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© 2020 IEEE.This study reports a novel cell classification method based on the observation of trajectories that cells inside a fluidic chamber follow under an externally applied acoustic field. Proposed method is significant both as a cell classification method and as a method for characterising the motion of various cell lines under different surface acoustic wave patterns. The difference is mainly due to the characteristic differences of cells such as mass, surface adhesiveness and cellular volume. We discuss the mechanisms that affect the interaction between cells and surface waves. Classification performance is tested using using support vector machine (SVM), max-likelihood and multilayer perceptron (MLP) methods and accuracy, sensitivity and specificity values are reported for each. The results indicate that the method can be used as a powerful classifier particularly for cells that are hard to distinguish visually. It is observed that for a given frequency, the motion characteristics of different cell lines differ due to the difference between dominant adhesion mechanism for that particular cell line. This observation can be utilized for the development of a frequency based cell manipulation method that is able to target specific cells using their characteristic frequencies. We discuss the potential of the proposed acoustic stimulation method as a cell manipulation technique particularly for uncoupling the motion of different cell lines.

© 2020 IEEE.In this study we present a novel untethered micro tool that is able to accomplish minimally invasive micro manipulation tasks in 2D and 3D cell cultures. We demonstrate the proposed system for targeted drug delivery, cell translation and mechanical cell stimulation applications. Due to the ability of the proposed system to control the motion of the micro tool in 6 DOF and obtain depth information through holographic visual feedback, we show that the microtool can be manipulated in a way such that the sample cell culture will go negligible mechanical stress. We show that the proposed system can be used for a variety of micro manipulation tasks without effecting the sample in question.

Colorectal cancer is the third most common cancer worldwide with a high mortality rate at the advanced stages. However, colorectal cancer is not a single type of tumor; its pathogenesis depends on the anatomical location of the tumor and differs between right side and left side of the colon. Tumors in the proximal colon (right side) and distal colon (left side) exhibit different molecular characteristics and histology. In the right-sided tumors, mutations in the DNA mismatch repair pathway are commonly observed; and these tumors generally have a flat histology. In the left-sided tumors, chromosomal instability pathway-related mutations, such as KRAS, APC, PIK3CA, p53 mutations are observed and these tumors demonstrate polypoid-like morphology. Therapy responses are totally different between these tumor entities. Left-sided colorectal cancer (LCRC) patients benefit more from adjuvant chemotherapies such as 5-fluorouracil (5-FU)-based regimes, and targeted therapies such as anti- epidermal growth factor receptor (EGFR) therapy, and have a better prognosis. Right-sided colorectal cancer (RCRC) patients do not respond well to conventional chemotherapies, but demonstrate more promising results with immunotherapies because these tumors have high antigenic load. For the development of effective therapy regimes and better treatment options, it is essential to evaluate right-sided and left-sided tumors as separate entities, and design the therapy regime considering the differences between these tumors.

Objective: To evaluate the antitumor effect of cetuximab as a single agent for the treatment of oral cavity cancers and to clarify the dose-dependent growth inhibitory effect in oral cavity squamous cell carcinoma cell line (OCSCCCL).

Introduction: About 80% of lung cancer cases are classified as “Non-Small Cell Lung Cancer (NSCLC)”. Case spesific, targeted therapies (precision medicine) are developed for advanced NSCLC. The main targets are the mutations of EGFR gene which are found in 10-30% of cases. Tyrosine kinase inhibitors (erlotinib, gefitinib, afatinib, osimertinib) are offered if the tumor has the mutations. At the 9-13th months of targeted tyrosine kinase therapy, drug resistance related EGFR T790M mutation may occur. Aim: Our goal is to identify the effect of liquid biopsy in the management of NSCLC and share the results of our genetic diagnosis center. Methods: We have examined 42 mutations of EGFR gene, in 114 NSCLC cases that referred to our center in 2017-2018. Plasma derived cell-free DNA (cfDNA) samples are used to identify 42 mutations of EGFR gene including exon 19 (Ex19del), exon 20 (T790M), exon 21 (L858R) variants by “Real-Time Quantitative PCR” (RT-PCR) method. Results: The EGFR mutations are found in 23 liquid biopsy cases (20%). Eleven of the cases (9.6%) have single sensitivity related mutation: Five cases have Ex19del, 4 cases have L858R, 2 cases have Ex20ins. In addition, one case has “Ex19del and G719X” together. The remaining 11 (9.6%) have the drug resistance related T790M mutation in addition to a sensitivity mutation: Six cases have “Ex19del ve T790M”, 4 cases have “L858R ve T790M”, 1 case has “L858R, S768I ve T790M”. The 11 cases with normal liquid biopsy result actually have a EGFR mutation in solid tissue biopsy. Conclusion: The liquid biopsy is successfully took its place in the identification of EGFR mutations of advanced NSCLC cases.

Background: KRAS mutations have a significant role in the consecutive activation of RAS.RAF.MEK.ERK pathway in colorectal cancer.Approximately 30.35% of sporadic colorectal cancers have KRAS mutation. While the predictive role of KRAS is commonly accepted at the present time, its prognostic role and association with different clinical and histopathological properties are currently unclear and inconsistent. The intent of this study, has been to evaluate the associations between KRAS gene mutations and clinicopathological features and survival times in Turkish colorectal cancer patients. Materials and Methods: In this study, the file records of 115 metastatic colorectal cancer patients who applied to the Department of Medical Oncology between 2000 and 2011 were monitored; data on clinicopathological features and survival times were collected. DNA.sequencing method with PCR amplification from archival paraffin blocks were used for KRAS mutation status analysis. The associations between KRAS mutation status and clinicopathological features and survival times were compared statistically. Results: While a significant association hadbeen determined between KRAS mutation status and tumor localization, there was no determined significant association with other clinicopathological properties. Similarly, there was no association between KRAS mutation status and survival parameters. Conclusions: As a result, the effect of KRAS mutation status on clinicopathological features, survival time and prognosis is unclear.

