Berrin Tunca | Uludag University (original) (raw)

Papers by Berrin Tunca

Research paper thumbnail of Circulating miR-195 as a Therapeutic Biomarker in Turkish Breast Cancer Patients

Background: Dysregulation of miRNA expression may be used as a biomarker for specific tumours bec... more Background: Dysregulation of miRNA expression may be used as a biomarker for specific tumours because it may contribute to development of cancer. Circulating miRNA profiles have been highlighted for their potential as predictive markers in heterogeneous diseases such as breast cancer. In the literature, there is evidence that miR-195 levels are differentially expressed pre-and post-operative periods in breast cancer patients. At the same time, miRNA expression levels may vary because of ethnic origins. This study aimed to determine expression levels and potential roles of miR-195 in Turkish breast cancer patients. Materials and Methods: The expression patterns of miR-195 were initially examined in breast cancer tissues (luminal A and B type) (n=96). Subsequently, blood samples were prospectively collected from preoperative and postoperative Turkish breast cancer patients and disease free controls. Total RNA was isolated, and the expression level of miR-195 was quantified by real-time PCR. Results: We found that miR-195 level was altered in Turkish breast cancer patients, with down-regulation evident in breast cancer tissues compared to normal adjacent specimens. Furthermore, circulating levels of miR-195 was significantly decreased in post-operative blood samples compared with pre-operative levels (p=0.01 and <0.05). However, miR-195 was significantly increased in pre-operative blood samples of the luminal B type (p= 0.04 and <0.05). Conclusions: This study represents the first report of a miR-195 expression profile in Turkish breast cancer patients. Our data suggests that miR-195 levels might be a clinically useful biomarker in the earliest stage of Turkish breast cancer patients.

Research paper thumbnail of Potential role of solid lipid nanoparticles in overcoming the acquired tamoxifen resistance of breast cancer

Journal of Biotechnology, 2017

and leaves can be seen at the same time; which is a very rare condition. In this study, "Colchicu... more and leaves can be seen at the same time; which is a very rare condition. In this study, "Colchicum pusillum" has been collected from the heights of Guzelyurt and investigated its anticancer activity on primary (Colo-320) and metastatic (Colo-741) human colon carcinoma cell lines. Different concentrations of bulb extracts were incubated for 24 and 48 h with Colo-320 and Colo-741 cells. Cell growth and cytotoxicity were measured by MTT assays. All concentrations of bulb extracts showed cytotoxic activity against all Colo-320 cells. According to the cell viability and cytotoxicity results, 20 mg/ml concentration of bulb extract of "Colchicum pusillum" was found the most active dose against Colo-741 cells, in 48 h. In addition, these MTT results; the immunohistochemical staining and signal pathways of "Colchicum pusillum" extracts are still investigated.

Research paper thumbnail of 759: Ficus carica latex inhibits GBM cell proliferation by modulating let-7d expression

European Journal of Cancer, 2014

Research paper thumbnail of Olea europaea Leaf Phenolics Oleuropein, Hydroxytyrosol, Tyrosol, and Rutin Induce Apoptosis and Additionally Affect Temozolomide against Glioblastoma: In Particular, Oleuropein Inhibits Spheroid Growth by Attenuating Stem-like Cell Phenotype

Life

The effects of Olea europaea leaf extract (OLE) phenolics, including oleuropein (OL), hydroxytyro... more The effects of Olea europaea leaf extract (OLE) phenolics, including oleuropein (OL), hydroxytyrosol (HT), tyrosol (TYR), and rutin against glioblastoma (GB), independently and in combination with temozolomide (TMZ), were investigated in T98G and A172 cells. Cell growth was assessed by WST-1, real-time cell analysis, colony formation, and cell cycle distribution assays. A dual acridine orange propidium iodide (AO/PI) staining and annexin V assay determined cell viability. A sphere-forming assay, an intracellular oxidative stress assay, and the RNA expression of CD133 and OCT4 investigated the GB stem-like cell (GSC) phenotype. A scratch wound-healing assay evaluated migration capacity. OL was as effective as OLE in terms of apoptosis promotion (p < 0.001) and GSC inhibition (p < 0.001). HT inhibited cell viability, GSC phenotype, and migration rate (p < 0.001), but its anti-GB effect was less than the total effect of OLE alone. Rutin decreased reactive oxygen species produc...

Research paper thumbnail of Kolo-rektal kanserli hasta ve yakınlarında genetik yatkınlığın araştırılması

Research paper thumbnail of The p53 status in patients with common variable immunodeficiency

Journal of Clinical Medicine and Research, 2012

Common variable immunodeficiency (CVID) comprises a heterogeneous group of primary antibody defic... more Common variable immunodeficiency (CVID) comprises a heterogeneous group of primary antibody deficiencies with complex clinical and immunological phenotypes. A high risk for cancer has been described for some types of cancer among patients with CVID. Mutations in p53, a critical tumor suppressor gene, are one of the most common genetic alterations in human cancers, therefore contributes to the complex network of molecular events leading to tumor formation. This prompted us to investigate the incidence of p53 gene mutations in patients with CVID and evaluated the predictive risk for tumor development. We investigated the presence of p53 mutations in patients with CVID, tumor samples and in the surgical margins of 34 patients with head and neck cancer using single strand conformational polymorphism and sequencing analysis. We investigated the presence of p53 mutations in genomic DNA samples of 20 patients with CVID and 10 healthy controls using polymerase chain reaction and heteroduplex analysis. None of the patients were found to have p53 gene mutations. Only one patient developed non-Hodgkin lymphoma (NHL) during nine years follow-up. P53 mutations was not also detected in tumor biopsy sample. We found no statistically significant association between the presences of p53 mutations in patients with CVID. Key words: Common variable immunodeficiency, p53 gene, tumor development, apoptosis.

