Ejc SupplementsPub Date : 2015-11-01Epub Date: 2015-11-23DOI: 10.1016/j.ejcsup.2015.08.026
E. Dmitrieva, N. Nurieva
{"title":"A115","authors":"E. Dmitrieva, N. Nurieva","doi":"10.1016/j.ejcsup.2015.08.026","DOIUrl":"10.1016/j.ejcsup.2015.08.026","url":null,"abstract":"<div><p>The Chelyabinsk region is a classic example of the technologically-saturated region. The index of pollution of atmospheric air is estimated as high. The Chelyabinsk region is among the areas of increased cancer risk. The incidence of head and neck cancer is steadily increasing, accounting for 20–25% of all cancer cases in Russia. Oropharyngeal cancer makes up 5.1% of all cancers.</p></div><div><h3>Materials and methods</h3><p>The object of the study was the population of the Chelyabinsk region. The analysis was conducted according to the materials of the annual reports of the statistics department of the Chelyabinsk district oncology dispensary.</p></div><div><h3>Results</h3><p>Out of the total cancer cases for the population of Chelyabinsk region in 2014, oro-pharyngeal cancer comprised 2.06%, including cancers of the lip (0.35%), tongue (0.47%), major salivary glands (0.22%), other unspecified parts of the mouth (0.52%), oropharynx (0.33%), nasopharynx (0.1%) and hypopharynx (0.07%). From 2008 to 2014, the incidence of oral and pharyngeal cancer among adult population of Chelyabinsk city and Chelyabinsk region showed an 8.8% increase. In the period from 2011 to 2014, the incidence of oral and pharyngeal cancer tended to increase, the overall rise being 71.8%. It should be noted that the oral and pharyngeal cancer incidence was 3 times higher in males than in females in 2013 and 2 times higher in 2014. One of the main indicators that determine the prognosis for the development of cancer, is the extent of tumor at time of diagnosis.</p><p>Out of the total cancer cases for the population of Chelyabinsk region in 2014, cancer of the oral cavity comprised 1.33%, pharyngeal cancer 0.6%, lip cancer 0.13%, ranking the 17th, 19th and 24th place respectively among the causes of death from all cancers. Analyzing the dynamics of mortality from cancer of the oral cavity and pharynx during the study period, it was revealed that the mortality rate increased by 0.7%.</p></div><div><h3>Conclusion</h3><p>Head and neck tumors are a rare group of clinically and biologically diverse neoplastic diseases. Among the residents of the Chelyabinsk region, men are 2–3 times more susceptible to cancer of the oral cavity and pharynx than women. High mortality rate is due to late referral of patients to specialized clinics; most head and neck cancer patients are diagnosed at advanced stages.</p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 15"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309002","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.2015.08.047
D. Korobkov , N. Plotnikova , G. Meltsaev , S. Kemaykin , A. Almyashev , S. Haritonov
{"title":"A75","authors":"D. Korobkov , N. Plotnikova , G. Meltsaev , S. Kemaykin , A. Almyashev , S. Haritonov","doi":"10.1016/j.ejcsup.2015.08.047","DOIUrl":"10.1016/j.ejcsup.2015.08.047","url":null,"abstract":"<div><p>Breast cancer is one of the most common cancers in women. The incidence of breast cancer in 2014 in the Republic of Mordovia was 69.9 per 100,000 female populations. Breast cancer occurs when excessive expression of oncoproteins switches in the case of transformation of proto-oncogene in PRADI. In primary breast tumors, mutations and the expression of the three oncogenes Her2/neu, C-mys, Int-2, as well as in supressonyh genes – the p53 gene and the retinoblastoma gene RB are the most common. Several studies found that oncogene – C-mys was expressed in 16.8% of primary breast cancer cases and in 35% cases with subsequent development of metastases. Proteins that stimulate the phosphorylation of mitogen-activated protein kinasescan activateunder