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A105: Morphological characteristics and clinical significance of tumor infiltrating CD20 B lymphocytes in gastric cancer A105:胃癌肿瘤浸润cd20b淋巴细胞的形态学特征及临床意义
Q3 Medicine Pub Date : 2015-11-01 DOI: 10.1016/j.ejcsup.2015.08.111
O. Tomchuk
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引用次数: 0
P11: Proteoglycans expression correlates with the phenotype of malignant and non-malignant EBV-positive B-cell lines P11:蛋白聚糖的表达与恶性和非恶性ebv阳性b细胞系的表型相关
Q3 Medicine Pub Date : 2015-11-01 DOI: 10.1016/J.EJCSUP.2015.08.112
A. Tsidulko, L. Matskova, L. Astakhova, I. Ernberg, E. Grigorieva
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引用次数: 0
A89: P450 1A subfamily as component of exosomes derived from HepG2 cells A89: P450 1A亚家族作为HepG2细胞外泌体的组成部分
Q3 Medicine Pub Date : 2015-11-01 DOI: 10.1016/J.EJCSUP.2015.08.116
E. V. Vorontsova, A. Grishanova, V. Lyakhovich
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引用次数: 0
P113 P113
Q3 Medicine Pub Date : 2015-11-01 DOI: 10.1016/j.ejcsup.2015.08.009
O. Berezina , A. Shadrina , E. Voropaeva , T. Pospelova , M. Filipenko

Background

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.

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.

Methods

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.

Results

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], p < 0.001) and AA MTHFD1 genotype (OR = 0.283, C.I. [0.130–0.613], p < 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

细胞甲基化系统在嘌呤核苷酸生物合成、基因和蛋白质活性调控等代谢过程中发挥着重要作用。叶酸代谢实体之间的不平衡会对核苷酸合成和DNA修复和甲基化系统产生不利影响,导致基因组不稳定和染色体分离受损,导致原癌基因异常表达和抑癌基因失活。这些过程可能是一系列癌症疾病发展的基础,包括非霍奇金淋巴瘤(NHL)。迄今为止,有相当多的研究调查了不同种族人群中叶酸代谢基因的snp与NHL风险的关系。由于这种疾病的低患病率使得采样困难,大多数这些研究的规模都很小,这可能是获得的结果经常相互矛盾的原因之一。本研究旨在探讨西西伯利亚地区叶酸基因中某些snp (MTHFR基因中的C677T和A1298C snp, MTR基因中的A2756G, SHMT1基因中的A66G, MTHFD1基因中的G1958A和CBS基因中的844ins68)在非霍奇金恶性淋巴瘤遗传易感性中的作用。方法对新西伯利亚市血液科中心不同类型非霍奇金淋巴瘤患者146例进行调查。采用标准的DNA分离方法,从静脉血白细胞和颊上皮细胞中分离基因组DNA。采用pcr -限制性片段长度多态性(RFLP)检测MTHFD1 G1958A和CBS 844ins68的snp。采用TaqMan探针对MTHFR、MTR、MTRR和SHMT1基因snp进行实时PCR等位基因识别分型。将患者snp的等位基因和基因型分布与新西伯利亚健康俄罗斯白种人的分布进行比较。结果测定了NHL患者和对照组叶酸代谢相关的7个snp的等位基因和基因型频率。所有这些snp的基因型频率在对照组均为Hardy-Weinberg平衡。NHL患者与对照组MTHFR、MTRR、CBS、SHMT1基因多态性位点等位基因频率及基因型差异均无统计学意义。然而,g1958a MTHFD1多态性显示与侵袭性NHL显著相关。1958年的一个等位基因(或= 0.578、C.I. [0.415 - -0.805], p & lt;0.001)和AA MTHFD1基因型(OR = 0.283, C.I. [0.130-0.613], p <0.0008)与侵袭性淋巴瘤风险降低相关。叶酸基因与惰性非霍奇金淋巴瘤之间的关系未被揭示。SNP G1958A导致在MTHFD酶的甲酰基四氢叶酸结构域发生Arg653Gln取代。这种酶的底物是四氢叶酸(THF)。THF的积累可能导致5,10-亚甲基四氢叶酸浓度的增加,这反过来可能提高胸苷酸合成和DNA甲基化的效率。总之,这些过程可能有助于抑制恶性转化。结论MTHFD1基因1958a SNP与NHL易感性有关。突变等位基因和基因型可能通过影响细胞内叶酸代谢物的浓度来决定保护作用。
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引用次数: 0
Barriers to the Entry of Biofield Healing Into "Mainstream" Healthcare. 生物场疗法进入 "主流 "医疗领域的障碍。
Q3 Medicine Pub Date : 2015-11-01 DOI: 10.7453/gahmj.2015.025.suppl
David J Hufford, Meredith Sprengel, John A Ives, Wayne Jonas

