Ejc Supplements最新文献

{"title":"P90","authors":"A. Ponomaryova ,&nbsp;E. Rykova ,&nbsp;N. Cherdyntseva ,&nbsp;E. Morozkin ,&nbsp;I. Zaporozhchenko ,&nbsp;T. Skvortsova ,&nbsp;A. Dobrodeev ,&nbsp;A. Zav’yalov ,&nbsp;S. Tuzikov ,&nbsp;V. Vlassov ,&nbsp;P. Laktionov","doi":"10.1016/j.ejcsup.2015.08.077","DOIUrl":"10.1016/j.ejcsup.2015.08.077","url":null,"abstract":"<div><h3>Background</h3><p>The analysis of circulating tumor nucleic acids (DNAs and RNAs) in the blood seems to be a promising approach for the development of the low-invasive methods of tumor detection, valuable for clinical practice. Detection of oncogenic and tumor suppressor miRNAs in the blood plasma/serum is evidence of their participation in pathogenesis and suggest the possibility of their use as tumor markers and targets for therapy. Thus, the determination of expression level of tumor-associated miRNAs in plasma can lead to significant progress in understanding the tumor development and treatment.</p></div><div><h3>Aim</h3><p>Estimation the changes in expression level of miRNAs (miR-19b, miR-25, miR-125b, miR-126, miR-205) in blood plasma from lung cancer patients during combined therapy and to estimate their value as disease monitoring markers.</p></div><div><h3>Materials and methods</h3><p>Blood samples were taken from patients (n<!--> <!-->=<!--> <!-->23) with non-small cell lung cancer treated at the Tomsk Cancer Research Institute. These samples were stabilized and fractionated into plasma and blood cells. MicroRNA was isolated from blood plasma using single-phase phenol-free extraction protocol and purified on silica-based spin columns (BioSilica Ltd, Novosibirsk, Russia). Concentration of five above mentioned miRNAs was measured by quantitative RT-PCR and normalized to miR-16 using dCt method.</p></div><div><h3>Results</h3><p>In this study we analyzed the dynamic expression changes of circulating DNA in blood plasma from lung cancer patients during the combined therapy. Circulating miRNAs were isolated from plasma samples of non-small cell lung cancer patients before treatment, within 30<!--> <!-->days after completing chemotherapy and 15<!--> <!-->days after surgery, by using developed methodological approach. In case of miR-19b and miR-125b analysis was found that the miRNA expression level correlates with clinical response to chemotherapy and surgery. Increasing level of miR-19b and decreasing level of miR-125b were associated with therapeutic response. Using Repeated measures ANOVA analysis we demonstrated that the miR-19b and miR-125b expression levels changes throughout three check-up points during the combined treatment are characterized by the significant cubic trend (<em>P</em> <!-->=<!--> <!-->0.00284 and <em>P</em> <!-->=<!--> <!-->0.029, respectively). Changes of miRNA-126 expression level during post-treatment follow-up were not characterized by the definite trend and not correlated with changes of other miRNAs expression level. It was shown the significant correlation between miRNA-25 and miRNA-205 expression levels, but was not found the trend of these miRNAs level changes.</p></div><div><h3>Conclusion</h3><p>The clinical utility of the circulating miR-19b and miR-125b expression analysis from this study remains to be validated in large cohorts of patients with different histological types of tumors, at the differ","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 43-44"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309900","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":"T26","authors":"Z. Pranjol ,&nbsp;N. Gutowski ,&nbsp;M. Hannemann ,&nbsp;J. Whatmore","doi":"10.1016/j.ejcsup.2015.08.078","DOIUrl":"10.1016/j.ejcsup.2015.08.078","url":null,"abstract":"<div><h3>Background</h3><p>Epithelial ovarian cancer frequently metastasizes to the omentum, a process that requires pro-angiogenic activation of HOMECs by tumour -secreted factors in their microenvironment. We have previously shown that ovarian cancer cells secrete a range of factors with possible roles in metastatic angiogenesis including the lysosomal proteases cathepsin D (CD) and cathepsin L (CL). However, the role of these proteases in ovarian cancer metastasis to the omentum is not fully understood.