Person: ÇEÇENER, GÜLŞAH
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ÇEÇENER
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GÜLŞAH
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Publication DPYD c.1905+1G>A promotes fluoropyrimidine-induced anemia, a prognostic factor in disease-free survival, in colorectal cancer(Mary Ann Liebert, Inc, 2021-04-01) Deligönül, Adem; Aksoy, Seçil; Tezcan, Gülçin; Tunca, Berrin; Kanat, Özkan; Çubukcu, Erdem; Yılmazlar, Tuncay; Öztürk, Ersin; Egeli, Ünal; Çeçener, Gülşah; Alemdar, Adem; Evrensel, Türkkan; DELİGÖNÜL, ADEM; AKSOY, SEÇİL; TEZCAN, GÜLÇİN; TUNCA, BERRİN; Kanat, Özka; ÇUBUKÇU, ERDEM; YILMAZLAR, AHMET TUNCAY; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; ALEMDAR, ADEM; EVRENSEL, TÜRKKAN; Sağlık Bilimleri Enstitüsü; Tıbbi Onkoloji Ana Bilim Dalı; 0000-0002-6400-4911; 0000-0002-5956-8755; 0000-0002-1619-6680; 0000-0001-8593-5101; 0000-0001-7904-883X; 0000-0002-3820-424X; HIZ-7332-2022; AAH-1420-2021; AAH-3843-2020; ESM-4544-2022; JDG-0330-2023; ABI-6078-2020; CYM-0930-2022; ETP-1691-2022; CKK-3621-2022; AAP-9988-2020; EXZ-0745-2022Background and Aim: In 10-30% of colorectal cancer (CRC) patients, toxic reactions occur after fluoropyrimidine-based chemotherapy. A dihydropyridine dehydrogenase (DPYD) gene variant, c.1905 + 1G>A, leads to intolerance to fluoropyrimidines. Due to the low frequency of this variant in many populations, the prevalence of fluoropyrimidine-induced hematologic side effects in CRC patients with the c.1905 + 1G>A variant is unclear. In this study, we investigated the prevalence of the DPYD c.1905 + 1 variants in a Turkish CRC cohort and the potential effects of these variants on fluoropyrimidine-induced hematologic side effects.Materials and Methods: The DPYD c.1905 + 1 variant was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis and confirmed by Sanger sequencing in peripheral blood samples of 100 CRC patients who received fluoropyrimidine-based chemotherapy and 60 healthy volunteers. The association of c.1905 + 1 variants with susceptibility to hematologic side effects was evaluated.Results: The DPYD c.1905 + 1G>A variant was more common in the CRC group than in the healthy control group (p = 0.001). The presence of the c.1905 + 1G>A variant was associated with thrombocytopenia (p = 0.039) and anemia (p = 0.035). CRC patients with fluoropyrimidine-induced anemia had shorter disease-free survival than CRC patients without fluoropyrimidine-induced anemia (p = 0.0009).Conclusions: Before administering fluoropyrimidine-based chemotherapy, genetic screening for the DPYD c.1905 + 1G>A variant should be performed with the aim of preventing anemia and anemia-induced complications in CRC patients.Publication NEAT1 Is a novel oncogenic LncRNA and correlated with miR-143 in pediatric oligodendrogliomas(Karger, 2021-03-19) Ak Aksoy, Seçil; Mutlu, Melis; Balçin, Rabia Nur; Taşkapılıoğlu, Mevlut Özgür; Tekin, Çağla; Kaya, Seçkin; Civan, Muhammet Nafi; Kocaeli, Hasan; Bekar, Ahmet; Eser Ocak, Pınar; Çeçener, Gülşah; Egeli, Ünal; Tolunay, Şahsine; Tunca, Berrin; Ak Aksoy, Seçil; Mutlu, Melis; BALÇIN, RABİA NUR; TAŞKAPILIOĞLU, MEVLÜT ÖZGÜR; Tekin, Çağla; KAYA, İSMAİL SEÇKİN; Civan, Muhammet Nafi; KOCAELİ, HASAN; BEKAR, AHMET; Eser Ocak, Pınar; ÇEÇENER, GÜLŞAH; EGELİ, ÜNAL; TOLUNAY, ŞAHSİNE; TUNCA, BERRİN; Tıp Fakültesi; Beyin Cerrahisi Ana Bilim Dalı; 0000-0001-5472-9065; 0000-0002-4256-2250; 0000-0003-0132-9927; 0000-0002-3820-424X; 0000-0001-7904-883X; 0000-0002-1619-6680; ADM-8457-2022; FPB-0403-2022; GXV-3107-2022; AAW-5254-2020; GDC-6329-2022; JGS-1849-2023; HKP-0793-2023; FDK-3229-2022; CGB-7869-2022; AAI-2073-2021; AAP-9988-2020; AAH-1420-2021; AAI-1612-2021; ABI-6078-2020Introduction: The noncoding RNAs (ncRNAs) play a role in biological processes of various cancers including gliomas. The majority of these transcripts are uniquely expressed in differentiated tissues or specific glioma types. Pediatric oligodendroglioma (POG) is a rare subtype of diffuse glioma and accounts for <1% of pediatric