Ejc Supplements最新文献

{"title":"P41","authors":"M. Kruchinina , A. Starikov , S. Kurilovich , V. Kruchinin , V. Volodin , S. Rykhlitskii , A. Gromov , S. Peltec , S. Shehovtsov , V. Generalov","doi":"10.1016/j.ejcsup.2015.08.052","DOIUrl":"10.1016/j.ejcsup.2015.08.052","url":null,"abstract":"<div><h3>Background</h3><p>The aim of this work was to assess the potential of the optical methods for studying erythrocytes (Er) and blood serum (BS) of patients with colorectal cancer (CC).</p></div><div><h3>Methods</h3><p>A total of 26 persons (52<!--> <!-->+<!--> <!-->8<!--> <!-->years old) with CC (histologically – adenocarcinoma) in the T1–2 stage (the 1st group consisting of 10 patients) and in the terminal stage T3–4 (the 2nd group involving 16 patients) were examined. The metastases (in the liver area) were detected in 6 patients; the remaining patients had no metastases. The degree of lymph node involvement in most patients was not determined, the ten corresponding N1. The control group consisted of 16 healthy people (50<!--> <!-->+<!--> <!-->6<!--> <!-->years old). Electric and viscoelastic Er parameters were investigated by dielectrophoresis, their membrane structure – by TLC and gas chromatography. The optical properties of BS were studied by the methods of ellipsometry. The reaction of the monoclonal antibody CD 24 with BS antigens of CC patients was studied by spectroscopic ellipsometry close to the conditions of surface plasmon resonance (SPR) (ProteOn XPR36 (BioRad).</p></div><div><h3>Results</h3><p>We observed significant differences in Er parameters, associated with the CC stage. Given in the 2nd group (T3–4) summarized rigidity, viscosity, electrical conductivity, the relative polarizability, indexes of aggregation and destruction were significantly higher than those in the 1st (T1–2) and in the control group (<em>p</em> <!--><<!--> <!-->0.001–0.05). At the same time the patients of the 2nd group had marked disturbances of Er deformability, leading to the development of microcirculatory disorders and tissue hypoxia with the expressed deficit of intracellular macroergs. We observed high levels of cholesterol fraction, oleic, stearic acids, high index of cholesterol/phospholipids (PHL) and low levels of total lipids, easily oxidable PHL, arachidonic acid, omega-3 index in Er membranes in the 2nd group in comparison with those in the 1st group of patients (<em>p</em> <!--><<!--> <!-->0.0001–0.03). Scanning ellipsometry showed marked heterogeneity in thickness and composition, the abundance of discontinuities in thin films of BS of patients in the 2nd group compared to the 1st one (<em>p</em> <!--><<!--> <!-->0.001). Increasing the refractive index in combination with the reduction in film thickness as CC stage was weighting has been observed (<em>p</em> <!--><<!--> <!-->0.01–0,<span><math><mrow><mo>⧹</mo></mrow></math></span>.05). The concentration of the antigens to the CD24 in the BS of patients (obtained by SPR) in the terminal stages of CC was higher than that in the T1–2 (<em>p</em> <!--><<!--> <!-->0.001). We revealed correlations between Er parameters, BS ellipsometry characteristics and biochemical parameters, which reflected the interaction between these components depending on the CC stage.</p></div><div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 29-30"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309547","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}

{"title":"A118","authors":"A. Kozlov","doi":"10.1016/j.ejcsup.2015.08.050","DOIUrl":"10.1016/j.ejcsup.2015.08.050","url":null,"abstract":"<div><p>The hypothesis of the possible evolutionary role of tumors suggests that hereditary tumors may supply evolving multicellular organisms with extra cell masses for the expression of newly evolving genes (Kozlov, 2014). After expression of novel genes in tumor cells, tumors may differentiate in new directions and give rise to new cell types, tissues and organs.</p><p>In the presentation, the bulk of data supporting the positive evolutionary role of tumors will be reviewed, obtained both in the lab of the author and from the literature sources.</p><p>The following issues will be addressed: the widespread occurrence of tumors in multicellular organisms; features of tumors that could be used in evolution; the relationship of tumors to evo-devo; examples of recapitulation of some tumor features in recently evolved organs; the types of tumors that might play the role in evolution; examples of tumors that already have played the role in evolution.