Pub Date : 2015-11-01DOI: 10.1016/J.EJCSUP.2015.08.101
A. V. Sosnina, A. V. Vankhalsky, E. Mikhailova, T. A. Kunts, N. Varaksin, A. Autenshlyus
{"title":"P64: Effect of polyclonal activators on cytokine-producing capacity of blood immunocompetent cells in adenoma and adenocarcinoma of the stomach","authors":"A. V. Sosnina, A. V. Vankhalsky, E. Mikhailova, T. A. Kunts, N. Varaksin, A. Autenshlyus","doi":"10.1016/J.EJCSUP.2015.08.101","DOIUrl":"https://doi.org/10.1016/J.EJCSUP.2015.08.101","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"56-57"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.EJCSUP.2015.08.101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310213","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}
Pub Date : 2015-11-01DOI: 10.1016/J.EJCSUP.2015.08.103
E. Starostina, D. Antonets, E. A. Borobova, L. Karpenko, A. Reguzova, O. Smirnova, A. Ilyichev, Bazhan Si
{"title":"P61: DNA-vaccines against melanoma: Design and investigation of antigenic properties","authors":"E. Starostina, D. Antonets, E. A. Borobova, L. Karpenko, A. Reguzova, O. Smirnova, A. Ilyichev, Bazhan Si","doi":"10.1016/J.EJCSUP.2015.08.103","DOIUrl":"https://doi.org/10.1016/J.EJCSUP.2015.08.103","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"57-58"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.EJCSUP.2015.08.103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310528","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}
Pub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.036
S. Hofmann, I. Bure, A. Agaimy, A. Hartmann, F. Haller, E. Moskalev
Aberrant alterations of DNA methylation patterns have been recognized as early and common events in oncogenesis emphasizing high therapeutic and preventive potential. Concurrent epigenetic silencing of multiple tumour suppressor genes has been reported in different tumours suggesting the existence of a directed program, whereby groups of genes are regulated by promoter methylation. The molecular bases of such a program remain largely unclear. Certain long non-coding RNAs (lncRNAs) have been recently identified that are responsible for target specificity of the histone modification complexes. It remains incompletely understood, however, if lncRNAs may play a role in patterning DNA methylation. In this study, we asked by using gastrointestinal stromal tumours as a model if an epigenetic related HOX Antisense Intergenic RNA, or HOTAIR, is involved in establishment of DNA methylation patterns. To this end, we first showed high up-regulation of HOTAIR in patient samples of high risk compared to low and intermediate risk groups (n = 66, p = 6.7 × 10−6), what is supported by the earlier reports on common carcinomas. Highest levels of HOTAIR endogenous expression were next detected also in cell lines GIST T1, GIST48b and GIST882. Stable knockdown of HOTAIR was achieved in GIST T1 and GIST48b cells by RNAi using lentiviral transduction. As expected epigenetic alterations due to HOTAIR knockdown could develop with a delay, genome-wide DNA methylation profiling was performed at passage 12 after the transduction on the Infinium HumanMethylation450 BeadChip platform in triplicates. DNA methylation data were analysed by an R package RnBeads. A total of 218 CpG sites got hypomethylated upon HOTAIR knockdown in GIST T1 and GIST48b cells (Δβ > 0.3, FDR < 0.05). These included potential tumour suppressors, transcription factors, tumour-specific antigens, genes related to angiogenesis or involved in metabolism. As confirmed by using bisulfite pyrosequencing for a representative locus, DNA methylation of 64% degree at promoter associated CpG sites of the potential tumour suppressor RASSF1 was almost entirely erased upon HOTAIR knockdown in GIST T1 cell line with concomitant up-regulation detected by qRT-PCR. Concordant with earlier reports, HOTAIR knockdown led to reduced migration potential in GIST T1 cells. Taken together, the results suggest that HOTAIR is one of the factors involved in establishment of specific DNA methylation patterns in GIST. While the molecular mechanism remains to be determined, it is plausible to assume a recruitment of DNA methyltransferases by the Polycomb repressive complex 2, which target specificity is determined by HOTAIR. The results further suggest the feasibility of manipulating DNA methylat
