Pub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.016
V. Bychkov, E. Nikitina, N. Litviakov
Background
The aim of the study was to identify the factors that determine outcome and overall survival of HNC patients of Tomsk region.
Materials and methods
Clinical data, morphological characteristics of tumors and outcomes were obtained for 91 patients. Data about lifestyle, food preferences, smoking history were obtained from the questionnaire (n = 35). All clinical samples were tested by AmpliSens HPV diagnostic kits (Russia) to determine prevalence of 12 high risk HPV types. Statistical analysis was performed using Kaplan–Meier method, Cox regression, Gehan test, Fisher test, Mann–Whitney and Kruskal–Wallis tests.
Results
Gender, age, smoking status, alcohol consumption, distance from harmful factors, professional hazards and duration of its exposure as well as tumor criteria such as T, N, G, the presence of keratinization, invasion into the underlying tissues, HPV-infection, chemotherapy and/or radiation therapy and response to the treatment were assessed for HNC patients. It was shown that the two-year survival rate was about 70%, and the five-year survival rate was about 32%. There was strong correlation between decreased overall survival and increased alcohol consumption (p = 0.03) as well as regional lymph nodes status (p = 0.01). Patients with early tumor stages and N0 lymph node status as well as patients receiving chemotherapy and/or radiotherapy showed trend towards to better survival (p = 0.09, p = 0.1, p = 0.09, respectively). Overall survival of patients with lymph node metastasis was higher in case of early tumor stages (p = 0.08) and in patients who had no alcohol consumption history (p = 0.06). Cox regression analysis was used to obtain the model describing overall survival of patients. The model with the highest level of significance includes 3 factors-nodal metastases, the presence of keratinization and radiotherapy. It was shown that the risk of death was 4.2 and 2.6-fold higher in case of lymph node metastases and keratinized cancer, and 2.7-fold lower in case of radiotherapy. It was also shown that metastasis occurred more frequently in cases with invasion into the underlying tissue of a primary tumor (p = 0.04) and in cases with a low tissue grade (p = 0.02). Association of alcohol consumption with questionnaire data was studied. It was shown that men’s preferably smokers consume alcohol more often than other patients (p = 0.006, p = 0.02, respectively). Our data showed that HPV prevalence was higher in smokers (p = 0.04), and in patients with early tumor stages (p = 0.07). Furthermore, response to radiotherapy was better in
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Pub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.020
N. Dashenkova, A. Mikaelyan
IGF signaling pathway plays an important role in the regulation of cell growth, proliferation, differentiation, apoptosis and survival. Deregulation of this pathway has been frequently identified in the development of hepatocellular carcinoma (HCC). IGF signaling pathway consists of IGF ligands (IGF-I and IGF-II), IGF binding proteins (IGFBP 1-7), and membrane-bound IGF receptors (IGF-1R, IGF-II/M6PR, and IGF-2R). The insulin-like growth factor binding proteins (IGFBPs) have several functions, such as IGF transporting, accumulation of IGF at the specific cell pools, inhibition and activation of ligand–receptor interaction. Furthermore, the Igfbps may act independently of IGF-pathway.
Diethylnitrosamine (DEN) was used for induction of hepatic tumorigenesis. The male mice, 2 weeks old, were injectedintraperitoneally with 20 mg/kg body weight of DEN. The liver tissue samples were collected 4, 6, 8, 12 months after injection. We performed a comprehensive histological analysis of all kinds of liver samples: tumors, tumor surrounding tissue and normal tissue. Dysplasia was observed 4 months after injection, at hepatocellular adenomas were identified 6–8 months after injection. In the experimental group, 100% of mice had multifocal HCC 12 months after injection. Evaluation of samples from the control group showed normal liver architecture and histology.
Western blot analysis showed the presence the HCC tumor marker alfa-fetoprotein only in tumor samples. High levels of Igf-1R and FoxO3 proteins were observed in tumor tissue in contrast to the surrounding and normal tissues 12 months after injection. The expression profiles of Igfbp-1,-2,-3,-4,-5,-6,-7, Igf-1R, FoxO3 were analyzed by real time PCR. The most significant results were observed 8 and 12 months after DEN injection. RT-PCR showed the dynamic increase in Igf-1R expression in tumor. Expression pattern of Igfbps has shown a high level of Igf-1,-2,-5,-6,-7 mRNA in surrounding tissue and Igfbp-1,-3,-5 in tumor compared to control. The expression of Igfbp-2,-4,-5,-6,-7 was up-regulated, whereas expression of Igfbp-1,-3 was down-regulated in surrounding tissue. The expression of Igfbp-4 was decreased in tumor samples. The expression levels of Igfbp-3,-4 in surrounding tissue and Igfbp-7 in tumor were the same as in the control. We detected high level of mRNA of FoxO3 in tumor.
