42 results on '"Hakan Savli"'
Search Results
2. The Mutation Profiles of K-RAS/N-RAS Genes in Metastatic Colorectal Cancer Patients
- Author
-
Seda EREN KESKİN, Eda GÜZDOLU, Nilüfer SERTDEMİR, Gülhan DEMİR, Deniz SÜNNETÇİ AKKOYUNLU, Devrim ÇABUK, Naci ÇİNE, and Hakan SAVLI
- Subjects
Oncology ,Metastatic Colorectal Cancer ,RAS oncogene ,KRAS ,NRAS ,EGFR-targeted therapy ,General Medicine ,EGRF-hedefli tedavi ,Metastatik kolorektal kanser ,RAS onkogeni ,Onkoloji - Abstract
Amaç: RAS genleri, Epidermal Büyüme Faktörü Reseptörü (EGFR) tarafından indüklenen RAS-MAPK Sinyal yolağının bir üyesidir. Bu yolaktaki genlerde meydana gelen mutasyonlar kanser gelişimini tetiklemektedir. Kolorektal kanserde (KRK), RAS genlerinde meydana gelen mutasyonlar EGFR hedefli tedaviye karşı direnç gelişimine neden olur. EGFR monoklonal antikorları, kemoterapötik ajanlar olarak metastatik kolorektal kanser tedavisinde yaygın şekilde kullanılmaktadır. KRAS mutasyonları KRK’nın 30-50%’sinde, NRAS mutasyonları ise 2-3%’ünde bulunur. Bu çalışmada, KRK’lı hastalarda KRAS/NRAS mutasyonlarını analiz etmeyi amaçladık. Yöntem: EGFR-hedefli tedaviye direnç gösteren 100 metastatik KRK hastası, Real-Time Polimeraz Zincir Reaksiyonu yöntemi ile KRAS mutasyonu (ekzon 2, 3, 4) ve NRAS mutasyonu (ekzon 2, 3, 4) durumu için tarandı.Bulgular: Bu çalışma sonucunda, KRAS mutasyonu oranı 48% ve NRAS mutasyonu oranı 1,92% olarak bulundu. En yaygın KRAS mutasyonları kodon 12’de saptandı. Kodon 12 mutasyonlarının dağılımı G12V (25%), G12D (23%), G12C (14,5%) olarak elde edildi.Sonuç: Çalışmamızda saptanan KRAS ve NRAS mutasyon sıklıkları benzer raporlar ile uyumlu bulundu. Sonuçlarımız, RAS mutasyonlarının test edilmesinin EGFR-hedefli tedaviden fayda sağlayacak hastaları belirlemede hayati rolünü desteklemektedir., Objective: RAS genes are members of the RAS/Mitogen activated protein kinase pathway which is induced by Epidermal Growth Factor Receptor (EGFR). Mutations in genes in this pathway trigger cancer development. In colorectal cancer, mutations in RAS genes cause resistance to EGRF- targeted therapy. In the treatment of metastatic colorectal cancer, EGFR’s monoclonal antibodies are widely used as chemotherapeutic agents. Kirsten-RAS mutations are found in 30-50% and N-RAS mutations are found in 2-3% of colorectal cancer. In this study, we aimed to analyze Kirsten-RAS /N-RAS mutations in patients with metastatic colorectal cancer.Methods: One hundred of metastatic colorectal cancer patients resistant to EGFR- targeted therapy were scanned for the Kirsten-RAS mutations status (exon 2,3,4) and N-RAS mutation status (Exon 2,3,4) by Real-Time PCR (Polymerase Chain Reaction) method. Results: As a result of this study, Kirsten-RAS mutation was found 48% and N-RAS mutation was 1.92%. The most common Kirsten-RAS mutations were in codon 12. The distribution of codon 12 mutations were obtained as G12V (25%), G12D (23%), G12C (14.5%). Conclusion: In our study, the frequencies of Kirsten-RAS and N-RAS mutations were compitable with similar reports. Our results have supported that testing RAS genes mutations have a vital role in identifying patients who benefit from Epidermal Growth Factor Receptor- targeted therapy.
- Published
- 2022
3. The role of next-generation sequencing in the examination of signaling genes in Brca1/2-negative breast cancer cases
- Author
-
Naci Cine, Cansu Ugurtas, Merve Gokbayrak, Duygu Aydin, Gulhan Demir, Seda Kuru, Deniz Sunnetci‐Akkoyunlu, Seda Eren‐Keskin, Turgay Simsek, Devrim Cabuk, Maksut Gorkem Aksu, Nuh Zafer Canturk, and Hakan Savli
- Subjects
Genetics ,Genetics (clinical) - Abstract
Breast cancer is the most prevalent malignancy in women worldwide. Although pathogenic variants in the BRCA1/2 genes are responsible for the majority of hereditary breast cancer cases, a substantial proportion of patients are negative for pathogenic variations in these genes. In cancers, the signal transduction pathways of the cell are usually affected first. Therefore, this study aimed to detect and classified genetic variations in non-BRCA signaling genes and investigate the underlying genetic causes of susceptibility to breast cancer.Ninety-six patients without pathogenic variants in the BRCA1/2 genes who met the inclusion criteria were enrolled in the study, and 34 genes were analyzed using next-generation sequencing (NGS) for genetic analysis.Based on the ClinVar database or American College of Medical Genetics criteria, a total of 55 variants of 16 genes were detected in 43 (44.8%) of the 96 patients included in the study. The pathogenic variants were found in the TP53, CHEK2, and RET genes, whereas the likely pathogenic variants were found in the FGFR1, FGFR3, EGFR, and NOTCH1 genes.The examination of signaling genes in patients who met the established criteria for hereditary breast cancer but were negative for BRCA1/2 pathogenic variants provided additional information for approximately 8% of the families. The results of the present study suggest that NGS is a powerful tool for investigating the underlying genetic causes of occurrence and progression of breast cancer.
- Published
- 2022
4. Time Dependent Gene Expression Analysis of Vitamin D3 (1,25 (OH)2 D3) Treated HL–60 Cells by Q-RT-PCR
- Author
-
Aylin Kanli, Hakan Savli, and Mehmet Doğan Gülkaç
- Subjects
Vitamin ,chemistry.chemical_compound ,chemistry ,Gene expression ,Molecular biology ,Q rt pcr - Published
- 2020
5. The diagnostic importance of pathogenic variants and variant coexistence determined by NGS-based liquid biopsy approach in patients with lung adenocarcinoma
- Author
-
Naci, Cine, Emin, Ali Sen, Gulhan, Demir, Merve, Gokbayrak, Eda, Guzdolu, Nilufer, Sertdemir, Duygu, Aydin, Omer, Kurtas, Seda, Reka, Deniz, Sunnetci-Akkoyunlu, Seda, Eren-Keskin, Kazim, Uygun, Devrim, Cabuk, Maksut, Gorkem Aksu, Nuh, Zafer Canturk, and Hakan, Savli
- Subjects
Lung Neoplasms ,Class I Phosphatidylinositol 3-Kinases ,Mutation ,Liquid Biopsy ,High-Throughput Nucleotide Sequencing ,Humans ,Adenocarcinoma of Lung ,Cell Biology ,Reactive Oxygen Species ,Molecular Biology - Abstract
Identification of driver mutations and rapid detection of genetic changes in lung cancer are critical in the management of the disease. Genetic structures of tumor tissues tend to change constantly and the possibility of emergence of new pathogenic variants that will create resistance to treatment. Liquid biopsy analysis has been one of the most effective approaches used to monitor and identify individual genetic changes.In this study, TP53, EGFR, MET, ALK, PIK3CA, MAP2K, ERBB2 and ROS genes in cf DNA samples of 324 patients with lung adenocarcinoma were screened for genetic variations by NGS method. Analysis of the data showed that there were a total of 755 variations in 324 patients.Pathogenic and possibly pathogenic variations were identified in 178 patients (54.9%) on TP53, 118 (36.4%) on EGFR, 55 (17.0%) on MET, 46 (14.2%) on ALK, 39 (12.0%) on MAP2K, 6 (1.9%) on ERBB2 and in 2 (0,6%) patients ROS genes. The detailed variant data of the genes included in the study were compared with the patients' stage status, metastasis status, smoking, age distribution and life span data, and the presence of possible significant relationships and candidate biomarkers for the molecular pathogenesis of the disease were investigated.As a result of data analysis, genetic changes associated with metastasis and adenocarcinoma formation were identified. It has been shown that variations identified in TP53, PIK3CA, MAP2K1 and EGFR genes can play critical roles in the pathogenesis and development of the disease.
- Published
- 2022
6. TP53, EGFR and PIK3CA gene variations observed as prominent biomarkers in breast and lung cancer by plasma cell-free DNA genomic testing
- Author
-
Ercan Ozden, Ulas Isik, Maksut Görkem Aksu, Eda Guzdolu, Nilüfer Sertdemir, Ömer Kurtaş, Naci Cine, Devrim Cabuk, Kazim Uygun, Seda Reka, Duygu Aydin, Deniz Sunnetci-Akkoyunlu, Merve Ertan Gökbayrak, Hakan Savli, Gulhan Demir, Bilge Dursun, Nuh Zafer Cantürk, and Seda Eren-Keskin
- Subjects
0106 biological sciences ,0301 basic medicine ,Adult ,Male ,Lung Neoplasms ,Class I Phosphatidylinositol 3-Kinases ,Bioengineering ,Breast Neoplasms ,Plasma cell ,01 natural sciences ,Applied Microbiology and Biotechnology ,Circulating Tumor DNA ,03 medical and health sciences ,Breast cancer ,010608 biotechnology ,medicine ,Biomarkers, Tumor ,Humans ,Liquid biopsy ,Lung cancer ,Gene ,Early Detection of Cancer ,Aged ,Aged, 80 and over ,Lung ,business.industry ,Liquid Biopsy ,Genetic Variation ,General Medicine ,Middle Aged ,medicine.disease ,ErbB Receptors ,030104 developmental biology ,medicine.anatomical_structure ,Cell-free fetal DNA ,Cancer research ,Female ,Personalized medicine ,Tumor Suppressor Protein p53 ,business ,Biotechnology - Abstract
Use of plasma cell-free DNA genomic testing, also know as liquid biopsy, reveals information for early detection and monitoring of solid tumors. Our study reports the analysis of 113 lung and 18 breast cancer patients using commercially available platforms. Lung and breast cancer panel hotspot regions on the genes were investigated. There was a significant increase in isolation efficiency with very fresh blood samples of at least 15 millilitres which were processed in minutes. TP53 gene variations were detected in both types of tumors. Additionally, associations were found for EGFR variations in lung tumors and PIK3CA variations in breast tumors. Mutation assessment of these three genes are recommended as useful biomarkers for predictive studies, to follow up tumor growth and for personalized treatment. Mutations observed in this study warrant further investigation for follow up studies and may justify expression studies. However, in our subsequent studies, we intensify our tumor profiling strategy with other methods. However in terms of true personalized medicine,future plans would include repeating these studies with ctDNA size analysis and methylation analysis of the non-coding region in the individual tumors.
