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A75 A75
Q3 Medicine Pub Date : 2015-11-01 DOI: 10.1016/j.ejcsup.2015.08.047
D. Korobkov , N. Plotnikova , G. Meltsaev , S. Kemaykin , A. Almyashev , S. Haritonov

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.

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.

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

乳腺癌是女性中最常见的癌症之一。2014年,摩尔多瓦共和国的乳腺癌发病率为每10万女性人口69.9例。在PRADI原癌基因转化的情况下,当癌蛋白过度表达转换时,乳腺癌发生。在原发性乳腺肿瘤中,三个致癌基因Her2/neu、C-mys、Int-2以及抑制基因p53基因和视网膜母细胞瘤基因RB的突变和表达是最常见的。一些研究发现,癌基因- C-mys在16.8%的原发性乳腺癌病例中表达,在随后发生转移的病例中表达的比例为35%。刺激有丝分裂原活化蛋白激酶磷酸化的蛋白质可以在生长因子的影响下被激活。乳腺癌的发展是由许多激素和生长因子的复杂相互作用调节的。目前,乳腺癌发展的主要理论之一是在肿瘤发展过程中增加的激素刺激增殖过程。肿瘤中激素失衡的表现之一是血液竞争抑制剂雌激素-孕酮的生物学效应有规律的降低,这与肿瘤的扩散阶段有关。雌激素过量在乳腺癌发病机制中的作用得到了以下事实的证实:在38岁之前接受过卵巢切除术的女性患乳腺癌的风险比未接受过此类手术的女性低1.5倍。脂质过氧化产物在瘤变区域的过度积累激活了破坏细胞间相互作用的机制,从而导致细胞膜脂质成分的破坏。研究小组包括112名在摩尔多瓦共和国国家卫生机构"国家肿瘤中心"接受治疗的患者。为了确定肿瘤的性质,所有患者都进行了免疫组织化学分析。在48%的乳腺癌病例中发现雄激素受体,肿瘤中雄激素受体的表达水平远低于雌激素和孕激素受体的表达水平。乳腺癌细胞中孕酮受体的低表达与肿瘤细胞中Ki-67抗原、HER-2癌蛋白的高表达相结合。HER-2(3+)和(2+)型患者与HER-2(0)和(1+)型患者相比,淋巴结多发转移更为频繁。HER-2癌蛋白在肿瘤细胞中的最高表达表明肿瘤细胞具有高转移潜力,预后较差。可以得出结论,乳腺癌的细胞和分子机制是复杂的。因此,癌变具有“多步骤”的性质,在同一克隆细胞中至少有两个或两个以上的突变——亲本和子代——才能产生恶性肿瘤。因此,致癌转化的发展并不一定意味着肿瘤形成的过程。
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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
P158 P158
Q3 Medicine Pub Date : 2015-11-01 DOI: 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

Background

Opisthorchiasis is a form of foodborne trematodiasis which is caused by liver flukes. It has been shown that a chronic Opisthorchiasis 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.

Materials and methods

28 patients with O. felineus 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 × 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 m/z 50–1000. The LC–MS data files were aligned by using the in-house developed alignment algorithm MS-Align 2 tool (www.ms-utils.org/msalign2).