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.

在本文中,我们阐述了生物场疗法进入当代主流科学和临床实践的障碍。托马斯-库恩(Thomas Kuhn,1922-1996 年)是 20 世纪最重要、也是最具争议性的科学哲学家之一。库恩从科学界的动态角度分析了科学及其革命性变化。库恩的方法有助于我们理解生物场疗法等非常规医学理论和实践。多年来,这些疗法被称为 "补充和替代医学"(CAM)。(1)生物场疗法非常适合整合模式,它提供了一种新颖的治疗干预方法,并且正在以一种能够与当前医学科学进行简单整合的方式发展。然而,由于其概念基础与有关现实本质的传统假设形成鲜明对比,它仍然游离于传统框架之外。
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引用次数: 0
T93 T93
Q3 Medicine Pub Date : 2015-11-01 DOI: 10.1016/j.ejcsup.2015.08.017
N. Cherdyntseva , M. Stakheyeva , N. Litviakov , M. Zavyalova , Y. Kukharev , J. Kzhyshkowska

Background

Risk of metastasis formation is provided by both tumor cell biological characteristics and the microenvironment features within the primary tumor along with local and systemic conditions for metastatic niche formation. The inflammatory infiltration has been shown to strongly impact on tumor progression (Whiteside, 2013). Dronca et al. (2011) showed that immunosuppressive factors in the tumor microenvironment may impair not only local immune responses but also disturb systemic immunity. Zitvogel et al. anticipate that the comprehension of the mechanisms governing the immunogenicity of cell death will have a profound impact on the design of anticancer therapies.To study the impact of immune system on clinical response to neoadjuvant chemotherapy and metastasis-free survival in breast cancer patients.

Materials and methods

350 patients with newly diagnosed invasive breast cancer treated with neoadjuvant chemotherapy (NAC) were enrolled into the study. The procedures were made in accordance with the Helsinki Declaration. Clinical response to chemotherapy, the 5-year metastasis-free survival and all major clinical and morphological parameters were determined. The original method of multidimensional data visualization was applied to present the immune system state as integral entirety in visual image for classification of patients with different risk of metastasis (NovoSpark Corporation, Canada). Copy number aberrations (CNA) of cytokine gene regions in tumor specimens were tested using high-density microarray platform CytoScanTM HD Array (Affymetrix, USA). Cytokine gene polymorphism was analyzed. Subpopulations of lymphocytes and macrophages were determined within the primary tumors by IHC.

Results

We found, that favorable clinical immediate response to preoperative chemotherapy was related to the high levels of IL-1beta, TNF-alpha and IL-10 production by peripheral mononuclear cells before the treatment. This correlation was further confirmed by data from the study on association between cytokine gene functional polymorphism and response to NAC. We used NovoSpark Corporation visualization approach allowing the representation the immune system state as integral unit and to discriminate breast cancer patients with high and low risk of haematogeneic metastasis. When estimated before cancer treatment, 95% of breast cancer patients had risk of metastasis. The neoadjuvant chemotherapy and surgical tumor removal reduced the risk of tumor progression to 62–71%. However, in a year after adjuvant chemo- and radiotherapy, the patient group with high risk of metastases increased to 81% again. Thus, the cancer treatment can change the primarily estimated outcome prognosis in breast cancer patients, and the monitoring of immune system is a promising approach to predict the risk of cancer progression or resistance to the therapy. We have found the connection between the profile of intra-tu