- Published
- 2019
7. Deregulated Levels of the NF-κB1, NF-κB2, and Rel Genes in Ukrainian Patients with Leukemia and Lymphoma in the Post-Chernobyl Period
- Author
-
S V Koval, Naci Cine, Hakan Savli, L M Sklyarenko, D F Gluzman, Ramis Ufuk Akkoyunlu, Deniz Sünnetçi, and M P Zavelevich
- Subjects
0301 basic medicine ,Male ,Neoplasms, Radiation-Induced ,Lymphoma ,Chronic lymphocytic leukemia ,Large granular lymphocytic leukemia ,0302 clinical medicine ,hemic and lymphatic diseases ,Cancer ,Leukemia, Radiation-Induced ,NF-kappa B ,Myeloid leukemia ,lcsh:Diseases of the blood and blood-forming organs ,Hematology ,Middle Aged ,Chronic leukemia ,B-Cell neoplasms ,Leukemia ,030220 oncology & carcinogenesis ,T-cell neoplasms ,Female ,Ukraine ,Research Article ,Adult ,lcsh:Internal medicine ,Myelodysplastic syndromes ,Real-Time Polymerase Chain Reaction ,03 medical and health sciences ,Young Adult ,NF-kappa B p52 Subunit ,medicine ,Humans ,Hairy cell leukemia ,lcsh:RC31-1245 ,Aged ,Acute leukemia ,lcsh:RC633-647.5 ,business.industry ,Transcription Factor RelA ,NF-kappa B p50 Subunit ,Thrombosis ,medicine.disease ,non-Hodgkin’s lymphoma ,030104 developmental biology ,Chernobyl Nuclear Accident ,Immunology ,Cancer research ,Genes, rel ,REL ,business - Abstract
Nuclear factor kappa B (NF-κB) is an important transcription factor in cancer and NF-κB activation has been seen in angiogenesis, tumor progression, and metastasis. Relationships between specific NF-κB gene networks, leukemogenesis, and radiation exposure are still unknown. Our aim was to study the expression levels of the NF-κB1, NF-κB2, and Rel genes in hematological malignancies in the post-Chernobyl period.We analyzed gene expression levels of NF-κB1, NF-κB2, and Rel in 49 B-cell chronic lymphocytic leukemia, 8 B-cell non-Hodgkin's lymphoma, 3 acute myeloid leukemia, 3 chronic myeloid leukemia, 2 hairy cell leukemia, 2 myelodysplastic syndrome, and 2 T-cell large granular lymphocytic leukemia patients using real-time polymerase chain reaction.Expression levels of NF-κB1, NF-κB2, and Rel genes were found to be deregulated.These results could be accepted as specific gene traces to radiation-induced leukemia or as potential candidates for new diagnostic biomarker studies. Larger experiments and non-exposed control malignant cell populations are needed to clarify these suggestions.Amaç: Nükleer faktör kappa B (NF-κB), kanserde önemli bir transkripsiyon faktörü olup aktivasyonu anjiyogenez, tümör gelişimi ve metastazın birçok basamağında görülmektedir. Spesifik NF-κB gen ağları, lökomogenez ve radyasyon maruziyeti arasındaki ilişki halen belirsizdir. Çalışmamızda Çernobil sonrası hematolojik kanserlerde NF-κB1, NF-κB2 ve Rel genlerinin ekspresyon düzeylerini incelemeyi amaçladık. Gereç ve Yöntemler: Gerçek zamanlı polimeraz zincir reaksiyonu ile 49 B-hücreli kronik lenfositik lösemi, 8 B-hücreli non-Hodgkin lenfoma, 3 akut myeloid lösemi, 3 kronik myeloid lösemi, 2 tüylü hücre lösemi, 2 miyelodisplastik sendrom ve 2 T-hücreli büyük granüler lenfositik lösemi hastasında NF-κB1, NF-κB2 ve Rel gen ekspresyon düzeylerini analiz ettik. Bulgular: NF-κB1, NF-κB2 ve Rel genlerine ait ekspresyon düzeyleri değişmiş olarak saptandı. Sonuç: Bu sonuçlar, radyasyonla indüklenmiş lösemilerdeki spesifik gen izleri veya yeni tanısal biyobelirteç çalışmalarına muhtemel aday önerileri olarak da kabul edilebilir. Bu düşünceleri açıklığa kavuşturmak için daha geniş deneyler ve radyasyon maruziyeti olmayan kontrol malign hücre popülasyonlarına ihtiyaç vardır.
- Published
- 2016
8. Molecular signatures of chronic periodontitis in gingiva: A genomic and proteomic analysis
- Author
-
Deniz Sunnetci-Akkoyunlu, Begum Alkan, Elif Busra Yilmaz, Bahadır Kan, V. Merve Balta, Busra Gurel, Naci Cine, Esra Guzeldemir-Akcakanat, Hakan Savli, Esen Gumuslu, Ahmet Tarik Baykal, Vakur Olgaç, and Emel Akgun
- Subjects
0301 basic medicine ,Proteomics ,Gingiva ,Genomics ,pERp1 ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Tandem Mass Spectrometry ,Gene expression ,Humans ,Gene ,Enoyl-CoA Hydratase ,Proteogenomics ,Inflammation ,Cell growth ,030206 dentistry ,Cell biology ,rab1 GTP-Binding Proteins ,030104 developmental biology ,Chronic Periodontitis ,Periodontics ,Chromatography, Liquid - Abstract
Background: To elucidate molecular signatures of chronic periodontitis (CP) using gingival tissue samples through omics-based whole-genome transcriptomic and whole protein profiling. Methods: Gingival tissues from 18 CP and 25 controls were analyzed using gene expression microarrays to identify gene expression patterns and the proteins isolated from these samples were subjected to comparative proteomic analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The data from transcriptomics and proteomics were integrated to reveal common shared genes and proteins. Results: The most upregulated genes in CP compared with controls were found as MZB1, BMS1P20, IGLL1/IGLL5, TNFRSF17, ALDH1A1, KIAA0125, MMP7, PRL, MGC16025, ADAM11, and the most upregulated proteins in CP compared with controls were BPI, ITGAM, CAP37, PCM1, MMP-9, MZB1, UGTT1, PLG, RAB1B, HSP90B1. Functions of the identified genes were involved cell death/survival, DNA replication, recombination/repair, gene expression, organismal development, cell-to-cell signaling/interaction, cellular development, cellular growth/proliferation, cellular assembly/organization, cellular function/maintenance, cellular movement, B-cell development, and identified proteins were involved in protein folding, response to stress, single-organism catabolic process, regulation of peptidase activity, and negative regulation of cell death. The integration and validation analysis of the transcriptomics and proteomics data revealed two common shared genes and proteins, MZB1 and ECH1. Conclusion: Integrative data from transcriptomics and proteomics revealed MZB1 as a potent candidate for chronic periodontitis. Kocaeli University
- Published
- 2018
9. Bortezomib and Arsenic Trioxide Activity on a Myelodysplastic Cell Line (P39): A Gene Expression Study
- Author
-
Bálint Nagy, Sara Galimberti, Giuseppe A. Palumbo, Hakan Savli, Mario Petrini, Martina Canesastraro, Francesco Di Raimondo, and Deniz Sünnetçi
- Subjects
lcsh:Internal medicine ,Antineoplastic Agents ,Klinikai orvostudományok ,Arsenicals ,NF-κB ,Bortezomib ,chemistry.chemical_compound ,Arsenic trioxide ,Cell Line, Tumor ,Gene expression ,MDS ,Humans ,Medicine ,Gene Regulatory Networks ,lcsh:RC31-1245 ,Gene ,Regulation of gene expression ,Estradiol ,Gene Expression Regulation, Leukemic ,business.industry ,lcsh:RC633-647.5 ,NF-kappa B ,Drug Synergism ,Leukemia, Myelomonocytic, Chronic ,Oxides ,Cell Cycle Checkpoints ,Orvostudományok ,Hematology ,lcsh:Diseases of the blood and blood-forming organs ,Neoplasm Proteins ,chemistry ,Proteasome ,Cell culture ,Disease Progression ,Cancer research ,FOXA1 ,business ,Proteasome Inhibitors ,Research Article ,Signal Transduction ,medicine.drug - Abstract
We aimed to understand the molecular pathways affected by bortezomib and arsenic trioxide treatment on myelomonocytoid cell line P39.Oligonucleotide microarray platforms were used for gene expression and pathway analysis. Confirmation studies were performed using quantitative real time PCR.Bortezomib treatment has shown upregulated DIABLO and NF-κBIB (a NF-κB inhibitor) and downregulated NF-κB1, NF-κB2, and BIRC1 gene expressions. Combination treatment of the two compounds showed gene expression deregulations in concordance by the results of single bortezomib treatment. Especially, P53 was a pathway more significantly modified and a gene network centralized around the beta estradiol gene. Beta estradiol, BRCA2, and FOXA1 genes were remarkable deregulations in our findings.Results support the suggestions about possible use of proteasome inhibitors in the treatment of high-risk myelodysplastic syndrome (MDS). NF-κB was observed as an important modulator in leukemic transformation of MDS.P39 hücre hattı üzerinde Bortezomib ve Arsenik Trioksid’in etkilediği moleküler altyolları anlamak amacıyla gen anlatım analizleri gerçekleştirdik. Bortezomib işlenmesi, DIABLO ve bir NF-κB inhibitorü olan NF-κIB’nin anlatım artışını ve NF-κB 1, NF-κB 2, BIRC1 genlerinin anlatım azalışını gösterdi. İki bileşiğin birlikte işlenmesi ise aynı genlerin anlatım düzensizliğini göstererek Bortezomibin tek başına işlenmesinin sonuçlarıyla uyum içindeydi. Özellikle, P53 hücre altyolu daha anlamlı bir değişikliğe uğradı ve Beta Estradiol geni çevresinde bir gen ağı biçimlendi. Beta Estradiol, BRCA2 ve FOXA1 genlerinin düzen değişiklikleri bulgularımız içinde en dikkat çekicileriydi. Sonuçlar proteazom inhibitörlerinin yüksek riskli myelodisplastik sendromda olası kullanımı düşüncesini desteklemektedir. NF-κB, MDS’nin lösemik transformasyonunda önemli bir düzenleyici olarak gözlenmiştir.