In conclusion, these data confirm previously existing assumption about paracrine effect of Igfbps on tumor growth and progression. Phosphorylation of FoxO3 protein may play an important role in survival of cancer cells. Our results showed up-regulation of Igfbp-2 and Igfbp-5 in tumor and tumor surrounding tissue. Igfbp-2 and Igfbp-5, well known activators of Igfs, can be pro-tumorigenic factors, which are important for hepatocarcinogenesis. Hence, therapeutic targeting of these proteins may offer options for intervention in
{"title":"A129","authors":"N. Dashenkova, A. Mikaelyan","doi":"10.1016/j.ejcsup.2015.08.020","DOIUrl":"10.1016/j.ejcsup.2015.08.020","url":null,"abstract":"<div><p>IGF signaling pathway plays an important role in the regulation of cell growth, proliferation, differentiation, apoptosis and survival. Deregulation of this pathway has been frequently identified in the development of hepatocellular carcinoma (HCC). IGF signaling pathway consists of IGF ligands (IGF-I and IGF-II), IGF binding proteins (IGFBP 1-7), and membrane-bound IGF receptors (IGF-1R, IGF-II/M6PR, and IGF-2R). The insulin-like growth factor binding proteins (IGFBPs) have several functions, such as IGF transporting, accumulation of IGF at the specific cell pools, inhibition and activation of ligand–receptor interaction. Furthermore, the Igfbps may act independently of IGF-pathway.</p><p>Diethylnitrosamine (DEN) was used for induction of hepatic tumorigenesis. The male mice, 2<!--> <!-->weeks old, were injectedintraperitoneally with 20<!--> <!-->mg/kg body weight of DEN. The liver tissue samples were collected 4, 6, 8, 12<!--> <!-->months after injection. We performed a comprehensive histological analysis of all kinds of liver samples: tumors, tumor surrounding tissue and normal tissue. Dysplasia was observed 4<!--> <!-->months after injection, at hepatocellular adenomas were identified 6–8<!--> <!-->months after injection. In the experimental group, 100% of mice had multifocal HCC 12<!--> <!-->months after injection. Evaluation of samples from the control group showed normal liver architecture and histology.</p><p>Western blot analysis showed the presence the HCC tumor marker alfa-fetoprotein only in tumor samples. High levels of Igf-1R and FoxO3 proteins were observed in tumor tissue in contrast to the surrounding and normal tissues 12<!--> <!-->months after injection. The expression profiles of Igfbp-1,-2,-3,-4,-5,-6,-7, Igf-1R, FoxO3 were analyzed by real time PCR. The most significant results were observed 8 and 12<!--> <!-->months after DEN injection. RT-PCR showed the dynamic increase in Igf-1R expression in tumor. Expression pattern of Igfbps has shown a high level of Igf-1,-2,-5,-6,-7 mRNA in surrounding tissue and Igfbp-1,-3,-5 in tumor compared to control. The expression of Igfbp-2,-4,-5,-6,-7 was up-regulated, whereas expression of Igfbp-1,-3 was down-regulated in surrounding tissue. The expression of Igfbp-4 was decreased in tumor samples. The expression levels of Igfbp-3,-4 in surrounding tissue and Igfbp-7 in tumor were the same as in the control. We detected high level of mRNA of FoxO3 in tumor.</p><p>In conclusion, these data confirm previously existing assumption about paracrine effect of Igfbps on tumor growth and progression. Phosphorylation of FoxO3 protein may play an important role in survival of cancer cells. Our results showed up-regulation of Igfbp-2 and Igfbp-5 in tumor and tumor surrounding tissue. Igfbp-2 and Igfbp-5, well known activators of Igfs, can be pro-tumorigenic factors, which are important for hepatocarcinogenesis. Hence, therapeutic targeting of these proteins may offer options for intervention in","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 11-12"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54308891","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.2015.08.028
R. Fadeev , M. Solovieva , S. Zakharov , I. Fadeeva , A. Senotov , A. Golenkov , V. Akatov
Acute myelomonocytic leukemia (FAB M4) is one of the most common forms of acute myeloid leukemia (AML). This AML form is characterized by rapid accumulation transformed myeloblasts and monoblasts in bone marrow, with the rapid suppression of normal hematopoiesis. Bone marrow microenvironment is one of the main factors determining drug resistance of leukemic cells. It is known that the adhesion of leukemic cells to mesenchymal stem cell and bone marrow extracellular matrix (laminin, collagen) enhances their drug resistance. However, it remains unknown whether the emergence of drug resistance when cell–cell contacts are formed only between leukemia cells, without the involvement of bone marrow stromal elements. We studied the role of cell aggregation in drug resistance of leukemic cells. We used the bone marrow mononuclear cells (BMMC) isolated from the patients with acute myelomonocytic leukemia. For the formation of multicellular aggregates, BMMC were cultivated in 96-well plates coated with 1.5% agarose. We showed that resistance of BMMC to bortezomib, doxorubicin and fludarabine in multicellular aggregates was increased. In three-dimensional multicellular aggregates of BMMC index IC50 for bortezomib, doxorubicin and fludarabine was 7 ± 1 ng/ml, 1 ± 0.4 mkM and 0.8 ± 0.05 mkM, respectively. In control condition, index IC50 bortezomib, doxorubicin and fludarabine was significantly lower, 2 ± 0.5 ng/ml, 0.3 ± 0.05 mkM and 0.07 ± 0.001 mkM, respectively. In multicellular aggregates of BMMC number of mitotic cells and expression of Ki-67 protein were not significantly different from the control. It has also been shown that cells in multicellular aggregates increased expression antiapoptotic protein Bcl-2. Suppression of BMMC aggregation by culturing the cells in medium containing 0.9% methylcellulose resulted in decreased IC50 index for bortezomib, doxorubicin and fludarabine, 2 ± 0.7 ng/ml, 0.12 ± 0.004 mkM and 0.04 ± 0.005 mkM, respectively. Expression of the Bcl-2 protein was also decreased. This work demonstrates the involvement of cell aggregation in the formation of drug resistance phenotype in leukemic cells.
The work was supported by the Russian Foundation for Basic Research (Russia) (No. 14-04-32183, 14- 04-32191), the scholarship of the President of the Russian Federation (Russia) (No. SP-6867.2013.4, SP-1519.2015.4), and by the Government of the Russian Federation (Russia) (No.14.Z50.31.0028).
