoxic action on 5 human cancer cell lines of different histogenesis at a concentration of 100 ßM. However, we observe that two complexes of antipirine derivatives with iodides of gadolinium and neodymium possess anti-tumor activity in experiments with transplantable solid tumors. Conclusion. The data obtained indicate the feasibility of further studies of these two complexes on a larger number of mice, with changing doses and routes of administration. We also suggest the investigation of these compounds on ascites tumors.
FUCOIDAN FROM BROWN ALGAE FUCUS EVANESCENS: NEW PERSPECTIVES IN THE TREATMENT OF ATHEROSCLEROSIS
Authors: Krizshanovsky S. P. , Kuznetsova T. A. , Geltser B. I. , Zaporozhets T. S. , Ermakova S. P. , Besednova N. N.
Published: November 2018

Objective. The purpose of the research is the experimental study of the possibility of correction of disorders of lipid metabolism, lipid peroxidation and antioxidant protection (POL-AOP), liver structure on the model of alimentary hyperlipidemia in mice. Materials and methods. Fucoidan, a sulfated polysaccharide with a molecular weight of 160 kDa, derived from brown algae Fucus evanescens. The alimentary hyperlipidemia model was reproduced in mice. The biochemical parameters of lipid metabolism, state of POL-AOP system and the liver structure by MRT were studied. Results. We revealed the ability of fucoidan at per os administration to animals to normalize the key parameters of lipid metabolism, indicators of POL-AOP system, liver anatomic-topographic structure. Conclusion. The ability of fucoidan to correct these parameters allows us to consider it as a basis for the development of new biological medicines for the treatment of atherosclerotic disorders.
Efficacy of combined treatment of experimental tumors with cytostatic agents and GMDP-A
Authors: Nemtsova E. R. , Bezborodova O. A. , Morozova N. B. , Vorontsova M. S. , Venediktova J. B. , Andreeva T. N. , Nesterova E. I. , Andronova T. M. , Yakubovskaya R. I.
Published: November 2018

Objective of the study. To evaluate the pharmacological effects of N-acetylglucosaminyl-N-acetylmuramyl-L-alanyl-D-glutamic acid (GMDP-A) as a modifier of biological reactions, i. e. to study its modifying action in regard to traditional cytostatic chemotherapy. Materials and methods. The used drug agents were GMDP-A, cisplatinum, gemcitabine, cyclophosphamide, 5-fluorouracil. The transplanted murine tumors were Р-388 lymphocytic leukemia and S-37 sarcoma (solid and ascites variants), B-16 melanoma, CC-5 squamous cell carcinoma of the cervix uteri, C-26 adenocarcinoma of the colon, and AKATOL carcinoma of the colon (solid tumor variants). Efficacy indices were inhibition of tumor growth, and increase of life span of animals. Results. In the models of transplanted tumors in conventional mice, the influence of GMDP-A has been studied on therapeutic efficacy of cisplatinum (Р-388, S-37, В16, CC-5), 5-fluorouracyl (C-26, AKATOL), gemcitabine and cyclophosphamide (P-388) by using variations in single and total doses, time of the start of the treatment, as well as the route and site of the injection. It has been shown that GMDP-A has modified the efficacy of some cytostatic agents (cisplatinum, gemcitabine and cyclophosphamide) enhancing their antitumor activity irrespective of the location of the site of injection in regard to the tumor node. Conclusion. The obtained results proved the potency of GMDP-A as a modifier of biological reactions.
The impact of a binary catalyst system «tereftal + ascorbic acid» on the central nervous system
Authors: Ermakova N. P. , Trofimov S. S. , Kulbachevskaya N. Y. , Konyaeva O. I. , Bukhman V. M. , Michailova L. M.
Published: November 2018