- Published
- 2015
10. Low frequency of HLA-B27 in ankylosing spondylitis and its relationship with clinical findings in patients from Turkey
- Author
-
Sevde Nur Fırat, Ayse Cefle, Baris Yilmazer, Hakan Savli, Ayten Yazici, and Fulya Cosan
- Subjects
musculoskeletal diseases ,030203 arthritis & rheumatology ,0301 basic medicine ,Ankylosing spondylitis ,medicine.medical_specialty ,HLA-B27 ,Disease onset ,Geographic area ,business.industry ,Human leukocyte antigen ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Internal medicine ,Medicine ,Positive relationship ,In patient ,Original Article ,skin and connective tissue diseases ,business ,Male to female - Abstract
Objective Human leukocyte antigen B27 (HLA-B27) is strongly associated with ankylosing spondylitis (AS). However, the association between clinical findings and HLA-B27 vary in terms of geographic area. This study aimed to determine the frequency of HLA-B27 positivity and its relationship with clinical findings. Material and methods All subjects fulfilling the modified New York diagnosis criteria for AS enrolled in study. The demographic data and histories of the patients were collected retrospectively from patient files. Polymerase chain reaction-based HLA-B27 analysis of all cases was performed. Results The male to female ratio was 2.5, and mean age of disease onset was 28.3 years. HLA-B27 positivity was detected in 115 patients (70%). Although there was no significant connection between the clinical findings and HLA-B27 positivity, there was a positive relationship between the presence of syndesmophytes and HLA-B27 positivity (p=0.044). The number of patients treated with anti-tumor necrosis factor was higher in the HLA-B27-positive group; however, the difference was not significant (39.1% and 28.9%, respectively). More patients were treated with anti-tumor necrosis factor in the HLA-B27-positive group than in the HLA-B27-negative group; however, the difference was not significant (39.1% and 28.9%, respectively). Conclusion Compared with northern Europe, HLA-B27-positive rate of patients with AS has been shown to be lower in Turkey. Except for the presence of syndesmophytes, there was not a statistically significant relationship between HLA-B27 positivity and clinical and radiologic findings.
- Published
- 2017
11. High Throughput FISH Analysis: A New, Sensitive Option For Evaluation of Hematological Malignancies
- Author
-
Deniz Sünnetçi, Seda Eren, Abdullah Hacıhanifioğlu, Duygu Yavuz, Naci Cine, Hakan Savli, Zeynep İlkay, and Nilüfer Üzülmez
- Subjects
Oncology ,lcsh:Internal medicine ,medicine.medical_specialty ,Microarray ,Lymphoblastic Leukemia ,hemic and lymphatic diseases ,Internal medicine ,Molecular genetics ,medicine ,lcsh:RC31-1245 ,Leukemia ,lcsh:RC633-647.5 ,business.industry ,Fish analysis ,Myeloid leukemia ,lcsh:Diseases of the blood and blood-forming organs ,Hematology ,medicine.disease ,Peripheral blood ,medicine.anatomical_structure ,molecular genetics ,Immunology ,Hematologic malignancies ,Bone marrow ,business ,Research Article - Abstract
Objective: The aim of this study was to determine the efficiency of the high throughput FISH analysis (HTFA) method for detecting genetic alterations in hematological malignancies, which is a new bacterial artificial chromosome array-based approach. Materials and Methods: We performed a HTFA study of bone marrow aspiration and peripheral blood samples of 77 cases (n=19 myelodysplastic syndrome, n=17 acute lymphoblastic leukemia, n=9 chronic myeloid leukemia, n=32 acute myeloid leukemia) with hematological malignancies during the periods of initial diagnosis, treatment, and/or follow-up. Results: Both numerical and structural abnormalities were detected by HTFA. We observed aberrations in 88% of our acute lymphoblastic leukemia patients, 25% of acute myeloid leukemia patients, and 31% of myelodysplastic syndrome patients. In chronic myeloid leukemia cases, aberration was not detected by HTFA. Conclusion: Our results showed that HTFA, combined with other methods, will gradually take a place in the routine diagnosis of hematologic malignancies.
- Published
- 2013
12. Investigation of the diagnostic value of chromosome analysis and bacterial artificial chromosome-based array comparative genomic hybridization in prenatal diagnosis
- Author
-
Hakan, Savli, Seda Eren, Keskin, and Naci, Cine
- Subjects
Adult ,Chromosome Aberrations ,Chromosomes, Artificial, Bacterial ,Comparative Genomic Hybridization ,Young Adult ,Adolescent ,Pregnancy ,Karyotyping ,Prenatal Diagnosis ,Humans ,Female ,Middle Aged - Abstract
To investigate the diagnostic value of bacterial artificial chromosome (BAC)-based array comparative genomic hybridization (CGH) and chromosome analysis in prenatal diagnosis.This study included the chromosome analysis and BAC-based array CGH analysis of 140 amniocentesis samples with prenatal diagnosis indications.Karyotype analysis showed trisomy 21 in 4 patients, trisomy 18 in 5 patients, monosomy X in 1 patient, and other anomalies in 3 patients. The BAC-based array CGH analysis showed 4 patients with trisomy 21, 4 patients with trisomy 18, and 1 patient with monosomy X as a numerical chromosome anomaly, while partial duplication was observed in chromosome 14 in 1 case as a structural anomaly.The array CGH is the most effective method available to complement cases where chromosome analysis, a gold standard in prenatal diagnosis, proves to be insufficient. Considering the inherent limitations of both methods, complementary features should be introduced in order to be able to give the most accurate data at the right time.
- Published
- 2016
13. Effects of curcumin on global gene expression profiles in the highly invasive human breast carcinoma cell line MDA-MB 231: A gene network-based microarray analysis
- Author
-
Naci Cine, Pornngarm Limtrakul, Hakan Savli, Deniz Sünnetçi, and Bálint Nagy
- Subjects
Cancer Research ,Oncogene ,Microarray ,Microarray analysis techniques ,Cell ,General Medicine ,Articles ,Biology ,Bioinformatics ,chemistry.chemical_compound ,medicine.anatomical_structure ,breast cancer ,Immunology and Microbiology (miscellaneous) ,chemistry ,Cancer cell ,Gene expression ,medicine ,Cancer research ,Curcumin ,gene expression ,curcumin ,Gene ,microarray - Abstract
Curcumin, or diferuloylmethane, is a major chemical component of turmeric (Curcuma longa Linn.) that has been consumed as a dietary spice through the ages. This yellow-colored polyphenol has a notably wide range of beneficial properties, including anti-inflammatory, antioxidant, antitumoral, anti-invasive and anti-metastatic activity. In the present study, microarray gene expression analysis was applied to identify the curcumin-regulated genes in a highly invasive human breast carcinoma cell line (MDA-MB 231). Cells were cultured with curcumin (20 μM) for 24 h; total RNA was isolated and hybridized to Whole Human Genome Microarray slides. Gene set enrichment analyses on our whole genome expression data revealed downregulation of the EGF pathway elements following curcumin treatment. Furthermore, gene network analysis identified a significantly relevant network among the differentially expressed genes, centered on the EGR1 and FOS genes. The members of these pathways and networks play an essential role in the regulation of cancer cell growth and development; the majority exhibited decreased expression levels following treatment with curcumin. These observations suggest that curcumin is an excellent candidate for the prevention and treatment of breast cancer.
- Published
- 2012
14. Microarray-based gene expression analysis of an animal model for closed head injury
- Author
-
Aydın Özbek, Hakan Savli, Belgin Bamaç, Deniz Sünnetçi, Tuncay Çolak, Naci Cine, Ömer Kurtaş, and Ümit Biçer
- Subjects
Male ,Oncology ,medicine.medical_specialty ,Pathology ,Microarray ,Traumatic brain injury ,Gene Expression ,Real-Time Polymerase Chain Reaction ,Brain Ischemia ,Head Injuries, Closed ,Internal medicine ,Gene expression ,medicine ,Animals ,Genetic Predisposition to Disease ,RNA, Messenger ,Rats, Wistar ,Gene ,General Environmental Science ,Analysis of Variance ,business.industry ,Microarray analysis techniques ,Gene Expression Profiling ,Microarray Analysis ,medicine.disease ,Rats ,Gene expression profiling ,Models, Animal ,Closed head injury ,General Earth and Planetary Sciences ,DNA microarray ,business ,Signal Transduction - Abstract
Traumatic brain injury (TBI) is a major cause of death and disability in both children and the elderly. Mortality from TBI is said account for 1-2% of all deaths. One-third to one-half of all traumatic deaths is due to head injury. Of those who survive, the majority is left with significant disabilities, including 3% who remain in a vegetative state and only approximately 30% who make a good recovery. Microarray studies and other genomic techniques facilitate the discovery of new targets for the treatment of diseases, which aids in drug development, immunotherapeutics and gene therapy. Gene expression profiling or microarray analysis enables the measurement of thousands of genes in a single RNA sample.In this study, adult Wistar-albino rats underwent TBI using a trauma device. Brain tissues and blood samples were taken for gene expression at 1, 12 and 48 h post-trauma and were then analysed via microarray. Total RNA was isolated using an RNeasy Mini Kit (QIAGEN-SampleAssay Technologies, Hilden, Germany) and tested using a 2100 Bioanalyzer (Agilent Technologies, Palo Alto, CA). Overall changes in gene expression were evaluated using Agilent Whole Rat Genome 4 × 44 K oligonucleotide arrays and analysed with GeneSpring (GeneSpring 6.1, Silicon Genetics, Redwood City, CA) software. Only genes with a signal-to-noise ratio of above 2 in the experiments were included in the statistical analysis.ANOVA (p0.05) was performed to identify differentially expressed probe sets. Additional filtering (minimum 2-fold change) was applied to extract the most differentially expressed genes based on the study groups (Control vs. 1st hour, Control vs. 12th hour, Control vs. 48th hour). Differentially expressed genes were detected via microarray analysis. A gene interaction-based network investigation of the genes that were identified via traditional microarray data analysis describes a significantly relevant gene network that includes the C1ql2, Cbnl, Sdc1, Bdnf, MMP9, and Cd47 genes, which were differentially expressed compared with the controls.In this study, we will review the current understanding of the genetic susceptibility of TBI with microarrays. Our results highlight the importance of genes that control the response of the brain to injury as well as the suitability of microarrays for identifying specific targets for further study.
- Published
- 2012
15. A case of del(13)(q14.2)(q31.3) associated with hypothyroidism, hypertriglyceridemia, hypercholesterolemia and total ophthalmoplegia
- Author
-
Deniz Sünnetçi, Nihan Malbora, Naci Cine, Cihan Meral, Hakan Savli, and Baris Malbora
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Dizygotic twin ,Hypercholesterolemia ,Chromosome Disorders ,Biology ,Hypothyroidism ,Pregnancy ,Internal medicine ,Diseases in Twins ,Twins, Dizygotic ,Genetics ,medicine ,Humans ,Abnormalities, Multiple ,Strabismus ,Chromosome 13 ,Hypertriglyceridemia ,Comparative Genomic Hybridization ,Chromosomes, Human, Pair 13 ,13q deletion syndrome ,Infant ,Karyotype ,General Medicine ,medicine.disease ,Hypotonia ,Endocrinology ,Failure to thrive ,Female ,Chromosome Deletion ,medicine.symptom - Abstract
13q deletion syndrome is caused by the absence of a portion of the long arm of chromosome 13. This syndrome is a rare condition characterized by a wide range of clinical findings. Phenotype varies with the location and size of the deletion. We report a female dizygotic twin with a proximal deletion of 13q and failure to thrive, hypotonia, and multiple anomalies included pytosis and total ophthalmology at right side, strabismus at left, bilateral iris heterochromia and telecantus. She had a broad nasal bridge with flat philtrum, micrognathia and antevert ear lobes. Her umbilicus had vanished. Her left coxa was dislocated and left toes were overlapped. She was also found to have hypertriglyceridemia, hypercholesterolemia, and hypothyroidism. Chromosome analysis showed a proximal deletion of chromosome 13 [karyotype 46,XX,del(13) (q14.2q31.3)] which was confirmed by high-resolution microarray based comparative genomic hybridization. The described patient is unique among similar rare cases with different deletion breakpoints. It is the first case of 13q14.2q31.3 deletion where the breakpoints are clearly defined, indicating the importance of detailed clinical description and high-resolution genomic analysis for characterization of rare genetic syndromes.