the influence of growth factors. Development of breast cancer is regulated by a complex interaction of many hormones and growth factors. Currently, one of the leading theories of developing breast cancer is the increased hormonal stimulation of proliferative processes in the development of neoplasia. One of the manifestations of hormonal imbalance in tumor during a regular decrease in blood competitive inhibitor of the biological effects of estrogen – progesterone, which is in correlation with the stage of the spread of neoplasia. The role of the overproduction of estrogen in the pathogenesis of breast cancer is confirmed by the fact that in women who underwent oophorectomy before the age of 38<!--> <!-->years, the risk of breast cancer development is 1.5 times less than in those who did not have such operation. Excessive accumulation of lipid peroxidation products in the area of neoplasia activates mechanisms violation of intercellular interaction that caused the destruction of the lipid components of membranes.</p><p>The study group included 112 patients treated at the State Institution of Health of the Republic of Mordovia “National Oncology Center”. To identify the nature of tumors, all patients underwent immunohistochemical analysis. Androgen receptors were found in 48% of breast cancer cases, the expression level of androgen receptor in the tumor was much lower than the expression level of estrogen and progesterone receptors. Low levels of progesterone receptor expression in breast cancer cells were combined with high levels of expression of Ki-67 antigen, HER-2 oncoprotein in tumor cells. Patients with HER-2 (3+) and (2+) had more frequent multiple metastases in lymph nodes compared to patients with HER-2 (0) and (1+) phenotypes. Maximum expression of HER-2 oncoprotein in tumor cells indicated high metastatic potential and poor prognosis.</p><p>It may be concluded that the cellular and molecular mechanisms of breast cancer are complex. Therefore, carcinogenesis has a “multistep” nature and at least two or more mutations in the cells of the same clone – parent and child are required to generate malignant tumors. Thus, the development of oncogenic transformation does not necessarily mean the pro","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 27"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309475","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.2015.08.076
E. Pisareva , N. Gutkina , S. Kovalenko , V. Shamanin
{"title":"P65","authors":"E. Pisareva , N. Gutkina , S. Kovalenko , V. Shamanin","doi":"10.1016/j.ejcsup.2015.08.076","DOIUrl":"10.1016/j.ejcsup.2015.08.076","url":null,"abstract":"<div><p>KRAS is component of Ras/MAPK signaling cascade that regulates cell proliferation and cell survival. Somatic mutations in KRAS gene are often found in tumors and affect the sensitivity of tumors to target therapy. Mutations in codons 12 or 13 of KRAS gene in colorectal cancer (CRC) are associated with resistance to anti-EGFR antibodies Cetuximab and Panitumumab. The objectives of this work were to develop PCR tests for detection mutations in KRAS gene and analyze the frequency of mutations in KRAS gene in CRC in Russia.</p><p>DNA sequencing by Sanger is the most common method for mutation analysis. However, the method has a sensitivity of 20% mutant allele, which is often not sufficient for the analysis of somatic mutations in tumors.</p><p>One of the most sensitive mutation analysis methods is allele-specific real-time PCR. This method allows to detect 1% of mutated DNA in the sample. This sensitivity is sufficient for analysis of mutations in tumor samples containing 2–5% or more of tumor cells in normal tissue.