Copyright © 2013 Wolters Kluwer Health, Inc. All rights reserved.5-Fluorouracil (5-FU), the mainstay of solid tumor chemotherapy over the past 40 years, induces grade III-IV toxicities in up to 15% of patients with polymorphisms in the dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), and methylenetetrahydrofolate reductase (MTHFR) genes. These toxicities include mucositis, neutropenia, nausea, diarrhea, myelosuppression, hand-foot syndrome, and rare ocular adverse effects. Here, we present the case of a female patient with rectal cancer who received 5-FU-based chemotherapy and developed grade III hand-foot syndrome and rare acute ocular adverse effects. Genetic analysis revealed that the patient had an 85T>C mutation in the DPYD gene resulting in a DPYD9A allele. The clinical and molecular observations indicate that DPYD deficiency may be responsible for the severe ocular adverse effects observed in 5-FU-treated patients. Application of personalized therapy based on molecular testing should help clinicians provide the most effective chemotherapy agents and dose modifications for each patient, although further population-based pharmacogenetic trials for the 5-FU metabolism-related genes are necessary to minimize adverse effects and enhance clinical outcomes.

WOS: 000437989600007 Background: Early detection of breast cancer is a key to the success of breast cancer management. Serum proteome analysis using Surface-Enhanced Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (SELDI-TOF-MS) generates useful information that can be utilized to describe exclusive prognostic and diagnostic biomarkers. Objective: This study aimed to use proteomics and bioinformatics to identify new biomarkers during the metastatic process of breast cancers that were classified as invasive lobular cancer or invasive ductal cancer. Method: Blood samples from 64 breast cancer patients [36 with invasive ductal cancer (14 of whom were lymph node positive); 28 with invasive lobular cancer (8 of whom were lymph node positive] were analyzed using IMAC 30 protein chips. The data acquired from the spectra were processed with univariate statistical analysis (Protein Chip Data Manager Software). Results: One-hundred-eighteen clusters were generated from the individual serum samples. Thirty-six proteins of the metastatic phenotype were found to be diagnostically accurate in cluster analysis. In the breast cancer group, a single candidate peak (m/z 1090.8) that was able to discriminate the metastatic progression was identified as a metastatic phenotype marker. Fifteen protein peaks were identified as markers to separate the histopathological subtypes as either invasive ductal cancer or invasive lobular cancer. Conclusion: In recent years, proteomic methods have rapidly become widespread in breast cancer research. This study revealed the pattern of a group of proteins that were not previously identified and are recommended as candidate markers to diagnose metastatic progression.

The journey of nucleic acid isolation and characterization has been a long one starting in the late 1800s. DNA isolation has led the way due to its stable chemical characteristic. Since its initial implementation the demand of molecular studies has evolved rapidly into studying a wide range of nucleic acids, including all types of RNAs, mitochondrial DNA, and nucleic acid materials of other organisms. The scientific advancements and the “omics” era certainly brought new challenges, forcing the technology to go into an enormous advancement in a relatively short period. In the early 1900s the range of methods, the material, and the field of applications were limited. During, nearly, the last three decades the procedures became automated, standardized, economic, user-friendly, nonhazardous, and less time-consuming. The manual organic or inorganic procedures had left their place to more robust and reliable solid-phase extraction techniques. There are a wide range of samples in which high-quality and high-yield nucleic acid isolation is carried out. These samples vary from whole blood to different types of tissues, hair, bones, saliva, urine, and many more. We are going to explore the principles of nucleic acid isolation, the basics of chemistry behind the scenery, manual and advanced techniques of isolation and quality check, and the means of good laboratory practice.

WOS: 000432828600007 Objective:The levels of serum amylase is an indicator of several diseases. Therefore, a routine amylase test is frequently requested in hospital emergency admissions. This research aims to evaluate the hospitalization and surgery rates of patients with high amylase levels. Methods: A retrospective clinical study was performed on 64,909 patients aged 53.30 +/- 19.45 years who had a serum amylase test at hospital admission in the emergency ward between 2011 and 2015. Age, gender, serum amylase levels, diagnosis, hospitalization, and surgery status of the patients were obtained from the electronic medical records. The diseases were classified into seven groups according to the International Statistical Classification of Diseases and Related Health Problems codes.The patients were divided into three groups with respect to amylase levels- group 1 (376 U/L).The results were statistically analyzed using the SPSS commercial tool package version 21.0.The x2 test and Fisher's exact probability test were adapted for categorical variables, while Student's t-test was performed for the unpaired data of continuous variables. Results:The hospitalization rate increased 2.4-fold and 4.7-fold and the surgery rate increased 1.6-fold and 1.4-fold in group 2 and group 3 compared to group 1, respectively. The hospitalization rate of the patients (N=571) in group 3 was 59.4%. Among them, only 93 patients were diagnosed with acute pancreatitis. Conclusion: Elevated serum amylase levels can predict hospitalization and surgery status. Amaç: Serum amilaz düzeyi birçok hastalığın göstergesidir. Bu yüzden, rutin amilaz testi hastaneye acil başvurularda sıklıkla istenmektedir. Bu araştırmanın amacı, yüksek amilaz düzeyine sahip hastalarda hastaneye yatış durumu ve cerrahi riskleri değerlendirmektir. Yöntemler: Acil serviste serum amilaz testi yapılmış, 53,30±19,45 yaşında 64909 hasta ile retrospektif klinik çalışma yapıldı. Yaş, cinsiyet, serum amilaz miktarı düzeyi, tanı, hastaların hastaneye yatış ve operasyonel durumlarına ait bilgiler tıbbi kayıtlar (Probel, Hastane İşletim Sistemi) kullanılarak elde edildi. Hastalıklar, ICD 10 kodlarına göre yedi grupta sınıflandırıldı. Serum amilaz düzeyleri amilaz konsantrasyonlarına göre üç gruba ayrıldı; Grup 1 (< 125 U/L), Grup 2 (125-375 U/L) and Grup 3 (> 376 U/L). Sonuçlar istatistiksel olarak SPSS ticari paket programı (versiyon 21,0) kullanılarak analiz edildi. Kategorik değişkenler için χ2 ve Fisher kesin olasılık testi; sürekli değişkenlerin eşleştirilmemiş verileri için ise Student t testi kullanıldı. Bulgular: Hastaneye yatış ve ameliyat oranlarının Grup 2 ve Grup 3’te Grup 1’e göre sırasıyla 2,4 ve 4,7 ve 1,6 ve 1,4 arttığı saptandı. Amilaz değeri 376 U/L üzerinde olan hastaların (N=571) hastaneye yatış oranları %59,4 idi. Bu hastalardan yalnızca 93’ünde akut pankreas iltihabı vardı. Sonuç: Yüksek serum amilaz düzeyi hastaneye yatış ve ameliyatı öngörmede kullanılan parametrelerden biri olabilir.