brain tumors. Because histologically POG resembles adult OG, the same treatment is applied as adults. However, the significance in predicting outcomes in POG patients is unclear. In this study, we aimed to investigate the prognostic significance of expression -profiles of microRNA (miRNA) and long noncoding RNA -(LncRNA) in POGs. Methods: We investigated the levels of 13 known miRNAs and 6 LncRNAs in tumor samples from 9 patients with primary POG by using RT-PCR and analyzed their association with outcomes. Results: The expression levels of miR-21, miR-106a, miR-10b, and LncRNA NEAT1 were higher, and the expression level of miR-143 was lower in POG tissues compared with normal brain tissues (p = 0.006, p = 0.032, p = 0.034, p = 0.002, and p = 0.001, respectively). High levels of NEAT1 and low expression of miR-143 were associated with decreased probability of short disease-free survival (p = 0.018 and p = 0.022, respectively). Discussion: NEAT1 and miR-143 levels could serve as reciprocal prognostic predictors of disease progression in patients with POG. New treatment models to regulate the expression levels of NEAT1 and miR-143 will bring a new approach to the therapy of POG.Publication The cytotoxic effect of usnic acid in malignant melanoma cells with different genomic profiles in the BRAF aspect(Verduci Publisher, 2022-01-01) Çolakoğlu, C.; Hacıefendi, A.; Eryılmaz, I. E.; Eskiler, G. G.; Egeli, U.; Çeçener, G.; Çolakoğlu , Ceyda; ERYILMAZ, IŞIL EZGİ; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; Tıp Fakültesi; Tıbbi Biyoloji Ana Bilim Dalı; 0000-0002-7471-5071; AEZ-2955-2022; GWV-3548-2022; AAH-1420-2021; AAP-9988-2020Objective: Malignant melanoma (MM) is the most aggressive skin cancer and treatment options are still limited in the late stages, generally accompanied by BRAF mutations. Usnic acid (UA), a well-known traditional lichen metabolite, has a promising and selective antitumoral activity. However, the effects of UA on MM cells with different genomic profiles in the BRAF aspect have not been investigated yet. In this study, we evaluated the effect of UA on BRAFV600E mutated-A2058 and wild-type MeWo cells.Materials and Methods: In the UA-treated cells, viability and cell death analysis were performed by using WST-1 and Annexin-V assays. Then, the death-related morphological changes were visualized by acridine orange(AO)/ethidium bromide (EB) staining. The cell cycle regulatory effect of UA was determined. Finally, time-dependent detection of acidic vesicular organelles (AVOs) was performed by live-cell imaging.Results: While MeWo viability significantly reduced to 53.8% and 28.6%, A2058 viability was detected as 61.3% and 50.3% at 50 and 100 mu M UA for 48 h. Thus, MeWo cells were found to be more sensitive to UA. Annexin-V and morphological analysis results showed that UA triggered mainly a vacuole-dependent cell death by the formation of AVOs, instead of apoptosis, in the MM cells. This effect was prominent in A2058 compared to MeWo. UA also slightly triggered apoptosis in MeWo cells. Thus, the cell cycle regulatory effect of UA on MM cells changed based on the cell death type triggered.Conclusions: Our results suggest that UA exerts the cytotoxic effects on MM cells by inducing vacuole-dependent cell death, most probably autophagy, and the UA response of MM cells with a different genomic profile in the BRAF aspect varies.Publication The regulatory effect of cabazitaxel on epithelial-mesenchymal transition in metastatic prostate cancer(Wolters Kluwer Medknow Publications, 2023-01-01) Eskiler, Gamze Guney; ERYILMAZ, IŞIL EZGİ; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; Tıp Fakültesi; Tıbbi Biyoloji Ana Bilim Dalı; 0000-0002-2088-9914; AAB-6011-2022Introduction:Epithelial-mesenchymal transition (EMT) is a critical mechanism that promotes cancer cells to metastasis. Therefore, EMT regulation has become an important target in anticancer therapy approaches in recent years. However, in metastatic prostate cancer (PC), the EMT regulatory effect