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Öğe Analysis of e6/e7 mrna gene expression by means of nuclisens easyq (nasba) technique in patientssuffering from cervical dysplasia with hpv positive(I r o g canada, ınc, 4900 cote st-luc, apt#212, montreal, quebec h3w 2h3, canada, 2017) Ciplak, B.; Yilmaz, E.; Otlu, B.; Coskun, E. I.; Sahin, N.; Tuncay, GObjective: In this study, the authors aimed at examining E6/E7 mRNA gene expression by means of NucliSENS EasyQ (NASBA) in patients in which HPV infection was detected and diagnosed with cervical dysplasia. Materials and Methods: This study included 77 patients diagnosed with cervical dysplasia. The patients were grouped based on cervico-vaginal smear anomalies. Digene HC2 DNA Collection Device transport medium was used for taking and keeping cervical samples, QIA symphony SP device, and QIAsymphony DSP AXpH DNA kit were used for HPV DNA extraction from cervical samples kept in transport medium, HPV Q24 complete kit, RotorGene and PyroMark Q24 for detection of HPV-DNA and determination of HPV types and NucliSENS Easy Q Genetic Analyzer technique for determination of E6/E7 gene expression in HPV positive samples. SPSS (Statistical Package for Social Sciences) Version 22.0 was employed in statistical evaluation of the research date. Results: The most common HPV was considered as type 16 in this study. When pathology specimens of patients in whom dysplasia was detected in their cervical biopsies were examined in terms of HPV E6/E7 mRNA expression, a statistically significant difference was found between the normal and pathology groups (p < 0.05). Conclusion: Today, the presence of HPV infection in etiology of cervical smear pathologies and dysplasia is undisputedly accepted. The main determinant factor of HPV virulence is the frequency of E6 and E7 gene expressions existing in the DNA structure and responsible for virulence. NucliSENS_Ea_syQ (NASBA) is a technique employed to analyze mRNA gene expression in an accurate, reliable, and rapid way. Parallel to the conclusions of studies in the literature, frequency of E6/E7 gene expression increases in proportion to the increasing dysplasia degree of cervical pathologies in the present study as well.Öğe An experimental study on the determination of gantry angle and ssd dependenciesof tld and mosfet dosimeter systems(Novim Medical Radiation Institute, 2017) Barlaz Us, S; Kaya Pepele, E.Background: The purpose of this study was to investigate the various gantry angle and SSD dependencies of TLD and MOSFET dosimeters. Materials and Methods: LiF (Mg) TLD and MOSFET were used in this study. Dosimeter systems were calibrated and then irradiated at various gantry angle and SSD by applying 6 MV photon energy. Results: Based on the results, MOSFET changes were found to be in 2% range between ±50 gantry angles and the rate of dose change was found to be increasing as gantry angle was at the extremes of graph. This increase was especially obvious in tail end of the asymmetric axes. Change in the gantry angle dependency of TLD was -2% till ± 60 gantry angle and -5% between 60 to 90. Dependency of SSD was ±1% for TLD and MOSFET. Conclusion: Results indicate that properties of dosimeters must be well known by users for accurate determination of the entire doses on the patient. These observations may lead to better treatment quality and prevention of probable dose errors.Öğe Systematic identification of cancer-specific mhc-binding peptides with raven(Taylor & francıs ınc, 530 walnut street, ste 850, phıladelphıa, pa 19106 usa, 2018) Akpolat, Nusret; Akatli, ANImmunotherapy can revolutionize anti-cancer therapy if specific targets are available. Immunogenic peptides encoded by cancer-specific genes (CSGs) may enable targeted immunotherapy, even of oligo-mutated cancers, which lack neo-antigens generated by protein-coding missense mutations. Here, we describe an algorithm and user-friendly software named RAVEN (Rich Analysis of Variable gene Expressions in Numerous tissues) that automatizes the systematic and fast identification of CSG-encoded peptides highly affine to Major Histocompatibility Complexes (MHC) starting from transcriptome data. We applied RAVEN to a dataset assembled from 2,678 simultaneously normalized