Results

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

肺吸虫病是一种由肝吸虫引起的食源性吸虫病。已有研究表明,慢性蛇胸腺病感染可增加患肝胆管癌的风险。人们普遍认为,寄生虫微环境(胆汁)中稳态的逐渐改变会导致肝吸虫诱导的癌症。然而,目前还没有系统的、分析驱动的研究证实这一假设。临床材料的有限获取和生物基质(胆汁)的极端复杂性都是该领域取得进展的重要“限速因素”。在这里,我们首次对胆管癌相关疾病患者收集的胆汁液进行跨平台质谱分析。我们发现,对胆汁汁等复杂生物基质的有效分析需要正交分析平台(例如,hplc - ms和HILIC-MS)的组合,以最大限度地覆盖代谢空间。材料与方法选取28例猫纹弓形虫感染患者和30例阴性对照。通过显微镜对胆汁进行分析,确认感染情况。采用无菌穿刺法从胆囊中采集胆汁标本,直接冷冻保存于- 80°C,待分析。样本被随机组织到由样本和质量控制(QC)组成的采集块中。实验用Dionex Ultimate 3000 LC系统(Thermo Scientific/Dionex,荷兰)进行,配备双梯度分离泵,允许平行LC分析,并连接到Impact UHR-qTOF质量分析仪(Bruker Daltonics,德国)。反相实验(RPLC)采用UHPLC BEH Shield RP18柱(100 × 2.1 mm, 1.7 μm) (Waters), HILIC实验采用Luna HILIC柱(100 × 2.00 mm, 3 μm) (Phenomenex,荷兰),在ESI正模式和负模式下分别获得RPLC和HILIC数据。数据采集速率设置为1hz,质量范围为m/z 50-1000。使用内部开发的比对算法MS-Align 2工具(www.ms-utils.org/msalign2).ResultsAfter)对LC-MS数据文件进行比对,生成数据预处理,包括比对、噪声滤波和选峰两个数据矩阵,其中RPLC为412个特征(代谢物),HILIC为428个特征(代谢物)。为了评估两个数据矩阵之间的相似程度,使用了RV系数(相关系数的多变量扩展)。该系数趋于平缓,为0.58,表明尽管数据集之间有很强的重叠,但仍有大量的“平台特异性”代谢物。如果应用单一平台策略,这些结构肯定会被忽略。结论本文首次对胆管癌相关疾病患者的胆汁液进行了跨平台质谱分析。我们表明,这两个平台的组合极大地提高了代谢组的覆盖范围,因此应该是复杂生物基质探索性研究的首选。工作是利用托木斯克地区通用中心的技术设备进行的,这些设备是由俄罗斯政府根据第14.594.21.0001号协议(RFMEFI59414X0001)授予的。本项目由托木斯克国立大学学术D.I.门捷列夫基金项目资助(No. 18.1.52.2015)。
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引用次数: 0
A104 A104
Q3 Medicine Pub Date : 2015-11-01 DOI: 10.1016/j.ejcsup.2015.08.086
V. Rybko, N. Khromova, M. Farmakovskaya, M. Novikova, B. Kopnin, P. Kopnin

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.

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 αSmooth-Muscle Actin (αSMA).

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.

MC1 but not MC2 started to express αSMA 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.

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.

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.

恶性肿瘤不仅包括肿瘤细胞,还包括各种正常细胞,如成纤维细胞、巨噬细胞或内皮细胞。这些正常细胞处于转化细胞的持续压力下,调节其特性并将其转化为促进肿瘤的细胞。肿瘤-间质相互作用发生在癌变的所有阶段。受体与配体结合后的Notch激活是胚胎和组织发生过程中直接的细胞间通讯方式,决定了分化、增殖等多种过程。先前的研究表明,在肿瘤中,这种信号级联不仅调节转化细胞的特性,还调节基质细胞的活性,即新生血管生成。Notch在肿瘤细胞和间质成纤维细胞之间的通讯中的作用尚未得到充分研究。肿瘤相关间质成纤维细胞(CAFs)是肿瘤分泌生长因子和蛋白酶、调节免疫反应和促进肿瘤干细胞龛形成的重要组成部分。CAFs类似于肌成纤维细胞,表达α平滑肌肌动蛋白(αSMA)。我们获得并鉴定了正常间充质细胞的培养物:肌成纤维细胞样(MF)和成纤维细胞样MC1和MC2,它们的Notch1表达不同。这些细胞培养对裸鼠结肠癌缺口配体jagged2阳性HCT116异种细胞的生长有不同的影响。MF细胞的促瘤活性最强,而notch1缺失的MC2细胞的促瘤活性最弱。MC1与肿瘤HCT116细胞体外共培养后开始表达αSMA, MC2不表达αSMA。根据荧光素酶报告基因,这种共同培养也会导致Notch激活。NICD (Notch胞内结构域)的表达激活了MC1和MC2,而MC1中Notch1的沉默在体外破坏了hct116介导的成纤维细胞的激活及其在体内的促肿瘤活性。间充质细胞中的Notch信号刺激TGFb的产生,导致自分泌和旁分泌受体的刺激。我们认为,在我们的实验系统中,这种细胞因子激活了成纤维细胞。我们还发现这个过程是p53依赖的。因此,我们已经证明Notch1参与肿瘤-基质相互作用,特别是其激活导致成纤维细胞转分化。notch1刺激的成纤维细胞能够产生TGFb并促进肿瘤生长。在我们的实验系统中,各种成纤维细胞的肿瘤刺激能力取决于它们在Notch激活后转分化为肌成纤维细胞的能力。
{"title":"A104","authors":"V. Rybko,&nbsp;N. Khromova,&nbsp;M. Farmakovskaya,&nbsp;M. Novikova,&nbsp;B. Kopnin,&nbsp;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}
引用次数: 0
P39a: The characterization of total circulating DNA from blood of healthy donors and cancer patients P39a:来自健康献血者和癌症患者血液的总循环DNA的特征
Q3 Medicine Pub Date : 2015-11-01 DOI: 10.1016/J.EJCSUP.2015.08.107
S. Tamkovich, A. Bondar, I. Morozov, N. Kirushina, V. Permyakova, V. Voitsitskiy, P. Laktionov
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引用次数: 0
P81 P81
Q3 Medicine Pub Date : 2015-11-01 DOI: 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

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.