Research paper thumbnail of The Investigation of genetic predisposition in patients with colorectal cancer and their relatives

Frajil bölgeler kromozomlar üzerinde boya almayan özel gap ve kırık noktalandır ve onlar çeşitli ... more Frajil bölgeler kromozomlar üzerinde boya almayan özel gap ve kırık noktalandır ve onlar çeşitli kültür koşullan ile oluşturulabilirler. Çeşitli çalışmalar frajil bölge ekspresyonunu arttıran ve birçok klastojenik ajan olduğunu göstermiştir. Biz de çalışmamızda periferik kan lenfositlerinde gözlediğimiz prometafaz kromozomlarda common frajil bölgelerin ekspresyonunu afidikolin, bromodeoksiuridin ve kafein ile indükledik. Kromozomal aberasyonlar ve frajil bölge ekspresyonlan, 32 kolon kanserli hasta, 30 asemptomatik kolon akraba, 36 rektum kanserli hasta, 30 rektum akraba ve 30 da yaşlan hasta ve akraba grupları ile uyumlu, ailesinde kanser hikayesi bulunmayan sağlıklı kontrol bireylerinden oluşan toplam 158 vakada değerlendirildi. Hem hasarlı hücre oram (P0.05). Biz iki grubumuzda da apbidicolin tip common frajil bölgeler belirledik. Kolon kanserli hastalar ve yakınlarında belirlediğimiz frajil bölgeler lp36, lp31, lp21, lq21, lq25, lq44, 2p24, 2pl6, 2q21, 2q33, 2q37, 3p21, 3pl4, 15...

Research paper thumbnail of Early-stage colon cancer with high MALAT1 expression is associated with the 5-Fluorouracil resistance and future metastasis

Molecular Biology Reports

Research paper thumbnail of Olea europaea leaf extract decreases tumour size by affecting the LncRNA expression status in glioblastoma 3D cell cultures

European Journal of Integrative Medicine, 2021

Abstract Introduction Glioblastoma (GB) is the most aggressive primary brain tumour. Temozolomide... more Abstract Introduction Glioblastoma (GB) is the most aggressive primary brain tumour. Temozolomide (TMZ) is a chemotherapy drug used in the treatment of GB. Despite treatment with TMZ, the prognosis of GB is poor. This study aimed to demonstrate the ability of Olea europaea leaf extract (OLE) alone and in combination with TMZ to suppress tumour aggressiveness by evaluating long non-coding RNA (LncRNA) and cancer stem cell (CSC) markers in GB cells using a three-dimensional (3D) model. Methods The Real-time PCR (RT-PCR) method was used to determine the effects of OLE on LncRNA and CSC markers associated with tumour aggressiveness. To explore the effect of OLE on tumour size, a 3D model was developed. Results It was found that OLE suppressed tumour aggressiveness with inhibited the MALAT1, SOX2 and NANOG (p Conclusion OLE may be a potential therapeutic agent that can be used in the treatment of GB, as it has been shown to reduce tumour size and increase the effect of TMZ.

Research paper thumbnail of Solid lipid nanoparticles in reversing the acquired tamoxifen-resistance

2017 E-Health and Bioengineering Conference (EHB), 2017

The anti-estrogen tamoxifen (Tam) is the most preferred option for patients with estrogen-recepto... more The anti-estrogen tamoxifen (Tam) is the most preferred option for patients with estrogen-receptor (ER)-positive breast cancer. However, multi-drug resistance (MDR) is a considerable clinical problem in the successful chemotherapeutic treatment. Members of the ATP-binding cassette (ABC) transporter family proteins play an important role in acquired drug resistance. Many studies have focused primarily on the clinical significance of P-gp (MDR1), BCRP and MRP1 members belong to ABC transporter superfamily on anticancer-drug resistance. Consequently, several strategies have been improved to overcome drug resistance. Nanoparticle drug delivery systems provide an increase in the intracellular concentration of the drugs as well as a reduction in toxicity of free-drug on healthy cells thanks to unique physical and biological properties. Solid lipid nanoparticles (SLNs) have been improved as an alternative colloidal drug delivery systems due to successful incorporation of both hydrophilic and hydrophobic compounds and their related benefits (controlled drug release, high entrapment efficiency and small size etc.) For this purpose, the aim of this study was to discuss the role of Tam-loaded solid lipid nanoparticles (SLNs) to overcome MDR and determine the ability of Tam-SLNs to induce apoptosis.

Research paper thumbnail of Utilisation de l'extrait obtenu à partir de feuilles d'olive noire dans le traitement du glioblastome

L'invention concerne l'utilisation de l'olive noire le traitement de tumeurs de type ... more L'invention concerne l'utilisation de l'olive noire le traitement de tumeurs de type glioblastome positif de cellules souches cancereuses qui sont traitees par temozolomide.

Research paper thumbnail of MikroRNA-106a’nın yüksek ekspresyonu kolorektal kanserlerde mikrosatellit instablite durumu ile ilişkilidir