{"title":"P152","authors":"S. Hofmann, I. Bure, A. Agaimy, A. Hartmann, F. Haller, E. Moskalev","doi":"10.1016/j.ejcsup.2015.08.036","DOIUrl":"10.1016/j.ejcsup.2015.08.036","url":null,"abstract":"<div><p>Aberrant alterations of DNA methylation patterns have been recognized as early and common events in oncogenesis emphasizing high therapeutic and preventive potential. Concurrent epigenetic silencing of multiple tumour suppressor genes has been reported in different tumours suggesting the existence of a directed program, whereby groups of genes are regulated by promoter methylation. The molecular bases of such a program remain largely unclear. Certain long non-coding RNAs (lncRNAs) have been recently identified that are responsible for target specificity of the histone modification complexes. It remains incompletely understood, however, if lncRNAs may play a role in patterning DNA methylation. In this study, we asked by using gastrointestinal stromal tumours as a model if an epigenetic related <em>HOX Antisense Intergenic RNA</em>, or <em>HOTAIR</em>, is involved in establishment of DNA methylation patterns. To this end, we first showed high up-regulation of <em>HOTAIR</em> in patient samples of high risk compared to low and intermediate risk groups (<em>n</em> <!-->=<!--> <!-->66, <em>p</em> <!-->=<!--> <!-->6.7<!--> <!-->×<!--> <!-->10<sup>−6</sup>), what is supported by the earlier reports on common carcinomas. Highest levels of <em>HOTAIR</em> endogenous expression were next detected also in cell lines GIST T1, GIST48b and GIST882. Stable knockdown of <em>HOTAIR</em> was achieved in GIST T1 and GIST48b cells by RNAi using lentiviral transduction. As expected epigenetic alterations due to <em>HOTAIR</em> knockdown could develop with a delay, genome-wide DNA methylation profiling was performed at passage 12 after the transduction on the Infinium HumanMethylation450 BeadChip platform in triplicates. DNA methylation data were analysed by an R package RnBeads. A total of 218 CpG sites got hypomethylated upon <em>HOTAIR</em> knockdown in GIST T1 and GIST48b cells (Δ<em>β</em> <!-->><!--> <!-->0.3, FDR<!--> <!--><<!--> <!-->0.05). These included potential tumour suppressors, transcription factors, tumour-specific antigens, genes related to angiogenesis or involved in metabolism. As confirmed by using bisulfite pyrosequencing for a representative locus, DNA methylation of 64% degree at promoter associated CpG sites of the potential tumour suppressor <em>RASSF1</em> was almost entirely erased upon <em>HOTAIR</em> knockdown in GIST T1 cell line with concomitant up-regulation detected by qRT-PCR. Concordant with earlier reports, <em>HOTAIR</em> knockdown led to reduced migration potential in GIST T1 cells. Taken together, the results suggest that <em>HOTAIR</em> is one of the factors involved in establishment of specific DNA methylation patterns in GIST. While the molecular mechanism remains to be determined, it is plausible to assume a recruitment of DNA methyltransferases by the Polycomb repressive complex 2, which target specificity is determined by <em>HOTAIR</em>. The results further suggest the feasibility of manipulating DNA methylat","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 20-21"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309173","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}
Pub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.048
D. Kokova , N. Dementeva , N. Cherdyntseva , A. Gratchev , Julia Kzhyshkowska
Background
Identification of DNA-based biomarkers of cancer cells is highly promising and rapidly developing direction that can advance early detection and therapy of malignancies. DNA adducts are felicitous markers of cancer, because their chemical structure is significantly different from that of mutated or methylated DNA, that allows to determine them with high precision using mass spectrometry. The aim of this work is to develop the methodology of sample preparation and its mass spectrometric analysis. Samples were prepared from the blood plasma and from the tumor tissue from lung cancer patients and from blood of healthy individuals.
Materials and methods
DNA was isolated from the blood plasma and tissue by using column method (BioSilica, Russia) The final yield from 1 ml of blood was 100 ng. DNA samples were subjected to acid hydrolysis (1 M HCl) at 70 °C. After 3 h, the hydrolysis was stopped by cooling on ice for 5 min and later on adding an equivalent amount of an alkali and a phosphate buffer solution (pH 7). To assess the extent of hydrolysis of the samples they were analysed by electrophoresis on a 1.2% agarose gel in Tris-acetate buffer. The samples were extracted at cartridge HF Bond Elut-C18 100 mg, 1 ml (Agilent Technologies, USA) and eluted in several fractions with a gradual increase of methanol in the eluent. Stream of nitrogen was applied to dry the extract. The samples were subjected to mass spectrometric analysis after pre-separation by UHLC Ultimate 3000 RS (Dionex, USA) in a column Dionex Acclaim RSLC 120 C18 (2.1 × 50 mm 120 A, 0.2 μm) flow rate of 0.5 ml/min using as eluents 0.1% solution of formic acid in water (A) and 0.1% solution of formic acid in atsetontrile (B). Elution was carried out in gradient mode: (%B): 0–3min (5%), 3–28min (5–95%), 28–30 min (95%), 30–31 min (95–5%), 31–35 min (5%). Mass spectrometry was carried out on ESI-qTOF ultrahigh resolution Maxis 4G (Bruker, Germany) in the positive ion detection mode range 50–1000 m/z, 2 Hz with the following settings electrospray ion source: CV 3800 V, Nebulizer gas 1 bar, Dry Gas 8 l/min, Dry Temp: 200 °C.
