Pub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.026
E. Dmitrieva, N. Nurieva
The Chelyabinsk region is a classic example of the technologically-saturated region. The index of pollution of atmospheric air is estimated as high. The Chelyabinsk region is among the areas of increased cancer risk. The incidence of head and neck cancer is steadily increasing, accounting for 20–25% of all cancer cases in Russia. Oropharyngeal cancer makes up 5.1% of all cancers.
Materials and methods
The object of the study was the population of the Chelyabinsk region. The analysis was conducted according to the materials of the annual reports of the statistics department of the Chelyabinsk district oncology dispensary.
Results
Out of the total cancer cases for the population of Chelyabinsk region in 2014, oro-pharyngeal cancer comprised 2.06%, including cancers of the lip (0.35%), tongue (0.47%), major salivary glands (0.22%), other unspecified parts of the mouth (0.52%), oropharynx (0.33%), nasopharynx (0.1%) and hypopharynx (0.07%). From 2008 to 2014, the incidence of oral and pharyngeal cancer among adult population of Chelyabinsk city and Chelyabinsk region showed an 8.8% increase. In the period from 2011 to 2014, the incidence of oral and pharyngeal cancer tended to increase, the overall rise being 71.8%. It should be noted that the oral and pharyngeal cancer incidence was 3 times higher in males than in females in 2013 and 2 times higher in 2014. One of the main indicators that determine the prognosis for the development of cancer, is the extent of tumor at time of diagnosis.
Out of the total cancer cases for the population of Chelyabinsk region in 2014, cancer of the oral cavity comprised 1.33%, pharyngeal cancer 0.6%, lip cancer 0.13%, ranking the 17th, 19th and 24th place respectively among the causes of death from all cancers. Analyzing the dynamics of mortality from cancer of the oral cavity and pharynx during the study period, it was revealed that the mortality rate increased by 0.7%.
Conclusion
Head and neck tumors are a rare group of clinically and biologically diverse neoplastic diseases. Among the residents of the Chelyabinsk region, men are 2–3 times more susceptible to cancer of the oral cavity and pharynx than women. High mortality rate is due to late referral of patients to specialized clinics; most head and neck cancer patients are diagnosed at advanced stages.
{"title":"A115","authors":"E. Dmitrieva, N. Nurieva","doi":"10.1016/j.ejcsup.2015.08.026","DOIUrl":"10.1016/j.ejcsup.2015.08.026","url":null,"abstract":"<div><p>The Chelyabinsk region is a classic example of the technologically-saturated region. The index of pollution of atmospheric air is estimated as high. The Chelyabinsk region is among the areas of increased cancer risk. The incidence of head and neck cancer is steadily increasing, accounting for 20–25% of all cancer cases in Russia. Oropharyngeal cancer makes up 5.1% of all cancers.</p></div><div><h3>Materials and methods</h3><p>The object of the study was the population of the Chelyabinsk region. The analysis was conducted according to the materials of the annual reports of the statistics department of the Chelyabinsk district oncology dispensary.</p></div><div><h3>Results</h3><p>Out of the total cancer cases for the population of Chelyabinsk region in 2014, oro-pharyngeal cancer comprised 2.06%, including cancers of the lip (0.35%), tongue (0.47%), major salivary glands (0.22%), other unspecified parts of the mouth (0.52%), oropharynx (0.33%), nasopharynx (0.1%) and hypopharynx (0.07%). From 2008 to 2014, the incidence of oral and pharyngeal cancer among adult population of Chelyabinsk city and Chelyabinsk region showed an 8.8% increase. In the period from 2011 to 2014, the incidence of oral and pharyngeal cancer tended to increase, the overall rise being 71.8%. It should be noted that the oral and pharyngeal cancer incidence was 3 times higher in males than in females in 2013 and 2 times higher in 2014. One of the main indicators that determine the prognosis for the development of cancer, is the extent of tumor at time of diagnosis.</p><p>Out of the total cancer cases for the population of Chelyabinsk region in 2014, cancer of the oral cavity comprised 1.33%, pharyngeal cancer 0.6%, lip cancer 0.13%, ranking the 17th, 19th and 24th place respectively among the causes of death from all cancers. Analyzing the dynamics of mortality from cancer of the oral cavity and pharynx during the study period, it was revealed that the mortality rate increased by 0.7%.</p></div><div><h3>Conclusion</h3><p>Head and neck tumors are a rare group of clinically and biologically diverse neoplastic diseases. Among the residents of the Chelyabinsk region, men are 2–3 times more susceptible to cancer of the oral cavity and pharynx than women. High mortality rate is due to late referral of patients to specialized clinics; most head and neck cancer patients are diagnosed at advanced stages.</p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 15"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.027
O. Ephimova , I. Grigoreva , T. Romanova , Y. Ragino , T. Suvorova , N. Tov
Background
To evaluate the clinical symptoms in pancreatic cancer patients (PCa) and compare some biochemical blood serum parameters in patients with different pathology of the pancreas (PCa, acute (OP) and chronic pancreatitis (CP)).
Materials and methods
During a one-time clinical research on the type of “series of cases” 130 patients were examined (42 patients with OP, 81 – CP and 7 patients with PCa). The diagnosis of PCa, OP, CP was verified by clinical and instrumental methods. Glucose, cholesterol, triglyceride and bilirubin serum levels were determined by ELISA.