Uludağ Üniversitesi Tıp Fakültesi Dergisi, 2021

Mikrosatellit instabilite (MSI), DNA tamir genlerindeki hatalardan kaynaklanan ve kolorektal kans... more Mikrosatellit instabilite (MSI), DNA tamir genlerindeki hatalardan kaynaklanan ve kolorektal kanserin (KRK) oluşmasına neden olan genetik bir durumdur. Sporadik KRK'larda MSI görülme sıklığı, prognoza olan etkisi literatürde çelişkilidir. Bununla birlikte MSI'ya sahip KRK'larda standart kemoterapi yetersiz kaldığı için yeni tedavi seçeneklerine ihtiyaç duyulmaktadır. micoRNA'lar (miRNA) kanserleşme sürecinde görev alan ve tanıda, prognozda ve tedavide belirteç olarak kullanılan küçük RNA molekülleridir. Mevcut çalışmada, Türk popülasyonuna ait sporadik gelişen KRK'larda MSI'nın görülme sıklığının tanımlanması ve bu tümörlerde miRNA'ların ekspresyon farklılıklarının belirlenmesi amaçlanmıştır. Çalışmada, sporadik KRK tanısı almış 63 hasta değerlendirildi. Hastalara ait arşiv tümör ve normal dokularından DNA ve RNA izolasyonları yapıldı. DNA örneklerinden fragment analizine dayalı MSI testi gerçekleştirildi. qRT-PCR kullanılarak 38 farklı miRNA'nın ekspresyon profili incelendi. 63 hastada MSI görülme oranı %23.8 olarak belirlendi. MSI ve mikrosatellit stabil (MSS) tümörler karşılaştırıldığında, MSI tümörlerde, miR-124 ve miR-106a'nın yüksek ve miR-145'in ise düşük ekspresyon gösterdiği belirlendi (p<0.05). Bununla birlikte miR-106a'nın yüksek ekspresyonunun cerrahi sonrası nüks gelişimi ile ilişkili olduğu saptandı (p=0.002). Elde edilen bulgular ışığında miR-106a'nın özellikle MSI genotipine sahip KRK tümörlerde hedeflenmesi ile KRK hastalarında yeni tedavi protokollerinin oluşturularak nüks oluşumunun engellenebileceğini öngörülmüştür. Anahtar Kelimeler: Sporadik Kolorektal Kanser. Mikrosatellit Ġnstability. MikroRNA. miR-106a. Upregulation of Microrna-106a is Associated with Microsatellite Instability Status in Colorectal Cancer ABSTRACT Microsatellite instability (MSI) is a genetic condition that results from errors in DNA repair genes and causes colorectal cancer (CRC). The incidence of MSI in sporadic CRCs and its effect on prognosis are contradictory in the literature. However, since standard chemotherapy is insufficient in CRCs with MSI, new treatment options are needed. micoRNAs (miRNAs) are small RNA molecules that take part in the cancer process and are used as markers in diagnosis, prognosis and treatment. In the study, it is aimed to define the prevalence of MSI in sporadically developing CRCs belonging to the Turkish population and to determine the expression differences of miRNAs in these tumors. 63 patients diagnosed with sporadic CRC were evaluated in the study. DNA and RNA isolations were made from archive tumor and normal tissues of the patients. MSI test was performed based on fragment analysis from DNA samples. The expression profiles of 38 different miRNAs were examined using qRT-PCR. In 63 patients, the incidence of MSI was determined as 23.8%. When MSI and microsatellite stable (MSS) tumors were compared, it was determined that miR-124 and miR-106a showed high expression and miR-145 low expression in MSI tumors (p <0.05). However, high expression of miR-106a was found to be associated with postoperative recurrence (p=0.002). In the light of the findings obtained, we think that by targeting miR-106a especially in CRC tumors with MSI genetype, recurrence can be prevented by creating new treatment protocols in these tumors.

Research paper thumbnail of Investigation of VHL gene associated with miR-223 in clear cell renal cell carcinoma

Molecular Biology Reports, 2021

BACKGROUND Clear cell type renal cell carcinoma (ccRCC) is the most common renal cell carcinoma (... more BACKGROUND Clear cell type renal cell carcinoma (ccRCC) is the most common renal cell carcinoma (RCC). In this study, we examined the expressions of VHL and miR-223 in ccRCC patients׳ tissues to investigate the possible role in the development of ccRCC. METHODS AND RESULTS This study collected five expression profiles (GSE36139, GSE3, GSE73731, GSE40435, and GSE26032) from Gene Omnibus Data. Expressions of VHL and miR-223 in paraffinized tumor and normal tissues of 100 Turkish patients' ccRCC tissues were determined by bioinformatic data mining and real-time quantitative polymerase chain reaction (qRT-PCR). The VHL gene was subjected to mutational analysis by DNA sequencing, and pVHL was analyzed using western blotting. Our study's t-test and Pearson correlation analysis showed that VHL gene expression in tumoral tissues with a - 0.39-fold decrease was not significantly lower than normal tissues (p = 0.441), and a 0.97-fold increase miR-223 (p = 0.045) was determined by real-time PCR. Also, as a result of DNA sequence analysis performed in the VHL gene, it was found that 26% of the patients have mutations. The mutations for (VHL):c.60C>A (p.Val20=) and (VHL):c.467delA (p.Tyr156Leu) was detected for the first time in Turkish patients. CONCLUSIONS The present study demonstrated that the differences in the expression levels of miR-223 have the potential to be biomarkers to determine the poor prognosis in ccRCC.

Research paper thumbnail of Mide Kanserinde Genetik ve Epigenetik Mekanizmaların Rolü

Research paper thumbnail of Coexistence of TERT C228T mutation and MALAT1 dysregulation in primary glioblastoma: new prognostic and therapeutic targets

Neurological Research, 2021

ABSTRACT Objective: This study was designed to conduct molecular classification based on IDH1/2, ... more ABSTRACT Objective: This study was designed to conduct molecular classification based on IDH1/2, TERT, ATRX, and DAXX changes in pediatric and adult primary glioblastoma (GB) and to analyze the potential interaction of LncRNA MALAT1 in the determined homogeneous subgroups. Methods: We analyzed the expression profiles of ATRX/DAXX and MALAT1 using the qRT-PCR method and IDH and TERT mutation status using DNA sequencing analysis in 85 primary pediatric and adult GB patients. Results: IDH1 mutation was observed in 5 (5.88%) and TERT mutation in 65 (76.47%) primary pediatric and adult GB patients. ATRX and DAXX were detected in 18 (21.18%) and 7 (8.24%) patients. TERT mutation and loss of ATRX/DAXX were associated with short overall survival (p < 0.001, p < 0.001, respectively). Patients carrying especially TERT C228T mutation had worse prognosis (p < 0.001). Six subgroups were obtained from the genetic analysis. Among the subgroups, MALAT1 was highly expressed in group A that had a single TERT mutation as compared to that in groups D and E (p = 0.001 and p < 0.001, respectively); further, high MALAT1 expression was associated with worse prognosis in patients with C228T mutation (p < 0.001). Conclusions: Our findings highlight that the presence of TERT C228T mutation and expression of MALAT1 can be used as primary targets during the follow-up of primary GB patients and in the development of new treatment strategies.