</p></div><div><h3>Aim</h3><p>To investigate whether proliferative effects of CD and CL are dependent on their catalytic activity in HOMECs.</p><p>To investigate the intracellular signalling kinases activated by CD and CL.</p></div><div><h3>Method</h3><p>HOMEC proliferation was assessed by using a colorimetric (WST1) assay. Potential signalling pathways were examined by phosphokinase array and ELISAs. pH experiments were carried out examine whether the observed effects were due to the catalytic activity of CD and CL.</p></div><div><h3>Result</h3><p>CD and CL (50<!--> <!-->ng/ml) significantly increased HOMEC proliferation to 141<!--> <!-->±<!--> <!-->27% (<em>p</em> <!-->=<!--> <!-->0.001, <em>n</em> <!-->=<!--> <!-->50) and 151%<!--> <!-->±<!--> <!-->34% (<em>p</em> <!-->=<!--> <!-->0.001, <em>n</em> <!-->=<!--> <!-->45) respectively vs. control (100%) 72<!--> <!-->h post-treatment. Inhibitors of CD and CL enzyme activity had no effect on HOMEC proliferation and subsequent pH data suggest a nonproteolytic mitogenic activity of these cathepsins. Both proteins induced phosphorylation of ERK1/2, AKT and p38<em>α</em> to ∼2, ∼1.5 and ∼1.5 folds respectively relative to total levels (compared to control).</p></div><div><h3>Conclusion</h3><p>CD and CL induced proliferation in HOMECs. CD and CL may non- proteolytically contribute to pro-angiogenic responses of the omental microvasculature. Induction of phosphorylation of proliferative kinases ERK1/2, AKT and p38<em>α</em> suggest possible downstream signalling cascades of these proteins.</p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 44"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309913","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":"P108","authors":"E. Rybalkina ,&nbsp;G. Pavlova ,&nbsp;N. Moiseeva ,&nbsp;O. Susova ,&nbsp;A. Mitrofanov ,&nbsp;D. Panteleev ,&nbsp;N. Pustogarov","doi":"10.1016/j.ejcsup.2015.08.085","DOIUrl":"10.1016/j.ejcsup.2015.08.085","url":null,"abstract":"<div><h3>Background</h3><p>Glioblastomas (GBL) are most aggressive brain tumors in adults. They are often radio- and chemotherapy resistant. The standard therapy of GBL includes surgery followed by radiotherapy with concomitant chemotherapy with temozolomide named temodal (imidazotetrazine derivative). Methylation of the O6-methylguanine-DNA-methyltransferase (MGMT) gene promoter is considered as predictor of better outcome of temodal therapy in comparison with the cases without MGMT promoter methylation (Stupp et al., 2009). The aim of this study is finding of additional predictors of temozolomide therapy effectiveness.</p></div><div><h3>Materials and methods</h3><p>We obtained primary cultures of GBL. The rate of GBL sensitivity to temozolomide was revealed by MTT test. Expression of multidrug resistance genes and genes which mediate temozolomide sensitivity (YB1, MDR1, MRP1, LRP, BCRP and MGMT) was determined by real time PCR. Protein localization and expression was revealed by immunohistochemical technique.</p></div><div><h3>Results</h3><p>We developed 14 primary GBL cultures. Staining for nestin was used for demonstration of neuronal origin of cell cultures. Analysis of gene expression and the rate of cell proliferation of the cultures showed that the rate of YB1 gene expression in slow proliferating cultures is significantly lower than in quickly proliferating cell populations. Cell cultures differed in temodal sensitivity 2–2.5-fold. We analyzed whether GBL cell sensitivity to temodal and the rate of several genes’ expression are correlated. We did not find the correlation between cell temodal sensitivity and the rate of MGMT gene expression. These data are in accordance with some results of another authors (Mullins et al., 2013; Brennan et al., 2013). However, we revealed positive correlation of the temodal sensitivity of GBL cultures and MVP/LRP expression (<em>r</em> <!-->=<!--> <!-->0.5592, <em>p</em> <!-->=<!--> <!