</p><p>In this study we developed and compared 3 new KRAS assays (1) real-time PCR with allele-specific primers; (2) real-time wild-type blocking PCR with LNA (locked nucleic acid) blocker; and (3) Sanger sequencing with LNA-blocker. First assay is a PCR test with seven reactions using allele-specific primers for detection and genotyping 7 mutations in 12 and 13 codons of KRAS gene. Second assay is real-time PCR with only a single pair of primers and LNA oligonucleotide blocker. LNA-blocker is an oligonucleotide which has a wild-type sequence of codons 12 and 13 of KRAS gene. LNA-blocker binds strongly to wild-type KRAS DNA and suppresses its amplification, but does not block amplification of mutant DNA. The real-time PCR with LNA -blocker can detect mutant DNA but does not genotype mutation. Such assay can be used as a simple and sensitive screening test for mutant KRAS cases if exact genotyping of mutation is not required. We also used LNA-blocker to increase sensitivity of Sanger sequencing. To evaluate sensitivity and specificity of new tests DNA standards were prepared with different ratios of normal and mutant alleles using normal human DNA without mutation and recombinant plasmids with mutations in KRAS (G12C, G12S, G12R, G12V, G12D, G12A, G13D). After optimization all three assays had sensitivity 5% of mutant alleles for the detection of mutations in KRAS gene, using 2.5–40<!--> <!-->ng of human DNA.</p><p>Performance of new assays for KRAS mutations was compared using 81 colorectal tumor samples. Before analysis relative content of tumor cells in the samples was evaluated by pathologist. If tumor content was less than 20% in the sample then regions with a maximum number of tumor cells were manually macrodissected before the DNA extraction. DNA was purified from formalin fixed paraffin embedded (FFPE) tissue using “FFPE-DNA Kit” (Biolink). All three assays had high sensitivity (95–100%) and specificity (100%) for detectio","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 42-43"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309876","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.2015.08.086
V. Rybko, N. Khromova, M. Farmakovskaya, M. Novikova, B. Kopnin, P. Kopnin
{"title":"A104","authors":"V. Rybko, N. Khromova, M. Farmakovskaya, M. Novikova, B. Kopnin, P. Kopnin","doi":"10.1016/j.ejcsup.2015.08.086","DOIUrl":"10.1016/j.ejcsup.2015.08.086","url":null,"abstract":"<div><p>Malignant tumors consist not only of neoplastic cells, but also of various normal cells, for example fibroblasts, macrophages or endothelial cells. These normal cells stand under constant pressure of transformed cells, regulating their properties and converting them into tumor-promoting cells. Tumor-stroma interaction takes place during all stages of carcinogenesis. Notch activation upon receptor binding with the ligand is a way of direct intercellular communication during embryo- and histogenesis, determining various processes like differentiation, proliferation, etc. It has been previously shown that in tumors this signaling cascade regulates not only properties of transformed cells, but also stromal cells activities, i.e. neoangiogenesis. The Notch role in communication between neoplastic cells and stromal fibroblasts is underinvestigated.</p><p>Cancer-associated stromal fibroblasts (CAFs) are an important component of tumors secreting growth factors and proteases, modulating immune reactions and contributing to cancer stem cells niches formation. CAFs resemble myofibroblasts and express <span><math><mrow><mi>α</mi></mrow></math></span>Smooth-Muscle Actin (<span><math><mrow><mi>α</mi></mrow></math></span>SMA).</p><p>We obtained and characterized cultures of normal mesenchymal cells: a myofibroblasts-like (MF), and fibroblasts-like MC1 and MC2, differing by Notch1 expression. These cell cultures variously influenced growth of colon cancer notch- ligand Jagged2-positive HCT116 xenographs in nude mice. MF cells were characterized by the strongest while Notch1-deficient MC2 by the weakest tumor-promoting activity.