Cancer is a combination of a variety of diseases that includes uncontrolled abnormal cells, which can grow in any part of the body, and have an ability to invade and metastasize other vital organs. Currently, the main techniques for the treatment of cancer are surgery, chemotherapy, and radiotherapy. In addition, hyperthermia induced by thermotherapy, photodynamic therapy and immunotherapy have a high potential for the treatment of various cancers. Although all of the these techniques are widely used for the management of cancer, they have several drawbacks, such as treatment-related morbidity, chemo- and radiotherapy resistance, and jeopardizing healthy cells. Therefore, the quest for optimizing cancer treatment is still ongoing in order to develop a new technique that may provide high success in tumor control without undesired side effects. Recent developments demonstrated that nanotechnology may offer new and effective approaches to fight cancer. To date, numerous studies have been reported on the utilization of different nanosized metal, metal oxides, and carbon based nanoparticles for the treatment and imaging of cancer. Recently explored two-dimensional carbon allotrope, graphene, has been shown as a good candidate for drug delivery platforms and hyperthermia, due to its unique physicochemical characteristics including easy functionalization and good biocompatibility, large surface-to-volume ratio, strong light-absorbing properties, and relatively simple preparation. Consequently, the purpose of this chapter is to present an overview about the graphene-based nanoparticles used in biomedical applications with a major focus on their synthesis, characterization, and use in the treatment and imaging of different types of cancer.

WOS: 000430743600009 PubMed ID: 29456844 Breast cancer (BC) is the most frequently diagnosed cancer that affects women worldwide. Early detection of BC is important to improve survival rates and decrease mortality. The aim of the present study was to investigate serum biomarkers using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to distinguish patients with BC from the healthy population and patients with benign breast diseases (BBDs). A total of 62 patients with invasive ductal carcinoma, as confirmed by histopathology, and 47 non-cancerous individuals (NCIs) [16 healthy controls (HCs) and 31 patients with BBD] were enrolled in the present study. Serum protein profiles were determined by SELDI-TOF-MS using an immobilized metal affinity capture array. Serum from patients with BC were compared with that from the HC group using univariate and multivariate statistical analyses. A total of 118 clusters were generated from the individual serum. Univariate analysis revealed that 5 peaks were significantly downregulated (m/z 1,452, 2,670, 3,972, 5,354 and 5,523; P

Objectives: The c-kit proto-oncogene (KIT) exon 9, 11, 13 and 17 activation mutations are associated with clinical behaviour in gastrointestinal stromal tumors with highly variable biological behaviour. The purpose of this study is to determine the frequency of KIT gene exon 9, 11, 13 and 17 mutations and associate them with histopathologic features for the first time in the Turkish population. Materials and Methods: DNAs were isolated from formalin fixed paraffin embedded tumour tissues of sixty patients diagnosed with gastrointestinal stromal tumor between 2006 and 2010, by spin column method. Isolated DNAs were sequenced by DNA sequencing system based on capillary electrophoresis for the presence of mutations in KIT gene exons 9, 11, 13 and 17. Results: KIT mutations frequencies determined for exon 9, 11, 13 and 17 were 8.3%, 47.5%, 11.7% and 1.7%, respectively. Correlation analysis revealed the presence of overall mutations and exon 11 mutations of males to be higher than those of females (p=0.004 and p=0.003). Small intestine tumor mutation frequency was higher than gastric tumors (p=0.05). Conclusion: This study represents the first mutational results from Turkish gastrointestinal stromal tumor patients. Our cases showed different mutational trends when compared to other reports, indicating the significance of personalized medicine, which could be intensified by the use of genotyping tools in cancer management. Redefining the molecular features associated with tumor behaviour is important for management of diagnostic and therapeutic processes in gastrointestinal stromal tumors.