肿瘤细胞生物学特性和原发肿瘤内的微环境特征以及转移生态位形成的局部和全身条件共同决定了转移形成的风险。炎症浸润已被证明对肿瘤进展有强烈影响(Whiteside, 2013)。Dronca等(2011)研究表明,肿瘤微环境中的免疫抑制因子不仅会损害局部免疫应答,还会干扰全身免疫。Zitvogel等人预计,对控制细胞死亡免疫原性的机制的理解将对抗癌疗法的设计产生深远的影响。研究免疫系统对乳腺癌患者新辅助化疗临床反应及无转移生存期的影响。材料与方法采用新辅助化疗(NAC)治疗的新诊断浸润性乳腺癌患者350例。这些程序是根据《赫尔辛基宣言》制定的。观察患者对化疗的临床反应、5年无转移生存期及所有主要临床和形态学参数。采用独创的多维数据可视化方法,将免疫系统状态作为一个整体呈现在视觉图像中,用于对不同转移风险的患者进行分类(NovoSpark Corporation, Canada)。采用高密度微阵列平台CytoScanTM HD Array (Affymetrix, USA)检测肿瘤标本中细胞因子基因区域拷贝数畸变(Copy number aberrations, CNA)。细胞因子基因多态性分析。用免疫组化法测定原发肿瘤内淋巴细胞和巨噬细胞亚群。结果我们发现,术前化疗的良好临床即时反应与治疗前外周单核细胞高水平的il -1 β、tnf - α和IL-10的产生有关。细胞因子基因功能多态性与NAC应答的相关性研究数据进一步证实了这一相关性。我们使用NovoSpark公司的可视化方法,将免疫系统状态作为一个整体单元来表示,并区分血液转移高风险和低风险的乳腺癌患者。在癌症治疗前估计,95%的乳腺癌患者有转移的风险。新辅助化疗和手术切除肿瘤将肿瘤进展的风险降低至62-71%。然而,在辅助化疗和放疗后一年,转移高风险患者组再次增加到81%。因此,癌症治疗可以改变乳腺癌患者最初估计的预后,免疫系统监测是预测癌症进展风险或治疗抵抗的一种很有前景的方法。我们已经发现了肿瘤内炎症因子与化疗疗效之间的联系。肿瘤细胞细胞因子基因位点的染色体异常(CNA -拷贝数畸变)-缺失和扩增可能影响细胞因子基因的表达。我们发现临床对NAC的反应与IL-10和CHI3L1 (YKL40)基因功能的获得密切相关。相反,由于相应的CNA导致的tnf - α和IL-17基因功能的丧失与NAC的良好应答相关。乳腺癌患者的无转移生存率与CNA密切相关。结论肿瘤生长及其播散对全身和肿瘤内免疫系统的激活参数需要进一步验证,以确定新辅助化疗疗效的新预后指标。
{"title":"T93","authors":"N. Cherdyntseva ,&nbsp;M. Stakheyeva ,&nbsp;N. Litviakov ,&nbsp;M. Zavyalova ,&nbsp;Y. Kukharev ,&nbsp;J. Kzhyshkowska","doi":"10.1016/j.ejcsup.2015.08.017","DOIUrl":"10.1016/j.ejcsup.2015.08.017","url":null,"abstract":"<div><h3>Background</h3><p>Risk of metastasis formation is provided by both tumor cell biological characteristics and the microenvironment features within the primary tumor along with local and systemic conditions for metastatic niche formation. The inflammatory infiltration has been shown to strongly impact on tumor progression (Whiteside, 2013). Dronca et al. (2011) showed that immunosuppressive factors in the tumor microenvironment may impair not only local immune responses but also disturb systemic immunity. Zitvogel et al. anticipate that the comprehension of the mechanisms governing the immunogenicity of cell death will have a profound impact on the design of anticancer therapies.To study the impact of immune system on clinical response to neoadjuvant chemotherapy and metastasis-free survival in breast cancer patients.</p></div><div><h3>Materials and methods</h3><p>350 patients with newly diagnosed invasive breast cancer treated with neoadjuvant chemotherapy (NAC) were enrolled into the study. The procedures were made in accordance with the Helsinki Declaration. Clinical response to chemotherapy, the 5-year metastasis-free survival and all major clinical and morphological parameters were determined. The original method of multidimensional data visualization was applied to present the immune system state as integral entirety in visual image for classification of patients with different risk of metastasis (NovoSpark Corporation, Canada). Copy number aberrations (CNA) of cytokine gene regions in tumor specimens were tested using high-density microarray platform CytoScanTM HD Array (Affymetrix, USA). Cytokine gene polymorphism was analyzed. Subpopulations of lymphocytes and macrophages were determined within the primary tumors by IHC.</p></div><div><h3>Results</h3><p>We found, that favorable clinical immediate response to preoperative chemotherapy was related to the high levels of IL-1beta, TNF-alpha and IL-10 production by peripheral mononuclear cells before the treatment. This correlation was further confirmed by data from the study on association between cytokine gene functional polymorphism and response to NAC. We used NovoSpark Corporation visualization approach allowing the representation the immune system state as integral unit and to discriminate breast cancer patients with high and low risk of haematogeneic metastasis. When estimated before cancer treatment, 95% of breast cancer patients had risk of metastasis. The neoadjuvant chemotherapy and surgical tumor removal reduced the risk of tumor progression to 62–71%. However, in a year after adjuvant chemo- and radiotherapy, the patient group with high risk of metastases increased to 81% again. Thus, the cancer treatment can change the primarily estimated outcome prognosis in breast cancer patients, and the monitoring of immune system is a promising approach to predict the risk of cancer progression or resistance to the therapy. We have found the connection between the profile of intra-tu","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 10"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54308814","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}
引用次数: 0
T35 T35
Q3 Medicine Pub Date : 2015-11-01 DOI: 10.1016/j.ejcsup.2015.08.044
F. Kisseljov, S. Vinokurova, N. Kisseljova, L. Pavlova, M. Fedorova, A. Katargin, A. Petrenko, L. Korolenkova