- Published
- 2012
16. Investigation of the diagnostic value of chromosome analysis and bacterial artificial chromosome-based array comparative genomic hybridization in prenatal diagnosis
- Author
-
Hakan SAVLI, Seda EREN KESKİN, and Naci ÇİNE
- Subjects
Prenatal diagnosis,bacterial artificial chromosome-based array comparative genomic hybridization,karyotyping ,General Medicine - Abstract
Background/aim: To investigate the diagnostic value of bacterial artificial chromosome (BAC)-based array comparative genomic hybridization (CGH) and chromosome analysis in prenatal diagnosis. Materials and methods: This study included the chromosome analysis and BAC-based array CGH analysis of 140 amniocentesis samples with prenatal diagnosis indications. Results: Karyotype analysis showed trisomy 21 in 4 patients, trisomy 18 in 5 patients, monosomy X in 1 patient, and other anomalies in 3 patients. The BAC-based array CGH analysis showed 4 patients with trisomy 21, 4 patients with trisomy 18, and 1 patient with monosomy X as a numerical chromosome anomaly, while partial duplication was observed in chromosome 14 in 1 case as a structural anomaly. Conclusion: The array CGH is the most effective method available to complement cases where chromosome analysis, a gold standard in prenatal diagnosis, proves to be insufficient. Considering the inherent limitations of both methods, complementary features should be introduced in order to be able to give the most accurate data at the right time.
- Published
- 2015
17. Microsurgical anatomy of membranous layers of the pituitary gland and the expression of extracellular matrix collagenous proteins
- Author
-
Bulent Sam, Savas Ceylan, Nurperi Gazioglu, Gözde Şirin, Ihsan Anik, Sibel Kokturk, Kenan Koc, Süreyya Ceylan, Naci Cine, and Hakan Savli
- Subjects
Microsurgery ,Pituitary gland ,Pathology ,medicine.medical_specialty ,Adenoma ,Extracellular matrix ,Type IV collagen ,Pituitary adenoma ,medicine ,Humans ,Sella Turcica ,Extracellular Matrix Proteins ,business.industry ,Dissection ,Anatomy ,medicine.disease ,Staining ,medicine.anatomical_structure ,Connective Tissue ,Connective tissue metabolism ,Pituitary Gland ,Cavernous sinus ,Surgery ,Collagen ,Neurology (clinical) ,business - Abstract
There are several reports about the microanatomical and histological features of sellar and parasellar membranous structures and clinical studies about MMP proteinase as a predictive factor. However, studies on collagen contents of sellar and parasellar membranous structures are limited. We demonstrated the membranous structures surrounding the pituitary gland and defined extracellular matrix (ECM) collagenous proteins, collagen I-IV expression patterns of sellar and parasellar connective tissues. The study was carried out on ten fresh postmortem human bodies at the Forensic Medicine Institution. Cavernous sinuses were resected with sellar structures and were stored at −80°C liquid nitrogen tanks. Medial wall of the cavernous sinus, pituitary capsule and pituitary tissue samples were obtained for RT-PCR. Opposite side specimens were used for histological and immune staining studies. Collagens I-IV were studied by immunohistochemical and reverse transcription polymerase chain reaction (RT-PCR) methods. The pituitary capsule and medial wall were identified as two different structures. The fibrous membrane, as the third membrane, was identified as staying whole in eight of ten specimens. Increased type IV collagen was determined in the pituitary gland, medial wall and pituitary capsule, respectively, in both RT-PCR and immunhistochemical studies. Immunhistochemical studies revealed that collagen I was strongly expressed in both the medial wall and pituitary gland. Increased type IV collagen was detected especially in pituitary tissue, the medial wall and the pituitary capsule by immune staining and RT-PCR. Type IV collagen was considered to be an important factor in the progression of adenoma and invasion.
- Published
- 2011
18. The frequency of MEFV gene mutations in behcet’s disease and their relation with clinical findings
- Author
-
Ayse Cefle, Ayten Yazici, and Hakan Savli
- Subjects
Adult ,Male ,Heterozygote ,medicine.medical_specialty ,Adolescent ,DNA Mutational Analysis ,Immunology ,Familial Mediterranean fever ,Behcet's disease ,Gene mutation ,medicine.disease_cause ,Compound heterozygosity ,Risk Assessment ,Gastroenterology ,Young Adult ,Gene Frequency ,Rheumatology ,Risk Factors ,Internal medicine ,Odds Ratio ,medicine ,Humans ,Immunology and Allergy ,Genetic Predisposition to Disease ,Allele ,Allele frequency ,Genetics ,Mutation ,Chi-Square Distribution ,business.industry ,Behcet Syndrome ,Middle Aged ,Pyrin ,medicine.disease ,MEFV ,Cytoskeletal Proteins ,Phenotype ,Case-Control Studies ,Disease Progression ,Female ,business - Abstract
Investigation of the relation between MEFV gene mutations and clinical findings of Behçet's disease. Genetic features of 100 patients with Behçet's disease (BD) and 100 healthy controls were analyzed. None of the individuals had a family history of FMF in the patient and control group, and none of the individuals in the control group had a family history of BD. MEFV gene analysis was performed in all the patients with BD and healthy controls; twelve different regions were scanned. In the BD group, mutations were detected in more than one region in 27 patients (27%). Twenty-five patients had heterozygous and two patients had compound heterozygous mutations (M680I-V726A and M694 V-A744S). The most frequent mutation was M694 V with an allelic frequency of 5%. The allelic frequencies of E148Q, M680I (G/C), and V726A were 3, 2, and 2%, respectively. The allelic frequencies of P369S, A744S, and K695R were 1, 1, and 0.5%. MEFV gene analysis revealed mutations in 27 (27%) of the individuals in the control group; the allelic frequency was 14%. The most frequent mutation was E148Q that was detected in 16 individuals. One individual was compound heterozygote (E148Q-M694 V). The allelic frequencies of E148Q, M694 V, V726A, and M680I were 8, 3, 1.5, and 0.5%, respectively. The allelic frequencies of K695R and P369S were 0.5 and 0.5%, respectively. The allelic frequency was similar in the two groups. There was not a significant relation between the mutations in the BD group and clinical findings.
- Published
- 2011
19. Unbalanced 3;22 translocation with 22q11 and 3p deletion syndrome
- Author
-
Selim Kurtoglu, Aslihan Kiraz, Sener Tasdemir, Hakan Savli, Munis Dundar, Filiz Hafo, Hilal Akalin, and Naci Cine
- Subjects
Adult ,Male ,Monosomy ,Pathology ,medicine.medical_specialty ,Chromosomes, Human, Pair 22 ,Biology ,Short stature ,Translocation, Genetic ,Young Adult ,22q11 Deletion Syndrome ,Pregnancy ,Genetics ,medicine ,Humans ,Abnormalities, Multiple ,Hypertelorism ,In Situ Hybridization, Fluorescence ,Genetics (clinical) ,Low-set ears ,medicine.diagnostic_test ,Infant, Newborn ,medicine.disease ,Karyotyping ,Chromosomal region ,Female ,Chromosomes, Human, Pair 3 ,Chromosome Deletion ,medicine.symptom ,Chromosome 22 ,Fluorescence in situ hybridization - Abstract
This report describes a 25-day-old Turkish boy with unbalanced 3;22 translocation that includes the 22q11.2 deletion and 3p25 deletion syndrome. The karyotype was 45, XY,der(3)t(3;22)-(p25;q11),-22. Although no immunological dysfunction could be demonstrated, the boy presented some manifestations of DiGeorge anomaly (DGA), which has been associated with monosomy for the same region of chromosome 22, velocardiofacial syndrome (VCFS), and the 3p deletion syndrome. Clinical features include short stature, hypertelorism, low set ears, cleft lip with cleft palate, short neck, truncus arteriosus, micropenis, clubfoot, over riding toes on right foot, four digits on left foot and growth delay. In addition he had feeding difficulties, respiratory infections, and developmental delay. Fluorescence in situ hybridization (FISH) studies confirmed loss of the proximal DiGeorge chromosomal region (DGCR). Array CGH analysis showed the deletion sites on chromosomes 3 and 22. This report documents a rare chromosomal aberration that causes the 22q11 and 3p deletion syndrome simultaneously. (C) 2010 Wiley-Liss, Inc.
- Published
- 2010
20. The prevalence of CYP2C19 mutations in Turkish patients with dyspepsia
- Author
-
Orhan Kocaman, Buğra Tolga Konduk, Sadettin Hülagü, Altay Celebi, Cem Aygun, Omer Senturk, and Hakan Savli
- Subjects
Adult ,Male ,medicine.medical_specialty ,Genotype ,Turkey ,Turkish ,CYP2C19 ,Gastroenterology ,law.invention ,Young Adult ,law ,Polymorphism (computer science) ,Internal medicine ,Prevalence ,medicine ,Humans ,Genetic Predisposition to Disease ,Dyspepsia ,Polymerase chain reaction ,business.industry ,Homozygote ,Cyp2c19 genotype ,Middle Aged ,language.human_language ,Genotype frequency ,Cytochrome P-450 CYP2C19 ,language ,Population study ,Female ,Aryl Hydrocarbon Hydroxylases ,business - Abstract
BACKGROUND/AIMS We aimed to determine the distribution of cytochrome P450 2C19 (CYP2C19) genotype frequencies in Turkish patients with dyspepsia. METHODS CYP2C19 genotype was determined in 100 Turkish patients with dyspepsia. DNA of the patients was isolated from whole blood and genotypes were detected by specific probes in real-time polymerase chain reaction (PCR). RESULTS The frequencies of heterozygous CYP2C19*2 and CYP2C19*3 genotypes were 13% and 1% in dyspeptic patients, respectively. Homozygous mutant CYP2C19*2 was detected at a rate of only 1% in the study population, and homozygous mutant genotype of CYP2C19*3 was not found. The frequencies of homozygous CYP2C19*2 and CYP2C19*3 genotypes were 86% and 99% in dyspeptic Turkish patients, respectively. CONCLUSIONS This is the first study investigating CYP2C19 polymorphism in dyspeptic Turkish patients. Our investigation revealed that the most common CYP2C19 genotype was wild type CYP2C19 in dyspeptic Turkish patients. Dyspeptic Turkish patients are extensive metabolizers for proton pump inhibitors. This finding might have impact on the clinical consequences for the treatment strategies in dyspepsia.