has not fully understood for cabazitaxel (Cbx), a third line taxane-based chemotherapeutic for metastatic castration-resistant PC.Aim:In this study, we investigated the antimetastatic and EMT-regulatory effects of Cbx on hormone-sensitive metastatic PC cells.Materials and Methods:The anticancer effects of Cbx were assessed by WST-1 and Annexin V analysis. The antimetastatic effect of Cbx was evaluated by wound healing and quantitative reverse transcription polymerase chain reaction through EMT-mesenchymal-to-epithelial transition (MET) markers as well as EMT-repressor microRNAs (miRNAs) in Cbx-treated LNCaP cells.Results:Our results showed that, in addition to its apoptotic and anti-migratory activities, Cbx exhibited the EMT-repressor effects through the prominent downregulation of matrix metalloproteinase-9 and Snail levels as EMT-promoting factors, and the significant upregulation of the certain miRNAs, including miR-205, miR-524, and miR-124, which play a role in EMT-repressing by targeting regulators of the EMT-associated genes.Conclusion:Although further evaluations are needed to improve the findings, we showed that, in addition to its classical taxane function, Cbx has a regulatory effect on EMT-MET cycling in hormone-sensitive metastatic PC.Publication RNA-based markers in biopsy cores with atypical small acinar proliferation: Predictive effect of T2E fusion positivity and MMP-2 upregulation for a subsequent prostate cancer diagnosis(Wiley, 2019-02-01) Eryılmaz, I. Ezgi; Vuruşkan, Berna Aytaç; Kaygısız, Onur; Egeli, Ünal; Tunca, Berrin; Kordan, Yakup; Çeçener, Gülşah; ERYILMAZ, IŞIL EZGİ; AYTAÇ VURUŞKAN, BERNA; KAYGISIZ, ONUR; TUNCA, BERRİN; ÇEÇENER, GÜLŞAH; Tıp Fakültesi; Tıbbi Patoloji Ana Bilim Dalı; 0000-0002-9790-7295; 0000-0001-7904-883X; 0000-0002-1619-6680; 0000-0002-9947-848X; 0000-0002-3820-424X; ABI-6078-2020; AAP-9988-2020; AAH-1420-2021; L-9439-2019; AAM-9726-2020; AAH-9746-2021; GWV-3548-2022Background Atypical small acinar proliferation (ASAP) is a precursor lesion of prostate cancer (PC), and PC develops from this suspicious focus or an unsampled malignant gland nearby. However, PC-related molecular alterations that could guide the timing of repeat biopsies and help monitor PC risk in ASAP-diagnosed patients have not been investigated. The purpose of this study was to first investigate the expression of seven different PC-related RNAs that included serine 2 (TMPRSS2): erythroblastosis virus E26 oncogene homolog (ERG) gene (TMPRSS2-ERG, T2E) fusion, alpha-methylacyl-CoA racemase (AMACR), kallikrein related peptidase 3 (KLK3), androgen receptor (AR), prostate cancer specific antigen 3 (PCA3), and matrix metalloproteinases (MMP)-2 and 9. Methods PC-related RNAs were evaluated using a real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) system in pathologically ASAP-diagnosed prostate biopsy cores from 55 patients presenting with a normal digital rectal examination and a PSA level of 4-10 ng/mL. Results We detected that positive T2E fusion status (P = 0.013) and the expression of AMACR (P = 0.016), AR (P = 0.016) and MMP-2 (P = 0.013) were independently and significantly associated with PC risk in ASAP patients. There were also several statistically significant correlations between expression levels. Additionally, we demonstrated that T2E fusion positive ASAP patients with higher MMP-2 expression were more likely to be diagnosed with PC at a subsequent biopsy during the follow-up period (P = 0.003). Conclusions Although, more clinical validations are needed for the stratification of PC risk in ASAP-diagnosed biopsy cores, our current results indicate that the coexistence of T2E fusion positivity with MMP-2 upregulation may help clinicians adjust their biopsy timetable and/or assessment of PC risk in ASAP-diagnosed patients with a PSA level of 4-10 ng/mL.Publication The expression and prognostic value of miR-146a and miR-155 in Turkish patients with multiple sclerosis(Taylor & Francis, 2022-03-04) Sarıdaş, Furkan; Ünlü, Havva