Epigenetics investigates mechanisms that control inheritance of gene expression program during somatic cell divisions. These mechanisms include regulation by DNA methylation, histone post-translational modifications and nucleosome positioning, functioning of regulatory non-coding RNAs, control of alternative splicing of mRNA precursors and high-order chromatin organization. Genome-wide loss of epigenetic stability and increased epigenetic plasticity are common features of all tumor types. In normal tissues epigenetic plasticity allow cells to response on environment signals. Thus, in tumor cells its constitutive activation leads to epigenetic heterogeneity that are the additional hallmark of the most of the classical cancers. Cervical cancers are one of the most interesting models for the analysis of the role of epigenetic changes in tumor progression. These types of tumors are associated with infection of human papilloma viruses of so-called high-risk group (HR-HPV) and characterized by well-defined stages of malignant conversion from intraepithelial neoplasias to carcinomas. The viral DNA can persist in episomal form or integrates into the host-cell genome.

Cellular genomes encode genetic information in their linear sequence, but appropriate gene expression requires chromosomes to fold into dynamic complex three-dimensional structures. Scaffold/matrix attachment regions (S/MARs) are specialized genomic DNA sequences that take part in organization of these structures. We demonstrated that methylation of S/MARs was required for their attachment to nuclear matrix and that methylation status of S/MARs was changed in cervical cancer cell compared to normal cells.