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.

Pre-transplant count of CD4+FOXP3+ Tregs was significantly higher compared to healthy controls (5.4 ± 2.9 vs 3.8 ± 1.9%; pU = 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%; pU = 0.016, and 10.1 ± 5.2 vs 6.1 ± 3.8%; pU = 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%, pU = 0.0005) and did not reach donors‘ values following 12 month (23.1 ± 13.5%, pU = 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.

Surprisingly, we have found high levels of circulating CD4+CD45RA- T cells co-expressing CD31 molecule i

大量研究表明,大剂量化疗和自体造血干细胞移植(AHSCT)导致造血细胞病患者持续低水平T细胞的长期免疫缺陷状态。适时的t细胞重建对于抗感染和抗肿瘤免疫应答的早期恢复至关重要。淋巴细胞的恢复是通过两种主要机制介导的——T细胞的稳态增殖和通过胸腺生成产生新的初始T细胞。已知,在AHSCT后的第一年,稳态增殖对于免疫能力宿主T细胞计数的恢复是重要的。大约从AHSCT后6个月胸腺开始填补T细胞库。我们研究了AHSCT后CD4+FOXP3+ Treg恢复的动态,以及Treg与临床结果之间的可能关系,因为淋巴细胞减少条件下Treg的抑制活性可能影响T细胞的外周扩增。AHSCT后胸腺活动通过测量CD4+ CD45RA+CD31+ naïve T细胞的数量来评估,即“近期胸腺移植物”(rte)。2009-2014年,109例非霍奇金淋巴瘤、霍奇金淋巴瘤和多发性骨髓瘤患者接受了AHSCT。流式细胞术检测AHSCT前、移植当日、移植后6个月和12个月循环CD4+FOXP3+ Tregs和CD4+CD45RA+CD31+ T细胞的含量。移植前CD4+FOXP3+ Tregs计数明显高于健康对照组(5.4±2.9 vs 3.8±1.9%;pU = 0.011;此处和以下数据以Mean±SD表示)。Tregs的百分比迅速恢复,并在移植时达到最初的高水平,随后在一年内下降,直到降至健康供体的值。移植时CD4+FOXP3+ Tregs在AHSCT后6个月和12个月内复发或疾病进展的患者中与非复发患者相比增加(11.0±6.1 vs 6.2±3.0%;pU = 0.016,和10.1±5.2 vs 6.1±3.8%;pU = 0.008)。移植前CD4+CD45RA+CD31+ T细胞计数明显低于健康对照组(17.1±11.4 vs 30.3±11.2%,pU = 0.0005), 12个月后未达到供者水平(23.1±13.5%,pU = 0.032)。在AHSCT后的第一年内,复发患者的rte数量与缓解患者相同。rte和Tregs之间没有明显的联系。令人惊讶的是,我们在AHSCT患者中发现了高水平的循环CD4+CD45RA- T细胞共表达CD31分子,因为该分子在健康对照组的记忆亚群中并不常见(20.7±12.0 vs 8.2±2.1%,pU <0.00001)。CD4+CD45RA-CD31+ T细胞相对数量与CD4+CD45RO+CD31+人群高度相关(rS=0.72;p & lt;0.00001)。CD4+CD45RA-CD31+ T细胞计数在AHSCT术后1个月内迅速恢复,恢复到移植前水平,并在随访期间保持不变。移植后1年内早期复发和缓解患者的CD4+CD45RA-CD31+ T细胞相对计数无差异。我们关于Tregs重组的数据可能证实了之前的假设,即在免疫恢复期间Tregs的存在保持了最佳的T细胞受体多样性。然而,这些细胞的过量导致增殖活性和免疫反应的抑制,并与早期复发有关。相反,相对缓慢的rte恢复决定了它们在移植后第一年内对生存缺乏影响。CD31分子在T细胞记忆亚群(CD4+CD45RA-和/或CD4+CD45RO+)中的生物学作用和出现方式尚不清楚。CD31+记忆T细胞在淋巴增生性疾病发病机制中的作用有待进一步研究。
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引用次数: 0
A94 A94
Q3 Medicine Pub Date : 2015-11-01 DOI: 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

Background

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).