</p><p>The discussion of experimental confirmation of nontrivial predictions of the hypothesis will include the analysis of evolutionary novelty of tumor-specifically expressed EST sequences; ELFNI – AS1, a human gene with possible microRNA function expressed predominantly in tumors and originated in primates; PBOV1, a human gene of the recent de novo origin with predicted highly tumor-specific expression profile; and the evolutionary novelty of human cancer/testis antigen genes; the data obtained on transgenic fish tumors regression model; and other data.</p><p>It can be concluded that expression of protogenes, evolutionarily young and/or novel genes in tumors might be a new biological phenomenon, a phenomenon of carcino-evo-devo genes, predicted by the hypothesis of evolution by tumor neofunctionalization.</p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 28-29"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309521","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}

{"title":"P107","authors":"S. Kovalenko ,&nbsp;G. Paul ,&nbsp;N. Matyash ,&nbsp;A. Kozyakov","doi":"10.1016/j.ejcsup.2015.08.049","DOIUrl":"10.1016/j.ejcsup.2015.08.049","url":null,"abstract":"&lt;div&gt;&lt;p&gt;Mutations in BRCA1 and CHEK2 genes associated with hereditary breast cancer were tested in 7920 randomly selected individuals of Novosibirsk (Russia). Mutations BRCA1 5382insC and CHEK2 1100delC were the most frequent, they were found in 0.25% and 0.4% of the general population respectively. We suggested to find mutations carriers by the screening of all breast/ovary cancer patients for the most frequent mutations (BRCA1 5382insC and CHEK2 1100delC) with subsequent analysis of the first-line relatives of cancer patients if one of the mutations was found.&lt;/p&gt;&lt;p&gt;From June 2013 till January 2015, all patients from Novosibirsk regional oncology hospital with the diagnosis of breast cancer and some patients with the diagnosis of ovary cancer were tested for mutations BRCA1 5382insC and CHEK2 1100delC. A total of 2655 cancer patients were analyzed independently of their family history. We found 122 mutations carriers, among them 99 patients with mutations in BRCA1 gene and 23 patients with mutation CHEK2 1100delC. Among mutation carriers, 105 patients agreed to have a medical genetic counseling and after pedigree analysis 193 first-line relatives aged above 25 years were elucidated. One hundred ten first-line relatives of mutation carriers were analyzed for the mutations presence and 40 mutations carriers were found among relatives.&lt;/p&gt;&lt;p&gt;From September 2013 till December 2013, 32 relatives of BRCA mutation carriers underwent breast MRI. In 5 cases, breast cancer was detected by MRI and all cancers except one were confirmed histologically with biopsy analysis. Importantly, all tumors were 5&lt;!--&gt; &lt;!--&gt;mm and less in size, stage I cancer was detected in all cases.&lt;/p&gt;&lt;p&gt;At a follow-up of 1.5&lt;!--&gt; &lt;!--&gt;years, all 105 mutation carrier probands were interviewed by phone regarding possible relapse and/or possible primary cancer in their relatives. Five of 105 probands lost to follow-up may have died. Among responding 100 patients, 2 died as reported by relatives, relapse was reported in 7 probands – mutation carrier probands, primary tumors were reported in 8 relatives of probands.&lt;/p&gt;&lt;p&gt;Mutation carrier probands reported one bilateral breast cancer, four ovary cancers, one bladder cancer and one non-specified oncogynecological tumor.&lt;/p&gt;&lt;p&gt;There were five cases of primary breast cancer, one ovary cancer, one colon cancer, one lung cancer among relatives of breast cancer patients with mutations. The frequency of tumors found in mutation carriers exceeded the average frequencies of cancer for this population.&lt;/p&gt;&lt;p&gt;The economic value of the regional genetic screening can be easily estimated according to the data obtained in this study and data on treatment cost for stage I and stage IV breast cancer. To summarize briefly, the screening of hot-spot mutations provides not only increase of lifespan expectancy and life quality for mutation carriers, but can be also a tool for financial saving of medical system due to the increase of early stage breast can","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 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.2015.08.049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309506","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}