</p><p>MC1 but not MC2 started to express <span><math><mrow><mi>α</mi></mrow></math></span>SMA upon co-cultivation in vitro with neoplastic HCT116 cells. Such co-cultivation also lead to Notch activation according to a luciferase reporter. NICD (Notch Intracellular Domain) expression activated MC1 and MC2, while Notch1 silencing in MC1 abrogated both HCT116-mediated activation of the fibroblasts in vitro and their tumor-promoting activity in vivo.</p><p>Notch signaling in mesenchymal cells stimulated TGFb production that lead to both autocrine and paracrine receptors stimulation. We believe that this cytokine activates fibroblasts in our experimental system. We also revealed that this process was p53-dependent.</p><p>So we have shown Notch1 to be involved in tumor-stroma interaction, particularly its activation leading to fibroblasts transdifferentiation. Notch1-stimulated fibroblasts are able to produce TGFb and to promote tumor growth in xenographs. The tumor-stimulating potency of various fibroblasts in our experimental system depends on their ability to transdifferentiate to myofibroblasts upon Notch activation.</p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 48"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310015","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.2015.08.027
O. Ephimova , I. Grigoreva , T. Romanova , Y. Ragino , T. Suvorova , N. Tov
{"title":"P83","authors":"O. Ephimova , I. Grigoreva , T. Romanova , Y. Ragino , T. Suvorova , N. Tov","doi":"10.1016/j.ejcsup.2015.08.027","DOIUrl":"10.1016/j.ejcsup.2015.08.027","url":null,"abstract":"<div><h3>Background</h3><p>To evaluate the clinical symptoms in pancreatic cancer patients (PCa) and compare some biochemical blood serum parameters in patients with different pathology of the pancreas (PCa, acute (OP) and chronic pancreatitis (CP)).</p></div><div><h3>Materials and methods</h3><p>During a one-time clinical research on the type of “series of cases” 130 patients were examined (42 patients with OP, 81 – CP and 7 patients with PCa). The diagnosis of PCa, OP, CP was verified by clinical and instrumental methods. Glucose, cholesterol, triglyceride and bilirubin serum levels were determined by ELISA.</p></div><div><h3>Results</h3><p>The mean age of patients with PCa was 63.6<!--> <!-->±<!--> <!-->4.9<!--> <!-->years, morbidity duration of PCa – 3.5<!--> <!-->±<!--> <!-->1.1<!--> <!-->months. Among patients with PCa, 83.3% of people – smoked, 16.7% – smoked every day. Half of the respondents PCa patients noted that over the last year they did not drink alcohol; 16.7% of people – drank alcohol several times a year, and 33.3% of patients consumed alcohol 1–2 times a month. BMI of PCa patients was equal to 26.3<!--> <!-->±<!--> <!-->3.5<!--> <!-->kg/m<sup>2</sup>, in OP patients – 23.8<!--> <!-->±<!--> <!-->1.0<!--> <!-->kg/m<sup>2</sup>, in CP patients – 26.3<!--> <!-->±<!--> <!-->0.6<!--> <!-->kg/m<sup>2</sup>, <em>p</em> <!-->><!--> <!-->0.05. In this case, 85.7% of PCa patients noted a significant decrease in body weight (11.7<!--> <!-->±<!--> <!-->6.0<!--> <!-->kg) for 3–4<!--> <!-->months after the onset of symptoms. There was no pain in 42.8% of PCa patients, and frequent pain noted only in 28.6% of persons. Among CP patients, frequent and persistent pain noted in 65.5% of patients and among OP patients in 48.6% of cases. All PCa patients experienced pain in the right upper quadrant. Pain was of low intensity in 75% of cases and moderate in 25% of cases. Elimination of pain was observed in half of the PCa patients, and 1/4 of patients continued to experience pain. Episodes of nausea and vomiting noted in 25% of PCa patients. Bloated feeling in the stomach and overflow were noted in 42.8% of the all surveyed PCa persons. The level of glucose in PCa patients exceeded the normal limits and was significantly higher compared to that in OP and CP patients (8.5<!--> <!-->±<!--> <!-->1.4<!--> <!-->mmol/L, 5.4<!--> <!-->±<!--> <!-->0.3 and 5.1<!