Results
The mean age of patients with PCa was 63.6 ± 4.9 years, morbidity duration of PCa – 3.5 ± 1.1 months. Among patients with PCa, 83.3% of people – smoked, 16.7% – smoked every day. Half of the respondents PCa patients noted that over the last year they did not drink alcohol; 16.7% of people – drank alcohol several times a year, and 33.3% of patients consumed alcohol 1–2 times a month. BMI of PCa patients was equal to 26.3 ± 3.5 kg/m2, in OP patients – 23.8 ± 1.0 kg/m2, in CP patients – 26.3 ± 0.6 kg/m2, p > 0.05. In this case, 85.7% of PCa patients noted a significant decrease in body weight (11.7 ± 6.0 kg) for 3–4 months after the onset of symptoms. There was no pain in 42.8% of PCa patients, and frequent pain noted only in 28.6% of persons. Among CP patients, frequent and persistent pain noted in 65.5% of patients and among OP patients in 48.6% of cases. All PCa patients experienced pain in the right upper quadrant. Pain was of low intensity in 75% of cases and moderate in 25% of cases. Elimination of pain was observed in half of the PCa patients, and 1/4 of patients continued to experience pain. Episodes of nausea and vomiting noted in 25% of PCa patients. Bloated feeling in the stomach and overflow were noted in 42.8% of the all surveyed PCa persons. The level of glucose in PCa patients exceeded the normal limits and was significantly higher compared to that in OP and CP patients (8.5 ± 1.4 mmol/L, 5.4 ± 0.3 and 5.1 ± 0.1 mmol/L, respectively, p < 0.05). Hyperbilirubinemia was detected in PCa patients – 89.9 ± 27.5 μmol/L; in OP and CP patients bilirubin levels were 32.2 ± 11.0 and 13.4 ± 1.8 μmol/L, respectively, which were significantly lower than those in patients with PCa, p < 0.05. Triglyceride levels did not differ in patients with different pancreas diseases (PCa – 1.7 ± 0.3, CP – 1.86 ± 0.1 and OP –1.88<
{"title":"P83","authors":"O. Ephimova , I. Grigoreva , T. Romanova , Y. Ragino , T. Suvorova , N. Tov","doi":"10.1016/j.ejcsup.2015.08.027","DOIUrl":"10.1016/j.ejcsup.2015.08.027","url":null,"abstract":"<div><h3>Background</h3><p>To evaluate the clinical symptoms in pancreatic cancer patients (PCa) and compare some biochemical blood serum parameters in patients with different pathology of the pancreas (PCa, acute (OP) and chronic pancreatitis (CP)).</p></div><div><h3>Materials and methods</h3><p>During a one-time clinical research on the type of “series of cases” 130 patients were examined (42 patients with OP, 81 – CP and 7 patients with PCa). The diagnosis of PCa, OP, CP was verified by clinical and instrumental methods. Glucose, cholesterol, triglyceride and bilirubin serum levels were determined by ELISA.</p></div><div><h3>Results</h3><p>The mean age of patients with PCa was 63.6<!--> <!-->±<!--> <!-->4.9<!--> <!-->years, morbidity duration of PCa – 3.5<!--> <!-->±<!--> <!-->1.1<!--> <!-->months. Among patients with PCa, 83.3% of people – smoked, 16.7% – smoked every day. Half of the respondents PCa patients noted that over the last year they did not drink alcohol; 16.7% of people – drank alcohol several times a year, and 33.3% of patients consumed alcohol 1–2 times a month. BMI of PCa patients was equal to 26.3<!--> <!-->±<!--> <!-->3.5<!--> <!-->kg/m<sup>2</sup>, in OP patients – 23.8<!--> <!-->±<!--> <!-->1.0<!--> <!-->kg/m<sup>2</sup>, in CP patients – 26.3<!--> <!-->±<!--> <!-->0.6<!--> <!-->kg/m<sup>2</sup>, <em>p</em> <!-->><!--> <!-->0.05. In this case, 85.7% of PCa patients noted a significant decrease in body weight (11.7<!--> <!-->±<!--> <!-->6.0<!--> <!-->kg) for 3–4<!--> <!-->months after the onset of symptoms. There was no pain in 42.8% of PCa patients, and frequent pain noted only in 28.6% of persons. Among CP patients, frequent and persistent pain noted in 65.5% of patients and among OP patients in 48.6% of cases. All PCa patients experienced pain in the right upper quadrant. Pain was of low intensity in 75% of cases and moderate in 25% of cases. Elimination of pain was observed in half of the PCa patients, and 1/4 of patients continued to experience pain. Episodes of nausea and vomiting noted in 25% of PCa patients. Bloated feeling in the stomach and overflow were noted in 42.8% of the all surveyed PCa persons. The level of glucose in PCa patients exceeded the normal limits and was significantly higher compared to that in OP and CP patients (8.5<!--> <!-->±<!--> <!-->1.4<!--> <!-->mmol/L, 5.4<!--> <!-->±<!--> <!-->0.3 and 5.1<!--> <!-->±<!--> <!-->0.1<!--> <!-->mmol/L, respectively, <em>p</em> <!--><<!--> <!-->0.05). Hyperbilirubinemia was detected in PCa patients – 89.9<!--> <!-->±<!--> <!-->27.5<!--> <!-->μmol/L; in OP and CP patients bilirubin levels were 32.2<!--> <!-->±<!--> <!-->11.0 and 13.4<!--> <!-->±<!--> <!-->1.8<!--> <!-->μmol/L, respectively, which were significantly lower than those in patients with PCa, <em>p</em> <!--><<!--> <!-->0.05. Triglyceride levels did not differ in patients with different pancreas diseases (PCa – 1.7<!--> <!-->±<!--> <!-->0.3, CP – 1.86<!--> <!-->±<!--> <!-->0.1 and OP –1.88<","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 15-16"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309017","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.2015.08.039