Materials and methods

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% (p < 0.05) was adopted for all tests.

Results

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, p < 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

背景:鳞状细胞癌是下唇最常见的恶性肿瘤。虽然下唇鳞状细胞癌生长缓慢,但高达29%的肿瘤会转移到颈部淋巴结。因此,鉴别能够提供有关这些病变侵袭性或转移性潜能的预后信息的生物标志物是很重要的。已知血管生成、淋巴管生成和增殖在肿瘤进展中起重要作用。因此,本研究的目的是分析Ki-67、CD34和Podoplanin在角化过度症和下唇鳞状细胞癌中的免疫组化表达。目的是评估使用这些标记物作为下唇鳞状细胞癌(LLSCC)形态侵袭性指标的可能性。材料与方法选择新西伯利亚地区肿瘤中心档案中71例下唇病变病例为研究对象。标本分为三组:下唇角化过度组22例;有角化的LLSCC 34例,无角化的LLSCC 15例。为了分析血管生成、淋巴管生成和增殖,我们对下唇活检材料进行了CD34(血管标志物)、Podoplanin(淋巴特异性标志物)和Ki-67(增殖标志物)的免疫染色。组织样品用10%的中性福尔马林固定,用标准组织学技术处理,包埋于石蜡中。免疫组化反应的所有步骤均采用BENCHMARK/XT玻片染色(Ventana)进行。对各组淋巴和血管体积密度及Ki-67细胞数值密度进行形态计量学分析,并采用非参数Mann-Whitney检验和Wilcoxon符号秩检验进行比较。显著性水平为5% (p <所有试验均采用0.05)。结果所有下唇角化过度和LLSCC患者Ki-67、CD34和Podoplanin均呈阳性。关于染色模式,在炎症浸润和肿瘤部位,标本显示CD34和Podoplanin主要是外周染色。相反,Ki-67的染色主要集中在角化过度和LLSCC的炎症浸润和肿瘤部位。与下唇角化过度症相比,LLSCC(有角化和没有角化)显示出更高数量的免疫阳性Ki-67细胞(分别为64%和77%,p <0.05)。发现角化LLSCC肿瘤细胞的增殖活性比未角化LLSCC高2倍。血管体积密度比较显示,角化过度患者的CD34+血管密度比无角化的LLSCC低77%,比有角化的LLSCC低64%。同时,未角质化的LLSCC血管体积密度比角质化的LLSCC高56%。淋巴管检查显示,角化过度患者的Podoplanin+淋巴管体积密度比无角化的LLSCC低50%,比有角化的LLSCC低24%。未发生角化的LLSCC的淋巴管体积密度比发生角化的LLSCC高51%。结论本研究显示,与角化过度和角化LLSCC相比,未角化LLSCC的血液和淋巴管发育更大,从而促进了转移的发生。
{"title":"A94","authors":"N. Bgatova ,&nbsp;I. Kulikova ,&nbsp;I. Kachesov ,&nbsp;R. Yui ,&nbsp;M. Ergazina ,&nbsp;S. Chepko ,&nbsp;N. Isakova ,&nbsp;Y. Borodin ,&nbsp;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> <!-->&lt;<!--> <!-->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> <!-->&lt;<!--> <!-->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}
引用次数: 0
A115 A115
Q3 Medicine Pub Date : 2015-11-01 DOI: 10.1016/j.ejcsup.2015.08.026
E. Dmitrieva, N. Nurieva

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.

Materials and methods

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.

Results

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.

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%.

Conclusion

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.