-->0.04). We found also the trend to negative correlation between GBL temodal sensitivity and YB1 gene expression (<em>r</em> <!-->=<!--> <!-->−0.43602, <em>p</em> <!-->=<!--> <!-->0.02) as well as MDR1 expression (<em>r</em> <!-->=<!--> <!-->−0.4195, <em>p</em> <!-->=<!--> <!-->0.02).</p></div><div><h3>Conclusion</h3><p>The rate of temodal sensitivity of GBL primary cultures is connected with the rate of the expression of MVP/LRP, YB1 and MDR1genes. It is likely that YB-1 protein affects temodal sensitivity by influence on DNA reparation. YB1 could also have an effect on MDR1 expression. MVP/LRP expression is independent factor of GBL prognosis.</p><p><em>This paper was completed with partial support from the</em> <span><em>Russian Foundation for Basic Research</em></span> <em>– Russia (Grant No.</em> <span><em>23-04-40204</em></span><em>).</em></p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 47-48"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310002","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":"T58: An important role of proteoglycans in the interactions of normal and cancer prostate cells with fibroblasts","authors":"A. V. Suhovskih, V. Kashuba, E. Grigorieva","doi":"10.1016/J.EJCSUP.2015.08.104","DOIUrl":"https://doi.org/10.1016/J.EJCSUP.2015.08.104","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"58-59"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.EJCSUP.2015.08.104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310537","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":"P85: Synthesis and anti-cancer effects of CpdA enantiomers, non-steroidal glucocorticoid receptor ligands","authors":"L. R. Tilova, O. Zadorozhnaya, A. Savinkova, K. Kirsanov, A. Ogloblina, G. Belitsky, I. Budunova, E. Lesovaya, M. Yakubovskaya","doi":"10.1016/J.EJCSUP.2015.08.110","DOIUrl":"https://doi.org/10.1016/J.EJCSUP.2015.08.110","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"61-62"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.EJCSUP.2015.08.110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310915","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":"P28","authors":"M. Aksenenko,&nbsp;T. Ruksha","doi":"10.1016/j.ejcsup.2015.08.002","DOIUrl":"10.1016/j.ejcsup.2015.08.002","url":null,"abstract":"<div><p>Melanoma is one of the aggressive cancer types. Mutations that lock the BRAF protein in an active state may cause excessive signaling in the pathway, leading to uncontrolled cell growth and survival. Primarily among the BRAF mutations observed in melanoma, over 90% are supposed to be at codon 600, resulting in substitution of glutamic acid for valine, V600E (T<!--> <!-->&gt;<!--> <!-->A transversion) located in exon 15, BRAFV600E. Of particular interest is BRAF negative melanoma. This type of melanoma is not sensitive to BRAF inhibitors and approaches to therapy require further study. We aimed to investigate the frequency of BRAF V600 mutations in 80 patients with primary melanoma and determine the relationship between mutations and clinical/pathologic features. Genomic DNA was extracted from biopsy specimens with prevalent percentage of tumor cells by DNA-sorb B isolation kit (Amplisense, Russia). BRAF V600E mutation was estimated by real-time PCR-based assay for the BRAF V600E mutation allele-specific DNA test (BioLink, Russia). Breslow thickness was assessed by applying commercial Infinity Capture, Infinity Analyze Software. The lymphocytic infiltration was determined in all tumors and classified as “brisk”, “nonbrisk”, and “absent” according to criteria established by Clark et al. Tumor infiltrating lymphocytes (TIL) were identified as lymphocytes within tumor nodes. “Brisk” infiltrate was determined in case of a diffuse presence of lymphocytes within tumor, “non-brisk” infiltrate was in focal location of lymphocytes and “absent” if no lymphocytes were present in a tumor. Mitotic activity was determined as mitotic count on 10 high power fields. For all patients, clinical and pathologic features were tested for significant association with BRAF V600E mutation status using simple cross tabulations, Fisher’s