E. Kaigorodova , N. Tarabanovskaya , E. Simolina , V. Perelmuter , M. Stakheeva , N. Cherdyntseva , O. Saveleva , L. Tashireva
Background
Despite the abundance of theoretical evidences displaying the considerable role of the “soil” in metastasis progression, the majority of cancer research and cancer therapy pathogenetic methods focused mainly on the tumor cells. There is still no clear clinical data showing the role of “soil” in the metastasis. Identification of factors and mechanisms driving the conditions promoting tumor dissemination may lead to therapeutic strategy to detect and prevent metastases at the earliest step. It has been established that bone marrow-derived hematopoietic progenitor cells home to pre-metastatic sites before tumor cells infiltrate in these sites. These hematopoietic progenitor cells form regulatory cell cluster of stromal microenvironment (premetastatic niche) to promote secondary tumor growth. In this context, the aim of our study was to evaluate the level of different pools of circulating tumor cells and bone marrow progenitor cells in the blood of patients with breast cancer in the dynamics of neoadjuvant chemotherapy.
Materials and methods
Patients (prospective study) with newly diagnosed invasive breast cancer in the age range 18–50 years and tumor volume of 2.0(> or =) cm, referred at the Tomsk Cancer Research Institute for treatment were included into the study. Eligibility criteria were as follows: the patient’s informed consent to participate in research; morphologically verified diagnosis of invasive carcinoma of non-specific type; luminal B-1, -2, triple negative (basal-like subtype included), HER2 positive breast cancer; T2-4N0-3M0; preserved menstrual function; satisfactory performance status (on a scale (< or =) ECOG 2). Exclusion Criteria were: other than luminal histological type of breast cancer, multiple primary cancer; chronic inflammatory diseases in the acute stage. Samples of venous blood taken from breast cancer patients before biopsy, after biopsy and after each subsequent course of neoadjuvant chemotherapy (NACHT) were served as a study material. The various pools of circulating tumor cells and bone-marrow derived progenitor cells were determined using monoclonal antibodies to EpCam, CD44, CD45, CD24, N-cadherin, CD34, CD133, CD202, VEGFR1 and CD90, labeled with different fluorochromes on flow cytometry BD FACSCanto ™ II.
Results
The study showed that each succeeding course of NACHT increased blood levels of circulating tumor cells, and bone marrow progenitor cells with a phenotype characteristic of EPC (endothelial progenitor cells) (CD34 + CD45–VEGFR + CD133 + CD202 +) and MSC (mesenchymal progenitor stem cells fibroblasts) (CD34–CD90 + VEGFR1–CD45–CD202–). Influence of the NACHT on hematopoietic stem cells HSC (VEGFR1 + CD34 + CD45lowSD202–) and progenitor cells HPC – CD34 + CD45 <
{"title":"T15","authors":"E. Kaigorodova , N. Tarabanovskaya , E. Simolina , V. Perelmuter , M. Stakheeva , N. Cherdyntseva , O. Saveleva , L. Tashireva","doi":"10.1016/j.ejcsup.2015.08.039","DOIUrl":"10.1016/j.ejcsup.2015.08.039","url":null,"abstract":"<div><h3>Background</h3><p>Despite the abundance of theoretical evidences displaying the considerable role of the “soil” in metastasis progression, the majority of cancer research and cancer therapy pathogenetic methods focused mainly on the tumor cells. There is still no clear clinical data showing the role of “soil” in the metastasis. Identification of factors and mechanisms driving the conditions promoting tumor dissemination may lead to therapeutic strategy to detect and prevent metastases at the earliest step. It has been established that bone marrow-derived hematopoietic progenitor cells home to pre-metastatic sites before tumor cells infiltrate in these sites. These hematopoietic progenitor cells form regulatory cell cluster of stromal microenvironment (premetastatic niche) to promote secondary tumor growth. In this context, the aim of our study was to evaluate the level of different pools of circulating tumor cells and bone marrow progenitor cells in the blood of patients with breast cancer in the dynamics of neoadjuvant chemotherapy.