{"title":"P119","authors":"R. Fadeev , M. Solovieva , S. Zakharov , I. Fadeeva , A. Senotov , A. Golenkov , V. Akatov","doi":"10.1016/j.ejcsup.2015.08.028","DOIUrl":"10.1016/j.ejcsup.2015.08.028","url":null,"abstract":"<div><p>Acute myelomonocytic leukemia (FAB M4) is one of the most common forms of acute myeloid leukemia (AML). This AML form is characterized by rapid accumulation transformed myeloblasts and monoblasts in bone marrow, with the rapid suppression of normal hematopoiesis. Bone marrow microenvironment is one of the main factors determining drug resistance of leukemic cells. It is known that the adhesion of leukemic cells to mesenchymal stem cell and bone marrow extracellular matrix (laminin, collagen) enhances their drug resistance. However, it remains unknown whether the emergence of drug resistance when cell–cell contacts are formed only between leukemia cells, without the involvement of bone marrow stromal elements. We studied the role of cell aggregation in drug resistance of leukemic cells. We used the bone marrow mononuclear cells (BMMC) isolated from the patients with acute myelomonocytic leukemia. For the formation of multicellular aggregates, BMMC were cultivated in 96-well plates coated with 1.5% agarose. We showed that resistance of BMMC to bortezomib, doxorubicin and fludarabine in multicellular aggregates was increased. In three-dimensional multicellular aggregates of BMMC index IC50 for bortezomib, doxorubicin and fludarabine was 7<!--> <!-->±<!--> <!-->1<!--> <!-->ng/ml, 1<!--> <!-->±<!--> <!-->0.4<!--> <!-->mkM and 0.8<!--> <!-->±<!--> <!-->0.05<!--> <!-->mkM, respectively. In control condition, index IC50 bortezomib, doxorubicin and fludarabine was significantly lower, 2<!--> <!-->±<!--> <!-->0.5<!--> <!-->ng/ml, 0.3<!--> <!-->±<!--> <!-->0.05<!--> <!-->mkM and 0.07<!--> <!-->±<!--> <!-->0.001<!--> <!-->mkM, respectively. In multicellular aggregates of BMMC number of mitotic cells and expression of Ki-67 protein were not significantly different from the control. It has also been shown that cells in multicellular aggregates increased expression antiapoptotic protein Bcl-2. Suppression of BMMC aggregation by culturing the cells in medium containing 0.9% methylcellulose resulted in decreased IC50 index for bortezomib, doxorubicin and fludarabine, 2<!--> <!-->±<!--> <!-->0.7<!--> <!-->ng/ml, 0.12<!--> <!-->±<!--> <!-->0.004<!--> <!-->mkM and 0.04<!--> <!-->±<!--> <!-->0.005<!--> <!-->mkM, respectively. Expression of the Bcl-2 protein was also decreased. This work demonstrates the involvement of cell aggregation in the formation of drug resistance phenotype in leukemic cells.</p><p>The work was supported by the <span>Russian Foundation for Basic Research</span> (Russia) (No. <span>14-04-32183</span>, <span>14- 04-32191</span>), the scholarship of the <span>President of the Russian Federation</span> (Russia) (No. <span>SP-6867.2013.4</span>, <span>SP-1519.2015.4</span>), and by the <span>Government of the Russian Federation</span> (Russia) (No.<span>14.Z50.31.0028</span>).</p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 16"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309031","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.2015.08.070
T. Nikitenko , O. Rymar , S. Malyutina , L. Shcherbakova , E. Veryovkin , S. Kurilovich , Yu. Ragino , M. Voevoda
Obesity, associated with metabolic syndrome, is considered a significant risk factor for colorectal cancer (CRC).
Purpose
To compare the levels of metabolic syndrome (MS) components in persons with CRC and control in the frame of nested “case-control” design.
Materials and Methods
The study was carried out on the basis of a comparison of databases from epidemiological study The HAPIEE project and CRC register. The patients examined in the HAPIEE project, who had developed CRC during 10-year follow-up period according to the register of cancer (n = 92, men-48, women-44, mean age 60.7 + 6.9 years) were included in analysis. The control group, matched by sex and age, was also formed from the HAPIEE database (n = 184, men-96, women-88, mean age 60.7 + 6.8 years). We used MS criteria’s according to NCEP ATP – III (2001). The data was processed using statistical program SPSS 13.0.
Results
Body mass index (BMI) and waist circumference (WC) had no significant differences in the studied groups, the average BMI value in CRC group was 28.6 + 5.3 kg/m2 vs 28.4 + 5.6 kg/m2 in control (p = 0.70) and WC value in CRC group was 94.1 + 11.7 cm vs 94.1 + 13.6 cm in control (p = 0.90). The percentage of patients with abdominal obesity was 41.3% in patients with CRC vs 42.9% in the control group (p = 0.70).
The average value of total cholesterol was equally high in both groups (246.8 + 52.5 mg/dL in patients with CRC and 239.8 + 47.0 mg/dL in the control group), with large individual variation but no significant difference (p = 0.27). The average level of HDL cholesterol in CRC group was within normal limits and also did not differ from control (p = 0.60). The average level of TG in CRC patients was slightly lower than in the control group: 127.2 + 58.5 mg/dl vs 144.6 + 80.8 mg/dL (p = 0.07). The average level of glucose did not differ in patients with CRC and in control: 5.9 + 1,2 mmol/l vs 6.1 + 2.1 mmol/L (p = 0.40). In patients with CRC systolic blood pressure was significantly lower than in control group: 142.1 + 21.3 mmHg vs 150.4 + 23.7 mmHg (p = 0.005). The level of diastolic blood pressure was slightly lower than in the control group compared to CRC (88.9 + 11.2 mmHg vs91.