--> <!-->±<!--> <!-->0.1<!--> <!-->mmol/L, respectively, <em>p</em> <!--><<!--> <!-->0.05). Hyperbilirubinemia was detected in PCa patients – 89.9<!--> <!-->±<!--> <!-->27.5<!--> <!-->μmol/L; in OP and CP patients bilirubin levels were 32.2<!--> <!-->±<!--> <!-->11.0 and 13.4<!--> <!-->±<!--> <!-->1.8<!--> <!-->μmol/L, respectively, which were significantly lower than those in patients with PCa, <em>p</em> <!--><<!--> <!-->0.05. Triglyceride levels did not differ in patients with different pancreas diseases (PCa – 1.7<!--> <!-->±<!--> <!-->0.3, CP – 1.86<!--> <!-->±<!--> <!-->0.1 and OP –1.88<","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 15-16"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309017","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.2015.08.022
N. Dementyeva , R. Derks , I. Kohler , N. Merzlikin , S. Shelepov , D. Kokova , A. Sazonov , O. Mayboroda , I. Saltikova
{"title":"P158","authors":"N. Dementyeva , R. Derks , I. Kohler , N. Merzlikin , S. Shelepov , D. Kokova , A. Sazonov , O. Mayboroda , I. Saltikova","doi":"10.1016/j.ejcsup.2015.08.022","DOIUrl":"10.1016/j.ejcsup.2015.08.022","url":null,"abstract":"<div><h3>Background</h3><p><em>Opisthorchiasis</em> is a form of foodborne trematodiasis which is caused by liver flukes. It has been shown that a chronic <em>Opisthorchiasis</em> infection increases a risk of cholagiocarcinoma of liver. It is commonly believed that a gradual change of homeostasis in a parasite microenvironment (bile) leads to liver fluke-induced cancer. Nevertheless, no systematic, analytically driven studies confirming this hypothesis have been published yet. The restricted access to clinical material and extreme complexity of the biological matrix (bile) both are the important “rate limiting factors” for a progress in the field. Here we present for the first time a cross-platform mass spectrometric analysis of bile juice collected from the patients with cholangiocarcinoma-associated diseases. We show that an effective analysis of such complex biological matrix as bile juice requires a combination of orthogonal analytical platforms (e.g. RPLC–MS and HILIC–MS) maximizing coverage of the metabolic space.</p></div><div><h3>Materials and methods</h3><p>28 patients with <em>O. felineus</em> infection and 30 negative controls were included in the study. The infection status was confirmed using microscopy analysis of the bile. Bile samples were collected from the gallbladder using sterile puncture, directly frozen and stored at −80<!--> <!-->°C until analysis. The samples were randomized and organized into the acquisition blocks consisting of the samples and quality controls (QC). Experiments were carried out with a Dionex Ultimate 3000 LC system (Thermo Scientific/Dionex, The Netherlands) equipped with a Dual Gradient Separation pump allowing for parallel LC analysis, and hyphenated to an Impact UHR-qTOF mass analyzer (Bruker Daltonics, Germany). Reversed-phase experiments (RPLC) were performed with an UHPLC BEH Shield RP18 column 100<!--> <!-->×<!--> <!-->2.1<!--> <!-->mm, 1.7<!--> <!-->μm (Waters) and HILIC experiments with a Luna HILIC column (Phenomenex, The Netherlands) of 100<!--> <span><math><mrow><mo>×</mo></mrow></math></span> <!-->2.00<!--> <!-->mm, 3<!--> <!-->μ<!--> <!-->m. RPLC data were acquired in ESI positive mode and HILIC in negative mode, respectively. The data acquisition rate was set to 1<!--> <!-->Hz over a mass range of <em>m</em>/<em>z</em> 50–1000. The LC–MS data files were aligned by using the in-house developed alignment algorithm MS-Align 2 tool (<span>www.ms-utils.org/msalign2</span><svg><path></path></svg>).</p></div><div><h3>Results</h3><p>After the data prepressing, which includes alignment, noise filtering and peak picking two data matrixes costing of 412 features (metabolites) for RPLC and 428 ones for HILIC were generated. To evaluate a degree of similarity between the two data matrixes the RV coefficient (a multivariate extension of correlation coefficient) was used. The coefficient has flattened at 0.58 showing that despite a strong overlap between the datasets there is a substantial number of the","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 12-13"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54308918","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.2015.08.009