Tezcan; Çeçener, Gülşah; Egeli, Ünal; Takanlou, Maryam Sabour; Takanlou, Leila Sabour; Tunca, Berrin; Zarifoğlu, Mehmet; Turan, Ömer Faruk; Taşkapılıoğlu, Özlem; SARIDAŞ, FURKAN; ÇEÇENER, GÜLŞAH; EGELİ, ÜNAL; TUNCA, BERRİN; ZARİFOĞLU, MEHMET; TURAN, ÖMER FARUK; Takanlou, Maryam Sabour; Takanlou, Leila Sabour; Taşkapılıoğlu, Özlem; 0000-0001-5945-2317; 0000-0002-0910-4258; 0000-0002-3820-424X; 0000-0001-7904-883X; 0000-0002-1590-4833; 0000-0002-6361-7150; 0000-0002-1619-6680; HSB-2700-2023; GYU-0252-2022; AAP-9988-2020; AAH-1420-2021; KGL-6846-2024; GRE-6268-2022; ABI-6078-2020; EHN-5825-2022; JDI-6091-2023; EBA-4926-2022Multiple sclerosis (MS) is an inflammatory, autoimmune demyelinating, and neurodegenerative disorder of the central nervous system. Interactions between environmental factors, predisposition genes, and determining genes appear to be involved in its etiology. Epigenetic mechanisms such as microRNA-mediated gene regulation can determine the susceptibility and severity of autoimmune diseases. Therefore, to determine the role of miR-146a and miR-155 in MS and its developmental stages, the expression levels in the serum of MS and clinically isolated syndrome (CIS) patients were compared with those of healthy controls. In the present study, the expression levels of miR-146a and miR-155 were assessed using quantitative Real-Time PCR in blood samples of 15 CIS patients and 61 relapsing-remitting multiple sclerosis (RRMS) patients alongside 32 healthy patients as controls. Furthermore, any associations with the clinicopathologic variables of the patients were also evaluated. Dysregulations were found only in the miR-146a and miR-155 expressions in the RRMS-Control group. When the RRMS patients were evaluated in terms of the characteristics of sex, annual attack rate, age of diagnosis, duration of follow-up, and immunomodulatory treatments used, no significant differences were observed. However, significant dysregulations were identified in miRNA expression in the vitamin D level, EDSS values, and the number of attacks. ROC curve analysis showed that miR-146a and miR-155 were significant in the RRMS-Control group for the area under the curve (AUC). It is possible that miR-146a may be associated with vitamin D deficiency and disease disability, while miR-155 may be associated with the number of attacks.Publication Synergistic effects of hormone therapy drugs and usnic acid on hormone receptor-positive breast and prostate cancer cells(Wiley, 2019-08-01) Eskiler, Gamze Güney; Yurdacan, Beste; ERYILMAZ, IŞIL EZGİ; Eryılmaz, Işıl Ezgi; Egeli, Unal; EGELİ, ÜNAL; Çeçener, Gülşah; ÇEÇENER, GÜLŞAH; Tunca, Berrin; TUNCA, BERRİN; Tıp Fakültesi; Tıbbi Biyoloji Ana Bilim Dalı; 0000-0001-7904-883X; 0000-0002-3820-424X; 0000-0002-1619-6680; AAH-1420-2021; AEA-0144-2022; AAP-9988-2020; ABI-6078-2020The aim of this study was to investigate the combined effects of usnic acid (UA) and Tamoxifen (Tam) or Enzalutamide (Enz) on hormone receptor-positive breast and prostate cancer (BC and PC), respectively. The antiproliferative and apoptotic effects of Tam or Enz alone and in combination with UA on MCF7 and LNCaP cancer cells were detected. The results of the WST-1 assay indicated that UA was a promising anticancer compound that significantly enhanced the effectiveness of hormone therapy drugs compared with each drug alone (combination index < 1). In addition, the combination of UA with Tam or Enz remarkably induced more cell cycle arrest at the G0/G1 phase and apoptosis than only drug-treated cells (P < 0.01). Consequently, our findings suggest that the combination of UA with Tam or Enz may be a potential therapeutic approach for the treatment of BC and PC and further studies are required to exploit the potential mechanisms of synergistic effects.Publication Prediction of breast cancer metastasis risk using circulating tumor markers: A follow-up study(Assoc Basic Medical Sci Federation Bosnia & Herzegovina Sarajevo, 2019-01-01) Çetintaş, Sibel; Tezcan, Gülçin; Tunca, Berrin; Egeli, Ünal; Gökgöz, Mustafa