{"title":"P96","authors":"T. Nikitenko , O. Rymar , S. Malyutina , L. Shcherbakova , E. Veryovkin , S. Kurilovich , Yu. Ragino , M. Voevoda","doi":"10.1016/j.ejcsup.2015.08.070","DOIUrl":"10.1016/j.ejcsup.2015.08.070","url":null,"abstract":"<div><p>Obesity, associated with metabolic syndrome, is considered a significant risk factor for colorectal cancer (CRC).</p></div><div><h3>Purpose</h3><p>To compare the levels of metabolic syndrome (MS) components in persons with CRC and control in the frame of nested “case-control” design.</p></div><div><h3>Materials and Methods</h3><p>The study was carried out on the basis of a comparison of databases from epidemiological study The HAPIEE project and CRC register. The patients examined in the HAPIEE project, who had developed CRC during 10-year follow-up period according to the register of cancer (<em>n</em> <!-->=<!--> <!-->92, men-48, women-44, mean age 60.7<!--> <!-->+<!--> <!-->6.9<!--> <!-->years) were included in analysis. The control group, matched by sex and age, was also formed from the HAPIEE database (<em>n</em> <!-->=<!--> <!-->184, men-96, women-88, mean age 60.7<!--> <!-->+<!--> <!-->6.8<!--> <!-->years). We used MS criteria’s according to NCEP ATP – III (2001). The data was processed using statistical program SPSS 13.0.</p></div><div><h3>Results</h3><p>Body mass index (BMI) and waist circumference (WC) had no significant differences in the studied groups, the average BMI value in CRC group was 28.6<!--> <!-->+<!--> <!-->5.3<!--> <!-->kg/m<sup>2</sup> vs 28.4<!--> <!-->+<!--> <!-->5.6<!--> <!-->kg/m<sup>2</sup> in control (<em>p</em> <!-->=<!--> <!-->0.70) and WC value in CRC group was 94.1<!--> <!-->+<!--> <!-->11.7<!--> <!-->cm vs 94.1<!--> <!-->+<!--> <!-->13.6<!--> <!-->cm in control (<em>p</em> <!-->=<!--> <!-->0.90). The percentage of patients with abdominal obesity was 41.3% in patients with CRC vs 42.9% in the control group (<em>p</em> <!-->=<!--> <!-->0.70).</p><p>The average value of total cholesterol was equally high in both groups (246.8<!--> <!-->+<!--> <!-->52.5<!--> <!-->mg/dL in patients with CRC and 239.8<!--> <!-->+<!--> <!-->47.0<!--> <!-->mg/dL in the control group), with large individual variation but no significant difference (<em>p</em> <!-->=<!--> <!-->0.27). The average level of HDL cholesterol in CRC group was within normal limits and also did not differ from control (<em>p</em> <!-->=<!--> <!-->0.60). The average level of TG in CRC patients was slightly lower than in the control group: 127.2<!--> <!-->+<!--> <!-->58.5<!--> <!-->mg/dl vs 144.6<!--> <!-->+<!--> <!-->80.8<!--> <!-->mg/dL (<em>p</em> <!-->=<!--> <!-->0.07). The average level of glucose did not differ in patients with CRC and in control: 5.9<!--> <!-->+<!--> <!-->1,2<!--> <!-->mmol/l vs 6.1<!--> <!-->+<!--> <!-->2.1<!--> <!-->mmol/L (<em>p</em> <!-->=<!--> <!-->0.40). In patients with CRC systolic blood pressure was significantly lower than in control group: 142.1<!--> <!-->+<!--> <!-->21.3<!--> <!-->mmHg vs 150.4<!--> <!-->+<!--> <!-->23.7<!--> <!-->mmHg (<em>p</em> <!-->=<!--> <!-->0.005). The level of diastolic blood pressure was slightly lower than in the control group compared to CRC (88.9<!--> <!-->+<!--> <!-->11.2<!--> <!-->mmHg vs91.","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 39-40"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309808","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.2015.08.087
S. Semina, M. Krasil’nikov
The efficiency of endocrine therapy for tumors is limited by the development of hormone resistance and progression of tumor cells to hormone-independent phenotype. Among these tumors – breast cancers, for which hormone therapy is one of the most common and effective methods of treatment, but only in cases, when the tumors retain their hormonal dependence. The mechanism of hormonal independence was found to be based on the fundamental properties of cancer cell including both downregulation of specific hormone receptors, and affecting of intracellular signalling, particularly – estrogen-independent growth signaling pathways. However, the role of the intercellular interactions in the progression of hormonal resistance is still unclear.
We hypothesize, that the formation of the clone of the hormone-resistant cells in the tumor, and the subsequent common growth of the hormone-resistant and sensitive cells may lead to spread the hormonal resistance to the sensitive cells – as a result of the secretion of the specific factors acting in the paracrine manner or via the direct cell–cell contacts. Here, using the estrogen-dependent breast cancer cells MCF-7 and the resistant subline MCF-7/T developed by long-term cultivation of MCF-7 cells in the presence of antiestrogen tamoxifen, we investigated the possible changes in the hormonal sensitivity of these cells caused by the co-cultivation in vitro. For this purpose MCF-7/T cells were transfected with the plasmid containing the gene of the green fluorescent protein (GFP), and GFP-positive hormone-resistant subline MCF-7/T/GFP+ was developed. The GFP expression should allow to distinguish the resistant and parental cells during co-cultivation.
