Ejc SupplementsPub Date : 2015-11-01Epub Date: 2015-11-23DOI: 10.1016/j.ejcsup.2015.08.081
D. Pszczółkowska, A. Ellert-Miklaszewska, A. Gieryng, M. Kijewska, P. Wiśniewski, B. Kamińska
{"title":"P142","authors":"D. Pszczółkowska, A. Ellert-Miklaszewska, A. Gieryng, M. Kijewska, P. Wiśniewski, B. Kamińska","doi":"10.1016/j.ejcsup.2015.08.081","DOIUrl":"10.1016/j.ejcsup.2015.08.081","url":null,"abstract":"<div><p>Malignant gliomas are fast-growing, heterogeneous and invasive brain tumors strongly infiltrated by non-tumor cells. Glioma attracts variety of immune cells, in particular microglia/macrophages and re-program these cells into immunosuppressive, tumor-supporting cells. Factors responsible for pro-invasive macrophage polarization and shaping tumor microenvironment in tumor-supporting manner are poorly known. We analyzed glioma secretome using proteomical approach and identified lactadherin (Mfge8) and osteopontin (Spp1) in microglia-activating fractions. Both osteopontin and lactadherin are <em>αvβ</em>3/<em>αvβ</em>5 integrin ligands able to interact with receptors present on microglia and macrophages and thus could be involved in pro-invasive polarization of microglia/macrophages. Moreover, both Spp1 and Mfge8 are overexpressed in glioma cells, but not in non-transformed astrocytes. C6 glioma cells stably expressing shRNA specific to lactadherin (shMfge8), osteopontin (shSpp1) and negative shRNA (shNeg) were implanted into striatum of Wistar rats. There was no difference in proliferation and viability of C6 glioma cells, cells stably expressing shRNA specific to lactadherin, ostopontin and negative shRNA in vitro, that demonstrates the negligible effect of autocrine production of both protein on tumor cell growth. Knockdown of Spp1 and Mfge8 resulted in significant reduction of tumor volume in rat model of glioma. Immunochemical analysis of brain sections revealed similar numbers of infiltrating microglia/macrophages (Iba1 staining), but the reduced number of ameboid, arginase 1 expressing cells in Mfge8 – depleted tumor. Treatment of endothelial cells with rhMFGE8 revealed significant effect of that protein on angiogenesis in vitro, however lactadherin-depleted tumors do not exhibit reduced blood vessel density in rat glioma model. FACS analysis showed that silencing of Spp1 does not affect total number of CD11b-positive cells, but strongly modulates microenvironment by leading to significant changes in percentage of Tc and Treg cells infiltrating tumor-bearing hemisphere. Our results suggest that glioma-derived integrin ligands are important factor in polarization of glioma infiltrating microglia/macrophages into the pro-invasive phenotype and its targeting could be a new therapeutic strategy.</p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 45-46"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ejc SupplementsPub Date : 2015-11-01DOI: 10.1016/J.EJCSUP.2015.08.126
G. Zhukova, A. Shikhliarova, T. Gudtskova, M. Bragina, I. Novikova, V. Zernov, T. Barteneva, O. Polozhentsev, A. Soldatov, M. Rudenko, E. Shirnina
{"title":"A66: Changes in experimental tumors and surrounding tissue under antitumor influence of magnetite nanoparticles introduced into the peritumoral area","authors":"G. Zhukova, A. Shikhliarova, T. Gudtskova, M. Bragina, I. Novikova, V. Zernov, T. Barteneva, O. Polozhentsev, A. Soldatov, M. Rudenko, E. Shirnina","doi":"10.1016/J.EJCSUP.2015.08.126","DOIUrl":"https://doi.org/10.1016/J.EJCSUP.2015.08.126","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"1 1","pages":"71-72"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.EJCSUP.2015.08.126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ejc SupplementsPub Date : 2015-11-01DOI: 10.1016/J.EJCSUP.2015.08.112
A. Tsidulko, L. Matskova, L. Astakhova, I. Ernberg, E. Grigorieva
{"title":"P11: Proteoglycans expression correlates with the phenotype of malignant and non-malignant EBV-positive B-cell lines","authors":"A. Tsidulko, L. Matskova, L. Astakhova, I. Ernberg, E. Grigorieva","doi":"10.1016/J.EJCSUP.2015.08.112","DOIUrl":"https://doi.org/10.1016/J.EJCSUP.2015.08.112","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"63"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.EJCSUP.2015.08.112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ejc SupplementsPub Date : 2015-11-01DOI: 10.1016/J.EJCSUP.2015.08.116
E. V. Vorontsova, A. Grishanova, V. Lyakhovich
{"title":"A89: P450 1A subfamily as component of exosomes derived from HepG2 cells","authors":"E. V. Vorontsova, A. Grishanova, V. Lyakhovich","doi":"10.1016/J.EJCSUP.2015.08.116","DOIUrl":"https://doi.org/10.1016/J.EJCSUP.2015.08.116","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"65-66"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.EJCSUP.2015.08.116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ejc SupplementsPub Date : 2015-11-01DOI: 10.1016/J.EJCSUP.2015.08.107
S. Tamkovich, A. Bondar, I. Morozov, N. Kirushina, V. Permyakova, V. Voitsitskiy, P. Laktionov