Introduction. Neurotoxicity is one of the specific systemic complications of anticancer chemotherapy. Detection in experimental animals complications of psychotropic or neurotropic action of the new drug is one of the most difficult challenges of preclinical toxicology. Preclinical toxicological study of the effect of a binary catalyst system «tereftal + ascorbic acid» on the central nervous system (CNS). Objective. The prediction of toxic effects of binary catalytic system in clinical application in patients. Materials and methods. The study was conducted on 300 male mice hybrids (CBA х C57 Bl/6J) F1. Have terephtal - russian drug. A binary catalyst system was injected intravenously once at close to the maximum tolerated dose - 50 mg/kg tereftal + 110 mg/kg ascorbic acid and in therapeutic dose - 20 mg/kg tereftal + 44 mg/kg ascorbic acid. The obtained data were compared with a control animal treated with saline solution and with the data of animals treated with one tereftal and one ascorbic acid in equivalent doses. To assess neurotoxicity tests used standard neuropharmacological screening. An assessment of emotional status, muscle tone were undertaken. Behavior was evaluated in the tests «open field» and «aggression». We evaluated the response to pain stimulation, the change in rectal body temperature. Higher integrative brain functions were investigated on the model of the conditioned reflex of passive avoidance. Estimated effect on convulsive readiness of the CNS. Results. The catalytic system changed the general condition of the animals. This was manifested, on the one hand, in the suppression of their overall activity (sluggishness, inactivity until weakness, muscle relaxation, the lowering side, the slowing of breathing), the other - to increase their excitability (when in group, some animals adopted a characteristic aggressive stands, in some cases seizures). These animals were observed exophthalmos, the appearance of the position «frog», posture «praying mouse», the desire to hide. The inhibitory effect of the catalytic system was dose-dependent. Observed inhibition of various forms of behavior, emotional status, decrease in body temperature and pain sensitivity, in the test for aggression - reducing the number of fights, in open field test - locomotor activity suppression. Spontaneous seizures in the provocation corazol binary catalytic system was not strengthened. Conclusion. The obtained data allow to predict toxic effects from the CNS during clinical use of binary catalytic system «tereftal + ascorbic acid»: total confusion, lethargy, physical inactivity, decrease in body temperature, increased anxiety and aggression and, in very rare cases, the occurrence of seizures.
Iron metabolism, ferroptosis and cancer
Authors: Vartanian A. A.
Published: November 2018

In 2012 the new, iron-dependent form of cell death - ferroptosis - distinct from apoptosis, autophagy and programmed necrosis at morphological, biochemical, and genetic levels has been described. In this review we will discuss the iron metabolism in physiological and pathological processes in humans, the molecular characteristics of ferroptosis and therapeutic options of cancer patients in the light of new data.
Quinazolinon derivatives for the treatment of neoplastic, parasitic and neurodegenerative diseases
Authors: Khachatryan D. S. , Misyurin V. A. , Baryshnikova M. A. , Golubtsova N. V. , Kolotaev A. V. , Matevosyan K. R.
Published: November 2018

In this review we discuss some biological activities of quinazolinon derivatives. The derivatives of quinazolinon possess their activity by binding to some proteins important for the survival, proliferation and metastasis of tumor cells. There are grounds to initiate clinical trials of these substances to create new treatment protocols for a wide range of cancer diseases, several parasitic diseases, and certain neurodegenerative diseases.
Detection of human papillomavirus type 16 oncogen E7 in surgical materials from Russian prostate cancer patients
Authors: Volgareva G. M. , Ermilova V. D. , Khachaturyan A. V. , Tatarskiy V. V. , Pavlova L. S.
Published: November 2018

Introduction. High indices of prostate cancer (PC) incidence and mortality as well as high speed of growth of these figures testify to urgency of research into PC origin as well as means of its prophylaxis. The problem of possible PC association with oncogenic human papillomaviruses (HPV) is still being disputable. Objective: to test whether surgical materials from PC patients in Russia harbour E7 oncogene of HPV type 16 (HPV16), the main HPV type responsible for cervical cancer. Materials and methods. Prostate tissues excised in the course of radical prostatectomy from 17 PC patients were tested by polymerase chain reaction. For better DNA preservation cryopreserved tumor specimens not treated with either formalin or paraffin were used. The PC typical multifocal type of growth was taken into account by microdissecting of cryostate cuts to accumulate homogeneous cells (cancerous, dysplastic or normal). Results. HPV16 E7 was registered in prostate tissues of 7 patients out of 17 examined including all those 5 cases for which DNA had been isolated from homogeneous sites of cancer cells. Conclusion. The result obtained enables one to admit that HPV16 may be harbored in prostates of Russian PC patients not infrequently.
Immunodeficient mice balb/c nude and modeling of various types of tumor growth for preclinical studies
Authors: Treshalina H. M.
Published: November 2018