Research paper thumbnail of Long non-coding RNAs as a predictive markers of group 3 medulloblastomas

Neurological Research, 2021

ABSTRACT Objective The appropriate treatments for the different molecular subgroups of medullobla... more ABSTRACT Objective The appropriate treatments for the different molecular subgroups of medulloblastomas are challenging to determine. Hence, this study aimed to examine the expression profiles of long non-coding RNAs (LncRNAs) to determine a marker that may be important for treatment selection in these subgroups. Methods Changes in the expression of LncRNAs in the tissues of patients with medulloblastoma, which are classified into four subgroups according to their clinical characteristics and gene expression profiles, were examined via reverse transcription polymerase chain reaction. Moreover, there association with patient prognosis was evaluated. Results The expression levels of MALAT1 and SNGH16 were significantly higher in patients with group 3 medulloblastoma than in those with other subtypes. Patients with high expression levels of MALAT1 and SNGH16 had a relatively shorter overall survival than those with low expression levels. Conclusions Patients with group 3 medulloblastoma have a high MALAT1 level, which is associated with poor prognosis. Therefore, MALAT1 can be a new therapeutic target in medulloblastoma.

Research paper thumbnail of Comparison of clinical and molecular wnt and shh subgroups in medulloblastoma tumor cases

Turkish Neurosurgery, 2020

AIM: To determine the Wnt and SHH subtypes at the molecular level, and to compare them clinically... more AIM: To determine the Wnt and SHH subtypes at the molecular level, and to compare them clinically by examining the changes in CTNNB1, AXIN, PTCH1, SMO, SUFU, and GLI1 mRNA expression in the medulloblastoma of a Turkish population determined according to patient selection criteria. In this context, the clinical distinction between Wnt and SHH groups are realized by considering the age, gender, survival time, location of the lesion, and radiological features of the patients. MATERIAL and METHODS: Molecular separation was performed by RT-PCR analysis of CTNNB1, AXIN, PTCH1, SMO, SUFU, and GLI1 mRNA expression changes. RESULTS: About 17.8% and 22.2% of the cases were included in the Wnt and the SHH group, respectively. When comparing group differences based on clinical and molecular data, 72.7% and 66.6% of matches were observed in the Wnt and the SHH group, respectively. CONCLUSION: It has been revealed that molecular analysis and grouping of patients with medulloblastoma can provide support for clinically determined subgroups.

Research paper thumbnail of Inhibitory Effects of Olea europaea Leaf Extract on Mesenchymal Transition Mechanism in Glioblastoma Cells

Nutrition and Cancer, 2020

Background: Glioblastoma (GB) is the most aggressive form of brain tumor. Despite the current tre... more Background: Glioblastoma (GB) is the most aggressive form of brain tumor. Despite the current treatment methods, the survival rate of patients is very low. Therefore, there is a need to develop new therapeutic agents. The migration and invasion capacity of GB cells is related to mesenchymal transition (MT) mechanism. Materials and Methods: The effect of OLE on MT was determined by analysis of the Twist, Snail, Zeb1, N-cadherin and E-cadherin genes in the EMT mechanism. The effect of OLE on cell migration was determined by wound healing test. Results: 2 mg/ml OLE reduced Twist, Snail, Zeb1 and N-cadherin expression and the combination of OLE þ TMZ (2 mg/ml OLE þ 350 mM TMZ) increased E-cadherin and reduced Twist, Zeb1 and N-cadherin. In addition, co-treatment with OLE increased TMZ-induced antiinvasion properties thought suppressing transcription factors of MT mechanism. Conclusion: OLE can enhance the anti-MT activities of TMZ against GB and provide strong evidence that combined treatment with OLE and TMZ has the potential to be an effective alternative approach in GB therapy.

Research paper thumbnail of The orange-red pigment from Penicillium mallochii: Pigment production, optimization, and pigment efficacy against Glioblastoma cell lines

Biocatalysis and Agricultural Biotechnology, 2020

Abstract The red-orange pigment producer strain Penicillium mallochii (TACB-16) used in this stud... more Abstract The red-orange pigment producer strain Penicillium mallochii (TACB-16) used in this study was isolated from beech tree bark in Balikesir, Turkey, and was identified by molecular methods (P. mallochii Genbank accession number: MG591446 ). P. mallochii Rivera, Urb & Seifert was first isolated from the caterpillars Rothschildia lebeau and Citheronia lobesis on Costa Rica and is a new record for Turkey. Little is known of this fungus. In this study, the pigment production of P. mallochii on different media was characterised, and the factors affecting the pigment production and efficacy against the human GB cell line T98G cell viability/cytotoxicity were inspected. The results showed that the pigment was resistant to different temperatures and pH values. The ~250 base pair of the ITS region was sequenced and submitted to the Genbank. The blast result of the sequence showed that our isolate displayed maximum similarity (100%) to P. mallochii. Glioblastoma (grade-IV astrocytoma, WHO) is the most lethal subtype of glioma and the survival rate of GB patients is still low. Our results suggest that the pigment exhibits anti-proliferative effects on the T98G cell line. The present study is the first to assess the cytotoxic effect of the pigment on the survival of GB cells. Further studies and validations are needed, but we suggest that the pigment might be used for in vitro and in vivo studies, food industry and for future medical drug studies.