{"title":"A91","authors":"E. Gashenko ,&nbsp;V. Lebedeva ,&nbsp;E. Tsykalenko ,&nbsp;G. Russkikh ,&nbsp;I. Brak ,&nbsp;T. Korolenko","doi":"10.1016/j.ejcsup.2015.08.030","DOIUrl":"10.1016/j.ejcsup.2015.08.030","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;The research for procathepsin B and endogenous inhibitors of cysteine proteases in tumor markers of human reproductive system is important for early diagnostics of cancer. Preform of cathepsin B and cystatins B and C also are universally involved into development of different tumors. Tumor cells as well as tumor-associated macrophages have been shown to secrete active forms of proteases and their inhibitors; however, their roles, especially those of proenzymes as markers of malignancy, are still under investigation.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim&lt;/h3&gt;&lt;p&gt;to evaluate procathepsin B and endogenous inhibitors of cysteine proteases cystatins B and C in tumors of reproductive system.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;p&gt;Serum and ascites fluid of 38 patients with ovarian cancer (among them 15 patients after treatment) and benign ovarian tumors (&lt;em&gt;n&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;9), endometrial cancer (&lt;em&gt;n&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;31, before treatment 14), mammalian cancer (&lt;em&gt;n&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;29, before treatment 18) of stages II–IV for all groups, from Department of Gynecology of Regional Oncology Center, Novosibirsk, were under investigation. Serum of practically healthy women aged 18–80 (&lt;em&gt;n&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;82) from Regional Diagnostic Center, Novosibirsk, was used as a control group. Serum of women with tumors of the reproductive system and ascites fluids of women with ovarian tumors (aged 18–80 years), before operation were used for assay of procathepsin B, cysteine protease inhibitors cystatins B and C. Serum procathepsin B concentration was measured by ELISA commercial kit for human (R&amp;D) USA; cystatin C using BioVendor commercial kits (Czechia), cystatin B – with help of ELISA kits for human (USCN Life Science Inc., Wuhan, China). Common biomarker of ovarian cancer, CA-125, was assayed by using a commercial kit (Vector, Koltsovo, Novosibirsk Region, Russia). Statistical analysis performed by one a way ANOVA Statistic 12, program with help of Kruskall–Wallis test and the Mann–Whitney &lt;em&gt;U&lt;/em&gt; test used to assess differences in procathepsin B or cystatins B and C levels between patient groups. Statistical analysis was performed with the soft package Statistics 12, with the level of significance being set at &lt;0.05.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;In serum of patients with endometrial cancer, ovarian cancer, mammalian cancer – significant increases in serum procathepsin B (&lt;em&gt;p&lt;/em&gt; &lt;!--&gt;&lt;&lt;!--&gt; &lt;!--&gt;0.001), cystatin B (&lt;em&gt;p&lt;/em&gt; &lt;!--&gt;&lt;&lt;!--&gt; &lt;!--&gt;0.05) and CA-125 (&lt;em&gt;p&lt;/em&gt; &lt;!--&gt;&lt;&lt;!--&gt; &lt;!--&gt;0.001) were noted. However, in patients with benign tumor increased serum common tumor marker CA-125 (&lt;em&gt;p&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.005 vs. healthy controls) was shown without any changes in serum level of procathepsin B, cystatins B and C. Concentrations procathepsin B and Cystatin B in serum and ascites of patients with ovarian tumor was used to assess differences in procathepsin B or cystatins B and C ","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 16-17"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309061","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}

{"title":"P114","authors":"P. Gervas ,&nbsp;V. Perelmuter","doi":"10.1016/j.ejcsup.2015.08.032","DOIUrl":"10.1016/j.ejcsup.2015.08.032","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Lung cancers are characterized by the genetic alterations that often affect a common group of oncogenic signaling pathways. Identification of biologically significant genetic alterations in lung cancer that lead to activation of oncogenes and inactivation of tumor suppressor genes has the potential to provide further therapeutic opportunities (Cooper, 2013). In this context, it is important that molecular aberrations may act as negative predictors of sensitivity to treatment. The discovery of driver oncogenes, such as activating mutations in the epidermal growth factor receptor gene (EGFR), has made personalized medicine for