Obtaining preclinical models of malignant growth in a variety of xenografts (heterotransplantation), usually the subcutaneous, is the most important area for the use of nude mice in oncology. In a review paper describes the characteristics of Balb/c nude mice obtained from Buffalo (USA) and introduced to the Federal State Budgetary Scientific Institution “N.N. Blokhin Russian Cancer Research Center» of the Russian Ministry of Health of the Russian Federation and systematized their application. There are various variants «palentology» models of tumor growth, allowing you to personalize the forecast performance of selected impacts for a particular patient. Detailed modeling of metastases of various human cancers: colon cancer, pancreas, esophagus, lung, breast and prostate glands, testicles and ovaries, tumors of the head and neck. The characteristic of orthotopic (“MetaMouse” model) and experimental confirmation of the value of the hypothesis of Paget’s “seed and soil”, postulating a paired part of the process of metastasis of cell and tissue components of the tumor. Describes the use of the subcutaneous xenografts as control cell lines in the study of oncogenic potencies of the various drugs that are recommended for cellular immunotherapy of human. Examples and main thematic literature in recent years.
Сytotoxicity of zinc (II) and cadmium (II) iodide complexes with antipyrine, caffeine and phenantroline
Authors: Golubeva I. S. , Barmashov A. E. , Rudakova A. A. , Baryshnikova M. A. , Rukk N. S. , Skryabina A. Yu. , Apryshko G. N.
Published: November 2018

Objective: to study the cytotoxic activity of the zinc (II) and cadmium (II) iodide complexes with antipyrine (AP), caffeine (caf) and 1,10-phenantroline (phen) in comparison with that of free ligands, zinc (II) and cadmium (II) iodides in vitro. Materials and methods. The cytotoxic activity of the zinc (II) and cadmium (II) iodide complexes with AP, caf and phen in comparison with that of free ligands, zinc (II) and cadmium (II) iodides was investigated by methylthiazole tetrazolium assay using 5 human tumor cell lines. Results. It has been found that all 3 cadmium complexes demonstrate cytotoxic activity towards all 5 cell lines with concentration of inhibition of 50 % cell growth 5.5-84.0 mkM. Cytotoxicity of the most active diiodo(1,10-phenantroline)cadmium was slightly above than that of the respective ligand. One zinc-containing complex (diiodo(1,10-phenantroline)zinc) demonstrated significant activity towards 3 cell lines. The Jurkat cells were the most sensitive to studied compounds. Conclusion. It seems that zinc (II) and cadmium (II) iodide complexes with organic ligands are promising ones as potential antitumor drugs for further investigations both in vitro and in vivo.
Pharmacokinetics of carotenoids and carotene containing compounds
Authors: Sergeev A. V. , Anan’Ev V. S. , Kapitanov A. B. , Korostelev S. A. , Bukreev Yu. M. , Vlasenkova N. K. , Prosalkova I. R. , Reshetnikova V. V. , Shubina I. Zh.
Published: November 2018