- Published
- 2009
21. Vascular endothelial growth factor (VEGF) polymorphisms in HELLP syndrome patients determined by quantitative real-time PCR and melting curve analyses
- Author
-
Petronella Hupuczi, János Rigó, Bálint Nagy, Barbara Rigó, Tibor Várkonyi, Hakan Savli, and Attila Molvarec
- Subjects
Adult ,Vascular Endothelial Growth Factor A ,HELLP Syndrome ,medicine.medical_specialty ,HELLP syndrome ,Clinical Biochemistry ,Single-nucleotide polymorphism ,Biology ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Biochemistry ,Gastroenterology ,Preeclampsia ,chemistry.chemical_compound ,Pregnancy ,Internal medicine ,Genotype ,medicine ,Humans ,Allele ,Biochemistry (medical) ,General Medicine ,Odds ratio ,medicine.disease ,Molecular biology ,Genotype frequency ,Vascular endothelial growth factor ,chemistry ,Case-Control Studies ,Female - Abstract
Background The vascular endothelial growth factor (VEGF) has a critical role in vasculogenesis and vascular permeability in several diseases including preeclampsia. There are at least 30 single nucleotide polymorphic (SNP) places on this gene. VEGF G+405C , C−2578A and C−460T SNPs are known to be related to VEGF production. VEGF polymorphisms were studied in preeclampsia, but not in HELLP syndrome. Therefore, we decided to determine the allele and genotype frequencies of VEGF G+405C , C−460T and C−2578A SNPs in healthy pregnant women and HELLP syndrome patients. Methods The authors introduced a quantitative real-time PCR method for the determination of the three VEGF SNPs. Blood samples were collected from 71 HELLP syndrome patients and 93 healthy controls. DNA was isolated by using silica adsorption method. The SNPs were determined by quantitative real-time PCR and melting curve analysis using LightCycler. Results There were significant differences in the allele and genotype frequencies of VEGF C−460T SNP between the two study groups. The T allele was present in 71.1% in the HELLP group, while in 53.8% in the controls ( p = 0.0014). The TT genotype occurred significantly more frequently in the HELLP group than in the control group (45.1% vs. 21.5%; p (for genotype frequencies) = 0.0011). The TT genotype carriers had an increased risk of HELLP syndrome, which was independent of maternal age and primiparity (adjusted odds ratio (OR) = 3.03, 95% confidence interval (CI) = 1.51–6.08; p = 0.002). Although the VEGF G+405C allele and genotype distributions did not differ significantly between the two groups, the CC genotype carriers were also found to have an increased risk for HELLP syndrome after adjustment for maternal age and primiparity (adjusted OR = 3.67, 95% CI = 1.05–12.75; p = 0.041). The VEGF C−2578A SNP was not associated with HELLP syndrome. Conclusions The quantitative real-time PCR combined with melting curve analyses is a fast and reliable method for the determination of VEGF SNPs. We found that the VEGF −460TT and +405CC genotype carriers have an increased risk of HELLP syndrome. As these two SNPs were previously observed to be related to production of the VEGF protein, we suppose that these VEGF polymorphisms – interacting with other genetic and environmental factors – could play a role in the development of HELLP syndrome.
- Published
- 2008
22. Gene-Expression Profiles in Generalized Aggressive Periodontitis: A Gene Network-Based Microarray Analysis
- Author
-
Esen Gumuslu, Deniz Sunnetci-Akkoyunlu, Hakan Savli, Begum Orucguney, Esra Guzeldemir-Akcakanat, Naci Cine, Bahadır Kan, and Elif Busra Yilmaz
- Subjects
0301 basic medicine ,Proteomics ,Microarray ,Gene regulatory network ,Computational biology ,Biology ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Gene expression ,medicine ,Aggressive periodontitis ,Humans ,Gene Regulatory Networks ,Gene ,Oligonucleotide Array Sequence Analysis ,Microarray analysis techniques ,Gene Expression Profiling ,Reproducibility of Results ,030206 dentistry ,medicine.disease ,Molecular biology ,030104 developmental biology ,Aggressive Periodontitis ,Periodontics ,DNA microarray - Abstract
In this study, molecular biomarkers that play a role in the development of generalized aggressive periodontitis (GAgP) are investigated using gingival tissue samples through omics-based whole-genome transcriptomics while using healthy individuals as background controls.Gingival tissue biopsies from 23 patients with GAgP and 25 healthy individuals were analyzed using gene-expression microarrays with network and pathway analyses to identify gene-expression patterns. To substantiate the results of the microarray studies, real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to assess the messenger RNA (mRNA) expression of MZB1 and DSC1. The microarrays and qRT-PCR resulted in similar gene-expression changes, confirming the reliability of the microarray results at the mRNA level.As a result of the gene-expression microarray studies, four significant gene networks were identified. The most upregulated genes were found as MZB1, TNFRSF17, PNOC, FCRL5, LAX1, BMS1P20, IGLL5, MMP7, SPAG4, and MEI1; the most downregulated genes were found as LOR, LAMB4, AADACL2, MAPT, ARG1, NPR3, AADAC, DSC1, LRRC4, and CHP2.Functions of the identified genes that were involved in gene networks were cellular development, cell growth and proliferation, cellular movement, cell-cell signaling and interaction, humoral immune response, protein synthesis, cell death and survival, cell population and organization, organismal injury and abnormalities, molecular transport, and small-molecule biochemistry. The data suggest new networks that have important functions as humoral immune response and organismal injury/abnormalities. Future analyses may facilitate proteomic profiling analyses to identify gene-expression patterns related to clinical outcome.
- Published
- 2015
23. A CGH array study in nonsyndromic (primary) autism patients: deletions on 16p13.11, 16p11.2, 1q21.1, 2q21.1q21.2, and 8p23.1
- Author
-
Seda Eren Keskin, Bülent Kara, Ramis Ufuk Akkoyunlu, Kudret Esen Gümüşlü, Naci Cine, Deniz Sünnetçi, and Hakan Savli
- Subjects
Male ,Adolescent ,Turkey ,Genome-wide association study ,In situ hybridization ,Genome ,Autism spectrum disorders,primary autism,CGH-array,deletion ,Health Care Sciences and Services ,mental disorders ,Clinical genetic ,medicine ,Humans ,Genetic Predisposition to Disease ,Sağlık Bilimleri ve Hizmetleri ,Autistic Disorder ,Child ,Gene ,Genetics ,Comparative Genomic Hybridization ,business.industry ,Infant, Newborn ,General Medicine ,medicine.disease ,Chromosomes, Human, Pair 1 ,Child, Preschool ,Chromosomes, Human, Pair 2 ,Autism ,Female ,Chromosome Deletion ,business ,Chromosomes, Human, Pair 16 ,Chromosomes, Human, Pair 8 ,Genome-Wide Association Study - Abstract
Background/aim: To detect specific molecular changes of DNA level in primary autism patients by using whole genome CGH array technology. Materials and methods: A cohort of 35 primary autism patients received clinical genetic testing by using an oligonucleotide-based CGH array platform to test for submicroscopic genomic deletions and duplications. Fluorescent in situ hybridization was performed in seven patients for confirmation of the results. Results: We found 16p13.11 deletion in thirteen patients, 16p11.2 deletion in twelve patients, 1q21.1 deletion in ten patients, 2q21.1q21.2 deletion in eight patients, and 8p23.1 deletion in seven patients. Conclusion: Our study indicates that genes in 16p13.11, 16p11.2, 1q21.1, 2q21.1q21.2, and 8p23.1 loci are potential predisposition and new suspicious regions for primary autism. Deletions in these regions should be investigated in further studies to understand pathogenesis of primary autism.
- Published
- 2015
24. Real-Time PCR analysis of af4 and dek genes expression in acute promyelocytic leukemia t (15;17)patients
- Author
-
Nazan Sarper, Günçağ Dinçol, Sema Sirma, Hakan Savli, Melih Aktan, Ugur Ozbek, Zafer Salcioglu, and Bálint Nagy
- Subjects
Adult ,Male ,Acute promyelocytic leukemia ,Adolescent ,Chromosomal Proteins, Non-Histone ,Clinical Biochemistry ,Down-Regulation ,Gene Expression ,T-15 ,Biology ,Klinikai orvostudományok ,Polymerase Chain Reaction ,Biochemistry ,Translocation, Genetic ,law.invention ,Leukemia, Promyelocytic, Acute ,law ,Complementary DNA ,Gene expression ,medicine ,Humans ,RNA, Messenger ,Child ,Poly-ADP-Ribose Binding Proteins ,Molecular Biology ,Gene ,Polymerase chain reaction ,Oncogene Proteins ,Chromosomes, Human, Pair 15 ,Nuclear Proteins ,Orvostudományok ,Middle Aged ,medicine.disease ,Molecular biology ,Up-Regulation ,DNA-Binding Proteins ,stomatognathic diseases ,Leukemia ,Real-time polymerase chain reaction ,Child, Preschool ,Molecular Medicine ,Female ,Transcriptional Elongation Factors ,Chromosomes, Human, Pair 17 - Abstract
Among several newly identified oncogenes, dek and af4 are attractive targets for researchers interested with leukemia. In this study quantitative Real-Time RT-PCR technique was used to define alterations in expression of dek and af4 genes associated with acute promyelocytic leukaemia (APL) t (15; 17). RNA samples obtained from bone marrow aspirates of fourteen APL patients, cDNA portions were labelled with Syber Green 1 dye and LightCycler analysis have been performed. Expression changes in patients were found not significant in comparison to healthy donors for af4 (P = 0.192) and dek (P = 0.0895). We suggest that af4 gene may have a role in leukomogenesis restricted to lymphoblastic lineage; also further studies must carry on with a larger series of patients in order to understand the relationship between the dek gene and APL. Our study was the first attempt for analysing dek and af4 genes in APL t (15; 17) patients by quantitative Real-Time RT-PCR. This rapid and sensitive method could be used to screen these genes in different types of leukaemia.