Results
It was found that the DNA which was cleaved with acid hydrolysis in the result contained single DNA bases. The samples were stable at 4 °C for at least 7 days. The optimal eluent for solid phase extraction of DNA is 80% solution of methanol in water. The number of DNA adducts was evaluated by the integrated value of the mass spectrometric response detector. It was shown that most amount of adducts 4-hydroxy-1-(3-pyridyl)-1- butanone and N3-(2-carbamoyl-2-hydroxyethyl)adenine was found in DNA samples derived from tumor tissue. The adduct N7-(2-carbamoyl-
基于dna的肿瘤细胞生物标志物的鉴定是一个非常有前途和快速发展的方向，可以促进恶性肿瘤的早期发现和治疗。DNA加合物是癌症的有利标记物，因为它们的化学结构与突变或甲基化的DNA明显不同，这使得使用质谱法可以高精度地确定它们。本工作的目的是发展样品制备及其质谱分析的方法。从肺癌患者的血浆和肿瘤组织以及健康人的血液中制备样品。材料和方法采用柱法(BioSilica, Russia)从血浆和组织中分离dna, 1 ml血液的最终产率为100 ng。DNA样品在70°C下进行酸水解(1 M HCl)。3小时后，通过在冰上冷却5分钟，然后加入等量的碱和磷酸盐缓冲溶液(pH 7)来停止水解。为了评估样品的水解程度，我们在Tris-acetate缓冲液中使用1.2%琼脂糖凝胶进行电泳分析。样品在HF Bond Elut-C18滤盒中提取100 mg, 1 ml (Agilent Technologies, USA)，分几段洗脱，洗脱液中甲醇的含量逐渐增加。用氮气流干燥提取物。样品采用美国Dionex公司的uhplc Ultimate 3000 RS进行预分离，色谱柱为Dionex公司的Acclaim公司RSLC 120 C18 (2.1 × 50 mm 120 a, 0.2 μm)，流速为0.5 ml/min，洗脱液为0.1%甲酸水溶液(a)和0.1%甲酸atsetontrile溶液(B)。洗脱液为梯度模式:(%B): 0-3min(5%)、3-28min(5-95%)、28-30 min(95%)、30-31 min(95-5%)、31-35 min(5%)。质谱分析在ESI-qTOF超高分辨率Maxis 4G (Bruker, Germany)上进行，正离子检测模式范围为50-1000 m/z, 2hz，设置电喷雾离子源:CV 3800 V, Nebulizer气体1 bar, Dry gas 8 l/min, Dry temperature: 200°C。结果发现酸水解裂解的DNA含有单个碱基。样品在4℃下稳定保存至少7天。固相萃取DNA的最佳洗脱液为80%甲醇水溶液。通过质谱响应检测器的积分值评估DNA加合物的数量。结果表明，肿瘤组织DNA样品中含有最多的加合物4-羟基-1-(3-吡啶基)-1-丁酮和N3-(2-氨基甲酰-2-羟乙基)腺嘌呤。在肿瘤组织样本和血浆DNA以及所有健康组织样本中发现了N7-(2-氨基甲酰-2-羟乙基)鸟嘌呤加合物。结论所建立的DNA样品制备和高分辨率质谱仪分析方案可以在100 ng的小DNA探针中检测DNA加合物的含量。我们发现，为了生成含有单个DNA碱基的样品而不破坏加合物的结构，与酶消化相比，酸水解更便宜，更实用。这项研究得到了俄罗斯科学技术综合体2014-2020年优先发展领域联邦研究与开发目标计划“早期检测肺癌分子特征的开发”(2014年8月5日№14.575.21.0064,RFMEFI57514X0064)的支持，并得到了托木斯克国立大学“竞争力提高计划”的支持。工作是利用托木斯克地区通用中心的技术设备进行的，这些技术设备是由俄罗斯政府根据第14.594.21.0001号协议(RFMEFI59414X0001)授予的。
{"title":"P156","authors":"D. Kokova , N. Dementeva , N. Cherdyntseva , A. Gratchev , Julia Kzhyshkowska","doi":"10.1016/j.ejcsup.2015.08.048","DOIUrl":"10.1016/j.ejcsup.2015.08.048","url":null,"abstract":"<div><h3>Background</h3><p>Identification of DNA-based biomarkers of cancer cells is highly promising and rapidly developing direction that can advance early detection and therapy of malignancies. DNA adducts are felicitous markers of cancer, because their chemical structure is significantly different from that of mutated or methylated DNA, that allows to determine them with high precision using mass spectrometry. The aim of this work is to develop the methodology of sample preparation and its mass spectrometric analysis. Samples were prepared from the blood plasma and from the tumor tissue from lung cancer patients and from blood of healthy individuals.</p></div><div><h3>Materials and methods</h3><p>DNA was isolated from the blood plasma and tissue by using column method (BioSilica, Russia) The final yield from 1<!--> <!-->ml of blood was 100<!--> <!-->ng. DNA samples were subjected to acid hydrolysis (1<!--> <!-->M HCl) at 70<!--> <!-->°C. After 3<!--> <!-->h, the hydrolysis was stopped by cooling on ice for 5<!--> <!-->min and later on adding an equivalent amount of an alkali and a phosphate buffer solution (pH 7). To assess the extent of hydrolysis of the samples they were analysed by electrophoresis on a 1.2% agarose gel in Tris-acetate buffer. The samples were extracted at cartridge HF Bond Elut-C18 100<!--> <!-->mg, 1<!--> <!-->ml (Agilent Technologies, USA) and eluted in several fractions with a gradual increase of methanol in the eluent. Stream of nitrogen was applied to dry the extract. The samples were subjected to mass spectrometric analysis after pre-separation by UHLC Ultimate 3000 RS (Dionex, USA) in a column Dionex Acclaim RSLC 120 C18 (2.1<!--> <!-->×<!--> <!-->50<!--> <!-->mm 120<!--> <!-->A, 0.2<!--> <!-->μm) flow rate of 0.5<!--> <!-->ml/min using as eluents 0.1% solution of formic acid in water (A) and 0.1% solution of formic acid in atsetontrile (B). Elution was carried out in gradient mode: (%B): 0–3min (5%), 3–28min (5–95%), 28–30<!--> <!-->min (95%), 30–31<!--> <!-->min (95–5%), 31–35<!--> <!-->min (5%). Mass spectrometry was carried out on ESI-qTOF ultrahigh resolution Maxis 4G (Bruker, Germany) in the positive ion detection mode range 50–1000<!--> <!-->m/z, 2<!--> <!-->Hz with the following settings electrospray ion source: CV 3800<!--> <!-->V, Nebulizer gas 1<!--> <!-->bar, Dry Gas 8 l/min, Dry Temp: 200<!--> <!-->°C.</p></div><div><h3>Results</h3><p>It was found that the DNA which was cleaved with acid hydrolysis in the result contained single DNA bases. The samples were stable at 4<!--> <!-->°C for at least 7<!--> <!-->days. The optimal eluent for solid phase extraction of DNA is 80% solution of methanol in water. The number of DNA adducts was evaluated by the integrated value of the mass spectrometric response detector. It was shown that most amount of adducts 4-hydroxy-1-(3-pyridyl)-1- butanone and N3-(2-carbamoyl-2-hydroxyethyl)adenine was found in DNA samples derived from tumor tissue. The adduct N7-(2-carbamoyl-","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 27-28"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309493","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}
Pub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.058
A. Leshchenko , N. Matsenko
Background
Breast cancer is the most common cause of death from cancer among women aged 40–69 years. According to WHO, about 1 million new cases of breast cancer are diagnosed annually worldwide, and nearly 500,000 die from it. In Russia, more than 55,000 women are diagnosed with breast cancer annually, and more than 22,000 die from it. Diagnosis and treatment of breast cancer is the primary and important social and medical problem.The increased expression of: (a) ER and PgR (70–75% of all cases of breast cancer) is an indication for hormone therapy, which is one of the simplest and most effective methods of systemic treatment of breast cancer; (b) receptor HER2/neu is a marker of highly aggressive form of breast cancer and indication for the use of targeted therapy Gertseptin; (c) proliferative factor Ki-67 reflects the ability of a tumor to metastasize.