To study the influence of the co-cultivation on the cell sensitivity to tamoxifen the parent MCF-7 cells (GFP-negative) were co-cultivate with the resistant MCF-7/T/GFP+/cells for 10 days, then the cells were treated with tamoxifen and the efficiency of growth inhibitory tamoxifen action was determined. We found, that the co -cultivation of the parent and resistant cells lead to increase in the resistance of the parent cell to tamoxifen, indicating the important role of the contacts, direct or indirect, between hormone sensitive and resistant cells in the development of hormone resistance.
In general, we evaluate the established results as the first evidence of the possible involvement of the cell–cell underrelations in the realization of the hormonal response, and suppose that the next investigations will give a new insights in the molecular mechanisms of this effects and its role in the formation of the hormone-resistant phenotype of the tumors.
{"title":"P38","authors":"S. Semina, M. Krasil’nikov","doi":"10.1016/j.ejcsup.2015.08.087","DOIUrl":"10.1016/j.ejcsup.2015.08.087","url":null,"abstract":"<div><p>The efficiency of endocrine therapy for tumors is limited by the development of hormone resistance and progression of tumor cells to hormone-independent phenotype. Among these tumors – breast cancers, for which hormone therapy is one of the most common and effective methods of treatment, but only in cases, when the tumors retain their hormonal dependence. The mechanism of hormonal independence was found to be based on the fundamental properties of cancer cell including both downregulation of specific hormone receptors, and affecting of intracellular signalling, particularly – estrogen-independent growth signaling pathways. However, the role of the intercellular interactions in the progression of hormonal resistance is still unclear.</p><p>We hypothesize, that the formation of the clone of the hormone-resistant cells in the tumor, and the subsequent common growth of the hormone-resistant and sensitive cells may lead to spread the hormonal resistance to the sensitive cells – as a result of the secretion of the specific factors acting in the paracrine manner or via the direct cell–cell contacts. Here, using the estrogen-dependent breast cancer cells MCF-7 and the resistant subline MCF-7/T developed by long-term cultivation of MCF-7 cells in the presence of antiestrogen tamoxifen, we investigated the possible changes in the hormonal sensitivity of these cells caused by the co-cultivation in vitro. For this purpose MCF-7/T cells were transfected with the plasmid containing the gene of the green fluorescent protein (GFP), and GFP-positive hormone-resistant subline MCF-7/T/GFP+ was developed. The GFP expression should allow to distinguish the resistant and parental cells during co-cultivation.</p><p>To study the influence of the co-cultivation on the cell sensitivity to tamoxifen the parent MCF-7 cells (GFP-negative) were co-cultivate with the resistant MCF-7/T/GFP+/cells for 10<!--> <!-->days, then the cells were treated with tamoxifen and the efficiency of growth inhibitory tamoxifen action was determined. We found, that the co -cultivation of the parent and resistant cells lead to increase in the resistance of the parent cell to tamoxifen, indicating the important role of the contacts, direct or indirect, between hormone sensitive and resistant cells in the development of hormone resistance.</p><p>In general, we evaluate the established results as the first evidence of the possible involvement of the cell–cell underrelations in the realization of the hormonal response, and suppose that the next investigations will give a new insights in the molecular mechanisms of this effects and its role in the formation of the hormone-resistant phenotype of the tumors.</p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 48-49"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310023","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.2015.08.088
Y. Shapovalova , D. Lytkina , L. Rasskazova , A. Gudima , V. Ryabov , A. Filimoshkin , I. Kurzina , J. Kzhyshkowska
Orthopedic oncologic prostheses are essential in postoperative therapy and improvement of life quality of oncological patients. However, construction and composition of implants has to be improved for better biocompatibility and reduction of inflammatory responses. The materials based on polylactic acid (PLA) and hydroxyapatite (HA) have been suggested as promising solution for implant coating in order to improve reconstruction of bone defects, to reduce risk of inflammation and implant rejection.
Objective
To obtain the bioresorbable composites using biocompatible poly-L-lactide (PLA) with HA and to evaluate its effect on bone remodeling rate.
Materials and methods
After dissolution of PLA∗ in chloroform the powder-like HA (d = 20–40 nm) was added under vigorous stirring (PLA: HA = 75:25). The PLA/HA suspension was sonicated (40 kHz) and precipitated in ethanol. Fine fibers (d = 0.1– 0.5 μm, of more than 2 mm length) were formed. The PLA/HA composite fibers were air-dried; they consisted of HA nanoparticles homogeneously distributed in the PLA matrix. The composites ability to participate in bone remodeling was estimated by determination of the polymer matrix dissolution rate and by formation of the CPL on the surface of the composites.