O. Berezina , A. Shadrina , E. Voropaeva , T. Pospelova , M. Filipenko
{"title":"P113","authors":"O. Berezina , A. Shadrina , E. Voropaeva , T. Pospelova , M. Filipenko","doi":"10.1016/j.ejcsup.2015.08.009","DOIUrl":"https://doi.org/10.1016/j.ejcsup.2015.08.009","url":null,"abstract":"<div><h3>Background</h3><p>Methylation systems in the cells play an important role in the metabolic processes such as purine nucleotide biosynthesis and gene and protein activity regulation. An imbalance between entities in folic acid metabolism can adversely affect nucleotide synthesis and the DNA repair and methylation system, which can cause genome instability and impairments in chromosome segregation, and lead to abnormal expression of proto-oncogenes and inactivation of tumor suppressor genes. These processes may underlie the development of a range of cancer disease, including Non-Hodgkin’s lymphomas (NHL). Quite a few studies investigating the association of SNPs in the folate-metabolizing genes with NHL risk in populations of different ethnic origin are available to date. Because the low prevalence of this disease makes sampling difficult, most of these studies have small sizes, which may be one of the reasons why results obtained are often conflicting.</p><p>The aim of this study was to investigate the role of some SNPs in folate genes (the C677T and A1298C SNPs in the MTHFR gene, A2756G in MTR, A66G in SHMT1, G1958A in MTHFD1 and 844ins68 in CBS) in genetic susceptibility to non-Hodgkin’s malignant lymphoma in the west-Siberian region.</p></div><div><h3>Methods</h3><p>146 unrelated patients from the Haematological Center (Novosibirsk city) with various types of NHL were investigated. Genomic DNA was isolated from leukocytes in venous blood and from buccal epithelium, using the standard methods of DNA separation. A PCR-restriction fragment length polymorphism (RFLP) assay was used to detect the MTHFD1 G1958A and CBS 844ins68 SNPs. Genotyping of the MTHFR, MTR, MTRR and SHMT1 gene SNPs was carried out by real-time PCR allelic discrimination with TaqMan probes. The alleles and genotypes distribution of SNPs in patients were compared with their distribution in healthy white Russian subjects from Novosibirsk.</p></div><div><h3>Results</h3><p>We determined the allele and genotype frequencies for seven SNPs in folate metabolism in NHL and control groups. For all these SNPs, the genotype frequencies were in Hardy–Weinberg equilibrium in the control group. There were no statistically significant differences in the frequencies of alleles and genotypes of polymorphic loci of MTHFR, MTRR, CBS, SHMT1 genes between patients with NHL and controls. However, theG1958A MTHFD1 polymorphism showed a significant association with aggressive NHL. The 1958A allele (OR<!--> <!-->=<!--> <!-->0.578, C.I. [0.415–0.805], <em>p</em> <!--><<!--> <!-->0.001) and AA MTHFD1 genotype (OR<!--> <!-->=<!--> <!-->0.283, C.I. [0.130–0.613], <em>p</em> <!--><<!--> <!-->0.0008) were associated with decreased risk of aggressive lymphoma. The association between folate genes and indolent non-Hodgkin’s lymphoma was not revealed. The SNP G1958A causes the Arg653Gln substitution occurring in the formyltetrahydrofolate domain of the MTHFD enzyme. The substrate for this enzyme is","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 5"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138398228","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.2015.08.007