Today, the “gold standard” of gene expression diagnostic of ER, PgR, HER2/neu and Ki-67 in breast cancer is immunohistochemistry (IHC) using foreign test systems (Ventana, Dako Inc, USA) . However, IHC diagnostics has some significant drawbacks. It leads up to 15–17% of cases of incorrect choice of drug therapy, which based on incorrect results of IHC studies. As a result, the significant group of patients do not receive effective treatment. Aim of the study Aim: the development a prototype of diagnostic test system for detection the receptor status of breast cancer, based on RT-PCR.
Materials and methods
Breast cancersamples consisted of 45 fresh-frozen tissue (FFT) samples of breast cancer (sites of malignant transformation and normal tissue from the same patients) and 59 FFPET sampleswere collected. All the samples had the IHC characteristic of receptor status of ER, PgR, HER2/neu and proliferation factor Ki-67 (Dako Inc., USA). Samples were submitted by SBIH NR “Novosibirsk Regional Oncology Center” (Novosibirsk, Russia). The experimental part of the study was divided into several stages: separation of mRNA from cells, obtaining cDNA (reverse transcription reaction), PCR in real-time and validation of the test system. Isolation of total RNA from FFT samples was performed using a set of “SV Total RNA Isolation system” according to the manufacturer’s instructions (Promega, USA). Isolation of total RNA from FFPET samples was performed using a set “ReliaPrep FFPE Total RNA Miniprep System” (Promega, USA) according to the manufacturer’s instructions. The concentration of total RNA was determined using a NanoDrop 1000 microspectrophotometer (Thermo Bioscience, USA) (RNA concentration were 15–660 ng/ml).
Results
For the reverse transcription reaction (RT) and PCR, the main parameters were selected. For RT: RNA incubation time and temperature of the reaction, enzyme concentration in the reaction mix. For PCR: the amount of DNA template, the number of primers, the concentration of magny ions, the concentration
{"title":"P71","authors":"A. Leshchenko , N. Matsenko","doi":"10.1016/j.ejcsup.2015.08.058","DOIUrl":"10.1016/j.ejcsup.2015.08.058","url":null,"abstract":"<div><h3>Background</h3><p>Breast cancer is the most common cause of death from cancer among women aged 40–69<!--> <!-->years. According to WHO, about 1 million new cases of breast cancer are diagnosed annually worldwide, and nearly 500,000 die from it. In Russia, more than 55,000 women are diagnosed with breast cancer annually, and more than 22,000 die from it. Diagnosis and treatment of breast cancer is the primary and important social and medical problem.The increased expression of: (a) ER and PgR (70–75% of all cases of breast cancer) is an indication for hormone therapy, which is one of the simplest and most effective methods of systemic treatment of breast cancer; (b) receptor HER2/neu is a marker of highly aggressive form of breast cancer and indication for the use of targeted therapy Gertseptin; (c) proliferative factor Ki-67 reflects the ability of a tumor to metastasize.</p><p>Today, the “gold standard” of gene expression diagnostic of ER, PgR, HER2/neu and Ki-67 in breast cancer is immunohistochemistry (IHC) using foreign test systems (Ventana, Dako Inc, USA) . However, IHC diagnostics has some significant drawbacks. It leads up to 15–17% of cases of incorrect choice of drug therapy, which based on incorrect results of IHC studies. As a result, the significant group of patients do not receive effective treatment. Aim of the study Aim: the development a prototype of diagnostic test system for detection the receptor status of breast cancer, based on RT-PCR.</p></div><div><h3>Materials and methods</h3><p>Breast cancersamples consisted of 45 fresh-frozen tissue (FFT) samples of breast cancer (sites of malignant transformation and normal tissue from the same patients) and 59 FFPET sampleswere collected. All the samples had the IHC characteristic of receptor status of ER, PgR, HER2/neu and proliferation factor Ki-67 (Dako Inc., USA). Samples were submitted by SBIH NR “Novosibirsk Regional Oncology Center” (Novosibirsk, Russia). The experimental part of the study was divided into several stages: separation of mRNA from cells, obtaining cDNA (reverse transcription reaction), PCR in real-time and validation of the test system. Isolation of total RNA from FFT samples was performed using a set of “SV Total RNA Isolation system” according to the manufacturer’s instructions (Promega, USA). Isolation of total RNA from FFPET samples was performed using a set “ReliaPrep FFPE Total RNA Miniprep System” (Promega, USA) according to the manufacturer’s instructions. The concentration of total RNA was determined using a NanoDrop 1000 microspectrophotometer (Thermo Bioscience, USA) (RNA concentration were 15–660<!--> <!-->ng/ml).</p></div><div><h3>Results</h3><p>For the reverse transcription reaction (RT) and PCR, the main parameters were selected. For RT: RNA incubation time and temperature of the reaction, enzyme concentration in the reaction mix. For PCR: the amount of DNA template, the number of primers, the concentration of magny ions, the concentration","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 32-33"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309629","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}
Pub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.093
S. Shevchenko , L. Mostovich , N. Kolesnikov , L. Gulyaeva
Preoperative differential diagnosis of benign thyroid nodules and thyroid cancer is an important issue of endocrinology. Preoperative identification of a tumor type allows a surgeon to determine an adequate surgical treatment and reduce complications. The cytological analysis of samples obtained by the fine-needle aspiration biopsy is limited in sensitivity and specificity and the core biopsy is not safe to be used in patients with thyroid nodes smaller than 2 cm. The most promising area in the preoperative diagnosis of malignant tumors is molecular biomarkers, which can be used to determine the surgical treatment and indications for the target therapy. BRAF V600E is the most frequent genetic alteration in thyroid cancer. It activates the MAP-kinase pathway which causes changes in expression levels of extracellular matrix proteins and some of their receptors. Changes in the expression of integrin receptors and their ligands, such as osteopontin and thrombospondin-1, contribute to tumor cell proliferation and migration. The C-Jun pathway is also very important in pathogenesis of thyroid cancer. Changes in its activity can affect the expression of GSTP enzyme which participates in hormone metabolism. Altered MiRNA expression has been observed in a variety of cancer states allowing their potential use as cancer biomarkers.