Results
The degradation rate of the polymer matrix was calculated by measuring concentration of lactic acid (by HPLC method), being released from PLA macromolecules as the result of the hydrolysis in the physiologic solution (pH 7, ω(NaCl) = 0.9%). The PLA degradation rate during the first 4 days of soaking of the substrates (d = 10 mm, S = 190 mm2, m = 0.20 ± 0.01 g) in the solution is rather high (Clactic acid = 10 wt%), while on day 5 it decreases and stays constant during the rest of the time. The HA content increase in the composite results in the enhanced hydrolysis of PLA, caused both by the partial acid-base interaction between PLA and HA, and due to presence of the phase boundaries. Interesting to note that pure PLA (without HA) is hardly hydrolyzed in the physiologic solution even on the 30-th day of the experiment. Formation of calcium phosphate layer (CPL) was done in the SBF media, simulating the mineral constituents of the blood plasma at 37 °C, over 28 days period. The total concentration of Ca2+ and Mg2+ ions in the SBF-solution was determined by daily trilonometry in the ammonia buffer with eriochrome black T as indicator. This investigation clearly shows that the substrates both of HA and PLA/HA promote the CLP formation on their surfaces. On day 14 of the substrates soaking in the SBF solution the
{"title":"P97","authors":"Y. Shapovalova , D. Lytkina , L. Rasskazova , A. Gudima , V. Ryabov , A. Filimoshkin , I. Kurzina , J. Kzhyshkowska","doi":"10.1016/j.ejcsup.2015.08.088","DOIUrl":"10.1016/j.ejcsup.2015.08.088","url":null,"abstract":"<div><p>Orthopedic oncologic prostheses are essential in postoperative therapy and improvement of life quality of oncological patients. However, construction and composition of implants has to be improved for better biocompatibility and reduction of inflammatory responses. The materials based on polylactic acid (PLA) and hydroxyapatite (HA) have been suggested as promising solution for implant coating in order to improve reconstruction of bone defects, to reduce risk of inflammation and implant rejection.</p></div><div><h3>Objective</h3><p>To obtain the bioresorbable composites using biocompatible poly-L-lactide (PLA) with HA and to evaluate its effect on bone remodeling rate.</p></div><div><h3>Materials and methods</h3><p>After dissolution of PLA<sup>∗</sup> in chloroform the powder-like HA (<em>d</em> <!-->=<!--> <!-->20–40<!--> <!-->nm) was added under vigorous stirring (PLA: HA<!--> <!-->=<!--> <!-->75:25). The PLA/HA suspension was sonicated (40<!--> <!-->kHz) and precipitated in ethanol. Fine fibers (<em>d</em> <!-->=<!--> <!-->0.1– 0.5<!--> <!-->μm, of more than 2<!--> <!-->mm length) were formed. The PLA/HA composite fibers were air-dried; they consisted of HA nanoparticles homogeneously distributed in the PLA matrix. The composites ability to participate in bone remodeling was estimated by determination of the polymer matrix dissolution rate and by formation of the CPL on the surface of the composites.</p></div><div><h3>Results</h3><p>The degradation rate of the polymer matrix was calculated by measuring concentration of lactic acid (by HPLC method), being released from PLA macromolecules as the result of the hydrolysis in the physiologic solution (pH 7, <em>ω</em>(NaCl)<!--> <!-->=<!--> <!-->0.9%). The PLA degradation rate during the first 4 days of soaking of the substrates (<em>d</em> <!-->=<!--> <!-->10<!--> <!-->mm, <em>S</em> <!-->=<!--> <!-->190<!--> <!-->mm<sup>2</sup>, <em>m</em> <!-->=<!--> <!-->0.20<!--> <!-->±<!--> <!-->0.01<!--> <!-->g) in the solution is rather high (Clactic acid<!--> <!-->=<!--> <!-->10<!--> <!-->wt%), while on day 5 it decreases and stays constant during the rest of the time. The HA content increase in the composite results in the enhanced hydrolysis of PLA, caused both by the partial acid-base interaction between PLA and HA, and due to presence of the phase boundaries. Interesting to note that pure PLA (without HA) is hardly hydrolyzed in the physiologic solution even on the 30-th day of the experiment. Formation of calcium phosphate layer (CPL) was done in the SBF media, simulating the mineral constituents of the blood plasma at 37<!--> <!-->°C, over 28 days period. The total concentration of Ca2+ and Mg2+ ions in the SBF-solution was determined by daily trilonometry in the ammonia buffer with eriochrome black T as indicator. This investigation clearly shows that the substrates both of HA and PLA/HA promote the CLP formation on their surfaces. On day 14 of the substrates soaking in the SBF solution the ","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 49-50"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310032","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.2015.08.090
O. Shatova, D. Kaplun, I. Zinkovych
Background
Metformin is a antidiabetic drug with anticancer properties. However, the mechanism action by which metformin affects various cancer cells still unknown. It is known that tumor growth is accompanied by changes in the metabolic cascade that includes overproduction of lactate and adenosine. The adenosine is released into the extracellular environment and regulates differentiation, proliferation, and angiogenesis of tumor mass. We found that lactate is activator of key enzyme of adenosine metabolism – adenosine deaminase (ADA).
Aim
The aim of our study was to investigate the catabolism of adenosine in the tumor while taking metformin.
Materials and methods
In this study we investigated the level of adenosine, inosine, hypoxanthine and ADA activity in 15 women aged 46–76 years, with breast cancer (BC) T2-4N1M0 (cancer tissues) during treatment with metformin, 1000 mg per day for 3 months. Control group – 15 women aged 46–76 years, with stage T2-4N1M0 breast cancer (cancer tissues) without metformin therapy.
Statistical analysis was performed using the license package StatSoft. Statistica 12.0.
Results
ADA activity during treatment with metformin was 2-fold increased: 12.1 ± 2.49 nmol/min*mg in comparison with 4.77 ± 0.943 nmol/min*mg. Concentration of catabolic products of adenosine degradation was increased before metformin therapy. Inosine level was 0.121 ± 0.041 micro mol/g tissue (BC tissues from women without metformin 0.042 ± 0.015 micro mol/g tissue). Hypoxanthine 2.45 ± 0.428 micro mol/g tissue (in comparison with 0.711 ± 0.269 micro mol/g tissue). Whereas, adenosine level in BC after metformin therapy was 0.226 ± 0.148 micro mol/g tissue (in comparison with 0.186 ± 0.056 micro mol/g tissue), that were not significantly different.