gene expression microarrays comprising 50 tumor entities, with a focus on oligo-mutated pediatric cancers, and 71 normal tissue types. RAVEN performed a transcriptome-wide scan in each cancer entity for gender-specific CSGs, and identified several established CSGs, but also many novel candidates potentially suitable for targeting multiple cancer types. The specific expression of the most promising CSGs was validated in cancer cell lines and in a comprehensive tissue-microarray. Subsequently, RAVEN identified likely immunogenic CSG-encoded peptides by predicting their affinity to MHCs and excluded sequence identity to abundantly expressed proteins by interrogating the UniProt protein-database. The predicted affinity of selected peptides was validated in T2-cell peptide-binding assays in which many showed binding-kinetics like a very immunogenic influenza control peptide. Collectively, we provide an exquisitely curated catalogue of cancer-specific and highly MHC-affine peptides across 50 cancer types, and a freely available software (https://github.com/JSGerke/RAVENsoftware) to easily apply our algorithm to any gene expression dataset. We anticipate that our peptide libraries and software constitute a rich resource to advance anti-cancer immunotherapy.Öğe Relation of basal vitamin D and parathyroid hormone levels to CD34+cell counts in multiple myeloma and lymphoma patients with stem cell mobilization(Pergamon-elsevıer scıence ltd, the boulevard, langford lane, kıdlıngton, oxford ox5 1gb, england, 2018) Kaya, A.; Kaya, E.; Erkut, M.; Kuku, IÖğe Retrospective and multicenter analysis of efficacy and safety of ruxolitinib in 176 Turkish patients with myelofibrosis: updated data(Pergamon-elsevıer scıence ltd, the boulevard, langford lane, kıdlıngton, oxford ox5 1gb, england, 2018) Özkan, MeralÖğe The ribosome inhibiting protein riproximin shows antineoplastic activity inexperimental pancreatic cancer liver metastasis(Spandıdos publ ltd, pob 18179, athens, 116 10, greece, 2018) Murtaja, Ahmed; Eyol, Ergul; Jiang Xiaoqi; Berger, Martin R.; Adwan, HassanPancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognoses of all malignancy types. To improve the survival of patients with PDAC, the development of novel anticancer agents is warranted. Riproximin (Rpx) is a newly identified plant lectin, which was isolated from Ximenia americana. The ribosome inactivating protein of type II exhibits potent anticancer activity as recently demonstrated. The rat PDAC cell line ASML was used for in vitro and in vivo studies. The antiproliferative effect of Rpx was assessed using an MTT assay. The modulation of proteins involved in apoptosis was evaluated using western blotting. Tumor-bearing nude rats were treated with Rpx, gemcitabine (GEM) or dinaline (DIN) as single agents, or a combination of Rpx with GEM, or DIN. Rpx was administered intraperitoneally at doses of 1.7-5.4 mu g/kg, three times/week, GEM was administered intravenously (50 mg/kg/week) and DIN perorally (10 mg/kg, 5 times/week). Rpx'inhibited ASML cell proliferation at IC50-values of 0.8-172 pM, caused apoptosis and reduced tumor growth significantly by 90% (P<0.05). The survival rate of rats was significantly increased (21.8 days for Rpx treated vs. 17.6 days for control rats; P=0.05). Higher doses of Rpx caused no further reduction in tumor size when compared with the low dose of Rpx or a combination of Rpx with GEM, or DIN. The standard drug GEM alone was less effective compared with Rpx. In addition, DIN was ineffective, and in combination, reduced the activity of Rpx. These results suggest that Rpx has an evident potential for use in pancreatic cancer treatment. Further experiments are required in order to elucidate its affinity for certain cancer cells and to optimize the combination therapy with other antineoplastic agents. KeywordsÖğe Prognostic factors of patients who received chemotherapy after cranial irradiation for non-small celllung cancer with brain metastases: A retrospective analysis of multicenter study (anatolian society ofmedical oncology)(Medknow publıcatıons & medıa pvt ltd, b-9, kanara busıness centre, off lınk rd, ghaktopar-e, mumbaı, 400075, ındıa, 2018) Elkiran, Emin TamerPurpose: Almost half of all patients diagnosed with non-small