The aim of this study was to evaluate integrins, angiogenic factors, GSTP and MiRNAs as potential biomarkers for the diagnosis and prognosis of thyroid cancer.
112 samples of papillary thyroid cancer (PTC) and 120 samples of benign nodular neoplasms were analyzed. The expression levels of the studied genes were determined by RT-PCR. The results were confirmed by immunohistochemical analysis. The BRAF V600E mutation was determined by allele-specific real-time PCR. The results showed that GSTP can be used for clinical settings as a cancer-specific marker for thyroid neoplasms with 83–88% sensitivity, 70–80% specificity and 76–84% diagnostic accuracy. Higher expression levels of integrins α2, α5, αv, α9, β1, β3 and IL-8, angiogenin, and VEGF were observed in malignant tumors in comparison with the normal thyroid tissue (p < 0.05). The BRAF V600E mutation was detected in 70% of all PTC cases. In the BRAF V600E positive PTC samples the levels of ITGA3 and ITGAV expression were higher than in the BRAF V600E negative ones (p < 0.05). The expression of miRNA 21, 221, 222, 155 was significantly increased in the cancer samples compared to the benign neoplasms. Thus, the studied molecular markers could be used for preoperative diagnosis of thyroid neoplasms and the treatment approach.
{"title":"P82a","authors":"S. Shevchenko , L. Mostovich , N. Kolesnikov , L. Gulyaeva","doi":"10.1016/j.ejcsup.2015.08.093","DOIUrl":"10.1016/j.ejcsup.2015.08.093","url":null,"abstract":"<div><p>Preoperative differential diagnosis of benign thyroid nodules and thyroid cancer is an important issue of endocrinology. Preoperative identification of a tumor type allows a surgeon to determine an adequate surgical treatment and reduce complications. The cytological analysis of samples obtained by the fine-needle aspiration biopsy is limited in sensitivity and specificity and the core biopsy is not safe to be used in patients with thyroid nodes smaller than 2<!--> <!-->cm. The most promising area in the preoperative diagnosis of malignant tumors is molecular biomarkers, which can be used to determine the surgical treatment and indications for the target therapy. BRAF V600E is the most frequent genetic alteration in thyroid cancer. It activates the MAP-kinase pathway which causes changes in expression levels of extracellular matrix proteins and some of their receptors. Changes in the expression of integrin receptors and their ligands, such as osteopontin and thrombospondin-1, contribute to tumor cell proliferation and migration. The C-Jun pathway is also very important in pathogenesis of thyroid cancer. Changes in its activity can affect the expression of GSTP enzyme which participates in hormone metabolism. Altered MiRNA expression has been observed in a variety of cancer states allowing their potential use as cancer biomarkers.</p><p>The aim of this study was to evaluate integrins, angiogenic factors, GSTP and MiRNAs as potential biomarkers for the diagnosis and prognosis of thyroid cancer.</p><p>112 samples of papillary thyroid cancer (PTC) and 120 samples of benign nodular neoplasms were analyzed. The expression levels of the studied genes were determined by RT-PCR. The results were confirmed by immunohistochemical analysis. The BRAF V600E mutation was determined by allele-specific real-time PCR. The results showed that GSTP can be used for clinical settings as a cancer-specific marker for thyroid neoplasms with 83–88% sensitivity, 70–80% specificity and 76–84% diagnostic accuracy. Higher expression levels of integrins <em>α</em>2, <em>α</em>5, <em>α</em>v, <em>α</em>9, <em>β</em>1, <em>β</em>3 and IL-8, angiogenin, and VEGF were observed in malignant tumors in comparison with the normal thyroid tissue (<em>p</em> <!--><<!--> <!-->0.05). The BRAF V600E mutation was detected in 70% of all PTC cases. In the BRAF V600E positive PTC samples the levels of ITGA3 and ITGAV expression were higher than in the BRAF V600E negative ones (<em>p</em> <!--><<!--> <!-->0.05). The expression of miRNA 21, 221, 222, 155 was significantly increased in the cancer samples compared to the benign neoplasms. Thus, the studied molecular markers could be used for preoperative diagnosis of thyroid neoplasms and the treatment approach.</p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 52"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310105","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}
Pub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.096
O. Shpileva
Cervical cancer is one of the most common female malignancies with incidence of 19.7 per 100,000 population in Russia in 2011 (Davydov, Aksel et al., 2011). Over 6000 women in Russia die of cervical cancer annually.