车里雅宾斯克地区是技术饱和地区的典型例子。据估计,大气污染指数较高。车里雅宾斯克地区是癌症风险增加的地区之一。头颈癌的发病率正在稳步上升,占俄罗斯所有癌症病例的20-25%。口咽癌占所有癌症的5.1%。材料与方法研究对象为车里雅宾斯克地区的人口。分析是根据车里雅宾斯克地区肿瘤药房统计部门的年度报告材料进行的。结果2014年车里雅宾斯克地区人口癌症病例中,口咽癌占2.06%,包括唇癌(0.35%)、舌癌(0.47%)、主要唾液腺癌(0.22%)、口腔其他未明确部位癌(0.52%)、口咽癌(0.33%)、鼻咽癌(0.1%)和下咽癌(0.07%)。2008 - 2014年,车里雅宾斯克市和车里雅宾斯克地区成人口腔癌和咽喉癌的发病率上升了8.8%。2011 - 2014年,口腔癌和咽喉癌的发病率呈上升趋势,总体上升71.8%。需要注意的是,2013年男性口腔癌和咽喉癌的发病率分别是女性的3倍和2倍。诊断时肿瘤的范围是决定肿瘤发展预后的主要指标之一。2014年车里雅宾斯克州人口癌症总病例中,口腔癌占1.33%,咽癌占0.6%,唇癌占0.13%,在所有癌症死亡原因中分别排名第17、19和24位。分析研究期间口腔癌和咽喉癌的死亡率动态,发现死亡率上升了0.7%。结论头颈部肿瘤是一种罕见的临床和生物学多样性的肿瘤疾病。在车里雅宾斯克地区的居民中,男性患口腔和咽喉癌的几率是女性的2-3倍。高死亡率是由于病人转诊较晚所致;大多数头颈癌患者在晚期才被诊断出来。
{"title":"A115","authors":"E. Dmitrieva,&nbsp;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}
引用次数: 0
P83 P83
Q3 Medicine Pub Date : 2015-11-01 DOI: 10.1016/j.ejcsup.2015.08.027
O. Ephimova , I. Grigoreva , T. Romanova , Y. Ragino , T. Suvorova , N. Tov

Background

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)).

Materials and methods

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.

Results

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/m2, in OP patients – 23.8 ± 1.0 kg/m2, in CP patients – 26.3 ± 0.6 kg/m2, p > 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, p < 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, p < 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<

目的探讨胰腺癌(PCa)患者的临床症状,比较不同胰腺病理(PCa、急性(OP)和慢性胰腺炎(CP))患者的一些血清生化指标。材料与方法在对“系列病例”类型的一次性临床研究中,对130例患者进行了检查,其中OP 42例,CP 81例,PCa 7例。通过临床和仪器方法验证前列腺癌、OP、CP的诊断。ELISA法测定血清葡萄糖、胆固醇、甘油三酯、胆红素水平。结果PCa患者平均年龄为63.6±4.9岁,发病时间为- 3.5±1.1个月。在PCa患者中,83.3%的人吸烟,16.7%的人每天吸烟。一半的PCa患者指出,在过去的一年里,他们没有喝酒;16.7%的人每年饮酒几次,33.3%的患者每月饮酒1-2次。PCa患者BMI = 26.3±3.5 kg/m2, OP患者BMI = 23.8±1.0 kg/m2, CP患者BMI = 26.3±0.6 kg/m2, p >0.05. 在本病例中,85.7%的PCa患者在出现症状后3-4个月内体重显著下降(11.7±6.0 kg)。42.8%的PCa患者无疼痛,只有28.6%的患者出现频繁疼痛。在CP患者中,65.5%的患者有频繁和持续的疼痛,OP患者中有48.6%的患者有频繁和持续的疼痛。所有PCa患者均出现右上腹疼痛。75%的病例为低强度疼痛,25%的病例为中度疼痛。一半的PCa患者疼痛消失,1/4的患者持续疼痛。25%的PCa患者出现恶心和呕吐。42.8%的PCa患者有胃胀感和溢水。PCa患者血糖水平超过正常范围,明显高于OP和CP患者(分别为8.5±1.4 mmol/L、5.4±0.3和5.1±0.1 mmol/L, p <0.05)。前列腺癌患者高胆红素血症为89.9±27.5 μmol/L;OP和CP患者胆红素水平分别为32.2±11.0和13.4±1.8 μmol/L,显著低于PCa患者,p <0.05. 不同胰腺疾病患者的甘油三酯水平无差异(PCa - 1.7±0.3,CP - 1.86±0.1,OP - 1.88±0.11 mmol/L, p >0.05)。但CP患者的总胆固醇明显高于PCa和OP患者(5.8±0.1、5.0±0.6和4.1±0.2 mmol/L, p <0.05)。在PCa患者中,一些胆固醇淤滞和肝细胞损伤指标也出现升高:ALP - 185.0±12.7 IU/L, ALT - 108.4±33.5 IU/L, AST - 85.3±31.5 IU/L,淀粉酶- 44.9±14.9 IU/L,纤维蛋白原- 2696.6±398.6 g/L。结论前列腺癌患者的非特异性临床体征(疼痛、消化不良)与胆道病理生化指标和内分泌胰功能不全相结合,说明早期胰腺和胆道病理鉴别诊断的必要性。
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引用次数: 0
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