DNA methylation plays an important role in the regulation of gene expression. We found that methylation of the regulatory sequences in the HPV16 genome specifically changes in transformed compared to the normal cervical epithelial cells. Next, we showed that methylation of the transcription factor binding sites modulates the viral oncogene expression. These data suggest that the HPV16 genome methylation may represent an important mechanism that initiates the development of HPV-associated tumors.

Using next generation sequencing, we identified pattern of differentially expressed microRNAs in clinical samples of the cervical lesions. We confirmed expression of microRNAs that have been described previously as well as identified new microRNAs that can be potentially involved in the development and progression of cervical cancer. Spectrum of differentially expressed microRNAs includes microRNAs targeting tumor-suppressor genes as well as oncogenes.

Telomerase is a key regulator of cell proliferation. This enzyme is silent in normal cells and activated in most of the tumors. Few forms of RNA (hTERT), encoded by telomerase gene were detected in different tumor cells and among them three forms (alfa, beta and gamma) are most well pronounced. We found that in cervical

表观遗传学研究体细胞分裂过程中基因表达程序的遗传控制机制。这些机制包括DNA甲基化、组蛋白翻译后修饰和核小体定位、调节性非编码rna的功能、mRNA前体选择性剪接的控制和高阶染色质组织。表观遗传稳定性的全基因组丧失和表观遗传可塑性的增加是所有肿瘤类型的共同特征。在正常组织中,表观遗传可塑性允许细胞对环境信号作出反应。因此,在肿瘤细胞中,其组成性激活导致表观遗传异质性,这是大多数经典癌症的额外标志。子宫颈癌是分析表观遗传变化在肿瘤进展中的作用的最有趣的模型之一。这些类型的肿瘤与所谓的高危人群(HR-HPV)的人乳头瘤病毒感染有关,其特征是从上皮内瘤变到癌的恶性转化的明确阶段。病毒DNA可以以附体形式存在或整合到宿主细胞基因组中。细胞基因组以其线性序列编码遗传信息,但适当的基因表达需要染色体折叠成动态复杂的三维结构。支架/基质附着区(S/MARs)是参与这些结构组织的特殊基因组DNA序列。我们证明了S/MARs的甲基化是其附着于核基质所必需的,并且与正常细胞相比,S/MARs的甲基化状态在宫颈癌细胞中发生了变化。DNA甲基化在基因表达调控中起着重要作用。我们发现,与正常宫颈上皮细胞相比,转化后的HPV16基因组中调控序列的甲基化发生了特异性变化。接下来,我们发现转录因子结合位点的甲基化调节了病毒癌基因的表达。这些数据表明,HPV16基因组甲基化可能是启动hpv相关肿瘤发展的重要机制。使用下一代测序,我们确定了宫颈病变临床样本中差异表达的microrna模式。我们证实了先前描述的microrna的表达,并鉴定了可能参与宫颈癌发生和进展的新microrna。差异表达的microRNAs谱包括靶向肿瘤抑制基因的microRNAs和靶向癌基因的microRNAs。端粒酶是细胞增殖的关键调控因子。这种酶在正常细胞中是沉默的,在大多数肿瘤中被激活。端粒酶基因编码的RNA (hTERT)在不同的肿瘤细胞中检测到几种形式,其中三种形式(α、β和γ)最为明显。我们发现在宫颈肿瘤中这三种形式的表达都显著增加。在某些情况下,我们还观察到邻近“正常组织”中hTERT的表达水平较高。这三种表达水平的相关性在疾病的不同阶段有所不同(上皮内瘤变和癌的三个阶段)。这三种hTERT形式的功能仍然没有得到很好的理解。
{"title":"T35","authors":"F. Kisseljov,&nbsp;S. Vinokurova,&nbsp;N. Kisseljova,&nbsp;L. Pavlova,&nbsp;M. Fedorova,&nbsp;A. Katargin,&nbsp;A. Petrenko,&nbsp;L. Korolenkova","doi":"10.1016/j.ejcsup.2015.08.044","DOIUrl":"10.1016/j.ejcsup.2015.08.044","url":null,"abstract":"<div><p>Epigenetics investigates mechanisms that control inheritance of gene expression program during somatic cell divisions. These mechanisms include regulation by DNA methylation, histone post-translational modifications and nucleosome positioning, functioning of regulatory non-coding RNAs, control of alternative splicing of mRNA precursors and high-order chromatin organization. Genome-wide