{"title":"P39a: The characterization of total circulating DNA from blood of healthy donors and cancer patients","authors":"S. Tamkovich, A. Bondar, I. Morozov, N. Kirushina, V. Permyakova, V. Voitsitskiy, P. Laktionov","doi":"10.1016/J.EJCSUP.2015.08.107","DOIUrl":"https://doi.org/10.1016/J.EJCSUP.2015.08.107","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"60"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.EJCSUP.2015.08.107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ejc SupplementsPub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.111
O. Tomchuk
{"title":"A105: Morphological characteristics and clinical significance of tumor infiltrating CD20 B lymphocytes in gastric cancer","authors":"O. Tomchuk","doi":"10.1016/j.ejcsup.2015.08.111","DOIUrl":"https://doi.org/10.1016/j.ejcsup.2015.08.111","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"62-63"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ejc SupplementsPub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.105
M. Suvorova, A. Tsapieva, A. Suvorov, E. P. Kiseleva
{"title":"A99: The influence of live Streptococcus pyogenes on the growth of solid murine tumors","authors":"M. Suvorova, A. Tsapieva, A. Suvorov, E. P. Kiseleva","doi":"10.1016/j.ejcsup.2015.08.105","DOIUrl":"https://doi.org/10.1016/j.ejcsup.2015.08.105","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"59"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ejc SupplementsPub Date : 2015-11-01DOI: 10.7453/gahmj.2015.025.suppl
David J Hufford, Meredith Sprengel, John A Ives, Wayne Jonas
{"title":"Barriers to the Entry of Biofield Healing Into \"Mainstream\" Healthcare.","authors":"David J Hufford, Meredith Sprengel, John A Ives, Wayne Jonas","doi":"10.7453/gahmj.2015.025.suppl","DOIUrl":"10.7453/gahmj.2015.025.suppl","url":null,"abstract":"<p><p>In this article, we describe barriers to the entry of biofield healing into mainstream contemporary science and clinical practice. We focus on obstacles that arise from the social nature of the scientific enterprise, an aspect of science highlighted by the influential work of Thomas Kuhn (1922-1996), one of the most important- and controversial-philosophers of science in the 20th century. Kuhn analyzed science and its revolutionary changes in terms of the dynamics within scientific communities. Kuhn's approach helps us understand unconventional medical theories and practices such as biofield healing. For many years, these were called \"complementary and alternative medicine\" (CAM). However, because most people use nonmainstream approaches in conjunction with conventional treatments, the National Institutes of Health and many practitioners now prefer \"Complementary and Integrative Medicine\" (CIM) where integrative implies \"bringing conventional and complementary approaches together in a coordinated way.\"(1) Biofield healing fits the integrative model well, provides a novel approach to therapeutic intervention, and is developing in a manner that can integrate with current medical science in simple ways. Yet, it still remains outside the conventional framework because of its conceptual bases, which contrast sharply with conventional assumptions regarding the nature of reality. </p>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"8 1","pages":"79-88"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78477518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ejc SupplementsPub Date : 2015-11-01Epub Date: 2015-11-23DOI: 10.1016/j.ejcsup.2015.08.039
E. Kaigorodova , N. Tarabanovskaya , E. Simolina , V. Perelmuter , M. Stakheeva , N. Cherdyntseva , O. Saveleva , L. Tashireva
{"title":"T15","authors":"E. Kaigorodova , N. Tarabanovskaya , E. Simolina , V. Perelmuter , M. Stakheeva , N. Cherdyntseva , O. Saveleva , L. Tashireva","doi":"10.1016/j.ejcsup.2015.08.039","DOIUrl":"10.1016/j.ejcsup.2015.08.039","url":null,"abstract":"<div><h3>Background</h3><p>Despite the abundance of theoretical evidences displaying the considerable role of the “soil” in metastasis progression, the majority of cancer research and cancer therapy pathogenetic methods focused mainly on the tumor cells. There is still no clear clinical data showing the role of “soil” in the metastasis. Identification of factors and mechanisms driving the conditions promoting tumor dissemination may lead to therapeutic strategy to detect and prevent metastases at the earliest step. It has been established that bone marrow-derived hematopoietic progenitor cells home to pre-metastatic sites before tumor cells infiltrate in these sites. These hematopoietic progenitor cells form regulatory cell cluster of stromal microenvironment (premetastatic niche) to promote secondary tumor growth. In this context, the aim of our study was to evaluate the level of different pools of circulating tumor cells and bone marrow progenitor cells in the blood of patients with breast cancer in the dynamics of neoadjuvant chemotherapy.</p></div><div><h3>Materials and methods</h3><p>Patients (prospective study) with newly diagnosed invasive breast cancer in the age range 18–50 years and tumor volume of 2.0(> or =)<!--> <!