Cancer microenvironment is a remarkably heterogeneous composition of cellular and non-cellular components, regulated by both external and intrinsic physical and chemical stimuli. Physical alterations driven by increased proliferation of neoplastic cells and angiogenesis in the cancer microenvironment result in the exposure of the cancer cells to elevated levels of flow-based shear stress. We developed a dynamic microfluidic cell culture platform utilizing eshopagael cancer cells as model cells to investigate the phenotypic changes of cancer cells upon exposure to fluid shear stress. We report the epithelial to hybrid epithelial/mesenchymal transition as a result of decreasing E-Cadherin and increasing N-Cadherin and vimentin expressions, higher clonogenicity and ALDH positive expression of cancer cells cultured in a dynamic microfluidic chip under laminar flow compared to the static culture condition. We also sought regulation of chemotherapeutics in cancer microenvironment towards phenotypic control of cancer cells. Such in vitro microfluidic system could potentially be used to monitor how the interstitial fluid dynamics affect cancer microenvironment and plasticity on a simple, highly controllable and inexpensive bioengineered platform.

Most of the gastrointestinal stromal tumors (GISTs) have gain-of-function mutations in the KIT gene, which can be used as a prognostic marker for the biological behavior of tumors, predictive marker for the response of tyrosine kinase inhibitors, and diagnostic marker. Researchers have focused on PDGFRA mutations because of both their prognostic and predictive potential and DOG1 positivity for diagnosis on GISTs. The aim of this study is to investigate the effect DOG1, PDGFRA, and KIT mutations on the prediction of the outcome for GIST management. Polymerase chain reaction was performed for KIT gene exons 9, 11, 13, and 17 and PDGFRA gene exons 12 and 18 with the genomic DNA of 46 GIST patients, and amplicons were sequenced in both directions. Immunocytochemical stainings were done by using primary antibodies. Molecular analysis revealed that the KIT mutation was observed in 63% of all cases, while the PDGFRA mutation was observed in 23.9% of cases. Significant relationships were found between age and KIT mutation, tumor location and KIT mutations, and tumor location and PDGFRA mutations (p ≤ 0.05). DOG1 positivity was detected in 65.2% of all GISTs and DOG1-positive cells had a higher KIT mutation ratio than DOG1-negative cells (p ≤ 0.05). KIT gene exon 11 mutations in DOG1-positive cells was higher than DOG1-negative cells (p ≤ 0.05). Conversely, KIT gene exon 13 mutations were higher in DOG1-negative cells than DOG1-positive cells (p ≤ 0.05). In this study, KIT mutation frequency was found similar with the European population; conversely, PDGFRA mutation frequency was similar with an Asian-Chinese-based study. KIT/PDGFRA mutations and tumor location can be used for the prediction of tumor behavior and the management of disease in GISTs. DOG1 positivity might be a candidate marker to support KIT and PDGFRA mutations, due to the higher DOG1 positivity in KIT exon 11 mutant and stomach- and small intestine-localized GISTs.

The antitumor agent actinomycin D has been used in the treatment of Wilms tumor for the past 40 years. Actinomycin D-induced hepatopathy-thrombocytopenia syndrome (HTS) is characterized as a rare syndrome. The mechanism underlying HTS may differ with individual multidrug resistance protein-1 (MDR1) genotype. The relationship between actinomycin D-related HTS and MDR1 gene mutations is presented in this case study of a pediatric patient with Wilms tumor. Our findings revealed that the girl had (-)1G>A, 1236C>T, 2677G>T, 3435C>T, and 61A>G MDR1 gene mutations. Understanding the function of genetic variants of MDR1 is an important aim for personalized cancer management.

Introduction Glioblastoma is the one of the most common primary malignant tumour of brain. Due to anatomical and physiological characteristics of brain, drug delivery to the tumour site is hampered. In glioblastoma, survival time is short and recurrence is generally inevitable. The metastatic dissemination of glioblastoma is relatively rare but it could be more aggressive. Therefore, in vitro and in silico studies are accelerated in terms of the investigation of molecular characteristics of metastatic glioblastoma. The aim of this study, to investigate the expressed biomarkers of immigrant glioblastoma cells and potential therapeutic targets by using in silico methods. Material and methods GEO (Gene Expression Omnibus) of the National Cancer Institute (NCI) provides is an international public repository of research society, which archives and freely distributes microarrays, next generation sequencing and other forms of high-resolution functional genomic data. Data set enumerated as GSE76018, is used for this research from GEO data portal. The data was analysed by using R software for statistical calculations and graphs. The level of the gene expression, and the resulting data were standardised by calculating a z-score, the fold changes (log2FC). As a threshold, | log2FC|≥2 and adjusted p-value was accepted as ≤0.05. Heat maps were drawn using a hierarchical clustering method in R-Bioconductor’s Heatplus library. Functional annotation tools and to understand biological meaning behind large list of genes analysed by using DAVID bioinformatics resources. Results and discussions JAK-STAT pathway is found by using DAVID bioinformatics database. IFNA8, IL9, SOCS1, JAK3, CSH1, IFNL2 and IL12RB2 genes have played an active role in charge of protein coding Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 pathway. So these genes affect the migration of glioblastomas and biomarkers is except to be effective at drug target. Sifalimumab and Rontalizumab connected to IFNA8, IL9 related to Enokizumab, also JAK3 linked to Tofacitinib. Conclusion As a result of our investigation, JAK-STAT pathway, which is known to be an important mediator of tumour cell survival, growth and invasion in glioblastomas was, identified the migratory phenotype indicator. In this pathway, seven genes as therapeutic targets and related drugs potentially identified. Further in vitro and in vivo validation studies should be done for the confirmation for the provided biomarkers and therapeutic targets.

Dokuz Eylul University Continuing Education Center has become a place, focusing on current and universal information transfer, bringing together the university students and also who live in Izmir and residential areas. Personal development is the lifelong process of understanding self-individual, developing and assessing the skills and qualities, considering their aims in life in order to achieve maximum potential. The course modules have been designed to provide in-depth training in the supporting of the academic progress, personal development, and long life learning on arts, literature and history. Personal development should be an important part of Lifelong Learning with multilayer training support.