Research paper thumbnail of Clinicopathologic features and genetic characteristics of the BRCA1/2 mutation in Turkish breast cancer patients

Cancer Genetics, 2019

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Circulating miR-195 as a Therapeutic Biomarker in Turkish Breast Cancer Patients

Background: Dysregulation of miRNA expression may be used as a biomarker for specific tumours bec... more Background: Dysregulation of miRNA expression may be used as a biomarker for specific tumours because it may contribute to development of cancer. Circulating miRNA profiles have been highlighted for their potential as predictive markers in heterogeneous diseases such as breast cancer. In the literature, there is evidence that miR-195 levels are differentially expressed pre-and post-operative periods in breast cancer patients. At the same time, miRNA expression levels may vary because of ethnic origins. This study aimed to determine expression levels and potential roles of miR-195 in Turkish breast cancer patients. Materials and Methods: The expression patterns of miR-195 were initially examined in breast cancer tissues (luminal A and B type) (n=96). Subsequently, blood samples were prospectively collected from preoperative and postoperative Turkish breast cancer patients and disease free controls. Total RNA was isolated, and the expression level of miR-195 was quantified by real-time PCR. Results: We found that miR-195 level was altered in Turkish breast cancer patients, with down-regulation evident in breast cancer tissues compared to normal adjacent specimens. Furthermore, circulating levels of miR-195 was significantly decreased in post-operative blood samples compared with pre-operative levels (p=0.01 and <0.05). However, miR-195 was significantly increased in pre-operative blood samples of the luminal B type (p= 0.04 and <0.05). Conclusions: This study represents the first report of a miR-195 expression profile in Turkish breast cancer patients. Our data suggests that miR-195 levels might be a clinically useful biomarker in the earliest stage of Turkish breast cancer patients.

Research paper thumbnail of Potential role of solid lipid nanoparticles in overcoming the acquired tamoxifen resistance of breast cancer

Journal of Biotechnology, 2017

and leaves can be seen at the same time; which is a very rare condition. In this study, "Colchicu... more and leaves can be seen at the same time; which is a very rare condition. In this study, "Colchicum pusillum" has been collected from the heights of Guzelyurt and investigated its anticancer activity on primary (Colo-320) and metastatic (Colo-741) human colon carcinoma cell lines. Different concentrations of bulb extracts were incubated for 24 and 48 h with Colo-320 and Colo-741 cells. Cell growth and cytotoxicity were measured by MTT assays. All concentrations of bulb extracts showed cytotoxic activity against all Colo-320 cells. According to the cell viability and cytotoxicity results, 20 mg/ml concentration of bulb extract of "Colchicum pusillum" was found the most active dose against Colo-741 cells, in 48 h. In addition, these MTT results; the immunohistochemical staining and signal pathways of "Colchicum pusillum" extracts are still investigated.

Research paper thumbnail of 759: Ficus carica latex inhibits GBM cell proliferation by modulating let-7d expression

European Journal of Cancer, 2014

Research paper thumbnail of Olea europaea Leaf Phenolics Oleuropein, Hydroxytyrosol, Tyrosol, and Rutin Induce Apoptosis and Additionally Affect Temozolomide against Glioblastoma: In Particular, Oleuropein Inhibits Spheroid Growth by Attenuating Stem-like Cell Phenotype

Life

The effects of Olea europaea leaf extract (OLE) phenolics, including oleuropein (OL), hydroxytyro... more The effects of Olea europaea leaf extract (OLE) phenolics, including oleuropein (OL), hydroxytyrosol (HT), tyrosol (TYR), and rutin against glioblastoma (GB), independently and in combination with temozolomide (TMZ), were investigated in T98G and A172 cells. Cell growth was assessed by WST-1, real-time cell analysis, colony formation, and cell cycle distribution assays. A dual acridine orange propidium iodide (AO/PI) staining and annexin V assay determined cell viability. A sphere-forming assay, an intracellular oxidative stress assay, and the RNA expression of CD133 and OCT4 investigated the GB stem-like cell (GSC) phenotype. A scratch wound-healing assay evaluated migration capacity. OL was as effective as OLE in terms of apoptosis promotion (p < 0.001) and GSC inhibition (p < 0.001). HT inhibited cell viability, GSC phenotype, and migration rate (p < 0.001), but its anti-GB effect was less than the total effect of OLE alone. Rutin decreased reactive oxygen species produc...

Research paper thumbnail of Kolo-rektal kanserli hasta ve yakınlarında genetik yatkınlığın araştırılması

Research paper thumbnail of The p53 status in patients with common variable immunodeficiency

Journal of Clinical Medicine and Research, 2012

Common variable immunodeficiency (CVID) comprises a heterogeneous group of primary antibody defic... more Common variable immunodeficiency (CVID) comprises a heterogeneous group of primary antibody deficiencies with complex clinical and immunological phenotypes. A high risk for cancer has been described for some types of cancer among patients with CVID. Mutations in p53, a critical tumor suppressor gene, are one of the most common genetic alterations in human cancers, therefore contributes to the complex network of molecular events leading to tumor formation. This prompted us to investigate the incidence of p53 gene mutations in patients with CVID and evaluated the predictive risk for tumor development. We investigated the presence of p53 mutations in patients with CVID, tumor samples and in the surgical margins of 34 patients with head and neck cancer using single strand conformational polymorphism and sequencing analysis. We investigated the presence of p53 mutations in genomic DNA samples of 20 patients with CVID and 10 healthy controls using polymerase chain reaction and heteroduplex analysis. None of the patients were found to have p53 gene mutations. Only one patient developed non-Hodgkin lymphoma (NHL) during nine years follow-up. P53 mutations was not also detected in tumor biopsy sample. We found no statistically significant association between the presences of p53 mutations in patients with CVID. Key words: Common variable immunodeficiency, p53 gene, tumor development, apoptosis.