E. Batorov, M. Tikhonova, I. Kryuchkova, V. Sergeevicheva, D. Batorova, S. Sizikova, G. Ushakova, A. Gilevich, A. Ostanin, E. Chernykh
{"title":"P81","authors":"E. Batorov, M. Tikhonova, I. Kryuchkova, V. Sergeevicheva, D. Batorova, S. Sizikova, G. Ushakova, A. Gilevich, A. Ostanin, E. Chernykh","doi":"10.1016/j.ejcsup.2015.08.007","DOIUrl":"10.1016/j.ejcsup.2015.08.007","url":null,"abstract":"<div><p>Numerous studies have shown that high-dose chemotherapy and autologous hematopoietic stem cell transplantation (AHSCT) led to a profound and long-lasting state of immunodeficiency characterized by persisting low levels of T cells in hemoblastosis patients. Well-timed T-cell reconstitution is crucial for early restoration of anti-infectious and anti- tumor immune response. Lymphocyte recovery is mediated through the two main mechanisms – a homeostatic proliferation of T cells and generation of new naive T cells via thymopoiesis. It is known, that homeostatic proliferation is important for the restoration of T cell count in immune competent host during the 1st year following AHSCT. Thymus begins to fill up T cell repertoire approximately from the 6th month following AHSCT.</p><p>We have investigated dynamics of CD4+FOXP3+ Treg recovery following AHSCT and possible relationship between Tregs and clinical outcomes since the suppressive activity of Tregs under lymphopenic conditions may influence on peripheral expansion of T cells. Thymic activity following AHSCT has been evaluated by measuring amounts of CD4+ CD45RA+CD31+ naïve T cells, i.e. “recent thymic emigrants” (RTEs).109 patients with non-Hodgkin’s lymphomas, Hodgkin’s lymphoma and multiple myeloma underwent AHSCT in 2009–2014. The content of circulating CD4+FOXP3+ Tregs and CD4+CD45RA+CD31+ T cells was evaluated using flow cytometry before AHSCT, at the day of engraftment, and following 6 and 12<!--> <!-->months.</p><p>Pre-transplant count of CD4+FOXP3+ Tregs was significantly higher compared to healthy controls (5.4<!--> <!-->±<!--> <!-->2.9 vs 3.8<!--> <!-->±<!--> <!-->1.9%; <em>pU</em> <!-->=<!--> <!-->0.011; here and below data presented as Mean<!--> <!-->±<!--> <!-->SD). Percentage of Tregs restored rapidly and reached initially high level at the time of engraftment, and then subsequently decreased within a year until it lowered to healthy donors‘ values. CD4+FOXP3+ Tregs at the time of engraftment were increased in patients with relapse or progression of disease within 6 and 12<!--> <!-->months following AHSCT compared to non-relapsed patients (11.0<!--> <!-->±<!--> <!-->6.1 vs 6.2<!--> <!-->±<!--> <!-->3.0%; <em>pU</em> <!-->=<!--> <!-->0.016, and 10.1<!--> <!-->±<!--> <!-->5.2 vs 6.1<!--> <!-->±<!--> <!-->3.8%; <em>pU</em> <!-->=<!--> <!-->0.008). Pre-transplant count of CD4+CD45RA+CD31+ T cells was significantly lower compared to healthy controls (17.1<!--> <!-->±<!--> <!-->11.4 vs 30.3<!--> <!-->±<!--> <!-->11.2%, <em>pU</em> <!-->=<!--> <!-->0.0005) and did not reach donors‘ values following 12<!--> <!-->month (23.1<!--> <!-->±<!--> <!-->13.5%, <em>pU</em> <!-->=<!--> <!-->0.032). Relapsed patients had the same quantity of RTEs as the patients with remission within the 1st year following AHSCT. There was no any significant association between RTEs and Tregs counts.</p><p>Surprisingly, we have found high levels of circulating CD4+CD45RA- T cells co-expressing CD31 molecule i","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 4"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54308691","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.2015.08.010
N. Bgatova , I. Kulikova , I. Kachesov , R. Yui , M. Ergazina , S. Chepko , N. Isakova , Y. Borodin , V. Konenkov