-->cm, referred at the Tomsk Cancer Research Institute for treatment were included into the study. Eligibility criteria were as follows: the patient’s informed consent to participate in research; morphologically verified diagnosis of invasive carcinoma of non-specific type; luminal B-1, -2, triple negative (basal-like subtype included), HER2 positive breast cancer; T2-4N0-3M0; preserved menstrual function; satisfactory performance status (on a scale (< or =) ECOG 2). Exclusion Criteria were: other than luminal histological type of breast cancer, multiple primary cancer; chronic inflammatory diseases in the acute stage. Samples of venous blood taken from breast cancer patients before biopsy, after biopsy and after each subsequent course of neoadjuvant chemotherapy (NACHT) were served as a study material. The various pools of circulating tumor cells and bone-marrow derived progenitor cells were determined using monoclonal antibodies to EpCam, CD44, CD45, CD24, N-cadherin, CD34, CD133, CD202, VEGFR1 and CD90, labeled with different fluorochromes on flow cytometry BD FACSCanto ™ II.</p></div><div><h3>Results</h3><p>The study showed that each succeeding course of NACHT increased blood levels of circulating tumor cells, and bone marrow progenitor cells with a phenotype characteristic of EPC (endothelial progenitor cells) (CD34<!--> <!-->+<!--> <!-->CD45–VEGFR<!--> <!-->+<!--> <!-->CD133<!--> <!-->+<!--> <!-->CD202<!--> <!-->+) and MSC (mesenchymal progenitor stem cells fibroblasts) (CD34–CD90<!--> <!-->+<!--> <!-->VEGFR1–CD45–CD202–). Influence of the NACHT on hematopoietic stem cells HSC (VEGFR1<!--> <!-->+<!--> <!-->CD34<!--> <!-->+<!--> <!-->CD45lowSD202–) and progenitor cells HPC – CD34<!--> <!-->+<!--> <!-->CD45<!--> <","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 22"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ejc SupplementsPub Date : 2015-11-01Epub Date: 2015-11-23DOI: 10.1016/j.ejcsup.2015.08.042
K. Kirsanov , E. Lesovaya , N. Shalginskikh , D. Naberezhnov , V. Glazunov , G. Belitsky , M. Yakubovskaya
{"title":"P88","authors":"K. Kirsanov , E. Lesovaya , N. Shalginskikh , D. Naberezhnov , V. Glazunov , G. Belitsky , M. Yakubovskaya","doi":"10.1016/j.ejcsup.2015.08.042","DOIUrl":"10.1016/j.ejcsup.2015.08.042","url":null,"abstract":"<div><h3>Purpose</h3><p>DNA minor groove is the main target of small molecules, which noncovalently and to a certain extent site-specifically bind to appropriate nucleotide sequences. Study of these substances can give rise to understanding the mechanistic relationship between sites of interaction and activity of appropriate enzymes with “houskeeping” function including helicases, topoisomerases, methyltransferases, demethylases and DNA/RNA-polymerases.</p></div><div><h3>Results</h3><p>We revealed for the first time that AT-specific minor groove binding ligands (MGBLs), in particular bisbenzimidazoles (Hoechst33258 and its derivatives), widely used in molecular and cell biology for DNA-staining, induce loss of heterozygosity at high frequency while point mutations and chromosome deletions at insignificant levels. Moreover, we demonstrated that the agents realized their genotoxic blastomogenic effects via homologous recombination mechanism exclusively. Lately the same mechanism of genotoxicity has been shown for MGBL carbazole derivative Curaxin, which is toxic for a broad range of tumor cell lines in vitro and inhibit tumor growth in different mouse models of cancer in vivo. Moreover, powerful antitumor activity has been demonstrated for Trabectedin, which binds to the DNA’s minor groove and alkylate guanine residues. All this provided a framework for wide-ranging investigation of cell response to MGBLs exposure, molecular mechanisms of their recombinogenic as also their anticancer activity. A special interest is paid to epigenetic mechanisms of MGBs action.</p><p>Our study aimed to examine the epigenetic effects of recombinogenic (Hoechst33342, Hoechst33258) and non-recombinogenic (DAPI, Diminazene, Pentamidine and Netropsin) MGBLs.</p><p>After we unmasked MGBLs’ recombinogenic activity, we hypothesized that their molecular mechanism of indirect DNA damage involves poly(ADP-ribose)polymerase-1 (PARP-1) activation. Surprisingly, we found that all AT-specific MGBLs preventing PARP-1 interaction with DNA inhibit its activation, and hence, the DNA-dependent pathway of PARP-1 activation function. These inhibitors effectively block PARP-1 activity in vivo, as it was demonstrated in a Drosophila experimental system and in human breast cancer-derived BT474 cell line.</p><p>Further epigenetic effects of these indirect genotoxic carcinogens were analyzed using HeLa cell population with epigenetically suppressed GFP-reporter gene as a model. All compounds had strong GFP- reactivation effect. The obtained results confirm scarce data of previous publications on the ability of DNA minor groove ligands to influence gene transcription process. Statistically significant results of changes of DNA methylation level were detected under 5-azaC and Hoechst 33258 treatment, but it was absent after Hoechst 33342 treatment. For the rest compounds significant loss of promoter region methylation was not observed. The common epigenetic marks of transcription include histon","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 24"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}