Research paper thumbnail of The Investigation of genetic predisposition in patients with colorectal cancer and their relatives

Frajil bölgeler kromozomlar üzerinde boya almayan özel gap ve kırık noktalandır ve onlar çeşitli ... more Frajil bölgeler kromozomlar üzerinde boya almayan özel gap ve kırık noktalandır ve onlar çeşitli kültür koşullan ile oluşturulabilirler. Çeşitli çalışmalar frajil bölge ekspresyonunu arttıran ve birçok klastojenik ajan olduğunu göstermiştir. Biz de çalışmamızda periferik kan lenfositlerinde gözlediğimiz prometafaz kromozomlarda common frajil bölgelerin ekspresyonunu afidikolin, bromodeoksiuridin ve kafein ile indükledik. Kromozomal aberasyonlar ve frajil bölge ekspresyonlan, 32 kolon kanserli hasta, 30 asemptomatik kolon akraba, 36 rektum kanserli hasta, 30 rektum akraba ve 30 da yaşlan hasta ve akraba grupları ile uyumlu, ailesinde kanser hikayesi bulunmayan sağlıklı kontrol bireylerinden oluşan toplam 158 vakada değerlendirildi. Hem hasarlı hücre oram (P0.05). Biz iki grubumuzda da apbidicolin tip common frajil bölgeler belirledik. Kolon kanserli hastalar ve yakınlarında belirlediğimiz frajil bölgeler lp36, lp31, lp21, lq21, lq25, lq44, 2p24, 2pl6, 2q21, 2q33, 2q37, 3p21, 3pl4, 15...

Research paper thumbnail of Early-stage colon cancer with high MALAT1 expression is associated with the 5-Fluorouracil resistance and future metastasis

Molecular Biology Reports

Research paper thumbnail of Olea europaea leaf extract decreases tumour size by affecting the LncRNA expression status in glioblastoma 3D cell cultures

European Journal of Integrative Medicine, 2021

Abstract Introduction Glioblastoma (GB) is the most aggressive primary brain tumour. Temozolomide... more Abstract Introduction Glioblastoma (GB) is the most aggressive primary brain tumour. Temozolomide (TMZ) is a chemotherapy drug used in the treatment of GB. Despite treatment with TMZ, the prognosis of GB is poor. This study aimed to demonstrate the ability of Olea europaea leaf extract (OLE) alone and in combination with TMZ to suppress tumour aggressiveness by evaluating long non-coding RNA (LncRNA) and cancer stem cell (CSC) markers in GB cells using a three-dimensional (3D) model. Methods The Real-time PCR (RT-PCR) method was used to determine the effects of OLE on LncRNA and CSC markers associated with tumour aggressiveness. To explore the effect of OLE on tumour size, a 3D model was developed. Results It was found that OLE suppressed tumour aggressiveness with inhibited the MALAT1, SOX2 and NANOG (p Conclusion OLE may be a potential therapeutic agent that can be used in the treatment of GB, as it has been shown to reduce tumour size and increase the effect of TMZ.

Research paper thumbnail of Solid lipid nanoparticles in reversing the acquired tamoxifen-resistance

2017 E-Health and Bioengineering Conference (EHB), 2017

The anti-estrogen tamoxifen (Tam) is the most preferred option for patients with estrogen-recepto... more The anti-estrogen tamoxifen (Tam) is the most preferred option for patients with estrogen-receptor (ER)-positive breast cancer. However, multi-drug resistance (MDR) is a considerable clinical problem in the successful chemotherapeutic treatment. Members of the ATP-binding cassette (ABC) transporter family proteins play an important role in acquired drug resistance. Many studies have focused primarily on the clinical significance of P-gp (MDR1), BCRP and MRP1 members belong to ABC transporter superfamily on anticancer-drug resistance. Consequently, several strategies have been improved to overcome drug resistance. Nanoparticle drug delivery systems provide an increase in the intracellular concentration of the drugs as well as a reduction in toxicity of free-drug on healthy cells thanks to unique physical and biological properties. Solid lipid nanoparticles (SLNs) have been improved as an alternative colloidal drug delivery systems due to successful incorporation of both hydrophilic and hydrophobic compounds and their related benefits (controlled drug release, high entrapment efficiency and small size etc.) For this purpose, the aim of this study was to discuss the role of Tam-loaded solid lipid nanoparticles (SLNs) to overcome MDR and determine the ability of Tam-SLNs to induce apoptosis.

Research paper thumbnail of Utilisation de l'extrait obtenu à partir de feuilles d'olive noire dans le traitement du glioblastome

L'invention concerne l'utilisation de l'olive noire le traitement de tumeurs de type ... more L'invention concerne l'utilisation de l'olive noire le traitement de tumeurs de type glioblastome positif de cellules souches cancereuses qui sont traitees par temozolomide.

Research paper thumbnail of MikroRNA-106a’nın yüksek ekspresyonu kolorektal kanserlerde mikrosatellit instablite durumu ile ilişkilidir