- Published
- 2004
25. THE EFFECT OF STIMULATED MICROGLIA CONDITIONED MEDIA ON BDNF GENE EXPRESSION OF STRIATAL ASTROCYTES: QUANTIFICATION BY REAL-TIME PCR
- Author
-
Nilufer Esen, M. Dogan Gulkac, and Hakan Savli
- Subjects
Cost effectiveness ,Cell Communication ,Striatum ,Polymerase Chain Reaction ,Rats, Sprague-Dawley ,Biological Factors ,Gene expression ,medicine ,Animals ,Cells, Cultured ,Cerebral Cortex ,Brain-derived neurotrophic factor ,Microglia ,Chemistry ,Brain-Derived Neurotrophic Factor ,General Neuroscience ,General Medicine ,Molecular biology ,Corpus Striatum ,Rats ,medicine.anatomical_structure ,Real-time polymerase chain reaction ,Gene Expression Regulation ,nervous system ,Astrocytes ,Culture Media, Conditioned ,RNA ,Neuroglia ,Neuroscience ,Astrocyte - Abstract
It is well accepted that there is mutual relation between glia-glia and glia-neuron in the central nervous system. In the present study, the authors aimed to evaluate the effect of microglia conditioned medium (MCM) on brain derived neurotrophic factor (BDNF) gene expression of astrocytes by quantitative real-time polymerase chain reaction (PCR). Real-time PCR is one of the most recent techniques for determination of gene expression. It is the first choice when sensitivity, specifity and cost effectiveness are concerned. The authors present, for the first time, the settings of real-time PCR for quantification of BDNF gene expression of rat strital astrocytes. Astrocytes that cultured- from the striatum were incubated with conditioned medium of either Zymosan A stiumulated or unstimulated microglia which were cultured from striatum and cortex of the rat pups. Our results have shown that incubation with stimulated striatal MCM induced BDNF gene expression of striatal astrocytes (1.33 fold) when compared to astrocytes treated with regular medium or unstimulated striatal MCM. We have also seen the similar effect with cortical MCM implying that effect of MCM does not change with regionally different microglia.
- Published
- 2004
26. Expression stability of six housekeeping genes: a proposal for resistance gene quantification studies of Pseudomonas aeruginosa by real-time quantitative RT-PCR
- Author
-
Ugur Ozbek, Aynur Karadenizli, Fetiye Kolayli, Haluk Vahaboglu, Hakan Savli, and Sibel Gundes
- Subjects
DNA, Bacterial ,Microbiology (medical) ,Mutant ,Sigma Factor ,Microbial Sensitivity Tests ,Muramoylpentapeptide Carboxypeptidase ,Biology ,Microbiology ,beta-Lactamases ,Anti-Infective Agents ,Bacterial Proteins ,Ciprofloxacin ,Multienzyme Complexes ,Drug Resistance, Bacterial ,Gene expression ,Acyl-Carrier Protein S-Malonyltransferase ,Humans ,Penicillin-Binding Proteins ,RNA, Messenger ,Gene ,DNA Primers ,Genetics ,Reverse Transcriptase Polymerase Chain Reaction ,DNA-Directed RNA Polymerases ,Gene Expression Regulation, Bacterial ,General Medicine ,Phenotype ,Random Amplified Polymorphic DNA Technique ,Housekeeping gene ,Reverse transcription polymerase chain reaction ,Real-time polymerase chain reaction ,Hexosyltransferases ,Mutation ,Peptidyl Transferases ,Pseudomonas aeruginosa ,Pyrroline Carboxylate Reductases ,Carrier Proteins ,rpoS ,Acyltransferases - Abstract
Constantly expressed genes are used as internal controls in relative quantification studies. Suitable internal controls for such studies have not yet been defined for Pseudomonas aeruginosa. In this study, the genes ampC, fabD, proC, pbp-2, rpoD and rpoS of P. aeruginosa were compared in terms of expression stability by real-time quantitative RT-PCR. A total of 23 strains with diverse resistance phenotypes were studied. Stability of expression among the housekeeping genes was assessed on the basis of correlation coefficients, with the best-correlated pair accepted as being the most stable one. Eventually, proC and rpoD formed the most stable pair (r = 0.958; P < 0.001). Next, in four ciprofloxacin-selected nfxC-like mutants, levels of oprD, oprM and oprN mRNA were compared with those of their wild-type counterparts. The comparison was made after correcting the raw values by the geometric mean of the internal control genes proC and rpoD. The level of oprN mRNA was significantly up-regulated, while the oprD gene was down-regulated (although this difference was statistically insignificant), in the mutants. This expression pattern was consistent with that of the expected expression profile of nfxC-type mutants; this experiment therefore lends further support to the use of proC and rpoD genes simultaneously as internal controls for such studies.
- Published
- 2003
27. STIMULATED MICROGLIA SUPERNATANTS INDUCED OVEREXPRESSION OF NEURONAL NITRIC OXIDE GENE IN ASTROCYTES
- Author
-
Hakan Savli and Nilüfer Esen
- Subjects
Nitric Oxide Synthase Type I ,Cell-free system ,Rats, Sprague-Dawley ,Gene expression ,medicine ,Animals ,Cells, Cultured ,Neurons ,chemistry.chemical_classification ,Cell-Free System ,Microglia ,biology ,Chemistry ,General Neuroscience ,General Medicine ,Rats ,Cell biology ,Nitric oxide synthase ,medicine.anatomical_structure ,Enzyme ,nervous system ,Cell culture ,Astrocytes ,Culture Media, Conditioned ,biology.protein ,Neuroglia ,Nitric Oxide Synthase ,Neuroscience ,Astrocyte - Abstract
The glia-glia, glia-neuron interactions are very complex and have not yet been clearly understood. Microglia gain reactivity in almost every type of brain insult and by affecting astrocytes and neurons, they determine the fate of damaged brain. In the present study we aimed to see the effect of stimulated microglia on nNOS and iNOS expression of astrocytes. The microglia cultures were stimulated with zymosanA and astrocytes were treated with the medium of microglia for 48 h. The results revealed that the astrocytes treated with microglia medium expressed more nNOS and iNOS than the ones treated with normal medium.
- Published
- 2003
28. Gene expression analysis of 1,25(OH)2D3-dependent differentiation of HL-60 cells: a cDNA array study
- Author
-
Seppo Pakkala, Hakan Savli, Yan Aalto, Bálint Nagy, and Sakari Knuutila
- Subjects
Gene expression profiling ,Regulation of gene expression ,SPI1 ,Cellular differentiation ,Complementary DNA ,MNDA ,Gene expression ,Hematology ,Biology ,Gene ,Molecular biology - Abstract
The alterations in gene expression associated with 1,25(OH)2D3-induced differentiation of HL-60 cells were studied in order to identify potential targets for further investigation of the genetic basis of acute myeloid leukaemia. Atlas human haematology filters, including 406 genes (Clontech), were used to study gene expression in response to 1,25(OH)2D3 (concentration, 5 x 10-8 mol/l) for 24 and 72 h. Compared with untreated cells, expression differences were found in 43 genes. Downregulated genes at both time-points were: IL2RA, CMYC, NPM, DEK, AF4, FLI1, htlf, MNDA, BCR, IKAROS, BPI and NFAT4. Upregulated genes at both time-points were IL1B, CD14 and MCL1. CD55, CD58, IRF2, CREB1, ATF4, RAC1, TIAR, KIAA0053, BAT2, BTK, RCK, EV12B and EDN were downregulated at 24 h, while SPI1, MKK3, BTG1 and IL8 were upregulated. At 72 h the upregulated genes were IL1RA, IL2RG, CXCR4, SCYA1, SCYA3, SCYA4, SCYA5, SCYA22, ANX2, CD83 and UPAR. cDNA array results were confirmed on randomly selected genes using quantitative real-time polymerase chain reaction for three upregulated (CXCR4, IL1B and CD14) and three downregulated (DEK, AF4 and FLI1) genes. Gene expression analysis after differentiation induction may provide a tool to study the roles of DEK, AF4 and FLI1 in cell proliferation and differentiation. To demonstrate the genes that initiate differentiation, sequential gene expression analysis has to be performed during the first 24 h of the differentiation process.
- Published
- 2002
29. Identification of ApoA1, HPX and POTEE genes by omic analysis in breast cancer
- Author
-
Muge Serhatli, Ahmet Tarik Baykal, Zafer Canturk, Deniz Sünnetçi, Naci Cine, and Hakan Savli
- Subjects
Adult ,Cancer Research ,HPX ,Omic Analysis ,Breast Neoplasms ,Microarray ,Biology ,Bioinformatics ,ApoA1 ,Breast cancer ,Antigens, Neoplasm ,Hemopexin ,Breast Cancer ,POTEE ,medicine ,Humans ,Gene ,Aged ,Proteomic Profile ,Oncogene ,Apolipoprotein A-I ,Proteomic Profiling ,Cancer ,General Medicine ,Genomics ,Middle Aged ,medicine.disease ,Omics ,Molecular medicine ,Gene Expression Regulation, Neoplastic ,Oncology ,Cancer research ,Female ,MMP-9 ,NF-Kappa B - Abstract
WOS: 000339983200027 PubMed ID: 24969553 Breast cancer is the most common cancer among women and accounts for 23% of all female types of cancers. It is well recognized that breast cancer represents a heterogeneous group of tumors, and the molecular events involved in the progression to cancer remain undetermined. Moreover, available prognostic and predictive markers are not sufficient for the accurate determination of the risk for many breast cancer patients. Thus, it is necessary to discover new molecular markers for accurate prediction of clinical outcome and individualized therapy. In the present study, we performed omics-based whole-genome trancriptomic and whole proteomic profiling with network and pathway analyses of breast tumors to identify gene expression patterns related to clinical outcome. A total of 20 samples from tumors and 14 normal appearing breast tissues were analyzed using both gene expression microarrays and LC-MS/MS. We identified 585 downregulated and 413 upregulated genes by gene expression microarrays. Among these genes, HPX, POTEE and ApoAl were the most significant genes correlated with the proteomic profile. Our data revealed that these identified genes are closely related to breast cancer and may be involved in robust detection of disease progression. Kocaeli University BAP [2009/022] This study was generously supported by Kocaeli University BAP (no. 2009/022). Label-free shotgun proteomic analysis and data analysis were designed and performed at the Department of Medical Biochemistry, School of Medicine, Istanbul Medipol University, Istanbul, Turkey and the Genetic Engineering and Biotechnology Institute, Marmara Research Center, TUBITAK, Kocaeli, Turkey. All microarray studies, gene network and gene set enrichments were analyzed at the Department of Medical Genetics, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey.