Conclusion
Thus, we have found that metformin significantly increases the rate of catabolism of adenosine, and this in turn reduces the inhibitory effect on the tumor microenvironment cytotoxic cells. Therefore, our data for the first time provide novel evidence for a mechanism that the anticancer activities of metformin are due to adenosine metabolism regulation.
{"title":"T9","authors":"O. Shatova, D. Kaplun, I. Zinkovych","doi":"10.1016/j.ejcsup.2015.08.090","DOIUrl":"10.1016/j.ejcsup.2015.08.090","url":null,"abstract":"<div><h3>Background</h3><p>Metformin is a antidiabetic drug with anticancer properties. However, the mechanism action by which metformin affects various cancer cells still unknown. It is known that tumor growth is accompanied by changes in the metabolic cascade that includes overproduction of lactate and adenosine. The adenosine is released into the extracellular environment and regulates differentiation, proliferation, and angiogenesis of tumor mass. We found that lactate is activator of key enzyme of adenosine metabolism – adenosine deaminase (ADA).</p></div><div><h3>Aim</h3><p>The aim of our study was to investigate the catabolism of adenosine in the tumor while taking metformin.</p></div><div><h3>Materials and methods</h3><p>In this study we investigated the level of adenosine, inosine, hypoxanthine and ADA activity in 15 women aged 46–76<!--> <!-->years, with breast cancer (BC) T2-4N1M0 (cancer tissues) during treatment with metformin, 1000<!--> <!-->mg per day for 3 months. Control group – 15 women aged 46–76<!--> <!-->years, with stage T2-4N1M0 breast cancer (cancer tissues) without metformin therapy.</p><p>Statistical analysis was performed using the license package StatSoft. Statistica 12.0.</p></div><div><h3>Results</h3><p>ADA activity during treatment with metformin was 2-fold increased: 12.1<!--> <!-->±<!--> <!-->2.49<!--> <!-->nmol/min*mg in comparison with 4.77<!--> <!-->±<!--> <!-->0.943<!--> <!-->nmol/min*mg. Concentration of catabolic products of adenosine degradation was increased before metformin therapy. Inosine level was 0.121<!--> <!-->±<!--> <!-->0.041<!--> <!-->micro<!--> <!-->mol/g tissue (BC tissues from women without metformin 0.042<!--> <!-->±<!--> <!-->0.015<!--> <!-->micro<!--> <!-->mol/g tissue). Hypoxanthine 2.45<!--> <!-->±<!--> <!-->0.428<!--> <!-->micro<!--> <!-->mol/g tissue (in comparison with 0.711<!--> <!-->±<!--> <!-->0.269<!--> <!-->micro<!--> <!-->mol/g tissue). Whereas, adenosine level in BC after metformin therapy was 0.226<!--> <!-->±<!--> <!-->0.148<!--> <!-->micro<!--> <!-->mol/g tissue (in comparison with 0.186<!--> <!-->±<!--> <!-->0.056<!--> <!-->micro<!--> <!-->mol/g tissue), that were not significantly different.</p></div><div><h3>Conclusion</h3><p>Thus, we have found that metformin significantly increases the rate of catabolism of adenosine, and this in turn reduces the inhibitory effect on the tumor microenvironment cytotoxic cells. Therefore, our data for the first time provide novel evidence for a mechanism that the anticancer activities of metformin are due to adenosine metabolism regulation.</p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 50-51"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310060","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.2015.08.092
S. Shevchenko , L, Mostovich , G. Logacheva , S. Svyatchenko , L. Gulyaeva
Papillary thyroid cancer (PTC) is the most common malignancy of the endocrine system. The most frequent genetic alteration in PTC is the BRAF V600E mutation, which affects the activation of several intracellular signaling pathways. As a result, changes in the expression levels of cell membrane integrin receptors and their ligands – extracellular matrix proteins – osteopontin (OPN) and thrombospondin -1 (TSP1) are observed. This process increases the metastatic potential of tumor cells. Thus, integrin receptors and their ligands are potential biomarkers of an aggressive PTC phenotype.
The aim of our study was to compare the gene expression profile of integrins ITGA2, ITGA3, ITGAV, ITGA6, ITGA9, ITGB1, ITGB3 and their ligands OPNa, OPNb, and TSP1 in PTC with different BRAF V600E mutation status.
Intraoperative thyroid tissue samples from 41 patients diagnosed with PTC (n = 26), diffuse nodular nontoxic goiter (n = 10) and follicular adenoma (n = 5) were analyzed to evaluate the expression levels of the investigated genes by real time RT-PCR. Fluorescent immunohistochemistry (IHC) was used to confirm the PCR results and to estimate the amount of protein products. For IHC, frozen and paraffin sections were used. The BRAF V600E mutation was determined using allele-specific amplification. Nonparametric criteria (Kruskal Wallis, Wilcoxon and Mann–Whitney tests) were used to evaluate group differences. P values of less than 0.05 were considered statistically significant.
The BRAF V600E mutation was observed in 12 PTC samples, which corresponds to 46% of PTC cases. An increase of gene expression level of ITGA3 (2.9-fold, p = 0.014), ITGAV (1.9-fold, p = 0.038), ITGB1 (1.7-fold, p = 0.026), OPNb (2.5-fold, p = 0.0001) and TSP1 (3.2-fold, p = 0.017) was identified in the PTC tissues, and a high gene expression level of OPNb (5.9-fold, p = 0.003) and TSP1 (12.1-fold, p = 0.005) was identified in the tissue samples of lymph node metastases compared to the conventionally normal tissue.