Uludağ Üniversitesi Tıp Fakültesi Dergisi, 2021

Mikrosatellit instabilite (MSI), DNA tamir genlerindeki hatalardan kaynaklanan ve kolorektal kans... more Mikrosatellit instabilite (MSI), DNA tamir genlerindeki hatalardan kaynaklanan ve kolorektal kanserin (KRK) oluşmasına neden olan genetik bir durumdur. Sporadik KRK'larda MSI görülme sıklığı, prognoza olan etkisi literatürde çelişkilidir. Bununla birlikte MSI'ya sahip KRK'larda standart kemoterapi yetersiz kaldığı için yeni tedavi seçeneklerine ihtiyaç duyulmaktadır. micoRNA'lar (miRNA) kanserleşme sürecinde görev alan ve tanıda, prognozda ve tedavide belirteç olarak kullanılan küçük RNA molekülleridir. Mevcut çalışmada, Türk popülasyonuna ait sporadik gelişen KRK'larda MSI'nın görülme sıklığının tanımlanması ve bu tümörlerde miRNA'ların ekspresyon farklılıklarının belirlenmesi amaçlanmıştır. Çalışmada, sporadik KRK tanısı almış 63 hasta değerlendirildi. Hastalara ait arşiv tümör ve normal dokularından DNA ve RNA izolasyonları yapıldı. DNA örneklerinden fragment analizine dayalı MSI testi gerçekleştirildi. qRT-PCR kullanılarak 38 farklı miRNA'nın ekspresyon profili incelendi. 63 hastada MSI görülme oranı %23.8 olarak belirlendi. MSI ve mikrosatellit stabil (MSS) tümörler karşılaştırıldığında, MSI tümörlerde, miR-124 ve miR-106a'nın yüksek ve miR-145'in ise düşük ekspresyon gösterdiği belirlendi (p<0.05). Bununla birlikte miR-106a'nın yüksek ekspresyonunun cerrahi sonrası nüks gelişimi ile ilişkili olduğu saptandı (p=0.002). Elde edilen bulgular ışığında miR-106a'nın özellikle MSI genotipine sahip KRK tümörlerde hedeflenmesi ile KRK hastalarında yeni tedavi protokollerinin oluşturularak nüks oluşumunun engellenebileceğini öngörülmüştür. Anahtar Kelimeler: Sporadik Kolorektal Kanser. Mikrosatellit Ġnstability. MikroRNA. miR-106a. Upregulation of Microrna-106a is Associated with Microsatellite Instability Status in Colorectal Cancer ABSTRACT Microsatellite instability (MSI) is a genetic condition that results from errors in DNA repair genes and causes colorectal cancer (CRC). The incidence of MSI in sporadic CRCs and its effect on prognosis are contradictory in the literature. However, since standard chemotherapy is insufficient in CRCs with MSI, new treatment options are needed. micoRNAs (miRNAs) are small RNA molecules that take part in the cancer process and are used as markers in diagnosis, prognosis and treatment. In the study, it is aimed to define the prevalence of MSI in sporadically developing CRCs belonging to the Turkish population and to determine the expression differences of miRNAs in these tumors. 63 patients diagnosed with sporadic CRC were evaluated in the study. DNA and RNA isolations were made from archive tumor and normal tissues of the patients. MSI test was performed based on fragment analysis from DNA samples. The expression profiles of 38 different miRNAs were examined using qRT-PCR. In 63 patients, the incidence of MSI was determined as 23.8%. When MSI and microsatellite stable (MSS) tumors were compared, it was determined that miR-124 and miR-106a showed high expression and miR-145 low expression in MSI tumors (p <0.05). However, high expression of miR-106a was found to be associated with postoperative recurrence (p=0.002). In the light of the findings obtained, we think that by targeting miR-106a especially in CRC tumors with MSI genetype, recurrence can be prevented by creating new treatment protocols in these tumors.

Research paper thumbnail of Investigation of VHL gene associated with miR-223 in clear cell renal cell carcinoma

Molecular Biology Reports, 2021

BACKGROUND Clear cell type renal cell carcinoma (ccRCC) is the most common renal cell carcinoma (... more BACKGROUND Clear cell type renal cell carcinoma (ccRCC) is the most common renal cell carcinoma (RCC). In this study, we examined the expressions of VHL and miR-223 in ccRCC patients׳ tissues to investigate the possible role in the development of ccRCC. METHODS AND RESULTS This study collected five expression profiles (GSE36139, GSE3, GSE73731, GSE40435, and GSE26032) from Gene Omnibus Data. Expressions of VHL and miR-223 in paraffinized tumor and normal tissues of 100 Turkish patients' ccRCC tissues were determined by bioinformatic data mining and real-time quantitative polymerase chain reaction (qRT-PCR). The VHL gene was subjected to mutational analysis by DNA sequencing, and pVHL was analyzed using western blotting. Our study's t-test and Pearson correlation analysis showed that VHL gene expression in tumoral tissues with a - 0.39-fold decrease was not significantly lower than normal tissues (p = 0.441), and a 0.97-fold increase miR-223 (p = 0.045) was determined by real-time PCR. Also, as a result of DNA sequence analysis performed in the VHL gene, it was found that 26% of the patients have mutations. The mutations for (VHL):c.60C>A (p.Val20=) and (VHL):c.467delA (p.Tyr156Leu) was detected for the first time in Turkish patients. CONCLUSIONS The present study demonstrated that the differences in the expression levels of miR-223 have the potential to be biomarkers to determine the poor prognosis in ccRCC.

Research paper thumbnail of Mide Kanserinde Genetik ve Epigenetik Mekanizmaların Rolü

Research paper thumbnail of Coexistence of TERT C228T mutation and MALAT1 dysregulation in primary glioblastoma: new prognostic and therapeutic targets

Neurological Research, 2021

ABSTRACT Objective: This study was designed to conduct molecular classification based on IDH1/2, ... more ABSTRACT Objective: This study was designed to conduct molecular classification based on IDH1/2, TERT, ATRX, and DAXX changes in pediatric and adult primary glioblastoma (GB) and to analyze the potential interaction of LncRNA MALAT1 in the determined homogeneous subgroups. Methods: We analyzed the expression profiles of ATRX/DAXX and MALAT1 using the qRT-PCR method and IDH and TERT mutation status using DNA sequencing analysis in 85 primary pediatric and adult GB patients. Results: IDH1 mutation was observed in 5 (5.88%) and TERT mutation in 65 (76.47%) primary pediatric and adult GB patients. ATRX and DAXX were detected in 18 (21.18%) and 7 (8.24%) patients. TERT mutation and loss of ATRX/DAXX were associated with short overall survival (p < 0.001, p < 0.001, respectively). Patients carrying especially TERT C228T mutation had worse prognosis (p < 0.001). Six subgroups were obtained from the genetic analysis. Among the subgroups, MALAT1 was highly expressed in group A that had a single TERT mutation as compared to that in groups D and E (p = 0.001 and p < 0.001, respectively); further, high MALAT1 expression was associated with worse prognosis in patients with C228T mutation (p < 0.001). Conclusions: Our findings highlight that the presence of TERT C228T mutation and expression of MALAT1 can be used as primary targets during the follow-up of primary GB patients and in the development of new treatment strategies.