</p></div><div><h3>Materials and methods</h3><p>Patients (prospective study) with newly diagnosed invasive breast cancer in the age range 18–50 years and tumor volume of 2.0(> or =)<!--> <!-->cm, referred at the Tomsk Cancer Research Institute for treatment were included into the study. Eligibility criteria were as follows: the patient’s informed consent to participate in research; morphologically verified diagnosis of invasive carcinoma of non-specific type; luminal B-1, -2, triple negative (basal-like subtype included), HER2 positive breast cancer; T2-4N0-3M0; preserved menstrual function; satisfactory performance status (on a scale (< or =) ECOG 2). Exclusion Criteria were: other than luminal histological type of breast cancer, multiple primary cancer; chronic inflammatory diseases in the acute stage. Samples of venous blood taken from breast cancer patients before biopsy, after biopsy and after each subsequent course of neoadjuvant chemotherapy (NACHT) were served as a study material. The various pools of circulating tumor cells and bone-marrow derived progenitor cells were determined using monoclonal antibodies to EpCam, CD44, CD45, CD24, N-cadherin, CD34, CD133, CD202, VEGFR1 and CD90, labeled with different fluorochromes on flow cytometry BD FACSCanto ™ II.</p></div><div><h3>Results</h3><p>The study showed that each succeeding course of NACHT increased blood levels of circulating tumor cells, and bone marrow progenitor cells with a phenotype characteristic of EPC (endothelial progenitor cells) (CD34<!--> <!-->+<!--> <!-->CD45–VEGFR<!--> <!-->+<!--> <!-->CD133<!--> <!-->+<!--> <!-->CD202<!--> <!-->+) and MSC (mesenchymal progenitor stem cells fibroblasts) (CD34–CD90<!--> <!-->+<!--> <!-->VEGFR1–CD45–CD202–). Influence of the NACHT on hematopoietic stem cells HSC (VEGFR1<!--> <!-->+<!--> <!-->CD34<!--> <!-->+<!--> <!-->CD45lowSD202–) and progenitor cells HPC – CD34<!--> <!-->+<!--> <!-->CD45<!--> <","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 22"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309333","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.2015.08.042
K. Kirsanov , E. Lesovaya , N. Shalginskikh , D. Naberezhnov , V. Glazunov , G. Belitsky , M. Yakubovskaya
Purpose
DNA minor groove is the main target of small molecules, which noncovalently and to a certain extent site-specifically bind to appropriate nucleotide sequences. Study of these substances can give rise to understanding the mechanistic relationship between sites of interaction and activity of appropriate enzymes with “houskeeping” function including helicases, topoisomerases, methyltransferases, demethylases and DNA/RNA-polymerases.
Results
We revealed for the first time that AT-specific minor groove binding ligands (MGBLs), in particular bisbenzimidazoles (Hoechst33258 and its derivatives), widely used in molecular and cell biology for DNA-staining, induce loss of heterozygosity at high frequency while point mutations and chromosome deletions at insignificant levels. Moreover, we demonstrated that the agents realized their genotoxic blastomogenic effects via homologous recombination mechanism exclusively. Lately the same mechanism of genotoxicity has been shown for MGBL carbazole derivative Curaxin, which is toxic for a broad range of tumor cell lines in vitro and inhibit tumor growth in different mouse models of cancer in vivo. Moreover, powerful antitumor activity has been demonstrated for Trabectedin, which binds to the DNA’s minor groove and alkylate guanine residues. All this provided a framework for wide-ranging investigation of cell response to MGBLs exposure, molecular mechanisms of their recombinogenic as also their anticancer activity. A special interest is paid to epigenetic mechanisms of MGBs action.
Our study aimed to examine the epigenetic effects of recombinogenic (Hoechst33342, Hoechst33258) and non-recombinogenic (DAPI, Diminazene, Pentamidine and Netropsin) MGBLs.
After we unmasked MGBLs’ recombinogenic activity, we hypothesized that their molecular mechanism of indirect DNA damage involves poly(ADP-ribose)polymerase-1 (PARP-1) activation. Surprisingly, we found that all AT-specific MGBLs preventing PARP-1 interaction with DNA inhibit its activation, and hence, the DNA-dependent pathway of PARP-1 activation function. These inhibitors effectively block PARP-1 activity in vivo, as it was demonstrated in a Drosophila experimental system and in human breast cancer-derived BT474 cell line.