lung cancer a reality. Despite the high initial results, NSCLC patients acquire resistance to tyrosine kinase inhibitors in the worldwide. There are several findings suggesting that the effect of tyrosine kinase inhibitors could be limited to patients harboring KRAS mutation. To date, a limited information regarding link of morphological portrait of adenocarcinomas with bearing of simultaneously concurrent mutations of KRAS and EGFR genes. The detection of concurrent gene mutation is usually carried out in a mixture of tumor cells. We plan to analyze EGFR and KRAS mutations in all clonal components (or morphological structures) of NSCLC tumors isolated by laser microdissection. So, we suggest that NSCLC clonal components might bear two concurrent EGFR and KRAS mutations simultaneously or different clonal components might bear either EGFR or KRAS mutations. The data obtained can predict resistance to EGFR-TKIs and affect therapeutic decision making.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;p&gt;The tumor samples were obtained from archived formalin-fixed paraffin-embedded tissue blocks. Paraffin was removed by xylene extraction, and the sample was subsequently lysed by proteinase K. The region containing the highest percentage of tumor cells (at least 50%) was dissected. Microscopes Axio Scope A1 and Axio Star plus (Carl Zeiss, Germany) was used to perform histological analysis. If necessary, tumour cells were carefully selected and removed from the samples by laser microdissection using a P.A.L.M. microlaser instrument (PALM AdhesiveCaps, P.A.L.M., Bernried, Germany). EGFR (exon 19 deletion and 21 L858R) and KRAS (Gly12Cys, Gly12Ser, Gly12Arg, Gly12Val, Gly12Asp, Gly12Ala, Gly13Asp) gene amplification was based on RT-PCR on CFX96 Real-Time System (Bio-Rad).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;A total of 115 patients with stage (IIIB–IV) of NSCLC with EGFR-TKI- sensitive mutations were eligible for the analysis. A rare coexistence of KRAS and EGFR mutations were observed in 3 patients (2.6%). The first sample was described as nonmucinous solid adenocarcinoma and has deletion of 19 exon of EGFR gene and G12C mutation of KRAS gene. The second sample was described as mucinous lepidic adenocarcinoma and has deletion of 19 exon of EGFR gene and G12D mutation of KRAS gene. The third sample was described as m","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 18"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309097","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}

{"title":"T32","authors":"T. Isayeva,&nbsp;M. Brandwein-Gensler","doi":"10.1016/j.ejcsup.2015.08.037","DOIUrl":"10.1016/j.ejcsup.2015.08.037","url":null,"abstract":"&lt;div&gt;&lt;p&gt;The most important development in head and neck oncology of the past decade is the demonstration that patients with human papillomavirus (HPV)-mediated oropharyngeal cancers have significantly improved outcomes, compared to HPV-negative counterpart patients.&lt;/p&gt;&lt;p&gt;We examined racial disparities among 102 oropharyngeal carcinoma (OPC) patients (30 African Americans, 72 Whites) comparing the present of HPV16/18 E6 and E7 oncoproteins, and p16Ink4A overexpression, with times to disease progression (DP) and disease specific survival (DSS). Expression of HPV16/18 transcripts was assessed by reverse transcription and polymerase chain reaction using type-specific E6/E7 primers; p16Ink4A was evaluated by immunohistochemistry. African Americans were significantly more likely to present with high T stage disease and receive nonsurgical treatment. HPV16/18 was present in 63% of patients; no racial differences were observed. Silenced p16Ink4A in OPC was significantly more common in African Americans (15/24) than Whites (20/69) (&lt;em&gt;p&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.004), and HPV16&lt;!--&gt; &lt;!--&gt;+&lt;!--&gt; &lt;!--&gt;African Americans (6/24) than HPV&lt;!--&gt; &lt;!--&gt;+&lt;!--&gt; &lt;!--&gt;Whites (2/42) (&lt;em&gt;p&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.023). Kaplan Meier analysis for DSS revealed a protective effect for p16Ink4A overexpression (&lt;em&gt;p&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.0028), HPV16+ (&lt;em&gt;p&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.036), and Whites (&lt;em&gt;p&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.0039). Shorter DSS was associated with primary definitive chemoradiation (&lt;em&gt;p&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.019) and T3/T4 disease (&lt;em&gt;p&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.0001). A protective effect with respect to disease progression was observed for HPV16+ (&lt;em&gt;p&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.007), Whites (&lt;em&gt;p&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.0006) and p16Ink4A overexpression (&lt;em&gt;p&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.0001). African Americans with OPC experience poorer outcomes likely due to p16Ink4A silencing, higher T stage, and nonsurgical treatment, but not lower rates of transcriptionally active HPV16/18.