The cervical cancer incidence shows a tendency towards increasing rates among young women (Chissov, 2009). Tomsk region has been found to be the territory of increased cancer risk for cervical cancer. The age-standardized incidence rate is 1.87 times higher in Tomsk region than in Russia, being 20.40/0000 (Pisareva, Odintsova et al., 2012). The highest incidence of cervical cancer is observed in women aged 15–39 years (Churuksaeva, Kolomiets, Shpileva, 2012). The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. Prevention of exposure to high risk HPV types by vaccination may prove to be the most efficient and logistically feasible preventive intervention for cervical cancer.
Epidemiological studies conducted at the Tomsk Cancer Research Institute have shown that the median age of patients with cervical intraepithelial neoplasia and cervical cancer is 39.9 ± 8.5, and 89.5% of women are HPV-positive. Prevalence of high-grade squamous intraepithelial lesion (H-SIL) peaks between ages 25 years and 30 years.
The predominant HPV type in screened women of Tomsk region as well as worldwide is HPV-16, reaching peak incidence in women aged 36–40 years (74%). In the older age group (from 51 to 60 years), HPV-18 is associated with 25% of cervical cancer cases. High prevalence of HPV-31 has been found in women under the age of 45 years with an incidence peak (17%) in the age group ⩽20 years.
The geographical widespread data on HPV type-distribution are essential for estimating the impact of vaccines on cervical cancer and cervical screening programs. Immunization against HPV for young women aged between 9 and 26 years, with a predominant age cohort 11–13 years, was introduced in Tomsk region in 2010. The aim of the HPV immunization program is to protect females before they reach an age when the risk of HPV infection increases. A total of 627 girls were vaccinated, and 1653 doses of vaccines were injected. The three- dose schedule was given to 414 (66%) girls and 2-dose schedule to 198 (31.6%) girls. Vaccine safety assessment was carried out. Adverse effects were observed in 9.6% of cases and were mainly characterized by dizziness and pain at the injection site. Vaccination was well tolerated.
When calculating socio-economic feasibility of the proposed technology , not only the economic damage caused by the high mortality of women from cervical cancer, but also the cost for treatment of precancerous cervical lesions were taken into account, as out of 25 women with undetected CINII-III, 10 will develop cervical cancer. There have been calculated the estimated dam
宫颈癌是最常见的女性恶性肿瘤之一，2011年俄罗斯发病率为19.7 / 10万人(Davydov, Aksel et al.， 2011)。俄罗斯每年有6000多名妇女死于宫颈癌。宫颈癌发病率在年轻妇女中呈现上升趋势(Chissov, 2009年)。托木斯克地区已被发现是宫颈癌风险增加的地区。托木斯克地区的年龄标准化发病率为20.40/000，是俄罗斯的1.87倍(Pisareva, Odintsova et al.， 2012)。宫颈癌发病率最高的是15-39岁的妇女(Churuksaeva, Kolomiets, Shpileva, 2012)。人乳头瘤病毒感染在子宫颈癌中的因果作用已被证明是毫无疑问的。通过接种疫苗预防暴露于高危型人乳头瘤病毒可能被证明是宫颈癌最有效和后勤上可行的预防干预措施。托木斯克癌症研究所进行的流行病学研究表明，宫颈上皮内瘤变和宫颈癌患者的中位年龄为39.9±8.5岁，89.5%的女性是hpv阳性。高级别鳞状上皮内病变(H-SIL)的患病率在25岁至30岁之间达到高峰。托木斯克地区和全世界筛查妇女中主要的HPV类型是HPV-16，在36-40岁妇女中发病率最高(74%)。在年龄较大的年龄组(51至60岁)中，25%的宫颈癌病例与HPV-18有关。HPV-31在45岁以下的女性中有较高的患病率，发病率高峰(17%)在20岁以下年龄组。HPV类型分布的地理分布数据对于估计疫苗对宫颈癌和子宫颈筛查计划的影响至关重要。托木斯克地区于2010年开始对年龄在9至26岁之间的年轻女性进行HPV免疫接种，主要年龄群为11-13岁。HPV免疫规划的目的是在女性达到感染HPV风险增加的年龄之前保护她们。总共有627名女孩接种了疫苗，并注射了1653剂疫苗。414名(66%)女孩接受了三剂方案，198名(31.6%)女孩接受了两剂方案。开展疫苗安全性评价。9.6%的病例出现不良反应，主要表现为注射部位头晕和疼痛。疫苗接种耐受良好。在计算拟议技术的社会经济可行性时，不仅考虑了宫颈癌妇女高死亡率造成的经济损失，还考虑了宫颈癌前病变的治疗费用，因为在25名未被发现的CINII-III型妇女中，有10名将发展为宫颈癌。对托木斯克地区宫颈癌造成的估计损害进行了计算，其中不仅考虑到宫颈癌前期的诊断和治疗费用，还考虑到与暂时永久性残疾有关的损失(社会福利，包括55岁以前的残疾养恤金)。计算表明，管理宫颈癌患者所造成的经济损失总额，可在2000万至4000万之间。每年卢布。因此，考虑到人乳头瘤病毒感染的流行和宫颈癌的经济影响，可以将宫颈癌的初级预防视为一项有效的公共卫生技术，不仅可以保护托木斯克地区妇女的生殖潜力，还可以保护她们的就业潜力。
{"title":"A139","authors":"O. Shpileva","doi":"10.1016/j.ejcsup.2015.08.096","DOIUrl":"10.1016/j.ejcsup.2015.08.096","url":null,"abstract":"<div><p>Cervical cancer is one of the most common female malignancies with incidence of 19.7 per 100,000 population in Russia in 2011 (Davydov, Aksel et al., 2011). Over 6000 women in Russia die of cervical cancer annually.</p><p>The cervical cancer incidence shows a tendency towards increasing rates among young women (Chissov, 2009). Tomsk region has been found to be the territory of increased cancer risk for cervical cancer. The age-standardized incidence rate is 1.87 times higher in Tomsk region than in Russia, being 20.40/0000 (Pisareva, Odintsova et al., 2012). The highest incidence of cervical cancer is observed in women aged 15–39<!--> <!-->years (Churuksaeva, Kolomiets, Shpileva, 2012). The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. Prevention of exposure to high risk HPV types by vaccination may prove to be the most efficient and logistically feasible preventive intervention for cervical cancer.