Further epigenetic effects of these indirect genotoxic carcinogens were analyzed using HeLa cell population with epigenetically suppressed GFP-reporter gene as a model. All compounds had strong GFP- reactivation effect. The obtained results confirm scarce data of previous publications on the ability of DNA minor groove ligands to influence gene transcription process. Statistically significant results of changes of DNA methylation level were detected under 5-azaC and Hoechst 33258 treatment, but it was absent after Hoechst 33342 treatment. For the rest compounds significant loss of promoter region methylation was not observed. The common epigenetic marks of transcription include histon
{"title":"P88","authors":"K. Kirsanov , E. Lesovaya , N. Shalginskikh , D. Naberezhnov , V. Glazunov , G. Belitsky , M. Yakubovskaya","doi":"10.1016/j.ejcsup.2015.08.042","DOIUrl":"10.1016/j.ejcsup.2015.08.042","url":null,"abstract":"<div><h3>Purpose</h3><p>DNA minor groove is the main target of small molecules, which noncovalently and to a certain extent site-specifically bind to appropriate nucleotide sequences. Study of these substances can give rise to understanding the mechanistic relationship between sites of interaction and activity of appropriate enzymes with “houskeeping” function including helicases, topoisomerases, methyltransferases, demethylases and DNA/RNA-polymerases.</p></div><div><h3>Results</h3><p>We revealed for the first time that AT-specific minor groove binding ligands (MGBLs), in particular bisbenzimidazoles (Hoechst33258 and its derivatives), widely used in molecular and cell biology for DNA-staining, induce loss of heterozygosity at high frequency while point mutations and chromosome deletions at insignificant levels. Moreover, we demonstrated that the agents realized their genotoxic blastomogenic effects via homologous recombination mechanism exclusively. Lately the same mechanism of genotoxicity has been shown for MGBL carbazole derivative Curaxin, which is toxic for a broad range of tumor cell lines in vitro and inhibit tumor growth in different mouse models of cancer in vivo. Moreover, powerful antitumor activity has been demonstrated for Trabectedin, which binds to the DNA’s minor groove and alkylate guanine residues. All this provided a framework for wide-ranging investigation of cell response to MGBLs exposure, molecular mechanisms of their recombinogenic as also their anticancer activity. A special interest is paid to epigenetic mechanisms of MGBs action.</p><p>Our study aimed to examine the epigenetic effects of recombinogenic (Hoechst33342, Hoechst33258) and non-recombinogenic (DAPI, Diminazene, Pentamidine and Netropsin) MGBLs.</p><p>After we unmasked MGBLs’ recombinogenic activity, we hypothesized that their molecular mechanism of indirect DNA damage involves poly(ADP-ribose)polymerase-1 (PARP-1) activation. Surprisingly, we found that all AT-specific MGBLs preventing PARP-1 interaction with DNA inhibit its activation, and hence, the DNA-dependent pathway of PARP-1 activation function. These inhibitors effectively block PARP-1 activity in vivo, as it was demonstrated in a Drosophila experimental system and in human breast cancer-derived BT474 cell line.</p><p>Further epigenetic effects of these indirect genotoxic carcinogens were analyzed using HeLa cell population with epigenetically suppressed GFP-reporter gene as a model. All compounds had strong GFP- reactivation effect. The obtained results confirm scarce data of previous publications on the ability of DNA minor groove ligands to influence gene transcription process. Statistically significant results of changes of DNA methylation level were detected under 5-azaC and Hoechst 33258 treatment, but it was absent after Hoechst 33342 treatment. For the rest compounds significant loss of promoter region methylation was not observed. The common epigenetic marks of transcription include histon","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 24"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309367","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.2015.08.047
D. Korobkov , N. Plotnikova , G. Meltsaev , S. Kemaykin , A. Almyashev , S. Haritonov
Breast cancer is one of the most common cancers in women. The incidence of breast cancer in 2014 in the Republic of Mordovia was 69.9 per 100,000 female populations. Breast cancer occurs when excessive expression of oncoproteins switches in the case of transformation of proto-oncogene in PRADI. In primary breast tumors, mutations and the expression of the three oncogenes Her2/neu, C-mys, Int-2, as well as in supressonyh genes – the p53 gene and the retinoblastoma gene RB are the most common. Several studies found that oncogene – C-mys was expressed in 16.8% of primary breast cancer cases and in 35% cases with subsequent development of metastases. Proteins that stimulate the phosphorylation of mitogen-activated protein kinasescan activateunder the influence of growth factors. Development of breast cancer is regulated by a complex interaction of many hormones and growth factors. Currently, one of the leading theories of developing breast cancer is the increased hormonal stimulation of proliferative processes in the development of neoplasia. One of the manifestations of hormonal imbalance in tumor during a regular decrease in blood competitive inhibitor of the biological effects of estrogen – progesterone, which is in correlation with the stage of the spread of neoplasia. The role of the overproduction of estrogen in the pathogenesis of breast cancer is confirmed by the fact that in women who underwent oophorectomy before the age of 38 years, the risk of breast cancer development is 1.5 times less than in those who did not have such operation. Excessive accumulation of lipid peroxidation products in the area of neoplasia activates mechanisms violation of intercellular interaction that caused the destruction of the lipid components of membranes.
The study group included 112 patients treated at the State Institution of Health of the Republic of Mordovia “National Oncology Center”. To identify the nature of tumors, all patients underwent immunohistochemical analysis. Androgen receptors were found in 48% of breast cancer cases, the expression level of androgen receptor in the tumor was much lower than the expression level of estrogen and progesterone receptors. Low levels of progesterone receptor expression in breast cancer cells were combined with high levels of expression of Ki-67 antigen, HER-2 oncoprotein in tumor cells. Patients with HER-2 (3+) and (2+) had more frequent multiple metastases in lymph nodes compared to patients with HER-2 (0) and (1+) phenotypes. Maximum expression of HER-2 oncoprotein in tumor cells indicated high metastatic potential and poor prognosis.