&lt;/p&gt;&lt;p&gt;We studied patients with oral cavity squamous cell carcinoma for HPV16 and HPV18, local immune response, p16 expression and outcome.&lt;/p&gt;&lt;p&gt;Overexpression of p16INK4a was uncommon in oral cavity squamous cell carcinoma (17/112 or 15.2%). HPV16 and HPV18 were detected in 22.6% and 11% patients respectively. We demonstrated that the presence of transcriptionally active HPV16 in oral cavity squamous cell carcinomas does not correlate with p16INK4a overexpression, enhanced local tumor immunity, or improved outcome. To investigate the possible mechanism of protective effect of HPV and p16INK4a, we have developed primary cancer cell lines from resections with known patterns of invasion. Given that cell lines derived from HPV-mediated oropharyngeal squamous cell carcinomas are less invasive than their HPV-negative counterparts, we tested the hypothesis that viral oncoproteins E6, E7, and p16INK4a can affect tumor invasion. We demonstrated that p16INK4a overexpression in two cancer","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 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.2015.08.037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309199","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}

{"title":"P74","authors":"I. Guzhova,&nbsp;M. Shevtsov,&nbsp;E. Komarova,&nbsp;D. Meshalkina,&nbsp;E. Kisel,&nbsp;B. Margulis","doi":"10.1016/j.ejcsup.2015.08.035","DOIUrl":"10.1016/j.ejcsup.2015.08.035","url":null,"abstract":"<div><p>The Hsp70 chaperone is one of the major components of tumor microenvironment displaying multiple not yet established functions. It was shown to stimulate innate and adaptive anti-tumor immunity in a variety of cancer models. These effects were due to active release of endogenous Hsp70 to an extracellular matrix and therefore the extracellular chaperone can be a trigger of multiple events in the whole tumor. Factors inducing Hsp70 release are heat stress, inhibitors of important signaling proteins, anticancer drugs and X-ray treatment. Recently we have shown that delivery of Hsp70 can be efficient pusher of its intracellular analogue to extracellular milieu. In this study we show that intracellular cycling of exo- and endogenous Hsp70s increases the sensitivity of cancer cells to cytotoxic lymphocytes. Moreover, the results of in vivo studies employing B16 mouse melanoma and C6 rat glioblastoma as targets proved the therapeutic relevance of exogenous Hsp70 in intra-tumoral application.</p><p>To uncover the mechanisms of the anticancer effect we used inhibitors and markers of intra- and extracellular protein transport. The data of these studies showed multiplicity of pathways using which exo-Hsp70 reaches cytosol and more usable ones was endocytosis. To be exported intracellular Hsp70 employs vesicular structures as well as intra-membrane lipid structures.</p><p>Analyzing Hsp70 molecule we found the domain with potential vector activity, i.g. cell penetrating function. This peptide was synthesized and shown to cross a cellular membrane with efficacy exceeding that the whole Hsp70 molecule. Furthermore, the new peptide was used as a carrier for the delivery inside living cells antibody to Hsp70. The resulting construct was found to reduce the resistance of tumor cells to pro-apoptotic effect of staurosporin.</p><p>Taking together these data, we can suggest that Hsp70 and its fragments can be effective players in communication between cells assembling functionally active tumor.</p><p><em>The work was supported by Grant of</em> <span><em>Russian Scientific Foundation</em></span> <em>(N</em> <span><em>14-50-00068</em></span><em>).</em></p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 20"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309150","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}