loss of epigenetic stability and increased epigenetic plasticity are common features of all tumor types. In normal tissues epigenetic plasticity allow cells to response on environment signals. Thus, in tumor cells its constitutive activation leads to epigenetic heterogeneity that are the additional hallmark of the most of the classical cancers. Cervical cancers are one of the most interesting models for the analysis of the role of epigenetic changes in tumor progression. These types of tumors are associated with infection of human papilloma viruses of so-called high-risk group (HR-HPV) and characterized by well-defined stages of malignant conversion from intraepithelial neoplasias to carcinomas. The viral DNA can persist in episomal form or integrates into the host-cell genome.</p><p>Cellular genomes encode genetic information in their linear sequence, but appropriate gene expression requires chromosomes to fold into dynamic complex three-dimensional structures. Scaffold/matrix attachment regions (S/MARs) are specialized genomic DNA sequences that take part in organization of these structures. We demonstrated that methylation of S/MARs was required for their attachment to nuclear matrix and that methylation status of S/MARs was changed in cervical cancer cell compared to normal cells.</p><p>DNA methylation plays an important role in the regulation of gene expression. We found that methylation of the regulatory sequences in the HPV16 genome specifically changes in transformed compared to the normal cervical epithelial cells. Next, we showed that methylation of the transcription factor binding sites modulates the viral oncogene expression. These data suggest that the HPV16 genome methylation may represent an important mechanism that initiates the development of HPV-associated tumors.</p><p>Using next generation sequencing, we identified pattern of differentially expressed microRNAs in clinical samples of the cervical lesions. We confirmed expression of microRNAs that have been described previously as well as identified new microRNAs that can be potentially involved in the development and progression of cervical cancer. Spectrum of differentially expressed microRNAs includes microRNAs targeting tumor-suppressor genes as well as oncogenes.</p><p>Telomerase is a key regulator of cell proliferation. This enzyme is silent in normal cells and activated in most of the tumors. Few forms of RNA (hTERT), encoded by telomerase gene were detected in different tumor cells and among them three forms (alfa, beta and gamma) are most well pronounced. We found that in cervical","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 25"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309431","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}
引用次数: 0
P123 P123
Q3 Medicine Pub Date : 2015-11-01 DOI: 10.1016/j.ejcsup.2015.08.064
E. Matiunina , A. Kozlov , A. Emelyanov