Caulerpa racemosa (Forsskal) is a green marine alga which spreads from tropical to warm-water regions. Due to having invasive capacity C racemosa var. cylindracea is a well-known biological pollution in Mediterranean Sea. One of the most important secondary metabolites of C. racemosa is Caulerpenyne (CPN). In the present study, antiproliferative and apoptotic effects of C. racemosa var. cylindracea extract and purified CPN on two well-known neuroblastoma cell lines, SHSY5Y and Kelly, are investigated. The antiproliferative and, additionally, newly attributed apoptotic effects of both C. racemosa var. cylindracea extract and purified CPN on SHSY5Y and Kelly cell lines have been shown in the present study. IC50 values are 0.59 +/- 0.06; 1.06 0.23 g wet alga/methanol and 5.64 +/- 0.09; 6.02 +/- 0.09 mu M CPN for C. racemosa var. cylindracea extract and purified CPN on SHSY5Y and Kelly cell lines, respectively. Percentages of apoptotic cells of SHSY5Y and Kelly in 0, 0.1 and 1 mu M CPN conditions were 1.00 +/- 0.71, 3.00 +/- 0.71 and 49.40 +/- 3.78, 39.60 +/- 6.19 and 78.00 +/- 2.74, 69.40 +/- 3.78, respectively. In conclusion, the present study shows the antiproliferative effect of C. racemosa var. cylindracea extract and newly attributed apoptotic effects of C. racemosa var. cylindracea this extract. Compared to other alkylating anticancer drugs, CPN and also C. racemosa var. cylindracea extract might be considered as an alternative native source of antitumor drugs. Inasmuch as both C. racemosa extract and CPN have shown both antiproliferative and apoptotic effects on SHSY5Y and Kelly cell lines, the CPN and CPN derivatives might be considered as multifunctional agents in cell metabolism. (c) 2006 Elsevier B.V. All rights reserved.

Ozkul, Aykut/0000-0001-5008-9443; BASKIN, A. Huseyin/0000-0003-3237-267X WOS: 000223407400006 PubMed: 15379444 Bovine herpesvirus 1 (BHV-1) is the aetiological agent of many disease types and may predispose infected animals, possibly through immunosuppression, to secondary bacterial infections. Immunosuppression may directly be associated with the induction of programmed cell death (PCD) in some virus-infected cells. Nitric oxide (NO) has an important mediating role against fungal, bacterial, protozoal, viral pathogens and tumours. BHV-1 induced apoptosis between 0.5-3 h postinfection (PI) in MDBK cells; however, between 3 and 6 h PI the PCD response was found to be decreased. It was interesting to see that BHV-1 inhibited staurosporin-induced PCD after 1 h. These results showed similarities with those obtained from herpes simplex type 1 infections in human epithelial cells. PCD response decreased 1 h following caspase-3 inhibitor applications, whereas NO response increased 3 h following infection in the presence of caspase-8 and -9 inhibitory peptides. In conclusion, BHV-1 inhibited the staurosporin-induced apoptotic response and also the NO response. We propose that this inhibition is caspase-3 dependent.

It is known that in the presence of oxygen radicals, anti-atherogenic nitric oxide is converted into pro-atherogenic products, which increase lipid peroxidation. In this study, plaque-free atherosclerotic tissues (n=26), atherosclerotic plaques (n=26) and fetal tissues (n=2; as control) were evaluated. High nitrite, but low malondialdehyde, levels in non-atherosclerotic tissues may show the protective role of nitric oxide from atherosclerosis. In plaque-developed tissues nitrite levels were three times, and lipid peroxidation levels were 10 times, higher than non-plaque developed tissues. In the atherosclerotic plaque forming process, the role of nitric oxide can be discovered according to the lipid peroxidation of tissues. In conclusion, the results of this study show an inversely proportional relation between pro-and anti-atherogenic effects of nitric oxide in the pathogenesis of atherosclerotic vascular diseases. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Data regarding the prognostic importance of BRAFV600 tumor mutations in high-risk, non-metastatic, stage 2 and 3 malignant melanoma (MM) patients are controversial. There is not sufficient information in the medical literature regarding the reliability of BRAF mutations as a predictive factor in prognosis and adjuvant treatment decision issues in this patient group. The data of 50 operated high-risk, non-metastatic, stage 2B/2C and 3 MM patients who received high-dose interferon alfa-2b therapy were evaluated retrospectively. BRAF mutations were analyzed by using microarray-based molecular methods. The associations between BRAF mutations and both clinicopathological characteristics and survival were assessed. Of the 50 patients, 52 % was female and 48 % was male, and the median age was 51.5 years. Twenty-three (46 %) and 27 (54 %) patients had stage 2B/2C and stage 3 disease, respectively. BRAF mutation was detected in 21 patients. The median overall survival (OS) was 58.1 months, whereas the median disease-free survival (DFS) was 22.7 months. When the OS and DFS were compared according to the BRAF mutation status, no difference was detected between the two groups. BRAF mutations were detected more frequently in tumors with mitosis and ulceration; however, no statistically significant difference was observed in other clinicopathological parameters. In conclusion, it is not appropriate to use BRAF mutations as a prognostic and predictive marker for selecting the treatment and assessing its outcomes in patients with early stage, high-risk MM.