It may be concluded that the cellular and molecular mechanisms of breast cancer are complex. Therefore, carcinogenesis has a “multistep” nature and at least two or more mutations in the cells of the same clone – parent and child are required to generate malignant tumors. Thus, the development of oncogenic transformation does not necessarily mean the pro
{"title":"A75","authors":"D. Korobkov , N. Plotnikova , G. Meltsaev , S. Kemaykin , A. Almyashev , S. Haritonov","doi":"10.1016/j.ejcsup.2015.08.047","DOIUrl":"10.1016/j.ejcsup.2015.08.047","url":null,"abstract":"<div><p>Breast cancer is one of the most common cancers in women. The incidence of breast cancer in 2014 in the Republic of Mordovia was 69.9 per 100,000 female populations. Breast cancer occurs when excessive expression of oncoproteins switches in the case of transformation of proto-oncogene in PRADI. In primary breast tumors, mutations and the expression of the three oncogenes Her2/neu, C-mys, Int-2, as well as in supressonyh genes – the p53 gene and the retinoblastoma gene RB are the most common. Several studies found that oncogene – C-mys was expressed in 16.8% of primary breast cancer cases and in 35% cases with subsequent development of metastases. Proteins that stimulate the phosphorylation of mitogen-activated protein kinasescan activateunder the influence of growth factors. Development of breast cancer is regulated by a complex interaction of many hormones and growth factors. Currently, one of the leading theories of developing breast cancer is the increased hormonal stimulation of proliferative processes in the development of neoplasia. One of the manifestations of hormonal imbalance in tumor during a regular decrease in blood competitive inhibitor of the biological effects of estrogen – progesterone, which is in correlation with the stage of the spread of neoplasia. The role of the overproduction of estrogen in the pathogenesis of breast cancer is confirmed by the fact that in women who underwent oophorectomy before the age of 38<!--> <!-->years, the risk of breast cancer development is 1.5 times less than in those who did not have such operation. Excessive accumulation of lipid peroxidation products in the area of neoplasia activates mechanisms violation of intercellular interaction that caused the destruction of the lipid components of membranes.</p><p>The study group included 112 patients treated at the State Institution of Health of the Republic of Mordovia “National Oncology Center”. To identify the nature of tumors, all patients underwent immunohistochemical analysis. Androgen receptors were found in 48% of breast cancer cases, the expression level of androgen receptor in the tumor was much lower than the expression level of estrogen and progesterone receptors. Low levels of progesterone receptor expression in breast cancer cells were combined with high levels of expression of Ki-67 antigen, HER-2 oncoprotein in tumor cells. Patients with HER-2 (3+) and (2+) had more frequent multiple metastases in lymph nodes compared to patients with HER-2 (0) and (1+) phenotypes. Maximum expression of HER-2 oncoprotein in tumor cells indicated high metastatic potential and poor prognosis.</p><p>It may be concluded that the cellular and molecular mechanisms of breast cancer are complex. Therefore, carcinogenesis has a “multistep” nature and at least two or more mutations in the cells of the same clone – parent and child are required to generate malignant tumors. Thus, the development of oncogenic transformation does not necessarily mean the pro","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 27"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309475","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.2015.08.076
E. Pisareva , N. Gutkina , S. Kovalenko , V. Shamanin
KRAS is component of Ras/MAPK signaling cascade that regulates cell proliferation and cell survival. Somatic mutations in KRAS gene are often found in tumors and affect the sensitivity of tumors to target therapy. Mutations in codons 12 or 13 of KRAS gene in colorectal cancer (CRC) are associated with resistance to anti-EGFR antibodies Cetuximab and Panitumumab. The objectives of this work were to develop PCR tests for detection mutations in KRAS gene and analyze the frequency of mutations in KRAS gene in CRC in Russia.
DNA sequencing by Sanger is the most common method for mutation analysis. However, the method has a sensitivity of 20% mutant allele, which is often not sufficient for the analysis of somatic mutations in tumors.
One of the most sensitive mutation analysis methods is allele-specific real-time PCR. This method allows to detect 1% of mutated DNA in the sample. This sensitivity is sufficient for analysis of mutations in tumor samples containing 2–5% or more of tumor cells in normal tissue.
In this study we developed and compared 3 new KRAS assays (1) real-time PCR with allele-specific primers; (2) real-time wild-type blocking PCR with LNA (locked nucleic acid) blocker; and (3) Sanger sequencing with LNA-blocker. First assay is a PCR test with seven reactions using allele-specific primers for detection and genotyping 7 mutations in 12 and 13 codons of KRAS gene. Second assay is real-time PCR with only a single pair of primers and LNA oligonucleotide blocker. LNA-blocker is an oligonucleotide which has a wild-type sequence of codons 12 and 13 of KRAS gene. LNA-blocker binds strongly to wild-type KRAS DNA and suppresses its amplification, but does not block amplification of mutant DNA. The real-time PCR with LNA -blocker can detect mutant DNA but does not genotype mutation. Such assay can be used as a simple and sensitive screening test for mutant KRAS cases if exact genotyping of mutation is not required. We also used LNA-blocker to increase sensitivity of Sanger sequencing. To evaluate sensitivity and specificity of new tests DNA standards were prepared with different ratios of normal and mutant alleles using normal human DNA without mutation and recombinant plasmids with mutations in KRAS (G12C, G12S, G12R, G12V, G12D, G12A, G13D). After optimization all three assays had sensitivity 5% of mutant alleles for the detection of mutations in KRAS gene, using 2.5–40 ng of human DNA.