Background. Some natural carotenoids have anti-carcinogenic, anti-mutagenic, and immunomodifying activity and may be considered as potential agents for chemoprevention of cancer. Objective: to study pharmacokinetics of beta-carotene, cantaxantene, lycopene, and carotene-containing compounds created on the base of the mentioned substances. Materials and methods. The study used carotene-containing drugs, which we previously created, such as Betask, Kaskatol, Tomatol, natural carotene-tocopherol complex derived from cankerberry. The research was conducted on mice, rats, rabbits, dogs, piglets, monkeys (Javanese macaque); the observations also involved healthy donors and patients with colorectal cancer before surgery. Carotenoid and retinoid detection was made by high performance liquid chromatography in blood plasma and liver tissue. Results. Comparative analysis of pharmacokinetics of the studied carotenoids demonstrates their relatively low absorption in animals. Bioavailability varies significantly among species; and it increases in the following order: dogs, rabbits, mice, rat, piglets, humans. Pharmacokinetics of carotenoids and carotene-containing compounds was studied with single and multiple administration per os. Cantaxantene and lycopene have a better bioavailability as compared to synthetic beta-carotene. Pharmacokinetics of synthetic carotenes and carotenoids of carotene-containing compounds has no significant differences. Beta-carotene in natural carotene-tocopherol complex has higher bioavailability (2-4 fold higher) as compared to synthetic beta-carotene. Regular complex administration into monkeys results in enhanced beta-carotene levels in blood serum of the animals and inhibits chemically induced carcinogenesis. The patients’ intake of beta-carotene in the pre-operational period was associated with the enhanced pro-vitamin levels in blood serum and stimulation of a number of cellular immune parameters. Conclusions. The studied carotenoids and carotene-containing compounds may be used in combined antitumor therapy and as treatment and prophylactics agents in cancer risk groups.
Antitumor activity of ormustine against transplantable solid murine tumors. Part I
Authors: Saprykina N. S. , Borisova L. M. , Kiseleva M. P. , Krasnov V. P. , Levit G. L. , Musiyak V. V. , Baryshnikova M. A. , Bukhman V. M. , Shprakh Z. S.
Published: November 2018

Background. Drugs of nitrosourea class are actively and successfully administered in oncology practice. However, at present, the search for new antitumor agents of this class is very urgent. Objective: to examine in vivo antitumor activity of ormustine, a new Russian drug from alkylnitrosourea class, against solid transplantable murine tumors: melanoma B16 and epidermoid Lewis lung carcinoma. Materials and methods. The assessment of antitumor activity of ormustine and a reference drug mustophoran (Les Labolatories Servier, France) was carried out in B6D2F1 mice. Ormustine was administered intravenously at a single dose of 50-135 mg/kg. Mustophoran was administered intravenously at a dose of 32 mg/kg twice (on days 2 and 9) and 3 times at a dose of 25 mg/kg (on days 2, 6 and 9). The follow-up period lasted till the death of animals. The antitumor effect of agents was assessed by the tumor growth inhibition and increase in life span of experimental mice compared to control animals. Results. It has been defined that the single intravenous dose of ormustine (125 mg/kg) is therapeutic for mice bearing melanoma B16 and epidermoid Lewis lung carcinoma. Conclusions. Ormustine possesses high antitumor effect against solid transplantable murine tumors. Ormustine is not inferior to mustophoran in the therapeutic effect against melanoma B16.
Research in vivo the qualities of potential antitumor amino-acid derivatives of glycosides of indolocarbazol
Authors: Golubeva I. S. , Yavorskaya N. P. , Goryunova O. V.
Published: November 2018

Background. The addition of active metabolites (in particular, amino acids) to the molecule affects the physicochemical and prodrug properties of derivatives of indolocarbazoles. Using computed chemoinformatics, probability antitumor activity of amino-acid derivatives of glycosides of indolocarbazol (AADGI) is predicted with low probability of their cytotoxic activity in vitro. Based on these data, a study of these compounds in vivo is conducted. Objective: the assessment of AADGI as potential antitumor medications. Materials and methods. Research antitumor activity of AADGI was done using murine tumor models - cervical cancer CC-5. Investigated compounds were injected to mice СВА abdominally 5-times daily with interval of 24 h. Observation of animals were continued till their death. Antitumor effect of compounds was assessed by criteria of tumor growth inhibition and increase in life expectancy of mice comparing to control animals. Results. The optimal dose for these series of compounds was titrated and this dose is 100 mg/kg. Antitumor activity of AADGI was assessed on CC-5. Conclusions. Based on data received we suggest an extended study in vivo of antitumor qualities of selected 5 leader AADGI.
Natural history of papillomaviruses in men – what is known?
Authors: Volgareva G. M.
Published: November 2018