cell lung cancer (NSCLC) have distant metastases at presentation. One-third of patients with NSCLC will have brain metastases. Without effective treatment, the median survival is only 1 month. However, it is difficult to treat brain metastases with systemic chemotherapy since the agents have difficulty crossing the blood-brain barrier. Therefore, it is important to estimate the patient's survival prognosis. The aim of this study was to analyze prognostic factors for survival in Turkish patients who received chemotherapy after cranial irradiation for NSCLC with brain metastases. Methods: We retrospectively reviewed 698 patients with brain metastases resulting from NSCLC. Ten potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with overall survival (OS). Results: Among the 10 variables for univariate analysis, six were identified to have prognostic significance; these included sex, smoking history, histology, number of brain metastases, extracranial metastases, and neurosurgical resection. Multivariate analysis by the Cox proportional hazard model showed that a smoking history, extracranial metastases, and neurosurgical resection were independent negative prognostic factors for OS. Conclusion: Smoking history, extracranial metastases, and neurosurgical resection were considered independent negative prognostic factors for OS. These findings may facilitate pretreatment prediction of survival and can be used for selecting patients for more appropriate treatment options.Öğe Neural precursor cell-expressed developmentally down-regulated 4-like: a new biomarker in the pathophysiology of endometrial cancer(SAGE PUBLICATIONS LTD, 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND, 2018) Yılmaz, Ercan; Gül, Mehmet; Melekoğlu, Rauf; Coşkun, Ebru İnci; Gül, Semir; Baştemur, Ayşe GülçinObjectives Endometrial cancer is the most frequent tumor of the female genital tract. Ubiquitin is a small protein (8.5 kDa) found in all eukaryotic cells, binds to substrate proteins via a three-phase enzymatic pathway referred to as ubiquitination and plays an important role in cellular stability. Neural precursor cell-expressed developmentally down-regulated 4-like (NEDD4L) functions in the last phase of this enzymatic process. In this study, we investigated NEDD4L protein expression in endometrial cancer. Methods The study participants were divided into patients with benign endometrial pathologies (Group 1, n=23), patients with endometrial hyperplasia (Group 2, n=21) and patients with endometrial cancer (Group 3, n=20). NEDD4L expression was detected by immunohistochemical staining and H scores were calculated to standardize staining intensity. Statistical analysis was performed using SPSS 16.0. Results NEDD4L expression levels according to H scores were significantly lower in patients diagnosed with endometrial cancer compared with those with benign endometrial pathologies. Conclusion NEDD4L is involved in maintaining cell stability, and reduced NEDD4L expression as a result of gene mutation may disrupt this balance in favor of tumorigenesis.Öğe Serum Syndechan-1 Levels in Patients with Nonsmall Cell Lung Cancer(Elsevıer scıence ınc, 360 park ave south, new york, ny 10010-1710 usa, 2018) Tek, I.; Yetkin, O.; Yetkin, G.; Iraz, M.Öğe Robust diagnosis of ewing sarcoma by immunohistochemical detection of super-enhancer-drivenewsr1-ets targets(Impact journals llc, 6666 e quaker st, ste 1, orchard park, ny 14127 usa, 2018) Akpolat, Nusret; Akatli, Ayse N.Ewing sarcoma is an undifferentiated small-round-cell sarcoma. Although molecular detection of pathognomonic EWSR1-ETS fusions such as EWSR1-FLI1 enables definitive diagnosis, substantial confusion can arise if molecular diagnostics are unavailable. Diagnosis based on the conventional immunohistochemical marker CD99 is unreliable due to its abundant expression in morphological mimics. To identify novel diagnostic immunohistochemical markers for Ewing sarcoma, we performed comparative expression analyses in 768 tumors representing 21 entities including Ewing-like sarcomas, which confirmed that CIC-DUX4-, BCOR-CCNB3-, EWSR1-NFATc2-, and EWSR1-ETS-translocated sarcomas are distinct entities, and revealed that ATP1A1, BCL11B, and GLG1 constitute specific markers for Ewing