Colorectal cancer has a heterogeneous nature that is influenced by the tumour site. Many improvements have been made in identifying and characterizing the genetic alterations between colon and rectal cancers. However, there is not enough information about KRAS mutational differences between rectosigmoid and colon cancers arising elsewhere in the large bowel. The aim of this study was to determine the differences in the frequency of KRAS genetic alterations between rectosigmoid cancers and colon cancers.Eighty-four patients diagnosed with colorectal cancer were included in this study. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumour tissue sections. KRAS mutation analysis which was designed to detect the seven most common KRAS gene mutations (Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13Asp) was performed. Chi-square test was used to test the association between mutation status and other variables.This study represents the first KRAS mutational results from Turkish rectosigmoid cancer patients. The KRAS mutation frequency of rectosigmoid tumours is higher (34.3%, 12/35) than that of colon-localized tumours (30.6%, 15/49). However, there is no significant correlation between the KRAS mutation status and tumour location (rectosigmoid and colon).KRAS mutation analysis has a predictive and prognostic value in identifying tumours that may be resistant to treatment. Our study shows that differences in the biological behaviour of rectosigmoid and colon cancers should be considered. This finding highlights the importance of personalized cancer management, which could be assisted by cancer genotyping tools.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. KIT gene mutations have great importance for GISTs. This study evaluated the relationship between KIT mutations and GIST clinicopathologic features to define region-specific and population-specific differences. Genomic DNA was extracted from 60 GISTs, and polymerase chain reaction was performed for KIT gene exons 9, 11, 13, and 17. Polymerase chain reaction amplicons were sequenced in both directions. This study represents the first mutation data of the KIT gene in GISTs from a Turkish population and reports novel mutations. The mutation rate in exon 11 (46.7%) was remarkably higher than those of the other exons (8.3% for exon 9; 11.7% for exon 13; 1.7% for exon 17). There was an association between malignancy potential and the presence of KIT mutations (odds ratio=3.18). Cases with mutations in codons W557-K558 in exon 11 had 11-fold greater risk of malignancy when compared with those without a mutation in this exon (odds ratio=11). We report different mutations than those previously reported, which emphasizes the importance of personalized medicine that could be empowered by the use of bioinformatics tools in the diagnostic process and therapeutic approaches.

Background: To investigate epidermal growth factor receptor (EGFR) gene mutations in patients with non-small cell lung cancer (NSCLC) and to analyze any relationship with clinicopathological features and prognosis. Materials and Methods: EGFR gene exons 18-21 in 48 specimens of paraffin-embedded tumor tissue from NSCLC patients were amplified by PCR, followed by direct sequencing and analysis of links to clinicopathological features and prognosis. Results: EGFR mutations were detected in 18 of 48 (42.6%) patients with NSCLC. There were 9 cases of mutations in exon 20, 7 in exon 19 and 2 in exon 21. Mutations were more frequently observed in women (5/7 pts, 71.4%) than in men (13/41 pts, 31.7%) (p=0.086) and in non-smokers (5/5 pts, 100%) than smokers (13/43 pts, 30.2%). There was negative correlation of EGFR mutations with smoking status (p=0.005). EGFR mutations were more frequently observed with adenocarcinoma histology (13/32 pts, 40.6%) than in other types (5/16 pts, 31.3%) (p=0.527). The patients with EGFR mutations had better survival than those with wild-type EGFR (p=0.08). There was no association of EGFR mutations with metastatic spread. Conclusions: EGFR mutations in NSCLC were here demonstrated more frequently in females, non-smokers and adenocarcinoma histology in the western region of Turkey. Patients with EGFR mutations have a better prognosis.

Dokuz Eylul University, Graduate School of Natural and Applied Sciences, Department of Chemistry, Izmir, Turkey Dokuz Eylul University, Institute of Health Sciences, Department of Basic Oncology, Izmir, Turkey Dokuz Eylul University, Faculty of Science, Department of Chemistry, Division of Biochemistry, Izmir, Turkey Dokuz Eylul University, Institute of Oncology, Department of Basic Oncology, Izmir, Turkey Dokuz Eylul University, Faculty of Medicine, Department of Biostatistics and Medical Informatics, Izmir, Turkey Dokuz Eylul University, Faculty of Medicine, Department of Medical Oncology, Izmir, Turkey

ABS TRACT Ob jec ti ve: Oxi da ti ve stress has be en imp li ca ted in the pat ho ge ne sis of ma le in fer ti lity. In this study, we ai med to me a su re the an ti o xi dant ca pa city in se mi nal plas ma in fer ti le and in fer ti le men using a re cently de ve lo ped au to ma ted me a su re ment met hod. Ma te ri al and Met hods: The study gro up inc lu ded samp les of 55 ma les from in fer ti le co up les, and 16 he althy vo lun te ers ser ved as the con trol gro up. All samp les had nor mal sperm pa ra me ters. Se mi nal to tal an ti o xi dant res pon se (TAR) and to tal oxi dant sta tus (TOS) we re de ter mi ned using co lo ri met ric met hods. Ox i da ti ve stress in dex (OSI) was cal cu la ted as [(TOS/TAR) ×100]. Fre e sulphydryl (SH) gro ups of se men samp les we re me a su red spec trop ho to met ri cally. Re sults: Se mi nal TAR was sig ni fi cantly lo wer and se mi nal TOS, OSI and SH ac ti vi ti es we re sig ni fi cantly hig her in in fer ti le gro up as com pa red with fer ti le do nors. The re we re po si ti ve cor re la ti ons bet we en TAR and sperm pa ra me ters such as +4 mo ti lity (r= 0.386, p< 0.01), and morp ho logy (r= 0.383, p< 0.01), whe re as sperm con cen tra ti ons (r= -0.333, p< 0.01) cor re la ted ne ga ti vely with TAR. In ad di ti on, TOS and OSI were, negatively cor related with sperm pa ra me ters such as mo ti lity, +4 mo ti lity and morp ho logy (p< 0.01, for all). Conc lu si on: In cre a sed oxi dant sta tus and dec re a sed an ti o xi dant res pon se and the cor re la ti on bet we en the se pa ra me ters and sperm func ti ons imp li ca ted that oxi da ti ve stress might play an im por tant ro le in ma le in fer ti lity. We fo und dec re a sed to tal an ti o xi dant res pon se in in fer ti le pa ti ents using a simp le, ra pid and re li ab le au to ma ted co lo ri met ric as say, which may su i tab le for use in any ro u ti ne an dro logy la bo ra tory.