Şehsuvar; Çecener, Gülsah; ÇETİNTAŞ, SİBEL; TUNCA, BERRİN; EGELİ, ÜNAL; GÖKGÖZ, MUSTAFA ŞEHSUVAR; ÇEÇENER, GÜLŞAH; Tıp Fakültesi; Genel Cerrahi Ana Bilim Dalı; 0000-0002-1619-6680; 0000-0001-7904-883X; 0000-0002-3820-424X; EWY-5692-2022; AAA-7047-2020; AAH-1420-2021; ABI-6078-2020; AAP-9988-2020Distant organ tumor dissemination is a major cause of breast cancer-related deaths. In 2010, we analyzed the prognostic importance of the circulating tumor markers (CTMs) cytokeratin 19 (CK19), CK20, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) in relation to the clinical and pathological characteristics of patients with breast cancer (BC). To assess the clinical utility of CK19, CK20 and EGFR in predicting distant metastasis in BC, here we report 7-year follow-up results of 77 patients. The patients with at least one positive CTM were classified as CTM(+) and those negative for all CTMs were assigned to CTM(-) group. In patients who received no treatment following CTM analysis, 25.0% had metastasis in CTM(+) and 10.0% in CTM(-) group. In patients who received one of the following therapies: chemotherapy, radiotherapy or hormone therapy, or the combinations of these therapies, the rate of metastasis was 33.3% in CTM(+) and 20.0% in CTM(-) group. Disease-free time was shorter in CTM(+) patients compared to CTM(-) group (28.83 +/- 10.76 and 41.38 +/- 9.5 months, respectively). According to multivariate Cox proportional hazard regression analysis, the presence of regional lymph node metastasis, Ki-67 expression, higher tumor grade and CTM expression status were predictors of poor prognosis associated with distant metastasis (p < 0.05). Also, CTM positivity was a factor associated with metastasis-related poor prognosis (HR = 0.492, p = 0.026). The mean survival for CTM(+) patients was shorter than that for CTM(-) patients (90.671 +/- 2.66 and 101.23 +/- 3.92 months, respectively; p > 0.05). Our findings demonstrate that CTM positivity may indicate a high metastasis risk; however, CTM negativity does not guarantee low metastasis risk. These results may encourage further preclinical investigation of CTMs, to evaluate the possible implications of these findings to the clinical setting.Publication Investigation of VHL gene associated with miR-223 in clear cell renal cell carcinoma(Springer, 2021-11-26) Ünal, Ufuk; Çeçener, Gülşah; Ünlü, Havva Tezcan; Vuruşkan, Berna Aytaç; Erdem, Ecem Efendi; Egeli, Ünal; Nazlıoğlu, Hülya Öztürk; Kaygısız, Onur; Tunca, Berrin; Vuruşkan, Hakan; Ünal, Ufuk; ÇEÇENER, GÜLŞAH; Ünlü, Havva Tezcan; AYTAÇ VURUŞKAN, BERNA; Erdem, Ecem Efendi; EGELİ, ÜNAL; ÖZTÜRK NAZLIOĞLU, HÜLYA; KAYGISIZ, ONUR; TUNCA, BERRİN; VURUŞKAN, HAKAN; Tıp Fakültesi; Tıbbi Biyoloji Ana Bilim Dalı; 0000-0003-4913-3616; 0000-0002-3820-424X; 0000-0002-0910-4258; 0000-0001-7904-883X; 0000-0002-9790-7295; 0000-0002-1619-6680; AAH-1420-2021; L-9439-2019; GYU-0252-2022; ABC-1357-2020; AAP-9988-2020; GYU-0252-2022; EEJ-1452-2022; ESY-2704-2022; FLN-9596-2022; ABI-6078-2020; EFH-9523-2022Background 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.Publication Olea europaea leaf extract decreases tumour size by affecting the LncRNA expression status in glioblastoma 3D cell cultures(Elsevier, 2021-05-21) Mutlu, Melis; Tunca, Berrin; Aksoy, Seçil Ak; Tekin, Çağla; Çeçener, Gülşah; Egeli, Ünal; Mutlu, Melis; TUNCA, BERRİN; AKSOY, SEÇİL; Tekin, Çağla; ÇEÇENER, GÜLŞAH; EGELİ, ÜNAL; İnegöl Meslek Yüksekokulu; Tıbbi Biyoloji Ana Bilim Dalı; 0000-0002-1619-6680; 0000-0002-3820-424X; 0000-0001-7904-883X; AAH-1420-2021; ADM-8457-2022; FPB-0403-2022; GDC-6329-2022; AAP-9988-2020; ABI-6078-2020Introduction: 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 < 0.05). OLE + TMZ also inhibited MALAT1, LOXL1-AS1, PVT1 and H19 ( p < 0.05) and OCT4, NANOG, SOX2 and CD133 ( p < 0.05). In addition, to reduce tumour aggressiveness in a 3D cell culture, the use of OLE and OLE + TMZ has been supported (47.11-fold, p < 0.0001 and 18.04-fold, p < 0.0001, respectively). 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.