The origin of evolutionary novel genes is connected with the origin and evolution of the novel organismal functions and the increase in morphological complexity of multicellular organisms. Novel gene acquire new or altered functions. Here we describe that evolutionary novel genes, expressed predominantly in transgenic fish tumors after their induced regression, determine progressive evolutionary characters and are conserved in human.

We used a sample of genes, which were activated in inducible krasV12 transgenic zebrafish tumors according to the results of RNASeq data. Genes from our sample were expressed after HCC regression upon kras inactivation. The search of orthologs by different tools, such as blastx and psiblast, with e-value cut off not less than 10–3 and query coverage more than 50%, discovered that considerable proportion of tumor-specifically expressed genes are evolutionary novel, i.e. their orthologs are not found in Lamprey. Nine tenths of these novel genes have orthologs in humans. Gene ontology (GO) data were used to analyze their functions. According to the results of GO, some of the genes have functions not characteristic to fish. Among known functions of the human orthologues of evolutionary novel genes of zebrafish (vs. Lamprey) there are some important morphogenetic functions. For example, genes ccdc40, lmx1ba and lepa acquired functions in lung, embryonic utera and placenta, i.e. organs originated in taxa higher than fish. A large proportion of genes from our sample are connected with retina type eye, heart and brain development.

进化新基因的起源与生物新功能的起源和进化以及多细胞生物形态复杂性的增加有关。新的基因获得新的或改变的功能。在这里,我们描述了进化的新基因,主要在转基因鱼肿瘤诱导回归后表达,决定了渐进进化特征,并在人类中保守。我们使用了一组基因样本,根据RNASeq数据的结果,这些基因在可诱导的krasV12转基因斑马鱼肿瘤中被激活。我们样本中的基因在kras失活后HCC消退后表达。通过blastx和psiblast等不同工具搜索同源物,e值切断不小于10-3,查询覆盖范围大于50%,发现相当一部分肿瘤特异性表达基因是进化新基因,即在七鳃鳗中没有发现它们的同源物。这些新基因中有十分之九在人类中有同源物。利用基因本体(GO)数据对其功能进行分析。根据氧化石墨烯的结果,一些基因具有非鱼类特有的功能。在斑马鱼(vs.七鳃鳗)进化新基因的人类同源物中,有一些重要的形态发生功能。例如,ccdc40、lmx1ba和lepa基因在肺、胚胎子宫和胎盘中获得功能,即起源于高于鱼类的分类群的器官。我们样本中的大部分基因与视网膜型眼睛、心脏和大脑发育有关。
{"title":"P123","authors":"E. Matiunina ,&nbsp;A. Kozlov ,&nbsp;A. Emelyanov","doi":"10.1016/j.ejcsup.2015.08.064","DOIUrl":"10.1016/j.ejcsup.2015.08.064","url":null,"abstract":"<div><p>The origin of evolutionary novel genes is connected with the origin and evolution of the novel organismal functions and the increase in morphological complexity of multicellular organisms. Novel gene acquire new or altered functions. Here we describe that evolutionary novel genes, expressed predominantly in transgenic fish tumors after their induced regression, determine progressive evolutionary characters and are conserved in human.</p><p>We used a sample of genes, which were activated in inducible krasV12 transgenic zebrafish tumors according to the results of RNASeq data. Genes from our sample were expressed after HCC regression upon kras inactivation. The search of orthologs by different tools, such as blastx and psiblast, with e-value cut off not less than 10–3 and query coverage more than 50%, discovered that considerable proportion of tumor-specifically expressed genes are evolutionary novel, i.e. their orthologs are not found in Lamprey. Nine tenths of these novel genes have orthologs in humans. Gene ontology (GO) data were used to analyze their functions. According to the results of GO, some of the genes have functions not characteristic to fish. Among known functions of the human orthologues of evolutionary novel genes of zebrafish (vs. Lamprey) there are some important morphogenetic functions. For example, genes ccdc40, lmx1ba and lepa acquired functions in lung, embryonic utera and placenta, i.e. organs originated in taxa higher than fish. A large proportion of genes from our sample are connected with retina type eye, heart and brain development.</p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 36"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309718","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}
引用次数: 1
P100 P100
Q3 Medicine Pub Date : 2015-11-01 DOI: 10.1016/j.ejcsup.2015.08.071
E. Nikitina , O. Cheremisina , D. Kulbakin , N. Litviakov

The purpose of the study was to access pattern of microRNA expression in tissue of precancerous lesions and larynx cancer.

A total of 25 people with a diagnosis of dysplasia II–III (n = 10), control group (dysplasia 0, n = 15) and larynx cancer patients (n = 46) were examined. Fresh frozen biopsies and adjacent normal epithelium were used. The diagnosis was verified by histology. All qRT-PCR data were analyzed using the Pfaffl analysis. Multiplex RT-PCR on miRNA templates were performed as described by Chen et al. (2005). TaqMan miRNA assays (Iyevleva et al., 2012) were used to quantify expression of mature miRNAs of interest (miR-18a, -21, -155, -200a, -200c, -205, -221, -494). Data were analyzed using Welsh t-test with a 5% FDR correction. According to our results, aberrant expression of some miRNAs was showed. There was no significant differences in miRNA expression in a total group (n = 25) although a trend towards overexpression of oncogenic miRNA-21 and -155 according to severity of dysplastic changes in a tissue were present. Detailed analysis showed significant overexpression of that miRNAs as well as miRNA-200c and -205 in a group of dysplasia II- III against control group (15 vs 10, p = 0.019, p = 0.045 and p = 0.020, p = 0.038, respectively) but these results did not meet 5% FDR correction.