- Published
- 2014
30. Synergistic antiproliferative effect of arsenic trioxide combined with bortezomib in HL60 cell line and primary blasts from patients affected by myeloproliferative disorders
- Author
-
Giuseppe A. Palumbo, Martina Canestraro, Hakan Savli, Sara Galimberti, Bálint Nagy, Daniele Tibullo, Simona Piaggi, Francesca Guerrini, Maria Rita Metelli, Mario Petrini, and Naci Cine
- Subjects
Cancer Research ,Myeloid ,Apoptosis ,Arsenicals ,Bortezomib ,TNF-Related Apoptosis-Inducing Ligand ,chemistry.chemical_compound ,Arsenic Trioxide ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Arsenic trioxide ,Oligonucleotide Array Sequence Analysis ,Caspase 8 ,Reverse Transcriptase Polymerase Chain Reaction ,Genetics ,Molecular Biology ,Cell Cycle ,NF-kappa B ,Myeloid leukemia ,Drug Synergism ,Oxides ,Orvostudományok ,Boronic Acids ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Proto-Oncogene Proteins c-bcl-2 ,Pyrazines ,medicine.drug ,HL60 ,Blotting, Western ,Caspase 3 ,HL-60 Cells ,Biology ,Klinikai orvostudományok ,medicine ,Biomarkers, Tumor ,Humans ,RNA, Messenger ,Cell Proliferation ,Myeloproliferative Disorders ,Gene Expression Profiling ,Receptors, TNF-Related Apoptosis-Inducing Ligand ,chemistry ,Immunology ,Cancer research ,Blast Crisis ,Reactive Oxygen Species ,Proto-Oncogene Proteins c-akt - Abstract
Both arsenic trioxide (ATO) and bortezomib show separate antileukemic activity. With the purpose of evaluating whether the combination of ATO and bortezomib would be an option for patients with acute leukemia, we incubated HL60 leukemic cells with ATO alone and in combination with bortezomib. ATO and bortezomib cooperated to induce cell death and to inhibit proliferation and apoptosis in a synergistic way. The combined treatment resulted in a stronger activation of caspase 8 and 9, moderate activation of caspase 3, and increased expression of Fas and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-DR5 receptors. When bortezomib was added, some proapoptotic genes (CARD9, TRAIL) were upregulated, and some antiapoptotic genes (BCL2, BCL3, FLICE) were downregulated. When coincubated, approximately 80% of cells showed altered mitochondrial membrane permeability. Moreover, ATO alone and in combination with bortezomib abrogated DNA-binding activity of nuclear factor kappa beta (NF-kappaB). Gene expression assays showed that more deregulated genes were related to proliferation of leukocytes, tumorigenesis, control of cell cycle, hypoxia and oxidative stress, cytokines, PI3K-AKT, ERK-MAPK, EGF pathways, and ubiquitination. Finally, in three cases of acute myeloid leukemia, the addition of bortezomib to ATO significantly increased cytotoxicity. We conclude that the combination of bortezomib and ATO may be efficacious in the treatment of myeloid disorders.
- Published
- 2009
31. Gene network and canonical pathway analysis in prostate cancer: a microarray study
- Author
-
Imre Romics, Hakan Savli, Attila Szendroi, and Bálint Nagy
- Subjects
Male ,Microarray ,Interleukin-1beta ,Clinical Biochemistry ,Gene regulatory network ,Down-Regulation ,Biology ,Polymerase Chain Reaction ,Biochemistry ,Prostate cancer ,Gene expression ,Biomarkers, Tumor ,medicine ,Humans ,Insulin-Like Growth Factor I ,Molecular Biology ,Gene ,DNA Primers ,Oligonucleotide Array Sequence Analysis ,Base Sequence ,Microarray analysis techniques ,Gene Expression Profiling ,NF-kappa B ,Prostatic Neoplasms ,Orvostudományok ,Prostate-Specific Antigen ,medicine.disease ,Actin cytoskeleton ,Up-Regulation ,Gene expression profiling ,Cancer research ,Molecular Medicine ,Original Article ,Egészségtudományok - Abstract
The molecular mechanism playing a role in the development of prostate cancer (PCA) is not well defined. We decided to determine the changes in gene expression in PCA tissues and to compare them to those in non-cancerous samples. Prostate tissue samples were collected by needle biopsy from 21 PCA and 10 benign prostate hyperplasic (BPH) patients. Total RNA was isolated, cDNA was synthesized, and gene expression levels were determined by microarray method. In the progression to PCA, 738 up-regulated and 515 down-regulated genes were detected in samples. Analysis using Ingenuity Pathway Analysis (IPA) software revealed that 466 network and 423 functions-pathways eligible genes were up-regulated, and 363 network and 342 functions-pathways eligible genes were down-regulated. Up-regulated networks were identified around IL-1beta and insulin-like growth factor-1 (IGF-1) genes. The NFKB gene was centered around two up- and down-regulated networks. Up-regulated canonical pathways were assigned and four of them were evaluated in detail: acute phase response, hepatic fibrosis, actin cytoskeleton, and coagulation pathways. Axonal guidance signaling was the most significant down-regulated canonical pathway. Our data provide not only networks between the genes for understanding the biologic properties of PCA but also useful pathway maps for future understanding of disease and the construction of new therapeutic targets.
- Published
- 2008
32. Effect of carbapenems on the transcriptional expression of the oprD, oprM and oprN genes in Pseudomonas aeruginosa
- Author
-
Ozden Hatirnaz, Haluk Vahaboglu, Hakan Savli, Fetiye Kolayli, Aynur Karadenizli, Erdener Balikci, Fatma Budak, and Kivanc Ergen
- Subjects
Microbiology (medical) ,Imipenem ,Transcription, Genetic ,Mutant ,Porins ,Microbial Sensitivity Tests ,medicine.disease_cause ,Microbiology ,Meropenem ,Polymerase Chain Reaction ,Drug Resistance, Bacterial ,medicine ,Humans ,RNA, Messenger ,Gene ,biology ,Pseudomonas aeruginosa ,RNA ,Membrane Transport Proteins ,General Medicine ,Gene Expression Regulation, Bacterial ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Anti-Bacterial Agents ,Pseudomonadales ,Thienamycins ,medicine.drug ,Pseudomonadaceae ,Bacterial Outer Membrane Proteins - Abstract
The effects of imipenem and meropenem on the transcriptional expression of resistance-related genes oprD, oprM and oprN in Pseudomonas aeruginosa were studied by quantitative real-time PCR. Four strains were examined: the type strain PT5 (PAO1), its derivatives M7 and PT149, and a clinical isolate, PaKT3. The derivative M7 is a nalB mutant, overexpressing the MexAB-OprM pump, and the derivative PT149 is a nfxC-type mutant, overexpressing the MexEF-OprN pump while it is down-regulated for the OprD protein. After 18 h incubation in broth, the cultures were divided into three portions. Two were supplemented with antibiotics and the other was left antibiotic-free as the control. After a further 45 min incubation, total RNA was isolated from the strains by guanidine denaturation and acid-phenol/chloroform extraction. DNA-free total RNAs were immediately reverse-transcribed by MMuLV reverse transcriptase. Concentrations of mRNAs obtained by quantitative PCR were expressed relative to uninduced portions of the strains. The results showed that oprD was relatively stable against carbapenem antibiotics. oprM was induced significantly by imipenem in only one strain and oprN was induced by imipenem in most of the strains. The responses at the mRNA level found here were unexpected and suggested a chaotic, unpredictable regulatory mechanism.
- Published
- 2004
33. Real-time PCR analysis of the apoptosis related genes in ATRA treated APL t(15;17) patients
- Author
-
Bálint Nagy, Ugur Ozbek, Günçağ Dinçol, Sema Sirma, Hakan Savli, and Melih Aktan
- Subjects
Acute promyelocytic leukemia ,Time Factors ,CD14 ,Clinical Biochemistry ,Retinoic acid ,Apoptosis ,HL-60 Cells ,Tretinoin ,T-15 ,Biology ,Klinikai orvostudományok ,Biochemistry ,Polymerase Chain Reaction ,Translocation, Genetic ,chemistry.chemical_compound ,Leukemia, Promyelocytic, Acute ,immune system diseases ,Gene expression ,medicine ,Humans ,neoplasms ,Molecular Biology ,Gene ,Chromosomes, Human, Pair 15 ,Gene Expression Profiling ,Orvostudományok ,medicine.disease ,Molecular biology ,Gene Expression Regulation, Neoplastic ,Real-time polymerase chain reaction ,chemistry ,Molecular Medicine ,Chromosomes, Human, Pair 17 - Abstract
All-trans retinoic acid (ATRA) treatment of the acute promyelocytic leukemia (APL) have subsequently resulted in cell apoptosis, but the molecular mechanism of this effect remains elusive. In order to understand a possible involvement of genes regulating apoptotic signal pathways, expression levels of bcl2, bax, dapk1, myc, bad, wt1, and mcl genes were analyzed during ATRA treatment in five APL patients with t (15;17) using Real- time PCR (LightCycler). Two samples from each patient were compared to each other: primary diagnostic sample and a sample taken at remission. Effect of the ATRA treatment was demonstrated by the concomitant induction of cd14 and il1beta genes in four patients. Also other apoptosis related genes were found down-regulated in general but especially the down regulated levels of wt1 and bax attract attention. Result suggested that ATRA dependent apoptosis of APL was under the control of both internal and external pathways without relationships to the amount of the blast populations. Ratio of bcl2 to bax may be more important for this regulation than the ratio of bcl2 to bad. Either bcl2 family or less known apoptosis related genes as wt1 will still be required to further studies in this setting.
- Published
- 2003
34. Gene expression analysis of 1,25(OH)2D3-dependent differentiation of HL-60 cells: a cDNA array study
- Author
-
Hakan, Savli, Yan, Aalto, Bálint, Nagy, Sakari, Knuutila, and Seppo, Pakkala
- Subjects
Calcitriol ,Gene Expression Regulation ,Gene Expression Profiling ,Humans ,Cell Differentiation ,HL-60 Cells ,Oncogenes ,Oligonucleotide Array Sequence Analysis - Abstract
The alterations in gene expression associated with 1,25(OH)2D3-induced differentiation of HL-60 cells were studied in order to identify potential targets for further investigation of the genetic basis of acute myeloid leukaemia. Atlas human haematology filters, including 406 genes (Clontech), were used to study gene expression in response to 1,25(OH)2D3 (concentration, 5 x 10-8 mol/l) for 24 and 72 h. Compared with untreated cells, expression differences were found in 43 genes. Downregulated genes at both time-points were: IL2RA, CMYC, NPM, DEK, AF4, FLI1, htlf, MNDA, BCR, IKAROS, BPI and NFAT4. Upregulated genes at both time-points were IL1B, CD14 and MCL1. CD55, CD58, IRF2, CREB1, ATF4, RAC1, TIAR, KIAA0053, BAT2, BTK, RCK, EV12B and EDN were downregulated at 24 h, while SPI1, MKK3, BTG1 and IL8 were upregulated. At 72 h the upregulated genes were IL1RA, IL2RG, CXCR4, SCYA1, SCYA3, SCYA4, SCYA5, SCYA22, ANX2, CD83 and UPAR. cDNA array results were confirmed on randomly selected genes using quantitative real-time polymerase chain reaction for three upregulated (CXCR4, IL1B and CD14) and three downregulated (DEK, AF4 and FLI1) genes. Gene expression analysis after differentiation induction may provide a tool to study the roles of DEK, AF4 and FLI1 in cell proliferation and differentiation. To demonstrate the genes that initiate differentiation, sequential gene expression analysis has to be performed during the first 24 h of the differentiation process.