{"title":"P48: Integrated analysis of genomic and transcriptomic data in clear-cell renal cell carcinoma","authors":"S. A. Solodskikh, V. Bashmakov, T. Gorbacheva, A. V. Panevina, A. Maslov, Andrey A. Mikhailov, I. Moshurov, V. Popov","doi":"10.1016/J.EJCSUP.2015.08.099","DOIUrl":"https://doi.org/10.1016/J.EJCSUP.2015.08.099","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"55"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.EJCSUP.2015.08.099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310189","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}

{"title":"A72: Particular qualities of the expression of markers of sensitivity to cytostatics at patients various solid tumours","authors":"A. Zhabina","doi":"10.1016/j.ejcsup.2015.08.125","DOIUrl":"https://doi.org/10.1016/j.ejcsup.2015.08.125","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"71"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310720","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}

{"title":"P113","authors":"T. Prudnikova ,&nbsp;N. Litvyakov ,&nbsp;N. Domanitskaya ,&nbsp;N. Cherdyntseva ,&nbsp;V. Belyavskaya","doi":"10.1016/j.ejcsup.2015.08.080","DOIUrl":"10.1016/j.ejcsup.2015.08.080","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Heparansulfate (HS) is a glycosaminoglycan present on the cell surface and in the extracellular matrix, which interacts with diverse signal molecules and is essential for many physiological processes including embryonic development, cell growth, inflammation, and blood coagulation. &lt;span&gt;d&lt;/span&gt;-glucuronyl C5-epimerase (GLCE) is a crucial enzyme in HS synthesis, converting &lt;span&gt;d&lt;/span&gt;-glucuronic acid (GlcA) to &lt;span&gt;l&lt;/span&gt;-iduronic acid (IdoA) to increase HS flexibility. Aberrant modification may result in wrong structure of polysaccharide chains of HS and defects of microenvironment associated with malignant transformation.We previously experimentally identified the GLCE polymorphism Ile597Val. Its localization close to the activity center of the enzyme and different physical parameters of the involved amino acids suggest that the polymorphism is functional. So, three different variants of GLCE dimers with different enzymatic activity may exist in heterozygous carriers. Bioinformatics’ search (PubMed resource) revealed interracial variations in allele frequency distribution. Unusual high frequency of allele G was shown for black race (45%) compared with white race (17%). Taking into account the increased resistance of negroid race to breast cancer, we assume a potential involvement of the GLCE polymorphism in breast cancer.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim&lt;/h3&gt;&lt;p&gt;The estimation of effects of GLCE functional polymorphism A2017G (Ile597Val) on the gene expression levels in normal and breast cancer cells and LOH in breast tumors.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;p&gt;Breast cancer patients (n&lt;!--&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;144.) had histologically verified diagnoses. Blood and breast cancer tissue samples as well as matched control tissues were collected from each patient during surgery. Genomic DNA was isolated by phenol extraction. Total RNA was isolated by TRIZol, RNA quantity was accessed by Qubit instrument with appropriate reagents and cDNA was obtained using First Strand cDNA Synthesis kit. SNP A2017G (rs3865014) was analyzed by Custom Real-Time SNP Array and GLCE expression levels were determined using Taq-Man-based Real-Time PCR (Applied Biosystems). Statistical analysis was carried out using a Statistika 9.0 software.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;AA genotype carriers had a 2-fold increase in GLCE mRNA levels in tumors compared with control surrounding tissues (0.37&lt;!--&gt; &lt;!--&gt;±&lt;!--&gt; &lt;!--&gt;0.77 versus 0.17&lt;!--&gt; &lt;!--&gt;±&lt;!--&gt; &lt;!--&gt;0.16, respectively, &lt;em&gt;p&lt;/em&gt; &lt;!--&gt;&lt;&lt;!--&gt; &lt;!--&gt;0.05). Oppositely, AG genotype carriers had a 1.5-fold decrease in GLCE mRNA levels in tumors compared with control surrounding tissues (0.39&lt;!--&gt; &lt;!--&gt;±&lt;!--&gt; &lt;!--&gt;0.29 versus 0.58&lt;!--&gt; &lt;!--&gt;±&lt;!--&gt; &lt;!--&gt;0.33, respectively, &lt;em&gt;p&lt;/em&gt; &lt;!--&gt;&lt;&lt;!--&gt; &lt;!--&gt;0.05 ). However, in any case,the GLCE expression in both normal tissues and breast tumors was more active in AG genotype carriers than in AA carriers. It is known that LOH is often associated ","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 45"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309932","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}