exact test, Pearson’s <em>χ</em>² test, and/or non-parametric Mann–Whitney <em>U</em> test. The <em>P</em> values lower 0.05 were considered as significant. BRAF V600E mutation was detected in 41.25% of tested tumours. Patients with BRAF-mutant and non-BRAF mutant melanoma were matched by age and gender. Superficial spreading melanomawas observed in 66.2% of patients with wild-type BRAF, nodular melanoma in 21.2%, both lentigo-melanoma and acral-lentiginous melanomain 6.3% and mucosal melanoma in 1 3.0% of patients. In wild-type BRAF melanoma patients, 59.7% tumors had “brisk” infiltrate, 14.8% – “non-brisk”, and 12 25.5% had no infiltrate. There was no found correlation between BRAF status and tumor localization, clinico-pathological type of tumor, TIL status, Breslow thickness and mitotic rate. However, when cases were stratified by age, it was revealed that melanoma patients aged above 80<!--> <!-->years were preferentially BRAF-negative (<em>p</em> <!-->&lt;<!--> <!-->0.05). BRAF-negative melanomas occurred significantly more frequent in superficial spreading type of the tumor. The localization of melanomas was differe","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 1"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54308582","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":"<div><h3>Background</h3><p>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.</p></div><div><h3>Aim</h3><p>to evaluate procathepsin B and endogenous inhibitors of cysteine proteases cystatins B and C in tumors of reproductive system.</p></div><div><h3>Materials and methods</h3><p>Serum and ascites fluid of 38 patients with ovarian cancer (among them 15 patients after treatment) and benign ovarian tumors (<em>n</em> <!-->=<!--> <!-->9), endometrial cancer (<em>n</em> <!-->=<!--> <!-->31, before treatment 14), mammalian cancer (<em>n</em> <!-->=<!--> <!-->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 (<em>n</em> <!-->=<!--> <!-->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 <em>U</em> 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.</p></div><div><h3>Results</h3><p>In serum of patients with endometrial cancer, ovarian cancer, mammalian cancer – significant increases in serum procathepsin B (<em>p</em> <!-->&lt;<!--> <!-->0.001), cystatin B (<em>p</em> <!-->&lt;<!--> <!-->0.05) and CA-125 (<em>p</em> <!-->&lt;<!--> <!-->0.001) were noted. However, in patients with benign tumor increased serum common tumor marker CA-125 (<em>p</em> <!-->=<!--> <!-->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":"<div><h3>Background</h3><p>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.</p></div><div><h3>Materials and methods</h3><p>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).</p></div><div><h3>Results</h3><p>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":"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":"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":"<div><p>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.</p><p>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) (<em>p</em> <!-->=<!--> <!-->0.004), and HPV16<!--> <!-->+<!--> <!-->African Americans (6/24) than HPV<!--> <!-->+<!--> <!-->Whites (2/42) (<em>p</em> <!-->=<!--> <!-->0.023). Kaplan Meier analysis for DSS revealed a protective effect for p16Ink4A overexpression (<em>p</em> <!-->=<!--> <!-->0.0028), HPV16+ (<em>p</em> <!-->=<!--> <!-->0.036), and Whites (<em>p</em> <!-->=<!--> <!-->0.0039). Shorter DSS was associated with primary definitive chemoradiation (<em>p</em> <!-->=<!--> <!-->0.019) and T3/T4 disease (<em>p</em> <!-->=<!--> <!-->0.0001). A protective effect with respect to disease progression was observed for HPV16+ (<em>p</em> <!-->=<!--> <!-->0.007), Whites (<em>p</em> <!-->=<!--> <!-->0.0006) and p16Ink4A overexpression (<em>p</em> <!-->=<!--> <!-->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.</p><p>We studied patients with oral cavity squamous cell carcinoma for HPV16 and HPV18, local immune response, p16 expression and outcome.</p><p>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}