sarcoma. Their high expression was validated by immunohistochemistry and proved to depend on EWSR1-FLI1-binding to highly active proximal super-enhancers. Automated cut-off-finding and combination-testing in a tissue-microarray comprising 174 samples demonstrated that detection of high BCL11B and/or GLG1 expression is sufficient to reach 96% specificity for Ewing sarcoma. While 88% of tested Ewing-like sarcomas displayed strong CD99-immunoreactivity, none displayed combined strong BCL11B-and GLG1-immunoreactivity. Collectively, we show that ATP1A1, BCL11B, and GLG1 are EWSR1-FLI1 targets, of which BCL11B and GLG1 offer a fast, simple, and cost-efficient way to diagnose Ewing sarcoma by immunohistochemistry. These markers may significantly reduce the number of misdiagnosed patients, and thus improve patient care.Öğe Pertuzumab, trastuzumab and taxane combination for visceral organ metastatic patients: real lifepractice results(Oxford unıv press, great clarendon st, oxford ox2 6dp, england, 2018) Esin, E.; Oksuzoglu, O. B. Cakmak; Bilici, A.; Cicin, I.; Yumuk, PFÖğe Posterıor reversıble leukoencephalopathy syndrome developıng secondary tosunıtınıb therapy ın a patıent wıth metastatıc renal cell carcınoma(Carbone edıtore, vıa quıntıno sella, 68, palermo, 90139, ıtaly, 2018) Kaplan, Nihal Bozdag; Harputluoglu, Hakan; Dikilitas, Mustafa; Elkiran, Emin Tamer; Temelli, OztunPosterior reversible encephalopathy syndrome (PRES) is characterized by vasogenic edema occurring generally in parietal and occipital areas of the brain as a result of different etiologic causes and it is diagnosed by means of clinical and radiologic assessment. Sunitinib is an orally administered tyrosine kinase inhibitor used in the treatment of renal cell carcinoma with its antiangiogenic and antitumor effects. Fatigue, nausea-vomiting, diarrhea, hypertension, cardiotoxicity, hypothyroidism, neutropenia, and skin toxicity are among common side effects associated with sunitinib therapy. The current report presents a female patient with metastatic papillary renal cell cancer who developed posterior reversible encephalopathy syndrome as determined by means of clinical and radiologic assessment at 8 months of sunitinib therapy and who completely recovered with antihypertensive, antiepileptic, and antiedema therapy.Öğe Cancer of unknown primary presenting with a giant shoulder mass in a young man: prostateadenocarcinoma(Kare publ, concord ıstanbul, dumlupınar mah, cıhan sk no 15, b blok 162 kadıkoy, ıstanbul, 00000, turkey, 2018) Atilla, Fatos Dilan; Topaloglu, Omercan; Pala, Emel Ebru; Arslan, CagatayCancer of unknown primary (CUP) is a metastatic tumor for which a standardized diagnostic workup fails to identify the site of origin at the time of making the diagnosis. The most frequent primary origin site is the lung and pancreas (40%), and the second most frequent primary origin site is the gastrointestinal system. For male patients with CUP, serum prostate specific antigen (PSA) level and free PSA/total PSA ratio should be determined; if necessary, immunohistochemical staining for PSA and P504S should be performed from the metastatic mass. Young patients with CUP should be attentively evaluated to establish the diagnosis and start treatment. We report the case of a young man who presented with a giant shoulder mass of unknown primary site and was diagnosed as having prostate adenocarcinoma.Öğe Cytotoxic effects of cucurbitacin ı and ecballium elaterium on breast cancer cells(Natural product communıcatıons, 2018) Yılmaz, Kadir; Karakuş, Fuat; Eyol, Ergül; Tosun, Emir; Yılmaz, İsmet; Unuvar, SongülThe objective of this study was to investigate the inhibitory effect of cucurbitacin I (CuI) and Ecballium elaterium L. (fruit juice and chloroform extract) on breast cancer cells (MCF-7 and MDA-MB-231). The Cul content of E. elaterium fruit juice and chloroform extract was quantified using high performance liquid chromatography. The cytotoxic effects of the fruit juice, chloroform extract and CuI were determined by MTT, wound healing and colony formation assays; all had an anti-proliferative activity on the breast cancer cells. Clarifying the mechanisms of cucurbitacins will enable the identification of new molecular targets for breast cancer therapy.