{"title":"A94","authors":"N. Bgatova , I. Kulikova , I. Kachesov , R. Yui , M. Ergazina , S. Chepko , N. Isakova , Y. Borodin , V. Konenkov","doi":"10.1016/j.ejcsup.2015.08.010","DOIUrl":"10.1016/j.ejcsup.2015.08.010","url":null,"abstract":"<div><h3>Background</h3><p>Squamous cell carcinoma is the most common malignancy in the lower lip. Although lower lip squamous cell carcinoma is slow growing, up to 29% of tumors develop metastases to the cervical lymph nodes. Thus, identification of biological markers that could provide prognostic information about the invasive or metastatic potential of these lesions is important. It is known that angiogenesis, lymphangiogenesis and proliferation play an important role in tumor progression. Therefore, the goal of this study was to analyze the immunohistochemical expression of Ki-67, CD34 and Podoplanin in hyperkeratosis and in squamous cell carcinoma of the lower lip. It was intended to assess the possibility of using such markers as indicators of morphological aggressiveness of squamous cell carcinoma of the lower lip (LLSCC).</p></div><div><h3>Materials and methods</h3><p>Seventy-one cases of the lower lip lesions, obtained from the files of Novosibirsk Regional Oncology Center were selected for this study. The specimens were divided into three groups: a lower lip hyperkeratosis group consisting of 22 cases; LLSCC with keratinization consisting of 34 cases and LLSCC without keratinization consisting of 15 cases. To analyze angiogenesis, lymphangiogenesis and proliferation, we performed immunostains of the lower lip biopsy material for the CD34, vascular marker, Podoplanin, lymphatic-specific markers and Ki-67, marker of proliferation. Tissue samples were fixed in 10% neutral formalin, processed by standard histological techniques and embedded in paraffin. All steps of the immunohistochemical reaction were performed by using BENCHMARK/XT slide stainer (Ventana). The lymphatic and blood vessels volume density and Ki-67 cells numerical density were morphometrically analyzed in all groups and compared using the non-parametric Mann–Whitney test and the Wilcoxon signed rank test. A level of significance of 5% (<em>p</em> <!--><<!--> <!-->0.05) was adopted for all tests.</p></div><div><h3>Results</h3><p>All cases of a lower lip hyperkeratosis and LLSCC were positive for Ki-67, CD34 and Podoplanin. With respect to the pattern of staining, specimens exhibited a predominantly peripheral staining for CD34 and Podoplanin in inflammatory infiltrates and tumor sites. In contrast, staining for Ki-67 was predominantly central in inflammatory infiltrates and tumor sites in hyperkeratosis and LLSCC. When compared to lower lip hyperkeratosis, LLSCC (both with keratinization and without keratinization) showed a higher number of immunopositive Ki-67 cells (by 64% and 77%, respectively, <em>p</em> <!--><<!--> <!-->0.05). It was found that proliferative activity of tumor cells in LLSCC with keratinization was 2 times higher than that in LLSCC without keratinization. Comparison of the volume density of blood vessels showed that the density of CD34+ – blood vessels in hyperkeratosis was lower by 77% than in LLSCC without keratinization and lower by 64% than in ","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 6"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54308718","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.2015.08.100
A. Solovieva, E. V. Vorontsova, A. Poveshchenko, E. Nechaeva, R. Maksyutov, P. Avrorov, O. Gricik, A. Shurlygina, V. Konenkov, K. E. Zubareva
{"title":"A29: Melanoma B16F10 causes redistribution of bone marrow cells on model of tumor–host interaction","authors":"A. Solovieva, E. V. Vorontsova, A. Poveshchenko, E. Nechaeva, R. Maksyutov, P. Avrorov, O. Gricik, A. Shurlygina, V. Konenkov, K. E. Zubareva","doi":"10.1016/J.EJCSUP.2015.08.100","DOIUrl":"https://doi.org/10.1016/J.EJCSUP.2015.08.100","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"55-56"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.EJCSUP.2015.08.100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310198","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}