Performance of new assays for KRAS mutations was compared using 81 colorectal tumor samples. Before analysis relative content of tumor cells in the samples was evaluated by pathologist. If tumor content was less than 20% in the sample then regions with a maximum number of tumor cells were manually macrodissected before the DNA extraction. DNA was purified from formalin fixed paraffin embedded (FFPE) tissue using “FFPE-DNA Kit” (Biolink). All three assays had high sensitivity (95–100%) and specificity (100%) for detectio
{"title":"P65","authors":"E. Pisareva , N. Gutkina , S. Kovalenko , V. Shamanin","doi":"10.1016/j.ejcsup.2015.08.076","DOIUrl":"10.1016/j.ejcsup.2015.08.076","url":null,"abstract":"<div><p>KRAS is component of Ras/MAPK signaling cascade that regulates cell proliferation and cell survival. Somatic mutations in KRAS gene are often found in tumors and affect the sensitivity of tumors to target therapy. Mutations in codons 12 or 13 of KRAS gene in colorectal cancer (CRC) are associated with resistance to anti-EGFR antibodies Cetuximab and Panitumumab. The objectives of this work were to develop PCR tests for detection mutations in KRAS gene and analyze the frequency of mutations in KRAS gene in CRC in Russia.</p><p>DNA sequencing by Sanger is the most common method for mutation analysis. However, the method has a sensitivity of 20% mutant allele, which is often not sufficient for the analysis of somatic mutations in tumors.</p><p>One of the most sensitive mutation analysis methods is allele-specific real-time PCR. This method allows to detect 1% of mutated DNA in the sample. This sensitivity is sufficient for analysis of mutations in tumor samples containing 2–5% or more of tumor cells in normal tissue.</p><p>In this study we developed and compared 3 new KRAS assays (1) real-time PCR with allele-specific primers; (2) real-time wild-type blocking PCR with LNA (locked nucleic acid) blocker; and (3) Sanger sequencing with LNA-blocker. First assay is a PCR test with seven reactions using allele-specific primers for detection and genotyping 7 mutations in 12 and 13 codons of KRAS gene. Second assay is real-time PCR with only a single pair of primers and LNA oligonucleotide blocker. LNA-blocker is an oligonucleotide which has a wild-type sequence of codons 12 and 13 of KRAS gene. LNA-blocker binds strongly to wild-type KRAS DNA and suppresses its amplification, but does not block amplification of mutant DNA. The real-time PCR with LNA -blocker can detect mutant DNA but does not genotype mutation. Such assay can be used as a simple and sensitive screening test for mutant KRAS cases if exact genotyping of mutation is not required. We also used LNA-blocker to increase sensitivity of Sanger sequencing. To evaluate sensitivity and specificity of new tests DNA standards were prepared with different ratios of normal and mutant alleles using normal human DNA without mutation and recombinant plasmids with mutations in KRAS (G12C, G12S, G12R, G12V, G12D, G12A, G13D). After optimization all three assays had sensitivity 5% of mutant alleles for the detection of mutations in KRAS gene, using 2.5–40<!--> <!-->ng of human DNA.</p><p>Performance of new assays for KRAS mutations was compared using 81 colorectal tumor samples. Before analysis relative content of tumor cells in the samples was evaluated by pathologist. If tumor content was less than 20% in the sample then regions with a maximum number of tumor cells were manually macrodissected before the DNA extraction. DNA was purified from formalin fixed paraffin embedded (FFPE) tissue using “FFPE-DNA Kit” (Biolink). All three assays had high sensitivity (95–100%) and specificity (100%) for detectio","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 42-43"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309876","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.2015.08.086
V. Rybko, N. Khromova, M. Farmakovskaya, M. Novikova, B. Kopnin, P. Kopnin
Malignant tumors consist not only of neoplastic cells, but also of various normal cells, for example fibroblasts, macrophages or endothelial cells. These normal cells stand under constant pressure of transformed cells, regulating their properties and converting them into tumor-promoting cells. Tumor-stroma interaction takes place during all stages of carcinogenesis. Notch activation upon receptor binding with the ligand is a way of direct intercellular communication during embryo- and histogenesis, determining various processes like differentiation, proliferation, etc. It has been previously shown that in tumors this signaling cascade regulates not only properties of transformed cells, but also stromal cells activities, i.e. neoangiogenesis. The Notch role in communication between neoplastic cells and stromal fibroblasts is underinvestigated.
Cancer-associated stromal fibroblasts (CAFs) are an important component of tumors secreting growth factors and proteases, modulating immune reactions and contributing to cancer stem cells niches formation. CAFs resemble myofibroblasts and express Smooth-Muscle Actin (SMA).
We obtained and characterized cultures of normal mesenchymal cells: a myofibroblasts-like (MF), and fibroblasts-like MC1 and MC2, differing by Notch1 expression. These cell cultures variously influenced growth of colon cancer notch- ligand Jagged2-positive HCT116 xenographs in nude mice. MF cells were characterized by the strongest while Notch1-deficient MC2 by the weakest tumor-promoting activity.
MC1 but not MC2 started to express SMA upon co-cultivation in vitro with neoplastic HCT116 cells. Such co-cultivation also lead to Notch activation according to a luciferase reporter. NICD (Notch Intracellular Domain) expression activated MC1 and MC2, while Notch1 silencing in MC1 abrogated both HCT116-mediated activation of the fibroblasts in vitro and their tumor-promoting activity in vivo.
Notch signaling in mesenchymal cells stimulated TGFb production that lead to both autocrine and paracrine receptors stimulation. We believe that this cytokine activates fibroblasts in our experimental system. We also revealed that this process was p53-dependent.