</p><p>Epidemiological studies conducted at the Tomsk Cancer Research Institute have shown that the median age of patients with cervical intraepithelial neoplasia and cervical cancer is 39.9<!--> <!-->±<!--> <!-->8.5, and 89.5% of women are HPV-positive. Prevalence of high-grade squamous intraepithelial lesion (H-SIL) peaks between ages 25<!--> <!-->years and 30<!--> <!-->years.</p><p>The predominant HPV type in screened women of Tomsk region as well as worldwide is HPV-16, reaching peak incidence in women aged 36–40 years (74%). In the older age group (from 51 to 60<!--> <!-->years), HPV-18 is associated with 25% of cervical cancer cases. High prevalence of HPV-31 has been found in women under the age of 45 years with an incidence peak (17%) in the age group ⩽20<!--> <!-->years.</p><p>The geographical widespread data on HPV type-distribution are essential for estimating the impact of vaccines on cervical cancer and cervical screening programs. Immunization against HPV for young women aged between 9 and 26<!--> <!-->years, with a predominant age cohort 11–13<!--> <!-->years, was introduced in Tomsk region in 2010. The aim of the HPV immunization program is to protect females before they reach an age when the risk of HPV infection increases. A total of 627 girls were vaccinated, and 1653 doses of vaccines were injected. The three- dose schedule was given to 414 (66%) girls and 2-dose schedule to 198 (31.6%) girls. Vaccine safety assessment was carried out. Adverse effects were observed in 9.6% of cases and were mainly characterized by dizziness and pain at the injection site. Vaccination was well tolerated.</p><p>When calculating socio-economic feasibility of the proposed technology , not only the economic damage caused by the high mortality of women from cervical cancer, but also the cost for treatment of precancerous cervical lesions were taken into account, as out of 25 women with undetected CINII-III, 10 will develop cervical cancer. There have been calculated the estimated dam","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 53-54"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310144","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}
Pub Date : 2015-11-01DOI: 10.1016/J.EJCSUP.2015.08.117
E. Voropaeva, T. Pospelova, Voevoda Mi, V. Maximov
{"title":"A36: The TP53 mutations in the Russian patients with de novo DLBCL","authors":"E. Voropaeva, T. Pospelova, Voevoda Mi, V. Maximov","doi":"10.1016/J.EJCSUP.2015.08.117","DOIUrl":"https://doi.org/10.1016/J.EJCSUP.2015.08.117","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"66"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.EJCSUP.2015.08.117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54311003","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}
Pub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.005
O. Bajenova, I. Evsyukov, S. O’Brien
Tumor markers play an important role in the identification of human malignancies. It has been shown that the carcinoembryonic antigen (CEA, CEACAM5) is a promoter of metastasis in epithelial cancers that is widely used as a clinical marker. The aim of this study is to elucidate the network of genes that are involved in the CEA-induced liver metastasis. Previously, we have shown that CEA is accumulated in the lungs and livers of rats by interacting with their macrophages. We identified and cloned a new gene (CEAR) for the CEA-binding protein, which is located on the surface of fixed liver macrophages, Kupffer cells (Bajenova et al, 2001). It has been shown that the interaction of CEA and CEAR proteins increases the production of IL-1, IL-10, IL-6, TNF-α cytokines (Thomas et al, 2011). This interaction changes the expression of liver adhesion molecules that enhances the survival of cancer cells to the liver. We also suggested that CEA synthesis by cancer cells may influence the E-cadherin adhesion junction complexes and have shown that CEA production violates the functional relationship between Ecadherin and its partners α-, β- and p120 catenin. A new type of interaction was discovered between the CEA and β-catenin and the increased amount of β-catenin in the nuclei of CEA producing cells. The data show that CEA production can cause the dissociation of cancer cells and trigger cancer progression. The CEA synthesis also alters splicing of p120 catenin protein and causes the release of soluble E-cadherin. Previously, CEA and epithelial E-cadherin were considered as independent tumor markers. Our data explain the correlation between the elevated levels of CEA and the increase in soluble E-cadherin in the progression of colorectal cancer (Bajenova et al, 2014).