Research paper thumbnail of Long non-coding RNAs as a predictive markers of group 3 medulloblastomas

Neurological Research, 2021

ABSTRACT Objective The appropriate treatments for the different molecular subgroups of medullobla... more ABSTRACT Objective The appropriate treatments for the different molecular subgroups of medulloblastomas are challenging to determine. Hence, this study aimed to examine the expression profiles of long non-coding RNAs (LncRNAs) to determine a marker that may be important for treatment selection in these subgroups. Methods Changes in the expression of LncRNAs in the tissues of patients with medulloblastoma, which are classified into four subgroups according to their clinical characteristics and gene expression profiles, were examined via reverse transcription polymerase chain reaction. Moreover, there association with patient prognosis was evaluated. Results The expression levels of MALAT1 and SNGH16 were significantly higher in patients with group 3 medulloblastoma than in those with other subtypes. Patients with high expression levels of MALAT1 and SNGH16 had a relatively shorter overall survival than those with low expression levels. Conclusions Patients with group 3 medulloblastoma have a high MALAT1 level, which is associated with poor prognosis. Therefore, MALAT1 can be a new therapeutic target in medulloblastoma.

Research paper thumbnail of Comparison of clinical and molecular wnt and shh subgroups in medulloblastoma tumor cases

Turkish Neurosurgery, 2020

AIM: To determine the Wnt and SHH subtypes at the molecular level, and to compare them clinically... more AIM: To determine the Wnt and SHH subtypes at the molecular level, and to compare them clinically by examining the changes in CTNNB1, AXIN, PTCH1, SMO, SUFU, and GLI1 mRNA expression in the medulloblastoma of a Turkish population determined according to patient selection criteria. In this context, the clinical distinction between Wnt and SHH groups are realized by considering the age, gender, survival time, location of the lesion, and radiological features of the patients. MATERIAL and METHODS: Molecular separation was performed by RT-PCR analysis of CTNNB1, AXIN, PTCH1, SMO, SUFU, and GLI1 mRNA expression changes. RESULTS: About 17.8% and 22.2% of the cases were included in the Wnt and the SHH group, respectively. When comparing group differences based on clinical and molecular data, 72.7% and 66.6% of matches were observed in the Wnt and the SHH group, respectively. CONCLUSION: It has been revealed that molecular analysis and grouping of patients with medulloblastoma can provide support for clinically determined subgroups.

Research paper thumbnail of Inhibitory Effects of Olea europaea Leaf Extract on Mesenchymal Transition Mechanism in Glioblastoma Cells

Nutrition and Cancer, 2020

Background: Glioblastoma (GB) is the most aggressive form of brain tumor. Despite the current tre... more Background: Glioblastoma (GB) is the most aggressive form of brain tumor. Despite the current treatment methods, the survival rate of patients is very low. Therefore, there is a need to develop new therapeutic agents. The migration and invasion capacity of GB cells is related to mesenchymal transition (MT) mechanism. Materials and Methods: The effect of OLE on MT was determined by analysis of the Twist, Snail, Zeb1, N-cadherin and E-cadherin genes in the EMT mechanism. The effect of OLE on cell migration was determined by wound healing test. Results: 2 mg/ml OLE reduced Twist, Snail, Zeb1 and N-cadherin expression and the combination of OLE þ TMZ (2 mg/ml OLE þ 350 mM TMZ) increased E-cadherin and reduced Twist, Zeb1 and N-cadherin. In addition, co-treatment with OLE increased TMZ-induced antiinvasion properties thought suppressing transcription factors of MT mechanism. Conclusion: OLE can enhance the anti-MT activities of TMZ against GB and provide strong evidence that combined treatment with OLE and TMZ has the potential to be an effective alternative approach in GB therapy.

Research paper thumbnail of The orange-red pigment from Penicillium mallochii: Pigment production, optimization, and pigment efficacy against Glioblastoma cell lines

Biocatalysis and Agricultural Biotechnology, 2020

Abstract The red-orange pigment producer strain Penicillium mallochii (TACB-16) used in this stud... more Abstract The red-orange pigment producer strain Penicillium mallochii (TACB-16) used in this study was isolated from beech tree bark in Balikesir, Turkey, and was identified by molecular methods (P. mallochii Genbank accession number: MG591446 ). P. mallochii Rivera, Urb & Seifert was first isolated from the caterpillars Rothschildia lebeau and Citheronia lobesis on Costa Rica and is a new record for Turkey. Little is known of this fungus. In this study, the pigment production of P. mallochii on different media was characterised, and the factors affecting the pigment production and efficacy against the human GB cell line T98G cell viability/cytotoxicity were inspected. The results showed that the pigment was resistant to different temperatures and pH values. The ~250 base pair of the ITS region was sequenced and submitted to the Genbank. The blast result of the sequence showed that our isolate displayed maximum similarity (100%) to P. mallochii. Glioblastoma (grade-IV astrocytoma, WHO) is the most lethal subtype of glioma and the survival rate of GB patients is still low. Our results suggest that the pigment exhibits anti-proliferative effects on the T98G cell line. The present study is the first to assess the cytotoxic effect of the pigment on the survival of GB cells. Further studies and validations are needed, but we suggest that the pigment might be used for in vitro and in vivo studies, food industry and for future medical drug studies.

Research paper thumbnail of Clinicopathologic features and genetic characteristics of the BRCA1/2 mutation in Turkish breast cancer patients

Cancer Genetics, 2019

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.