So we have shown Notch1 to be involved in tumor-stroma interaction, particularly its activation leading to fibroblasts transdifferentiation. Notch1-stimulated fibroblasts are able to produce TGFb and to promote tumor growth in xenographs. The tumor-stimulating potency of various fibroblasts in our experimental system depends on their ability to transdifferentiate to myofibroblasts upon Notch activation.
{"title":"A104","authors":"V. Rybko, N. Khromova, M. Farmakovskaya, M. Novikova, B. Kopnin, P. Kopnin","doi":"10.1016/j.ejcsup.2015.08.086","DOIUrl":"10.1016/j.ejcsup.2015.08.086","url":null,"abstract":"<div><p>Malignant tumors consist not only of neoplastic cells, but also of various normal cells, for example fibroblasts, macrophages or endothelial cells. These normal cells stand under constant pressure of transformed cells, regulating their properties and converting them into tumor-promoting cells. Tumor-stroma interaction takes place during all stages of carcinogenesis. Notch activation upon receptor binding with the ligand is a way of direct intercellular communication during embryo- and histogenesis, determining various processes like differentiation, proliferation, etc. It has been previously shown that in tumors this signaling cascade regulates not only properties of transformed cells, but also stromal cells activities, i.e. neoangiogenesis. The Notch role in communication between neoplastic cells and stromal fibroblasts is underinvestigated.</p><p>Cancer-associated stromal fibroblasts (CAFs) are an important component of tumors secreting growth factors and proteases, modulating immune reactions and contributing to cancer stem cells niches formation. CAFs resemble myofibroblasts and express <span><math><mrow><mi>α</mi></mrow></math></span>Smooth-Muscle Actin (<span><math><mrow><mi>α</mi></mrow></math></span>SMA).</p><p>We obtained and characterized cultures of normal mesenchymal cells: a myofibroblasts-like (MF), and fibroblasts-like MC1 and MC2, differing by Notch1 expression. These cell cultures variously influenced growth of colon cancer notch- ligand Jagged2-positive HCT116 xenographs in nude mice. MF cells were characterized by the strongest while Notch1-deficient MC2 by the weakest tumor-promoting activity.</p><p>MC1 but not MC2 started to express <span><math><mrow><mi>α</mi></mrow></math></span>SMA upon co-cultivation in vitro with neoplastic HCT116 cells. Such co-cultivation also lead to Notch activation according to a luciferase reporter. NICD (Notch Intracellular Domain) expression activated MC1 and MC2, while Notch1 silencing in MC1 abrogated both HCT116-mediated activation of the fibroblasts in vitro and their tumor-promoting activity in vivo.</p><p>Notch signaling in mesenchymal cells stimulated TGFb production that lead to both autocrine and paracrine receptors stimulation. We believe that this cytokine activates fibroblasts in our experimental system. We also revealed that this process was p53-dependent.</p><p>So we have shown Notch1 to be involved in tumor-stroma interaction, particularly its activation leading to fibroblasts transdifferentiation. Notch1-stimulated fibroblasts are able to produce TGFb and to promote tumor growth in xenographs. The tumor-stimulating potency of various fibroblasts in our experimental system depends on their ability to transdifferentiate to myofibroblasts upon Notch activation.</p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 48"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.105
M. Suvorova, A. Tsapieva, A. Suvorov, E. P. Kiseleva
{"title":"A99: The influence of live Streptococcus pyogenes on the growth of solid murine tumors","authors":"M. Suvorova, A. Tsapieva, A. Suvorov, E. P. Kiseleva","doi":"10.1016/j.ejcsup.2015.08.105","DOIUrl":"https://doi.org/10.1016/j.ejcsup.2015.08.105","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"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.2015.08.105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310560","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.2015.08.126
G. Zhukova, A. Shikhliarova, T. Gudtskova, M. Bragina, I. Novikova, V. Zernov, T. Barteneva, O. Polozhentsev, A. Soldatov, M. Rudenko, E. Shirnina
{"title":"A66: Changes in experimental tumors and surrounding tissue under antitumor influence of magnetite nanoparticles introduced into the peritumoral area","authors":"G. Zhukova, A. Shikhliarova, T. Gudtskova, M. Bragina, I. Novikova, V. Zernov, T. Barteneva, O. Polozhentsev, A. Soldatov, M. Rudenko, E. Shirnina","doi":"10.1016/J.EJCSUP.2015.08.126","DOIUrl":"https://doi.org/10.1016/J.EJCSUP.2015.08.126","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"1 1","pages":"71-72"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.EJCSUP.2015.08.126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310735","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.2015.08.107
S. Tamkovich, A. Bondar, I. Morozov, N. Kirushina, V. Permyakova, V. Voitsitskiy, P. Laktionov
{"title":"P39a: The characterization of total circulating DNA from blood of healthy donors and cancer patients","authors":"S. Tamkovich, A. Bondar, I. Morozov, N. Kirushina, V. Permyakova, V. Voitsitskiy, P. Laktionov","doi":"10.1016/J.EJCSUP.2015.08.107","DOIUrl":"https://doi.org/10.1016/J.EJCSUP.2015.08.107","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"60"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.EJCSUP.2015.08.107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310855","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号