Background: Surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF) is an approach to biomarker discovery that combines chromatography and mass spectrometry. We aimed to consider the efficacy of Bc1, Bc2, and Bc3 serum biomarkers on early detection of breast cancer (BC) in this study. Study Design: In this prospective study, 91 patients who were admitted to our hospital between January 2007 and July 2008 were included. Serum samples from 91 women were stored at -80 °C until use. The cancer group included 27 cases of BC. The benign breast disease group included 24 women with benign breast diseases and control group 37 age-matched apparently healthy women. The data obtained for these three groups of patients was worked out for each serum biomarker (Bc1, Bc2, and Bc3) by using SELDI-TOF individually and compared with each other separately and evaluated statistically. Results: Bc2 possesses the highest individual diagnostic power. Bc2 was statistically significant in comparison between the malignant disease group, control group and benign disease group. Bc1 was statistically significant in the malignant disease group compared to control group as well as in the benign disease group compared to control group. Thus Bc1, rather than showing malignant progression, it shows tumoral progression or inflammatory process. Bc3 was found upregulated in all malignant cases; however, it was not statistically significant compared to the benign disease group or the control group. Conclusions: It has been shown that Bc2 profiles might be useful in clinical practice to improve BC diagnosis. However none of the proteomics reach reasonable AUC values for the discrimination of the BC. Additional confirmation in larger and similarly-designed prospective studies is needed to consider of the efficacy of Bc1 and Bc2 in early diagnosis of the BC.

Despite the lifetimes that increased in breast cancers due to the the early screening programs and new therapeutic strategies, many cases still are being lost due to the metastatic relapses. For this reason, new approaches such as the proteomic techniques have currently become the prime objectives of breast cancer researches. Various omic-based techniques have been applied with increasing success to the molecular characterisation of breast tumours, which have resulted in a more detailed classification scheme and have produced clinical diagnostic tests that have been applied to both the prognosis and the prediction of outcome to the treatment. Implementation of the proteomics-based techniques is also seen as crucial if we are to develop a systems biology approach in the discovery of biomarkers of the early diagnosis, prognosis and prediction of the outcome of the breast cancer therapies. In this review, we discuss the studies that have been conducted thus far, for the discovery of diagnostic, prognostic and predictive biomarkers, and evaluate the potential of the discriminating proteins identified in this research for clinical use as breast cancer biomarkers.

Objective: Male factor infertility accounts for 30% to 50% of the total infertile couples seeking for infertility treatment. In about 40-60% of these men, a specific etiology can not be found. The aim of this study was to confirm the presence of eotaxin and interleukin-4 (IL-4) in human seminal plasma, to show the differences between eotaxin and IL-4 concentrations in fertile and infertile men, and to show the potential relationship between eotaxin and IL-4 levels in semen and spermiogram parameters. In literature, this is the first study that evaluates eotaxin in the human seminal plasma. Material and Methods: The participant of the study was 55 infertile males with abnormal semen parameters as study group and 16 healthy volunteers with normal sperm parameters as the control group. Semen samples were classified according to criteria of the World Health Organization Laboratory Manual. The Morphology of the smears was scored using Kruger's strict criteria. Seminal eotaxin and IL-4 levels were measured by bead based immunoassay multiplex methods. Results: Seminal eotaxin levels were significantly higher in infertilite group compared to fertile donors. There were negative correlations between eotaxin concentrations and parameters such as motility (r= -0.293, p< 0.01) and, +4 motility (r= -0.307, p< 0.01) in the study group. IL-4 levels were similar in fertile and infertile seminal plasma. There were positive correlations between eotaxin and IL-4 levels (r= 0.436 p< 0.01). The receiver operating characteristic curve (ROC) analysis revealed a diagnostic value for eotaxin activity with respect to male factor infetility in case group, with an area under curve of 0.69 (95% confidence interval= 0.55-0.84). Conclusion: Increased levels of eotaxin may play a role in the pathogenesis of male infertility.

Ozkul, Aykut/0000-0001-5008-9443; BASKIN, A. Huseyin/0000-0003-3237-267X WOS: 000233681500008 PubMed: 16363149 Apoptosis seems to play an important role in the pathogenic profile of bovine herpesvirus 1 (BHV-1) infection. Nitric oxide (NO) is also important as a signal Molecule. In this study, apoptosis was selectively induced in HEp-2 cells in the early stage [1-3 h postinfection (PI)] of BHV-1 multiplication, and this apoptotic process was realised through the caspase-8, and partially through the caspase-3, pathway. BHV-1 infection inhibited staurosporine- (SS-) induced apoptosis only if the SS was added at 6 h PI. The results of this Study showed that the 'NO-apoptosis' relation was realised through the caspase-8 pathway ('outer membrane receptor' pathway) at a later stage of infection in apoptosis induced by BHV-1 + SS. Our previous report (Yazici et al., 2004) and this Study together showed that BHV-1 might induce and inhibit cell-type-specific pathways of apoptosis.