Data showed overexpression of the same microRNA (-205, -155, -200 and -21) in larynx cancer patients compared to control group (46 vs 15, p = 0.0002, p = 0.008, p = 0.009, p = 0.013, respectively). It should be pointed that microRNA pattern both in larynx cancer and patients with dysplasia II-III was very close showing similarity of these groups at molecular level. Frequency of cases with microRNA-205 overexpression was 2.98 times higher in cancer patients than in those who had no malignant transformation (CI 95%, 1.41–16.26, p = 0.007). Data showed that up regulation of microRNA-205 could be a marker of disease progression (OR = 4.79). Three other microRNAs did not show any promising results as biomarkers of cancer progression but data obtained has interesting fundamental value.

These miRs (-21, -155, -205 and -200c) are known to be regulators of processes that play an emergent role in carcinogenesis and our results obtained in vivo highlight and expand knowledge about some aspects of larynx cell transformation. Data suggest that miRNAs changing its expression according to dysplasia progress and could be important players in complex process of carcinogenesis as well as could be potential markers of disease progression.

本研究的目的是获取microRNA在癌前病变和喉癌组织中的表达模式。共检查诊断为II-III型发育不良的25例(n = 10),对照组(0例,n = 15)和喉癌患者(n = 46)。采用新鲜冷冻活检和邻近正常上皮。该诊断经组织学证实。所有qRT-PCR数据均采用Pfaffl分析。按照Chen等人(2005)的描述,对miRNA模板进行多重RT-PCR。TaqMan miRNA测定法(Iyevleva et al., 2012)用于量化感兴趣的成熟miRNA (miR-18a, -21, -155, -200a, -200c, -205, -221, -494)的表达。数据分析采用威尔士t检验,FDR校正为5%。根据我们的研究结果,一些mirna出现了异常表达。总的组(n = 25) miRNA表达没有显著差异,尽管根据组织中发育不良变化的严重程度存在致癌miRNA-21和-155的过表达趋势。详细分析显示,与对照组相比,II- III型发育不良组的miRNAs以及miRNA-200c和-205显著过表达(分别为15比10,p = 0.019, p = 0.045和p = 0.020, p = 0.038),但这些结果不符合5%的FDR校正。数据显示,与对照组相比,喉癌患者中相同的microRNA(-205, -155, -200和-21)过表达(分别为46 vs 15, p = 0.0002, p = 0.008, p = 0.009, p = 0.013)。需要指出的是,喉癌和II-III型发育不良患者的microRNA模式非常接近,在分子水平上具有相似性。microRNA-205在肿瘤患者中的过表达频率是未发生恶性转化患者的2.98倍(CI 95%, 1.41 ~ 16.26, p = 0.007)。数据显示,microRNA-205的上调可能是疾病进展的标志(OR = 4.79)。另外三种microrna作为癌症进展的生物标志物没有显示出任何有希望的结果,但获得的数据具有有趣的基础价值。已知这些miRs(-21、-155、-205和-200c)是在癌变过程中发挥紧急作用的过程的调节因子,我们在体内获得的结果突出并扩展了对喉部细胞转化某些方面的认识。数据表明,mirna根据发育不良的进展改变其表达,可能在复杂的癌变过程中发挥重要作用,也可能是疾病进展的潜在标志物。
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引用次数: 0
A29: Melanoma B16F10 causes redistribution of bone marrow cells on model of tumor–host interaction A29:黑色素瘤B16F10在肿瘤-宿主相互作用模型中引起骨髓细胞的重新分布
Q3 Medicine Pub Date : 2015-11-01 DOI: 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
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引用次数: 0
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Ejc Supplements
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