In the samples with advanced cancer (T3, T4, TNM) the expression levels of ITGA3, ITGA6 and ITGA9 were higher compared to the T1 samples. MRNA levels of ITGA3 and ITGAV were significantly higher in the PTC BRAF V600E positive samples than in the BRAF V600E negative samples.
Elevated levels of OPNa (11.4-fold, p = 0.0112), OPNb (10.2-fold, p = 0.0216) and TSP1 (33.5-fold, p = 0.0005) genes were observed in the follicular adenoma samples compared to the PTC tissues. For ITGA2 and ITGB3 there was a significant increase of expression in the PTC tissues compared to the benign thyroid tumors (8.9-fold, p = 0.
{"title":"P82","authors":"S. Shevchenko , L, Mostovich , G. Logacheva , S. Svyatchenko , L. Gulyaeva","doi":"10.1016/j.ejcsup.2015.08.092","DOIUrl":"10.1016/j.ejcsup.2015.08.092","url":null,"abstract":"<div><p>Papillary thyroid cancer (PTC) is the most common malignancy of the endocrine system. The most frequent genetic alteration in PTC is the BRAF V600E mutation, which affects the activation of several intracellular signaling pathways. As a result, changes in the expression levels of cell membrane integrin receptors and their ligands – extracellular matrix proteins – osteopontin (OPN) and thrombospondin -1 (TSP1) are observed. This process increases the metastatic potential of tumor cells. Thus, integrin receptors and their ligands are potential biomarkers of an aggressive PTC phenotype.</p><p>The aim of our study was to compare the gene expression profile of integrins ITGA2, ITGA3, ITGAV, ITGA6, ITGA9, ITGB1, ITGB3 and their ligands OPNa, OPNb, and TSP1 in PTC with different BRAF V600E mutation status.</p><p>Intraoperative thyroid tissue samples from 41 patients diagnosed with PTC (<em>n</em> <!-->=<!--> <!-->26), diffuse nodular nontoxic goiter (<em>n</em> <!-->=<!--> <!-->10) and follicular adenoma (<em>n</em> <!-->=<!--> <!-->5) were analyzed to evaluate the expression levels of the investigated genes by real time RT-PCR. Fluorescent immunohistochemistry (IHC) was used to confirm the PCR results and to estimate the amount of protein products. For IHC, frozen and paraffin sections were used. The BRAF V600E mutation was determined using allele-specific amplification. Nonparametric criteria (Kruskal Wallis, Wilcoxon and Mann–Whitney tests) were used to evaluate group differences. <em>P</em> values of less than 0.05 were considered statistically significant.</p><p>The BRAF V600E mutation was observed in 12 PTC samples, which corresponds to 46% of PTC cases. An increase of gene expression level of ITGA3 (2.9-fold, <em>p</em> <!-->=<!--> <!-->0.014), ITGAV (1.9-fold, <em>p</em> <!-->=<!--> <!-->0.038), ITGB1 (1.7-fold, <em>p</em> <!-->=<!--> <!-->0.026), OPNb (2.5-fold, <em>p</em> <!-->=<!--> <!-->0.0001) and TSP1 (3.2-fold, <em>p</em> <!-->=<!--> <!-->0.017) was identified in the PTC tissues, and a high gene expression level of OPNb (5.9-fold, <em>p</em> <!-->=<!--> <!-->0.003) and TSP1 (12.1-fold, <em>p</em> <!-->=<!--> <!-->0.005) was identified in the tissue samples of lymph node metastases compared to the conventionally normal tissue.</p><p>In the samples with advanced cancer (T3, T4, TNM) the expression levels of ITGA3, ITGA6 and ITGA9 were higher compared to the T1 samples. MRNA levels of ITGA3 and ITGAV were significantly higher in the PTC BRAF V600E positive samples than in the BRAF V600E negative samples.</p><p>Elevated levels of OPNa (11.4-fold, <em>p</em> <!-->=<!--> <!-->0.0112), OPNb (10.2-fold, <em>p</em> <!-->=<!--> <!-->0.0216) and TSP1 (33.5-fold, <em>p</em> <!-->=<!--> <!-->0.0005) genes were observed in the follicular adenoma samples compared to the PTC tissues. For ITGA2 and ITGB3 there was a significant increase of expression in the PTC tissues compared to the benign thyroid tumors (8.9-fold, <em>p</em> <!-->=<!--> <!-->0.","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 51-52"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310089","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.2015.08.122
T. Zavarykina, A. Byrdennyy, V. Loginov, M. V. Atkarskaya, Zhizhina Gp
{"title":"A84: Polymorphic markers Arg72Pro and Gln157Lys of TP53 gene in nonsmall cell lung cancer","authors":"T. Zavarykina, A. Byrdennyy, V. Loginov, M. V. Atkarskaya, Zhizhina Gp","doi":"10.1016/j.ejcsup.2015.08.122","DOIUrl":"https://doi.org/10.1016/j.ejcsup.2015.08.122","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"69"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310673","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.2015.08.128
M. Zhuravkov, N. Romanova
{"title":"P76: Mechanics–mathematical models of changing of human cells properties under the cancer action","authors":"M. Zhuravkov, N. Romanova","doi":"10.1016/J.EJCSUP.2015.08.128","DOIUrl":"https://doi.org/10.1016/J.EJCSUP.2015.08.128","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"72-73"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.EJCSUP.2015.08.128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310784","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}
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