- Published
- 2002
35. The Antidepressant Agomelatine Improves Memory Deterioration and Upregulates CREB and BDNF Gene Expression Levels in Unpredictable Chronic Mild Stress (UCMS)-Exposed Mice
- Author
-
Oguz Mutlu, Guner Ulak, Esen Gumuslu, Furuzan Akar, Hakan Savli, Faruk Erden, Ipek Komsuoglu Celikyurt, Deniz Sünnetçi, and Naci Cine
- Subjects
Agonist ,medicine.medical_specialty ,Elevated plus maze ,medicine.drug_class ,Clinical Biochemistry ,Hippocampus ,Morris water navigation task ,melatonin ,CREB ,Bioinformatics ,memory ,Melatonin ,Internal medicine ,medicine ,Agomelatine ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,Original Research ,biology ,business.industry ,lcsh:RM1-950 ,General Medicine ,BDNF ,lcsh:Therapeutics. Pharmacology ,Endocrinology ,depression ,biology.protein ,Antidepressant ,business ,agomelatine ,medicine.drug - Abstract
Agomelatine, a novel antidepressant with established clinical efficacy, acts as an agonist of melatonergic MT 1 and MT 2 receptors and as an antagonist of 5-HT 2C receptors. The present study was undertaken to investigate whether chronic treatment with agomelatine would block unpredictable chronic mild stress (UCMS)-induced cognitive deterioration in mice in passive avoidance (PA), modified elevated plus maze (mEPM), novel object recognition (NOR), and Morris water maze (MWM) tests. Moreover, the effects of stress and agomelatine on brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) messenger ribonucleic acid (mRNA) levels in the hippocampus was also determined using quantitative real-time polymerase chain reaction (RT-PCR). Male inbred BALB/c mice were treated with agomelatine (10 mg/kg, i.p.), melatonin (10 mg/kg), or vehicle daily for five weeks. The results of this study revealed that UCMS-exposed animals exhibited memory deterioration in the PA, mEPM, NOR, and MWM tests. The chronic administration of melatonin had a positive effect in the PA and +mEPM tests, whereas agomelatine had a partial effect. Both agomelatine and melatonin blocked stress-induced impairment in visual memory in the NOR test and reversed spatial learning and memory impairment in the stressed group in the MWM test. Quantitative RT-PCR revealed that CREB and BDNF gene expression levels were downregulated in UCMS-exposed mice, and these alterations were reversed by chronic agomelatine or melatonin treatment. Thus, agomelatine plays an important role in blocking stress-induced hippocampal memory deterioration and activates molecular mechanisms of memory storage in response to a learning experience.
- Published
- 2014
36. CB1093, a novel vitamin D analog; effects on differentiation and clonal growth on HL-60 and de novo leukemia cells
- Author
-
L Binderup, Seppo Pakkala, Ilkka Pakkala, Sakari Knuutila, and Hakan Savli
- Subjects
Cancer Research ,Cellular differentiation ,chemistry.chemical_element ,Antineoplastic Agents ,HL-60 Cells ,Biology ,Calcium ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Calcitriol ,Vitamin D and neurology ,medicine ,Tumor Cells, Cultured ,Animals ,Humans ,030304 developmental biology ,0303 health sciences ,Leukemia ,Dose-Response Relationship, Drug ,Cell growth ,Superoxide ,Cell Differentiation ,Hematology ,medicine.disease ,Molecular biology ,In vitro ,3. Good health ,Clone Cells ,Rats ,Oncology ,chemistry ,Biochemistry ,030220 oncology & carcinogenesis ,Toxicity ,Cell Division - Abstract
We studied the effects of a novel vitamin D analog CB1093, EB1089 (one of the most antileukemic analogs yet) and 1α,25(OH)2D3 both on HL-60 cells and cells from 13 AML patients. Differentiation was measured both by induction of superoxide production and non-specific esterase. Cell proliferation was assessed by colony assay and 3H-thymidine incorporation. The effect on serum calcium was measured in rats. The CB1093 proved to be the most efficient of the analogs tested so far, both in inducing differentiation and in inhibiting proliferation. This, combined with its low hypercalcemic effect shown here, makes it a promising candidate for preclinical animal studies.
- Published
- 1997
37. Histone deacetylase inhibitor ITF2357 is effective on the P39 cells. A gene expression study
- Author
-
Mario Petrini, Bálint Nagy, G.A. Palumbo, Sara Galimberti, Hakan Savli, and M. Canestraro
- Subjects
Cancer Research ,Histone deacetylase 5 ,HDAC11 ,medicine.drug_class ,business.industry ,Histone deacetylase 2 ,HDAC10 ,HDAC9 ,Histone deacetylase inhibitor ,SAP30 ,HDAC4 ,Oncology ,hemic and lymphatic diseases ,Cancer research ,medicine ,business - Abstract
18024 Background: ITF2357 is a histone deacetylase inhibitor that has been reported to induce apoptosis in myeloma and acute leukemia. We assessed if ITF2357 would exert an anti-proliferative and p...
- Published
- 2008
38. Bortezomib combined with histone deacetylase inhibitor ITF2357 or arsenic trioxide exerts aynergistic anti-proliferative and pro-apoptotic effect on P39 cells
- Author
-
G.A. Palumbo, Mario Petrini, Sara Galimberti, Hakan Savli, M. Canestraro, and Bálint Nagy
- Subjects
Cancer Research ,business.industry ,medicine.drug_class ,Bortezomib ,Myelodysplastic syndromes ,Histone deacetylase inhibitor ,Anti proliferative ,medicine.disease ,Transformation (genetics) ,chemistry.chemical_compound ,Oncology ,chemistry ,Cell culture ,Apoptosis ,Cancer research ,Medicine ,Arsenic trioxide ,business ,medicine.drug - Abstract
18022 Background: NF-kB is constitutively activated in the P39 cell line and its activity levels are higher in advanced myelodysplastic syndromes (MDS), with a higher risk of transformation into ac...
- Published
- 2008
39. Deregulated Levels of the NF-κB1, NF-κB2, and Rel Genes in Ukrainian Patients with Leukemia and Lymphoma in the Post-Chernobyl Period
- Author
-
Hakan Savlı, Ramis Ufuk Akkoyunlu, Naci Çine, Daniil F. Gluzman, Michael P. Zavelevich, Lilia M. Sklyarenko, Stella V. Koval, and Deniz Sünnetçi
- Subjects
chronic lymphocytic leukemia ,non-hodgkin's lymphoma ,b-cell neoplasms ,cancer ,thrombosis ,t-cell neoplasms ,acute leukemia ,myelodysplastic syndromes ,chronic leukemia ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
INTRODUCTION: Nuclear factor kappa B (NF-κB) is an important transcription factor in cancer and NF-κB activation has been seen in angiogenesis, tumor progression, and metastasis. Relationships between specific NF-κB gene networks, leukemogenesis, and radiation exposure are still unknown. Our aim was to study the expression levels of the NF-κB1, NF-κB2, and Rel genes in hematological malignancies in the post-Chernobyl period. METHODS: We analyzed gene expression levels of NF- κB1, NF-κB2, and Rel in 49 B-cell chronic lymphocytic leukemia, 8 B-cell non-Hodgkin's lymphoma, 3 acute myeloid leukemia, 3 chronic myeloid leukemia, 2 hairy cell leukemia, 2 myelodysplastic syndrome, and 2 T-cell large granular lymphocytic leukemia patients using realtime polymerase chain reaction. RESULTS: Expression levels of NF-κB1, NF-κB2, and Rel genes were found to be deregulated. DISCUSSION AND CONCLUSION: These results could be accepted as specific gene traces to radiation-induced leukemia or as potential candidates for new diagnostic biomarker studies. Larger experiments and non-exposed control malignant cell populations are needed to clarify these suggestions.
- Published
- 2016
- Full Text
- View/download PDF
40. Bortezomib and Arsenic Trioxide Activity on a Myelodysplastic Cell Line (P39): A Gene Expression Study
- Author
-
Hakan Savlı, Sara Galimberti, Deniz Sünnetçi, Martina Canestraro, Giuseppe Palumbo, Balint Nagy, Francesco Di Raimondo, and Mario Petrini
- Subjects
Bortezomib ,Arsenic trioxide ,NF-κB ,MDS ,Gene expression ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Objective: We aimed to understand the molecular pathways affected by bortezomib and arsenic trioxide treatment on myelomonocytoid cell line P39. Materials and Methods: Oligonucleotide microarray platforms were used for gene expression and pathway analysis. Confirmation studies were performed using quantitative real time PCR. Results: Bortezomib treatment has shown upregulated DIABLO and NF-κBIB (a NF-κB inhibitor) and downregulated NF-κB1, NF-κB2, and BIRC1 gene expressions. Combination treatment of the two compounds showed gene expression deregulations in concordance by the results of single bortezomib treatment. Especially, P53 was a pathway more significantly modified and a gene network centralized around the beta estradiol gene. Beta estradiol, BRCA2, and FOXA1 genes were remarkable deregulations in our findings. Conclusion: Results support the suggestions about possible use of proteasome inhibitors in the treatment of high-risk myelodysplastic syndrome (MDS). NF-κB was observed as an important modulator in leukemic transformation of MDS.
- Published
- 2015
- Full Text
- View/download PDF
41. High Throughput FISH Analysis: A New, Sensitive Option For Evaluation of Hematological Malignancies
- Author
-
Hakan Savlı, Seda Eren, Nilüfer Üzülmez, Zeynep İlkay, Duygu Yavuz, Deniz Sünnetçi, Abdullah Hacıhanifioğlu, and Naci Çine
- Subjects
hematologic malignancies ,leukemia ,molecular genetics ,microarray ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
OBJECTIVE: The aim of this study was to determine the efficiency of the high throughput FISH analysis (HTFA) method for detecting genetic alterations in hematological malignancies, which is a new bacterial artificial chromosome array-based approach. METHODS: We performed a HTFA study of bone marrow aspiration and peripheral blood samples of 77 cases (n=19 myelodysplastic syndrome, n=17 acute lymphoblastic leukemia, n=9 chronic myeloid leukemia, n=32 acute myeloid leukemia) with hematological malignancies during the periods of initial diagnosis, treatment, and/or follow-up. RESULTS: Both numerical and structural abnormalities were detected by HTFA. We observed aberrations in 88% of our acute lymphoblastic leukemia patients, 25% of acute myeloid leukemia patients, and 31% of myelodysplastic syndrome patients. In chronic myeloid leukemia cases, aberration was not detected by HTFA. CONCLUSION: Our results showed that HTFA, combined with other methods, will gradually take a place in the routine diagnosis of hematologic malignancies.
- Published
- 2013
- Full Text
- View/download PDF
42. [Untitled]
- Author
-
Esen Gumuslu, Oguz Mutlu, Deniz Sunnetci, Guner Ulak, Ipek K. Celikyurt, Naci Cine, Furuzan Akar, Hakan Savlı, and Faruk Erden
- Subjects
agomelatine ,melatonin ,depression ,memory ,BDNF ,CREB ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract non disponibile
- Published
- 2014
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.