Herpes simplex virus type-1 (HSV-1) and type-2 (HSV-2) are among the most "successful" pathogens and code for a variety of proteins to direct the apoptosis/necrosis responses of the cells they infect. Nitric oxide (NO) is an important intracellular signaling molecule in pathological processes. Acyclovir (ACV) is a chain terminator that targets the viral DNA polymerase as an antiviral agent. In this study, NO signals, and apoptosis/necrosis responses of HEp-2 cells were compared when infected by HSV-1 and -2 for 24 hours against non toxic doses (starting from 48.8, 24.4, 12.2, 6.1, 3 to 1.5 microg/mL) of ACV. In 48.8, 24.4 and 12.2 microg/mL of ACV, HSV-1 had an "upregulating effect" whereas HSV-2 had a "downregulating effect" on NO production, and in 6.1, 3 and 1.5 microg/mL of ACV HSV-1 had a "down-regulating effect" whereas HSV-2 had an "upregulating effect" on NO responses (HSV-1 had a "downregulating effect" on NO production whereas HSV-2 had an "upregulating effect" on NO production without any ACV). In 48.8, 24.4 and 12.2 microg/mL of ACV, HSV-1 had an "anti-apoptotic effect" whereas HSV-2 had a stimulation on "apoptotic effect", and in 6.1, 3 and 1.5 microg/mL of ACV HSV-1 had an "apoptotic effect" and HSV-2 turned to "its natural viral apoptotic effect level" (HSV-1 had an "natural viral apoptotic effect" whereas HSV-2 had a "natural viral apoptotic effect" on apoptosis response without any ACV). In 48.8, and 24.4 microg/mL of ACV, HSV-1 had significant "necrotic effect" on necrotic cellular death, "necrosis" increased in 12.2, 6.1, 3 and 1.5 microg/mL of ACV (HSV-1 had a negligible "necrotic effect" on HEp-2 cells alone), and HSV-2 had a "natural viral necrotic effect" alone; and also in all non toxic ACV concentrations. These results showed that HSV-1 and -2 had different "strategies" on apoptosis/necrosis and NO with and without non toxic ACV. These differences deserve further studies in order to explain the interactions between apoptotic/anti apoptotic, necrotic genes and NO, and ACV in HSV-1 and HSV-2 infections respectively.

Objective: As a result of advances in computer and internet technology, access to information and knowledge source have become widely available. In the modern world, it is becoming more important rapid access to information. These rapid advances in technology, also led to changes in the behavior in the medical field that require rapid access to relevant, accurate and reliable knowledge. The aim of this study İnciraltı Yerleşkesinde biyoistatistik ve biyoinformatik program kullanım sıklığı ve farkındalığı was conducted to determine the purpose and frequency of the computer, biostatistical programs and bioinformatics at the Dokuz Eylül University Faculty of Medicine. Methods: Statistical analysis was performed using SPSS 15.0 statistical program. The statistical analysis; chi-square test, t-test was used. Statistical significance level of p Results: The study sample size was calculated as 285 cases (5% deviation and 95% confidence level). Of those who participated in the study were found that 58.3% of the physician used the statistical software package and 31.7% of them have a personal computer in working area. Conclusion: Today, the use of computer technology, internet tools and statistical packages in the medical field is required. Therefore, teaching the use of computers during the training of the staff is important, Amaç: Bilgisayar ve internet teknolojilerindeki gelişmeler sonucunda bilgiye ulaşma ve bilgi gereksinimlerini karşılama konusundaki seçeneklerimiz artmıştır. Modern dünyada bilgiye hızlı ulaşmak giderek daha önemli bir boyuta gelmektedir. Teknoloji alanındaki hızlı gelişmeler güncel, anlamlı, doğru ve güvenilir bilginin hızlı erişimini gerektiren tıp alanındaki bilgi arama davranışlarında da değişikliklere neden olmuştur. Bu çalışma Dokuz Eylül Üniversitesi Tıp Fakültesinde çalışan hekimlerin bilgisayar, istatistik ve biyoinformatik programlarını kullanım amaçları ve sıklığını belirlemek amacıyla yapılmıştır. Yöntemler: İstatistiksel analiz SPSS 15.0 istatistik paket programı kullanılarak yapıldı. İstatistiksel çözümlemede; ki-kare testi, t testi kullanıldı. Yüzde ve ortalamalar alınarak karşılaştırma yapıldı. İstatistik anlamlılık düzeyi p

The master two-dimensional (2-D) gel database of human keratinocytes currently lists 3087 cellular proteins (2168 isoelectric focusing, IEF; and 919 none-quilibrium pH gradient electrophoresis, NEPHGE), many of which correspond to posttranslational modifications, 890 polypeptides have been identified (protein name, organelle components, etc.) using one or a combination of procedures that include (i) comigration with known human proteins, (ii) 2-D gel immunoblotting using specific antibodies (iii) microsequencing of Coomassie Brilliant Blue stained proteins, (iv) mass spectrometry and (v) vaccinia virus expression of full length cDNAs. These are listed both in alphabetical order and with increasing SSP number, together with their M(r), pI, cellular localization and credit to the investigator(s) that aided in the identification. Furthermore, we list 239 microsequenced proteins recorded in the database. We also report a database of proteins recovered from the medium of noncultured, unfractionated keratinocytes. This database lists 398 polypeptides (309 IEF; 89 NEPHGE) of which 76 have been identified. The aim of the comprehensive databases is to gather, through a systematic study of keratinocytes, qualitative and quantitative information on proteins and their genes that may allow us to identify abnormal patterns of gene expression and, ultimately, to pinpoint signaling pathways and components affected in various skin diseases, cancer included.