We carried out a comparative transcriptome analysis of CEA-producing cell lines. The RNA transcriptome libraries were obtained and sequenced. By pairwise comparisons of CEA producing and non-producing cell lines using Cummerband program, we selected the set of genes (90 total genes) whose expression have been changed in the CEA-producing cell lines (overexpressed or downregulated). The biological processes that are linked to this differential gene expression were identified by Gene Set Enrichment Analysis (GSEA). In total, 8 significantly enriched GO terms related to the cellular components and biological processes were identified. Using KEGG and GO databases, we also identified the signaling pathways involved in the response to CEA. These findings have direct medical application, since they allow not only to establish the relationships between the existing biomarkers but also to discover the new ones. These biomarkers can be used for diagnosis and monitoring of metastatic carcinomas and for the drug development.
肿瘤标志物在人类恶性肿瘤的鉴别中起着重要的作用。研究表明，癌胚抗原(CEA, CEACAM5)是上皮性癌症转移的启动子，被广泛用作临床标志物。本研究的目的是阐明参与cea诱导的肝转移的基因网络。先前，我们已经证明CEA通过与巨噬细胞相互作用在大鼠的肺和肝脏中积累。我们鉴定并克隆了一个cea结合蛋白的新基因(CEAR)，该基因位于固定肝巨噬细胞Kupffer细胞表面(Bajenova et al, 2001)。研究表明，CEA和CEAR蛋白的相互作用增加了IL-1、IL-10、IL-6、TNF-α细胞因子的产生(Thomas et al, 2011)。这种相互作用改变了肝脏粘附分子的表达，从而增强了癌细胞在肝脏中的存活。我们还提出，癌细胞合成CEA可能影响E-cadherin粘附连接复合物，并表明CEA的产生破坏了E-cadherin及其伙伴α-、β-和p120 catenin之间的功能关系。发现了CEA与β-连环蛋白之间的一种新的相互作用，并在CEA产生细胞的细胞核中发现了β-连环蛋白的增加。数据显示，CEA的产生可以引起癌细胞的分离并引发癌症的进展。CEA的合成也改变了p120连环蛋白的剪接，并导致可溶性e -钙粘蛋白的释放。此前，CEA和上皮E-cadherin被认为是独立的肿瘤标志物。我们的数据解释了CEA水平升高与结直肠癌进展中可溶性e -钙粘蛋白增加之间的相关性(Bajenova et al .， 2014)。我们对产生cea的细胞系进行了比较转录组分析。获得RNA转录组文库并进行测序。利用Cummerband程序对CEA产生细胞系和非产生细胞系进行两两比较，筛选出CEA产生细胞系中表达发生变化(过表达或下调)的基因组(共90个基因)。通过基因集富集分析(GSEA)鉴定了与这种差异基因表达相关的生物学过程。总共鉴定了8个与细胞成分和生物过程相关的显著富集的氧化石墨烯术语。利用KEGG和GO数据库，我们还确定了参与CEA反应的信号通路。这些发现有直接的医学应用，因为它们不仅可以建立现有生物标志物之间的关系，还可以发现新的生物标志物。这些生物标志物可用于转移性癌的诊断和监测以及药物开发。
{"title":"T125","authors":"O. Bajenova, I. Evsyukov, S. O’Brien","doi":"10.1016/j.ejcsup.2015.08.005","DOIUrl":"10.1016/j.ejcsup.2015.08.005","url":null,"abstract":"<div><p>Tumor markers play an important role in the identification of human malignancies. It has been shown that the carcinoembryonic antigen (CEA, CEACAM5) is a promoter of metastasis in epithelial cancers that is widely used as a clinical marker. The aim of this study is to elucidate the network of genes that are involved in the CEA-induced liver metastasis. Previously, we have shown that CEA is accumulated in the lungs and livers of rats by interacting with their macrophages. We identified and cloned a new gene (CEAR) for the CEA-binding protein, which is located on the surface of fixed liver macrophages, Kupffer cells (Bajenova et al, 2001). It has been shown that the interaction of CEA and CEAR proteins increases the production of IL-1, IL-10, IL-6, TNF-<em>α</em> cytokines (Thomas et al, 2011). This interaction changes the expression of liver adhesion molecules that enhances the survival of cancer cells to the liver. We also suggested that CEA synthesis by cancer cells may influence the E-cadherin adhesion junction complexes and have shown that CEA production violates the functional relationship between Ecadherin and its partners <em>α</em>-, <em>β</em>- and p120 catenin. A new type of interaction was discovered between the CEA and <em>β</em>-catenin and the increased amount of <em>β</em>-catenin in the nuclei of CEA producing cells. The data show that CEA production can cause the dissociation of cancer cells and trigger cancer progression. The CEA synthesis also alters splicing of p120 catenin protein and causes the release of soluble E-cadherin. Previously, CEA and epithelial E-cadherin were considered as independent tumor markers. Our data explain the correlation between the elevated levels of CEA and the increase in soluble E-cadherin in the progression of colorectal cancer (Bajenova et al, 2014).</p><p>We carried out a comparative transcriptome analysis of CEA-producing cell lines. The RNA transcriptome libraries were obtained and sequenced. By pairwise comparisons of CEA producing and non-producing cell lines using Cummerband program, we selected the set of genes (90 total genes) whose expression have been changed in the CEA-producing cell lines (overexpressed or downregulated). The biological processes that are linked to this differential gene expression were identified by Gene Set Enrichment Analysis (GSEA). In total, 8 significantly enriched GO terms related to the cellular components and biological processes were identified. Using KEGG and GO databases, we also identified the signaling pathways involved in the response to CEA. These findings have direct medical application, since they allow not only to establish the relationships between the existing biomarkers but also to discover the new ones. These biomarkers can be used for diagnosis and monitoring of metastatic carcinomas and for the drug development.</p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 3"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54308649","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号