Up till now human papillomaviruses (HPV) draw attention of biologists and clinicians owing mostly to the fact that some members of this group cause cervical cancer in women. However it is clear that both women and men take part in HPV distribution throughout population. Data get accumulated on peculiarities of HPV natural history in men when compared with women, as well as on capability of oncogenic HPV to induce cancer in several male organs. The present paper is an attempt to synthesize literature data on specific features of HPV natural history in men. Elucidation of these features is important for working out efficient approaches for prevention of HPV-associated malformation with regard to gender specificities.
Mechanisms of resistance to anti-Pd-1 therapy in metastatic cutaneous melanoma
Authors: Zhulikov Ya. A. , Samoylenko I. V. , Demidov L. V.
Published: November 2018

The appearance of modulators immune synapse in clinical practice has become a revolution in metastatic skin melanoma treatment. However, blockade PD-1 allows to achieve objective response in only 30–40 % of patients. Recently, many mechanisms of primary resistance of melanoma to immunotherapy studied, they related both to the characteristics of the tumor and the tumor microenvironment. The response to anti-PD-1 therapy usually is durable, but acquired resistance emerges in 25 % of patients, who had an objective response to this treatment. This review will describe the main mechanisms of resistance to anti-PD-1 therapy in metastatic skin melanoma and possible ways of their overcoming.
DIsseminated tumor cells of luminal breast cancer patients .
Authors: Ryabchikov D. A. , Beznos O. A. , Dudina I. A. , Vorotnikov I. K. , Denchik D. A. , Chulkova S. V. , Talipov O. A. , Tupitsyn N. N.
Published: November 2018

Introduction. There is ample evidence that disseminated tumor cells (DTC), which are found in the bone marrow (BM) of patients with breast cancer (BC), including early stages, are progenitors of subsequent distant metastasis. Therefore, BM-DTC represent an additional tool for understanding carcinogenesis and estimating prognosis. Nevertheless, the existing data are controversial. The purpose of the study – to determine the frequency of DTC detection in BM of patients with luminal BC and also its relationship with some clinical and immunophenotypic parameters. Materials and methods. BM bioptates of 65 luminal BC patients were analyzed for the presence of DTC by Attune Acoustic Focusing Cytometer. For the first time in Russia, the sensitivity of the DTC detection method in the BM to the level of 1 × 10–7 myelocaryocytes was increased. Results. In BM, DTC were detected in 40 % of patients, and this finding did not correlate with stage of BC and degree of malignancy. The level of CD8+ lymphocytes in patients with DTC in the BM was significantly lower and amounted to 39,2 % versus 48,1 % in patients without DTC (p = 0,011). The content of myelocaryocytes with DTC-positive status was 1,6 times lower than in the absence of DTC (р = 0,007). Other parameters of the myelogram did not differ significantly. Moreover, no significant correlations were found between the presence of DTC in BM and the breast tumor immunophenotype (HLA-I: p = 0,74; HLA-DR: p = 0,93; CD71: p = 0,46). Conclusion. The presence of BM-DTC is more interrelated with myelogram and subpopulation of BM lymphocytes than with the clinical characteristics of tumor.
Complex anti-ichemic therapy of the early postoperative period of organ-preserving operational treatment of renal cellular cancer
Authors: Shormanov I. S. , Los’ M. S. , Titov K. S.
Published: November 2018

Currently it is a constant search for new and effective methods of protection against ischemic injury in limb-salvage surgery on kidneys. Objective – improvement of functional results of surgical treatment, reducing the time of hospitalization. Materials and methods. We conducted a clinical trial involving 69 patients. Time “warm ischemia” – 14,2 ± 2,4 min. All performed on the kidney sparing surgery for renal cell carcinoma for elective indications. After surgery, the study group (n = 35) held sessions of hyperbaric oxygenation parallel receiving α-tocopherol acetate. The control group included 34 patients. The analysis of inflammatory changes in tindicators of total blood test, glomerular filtration rate, the state of immunity, peripheral circulation, renal function, the assessment of quality of life was performed. Results. The scheme of post-operative rehabilitation of patients with renal cell carcinoma helps to activate the anti-inflammatory and immune response to surgical treatment, more rapid and complete restoration of blood flow and function of organ operated. Conclusion. This reduces the incidence of postoperative complications and period of hospitalization.