Ozturk Lab. on Cancer Mechanisms and Theranostics

OVERVIEW

Hepatocellular cancers can be sub-grouped into hepatocellular carcinomas (HCCs) and cholangiocarcinomas that affect mostly adults, and childhood hepatoblastomas. HCCs are the third most common cause of death from cancer, with more than one million patients dying worldwide each year. These tumors show extreme heterogeneity in their genomic aberrations and their epigenetic status is ill-defined. They are naturally resistant to chemotherapy and radiotherapy and the five-year survival rate of affected patients is very low. In order to discover new targets and new anti-tumor drugs, it is important to better characterize molecular mechanisms of hepatocellular cancers.

RESEARCH INTERESTS

Our primary goal is to discover novel disease markers, genetic and epigenetic targets and to develop targeted therapies for hepatocellular cancers by exploring their genetic, epigenetic and phenotypic features. Currently, our major research interests are:

1- Mechanisms of escape from senescence-based growth control: we are using cell lines (in vitro and tumors generated in immunodeficient mice), as well as patient-derived material for these studies.

2- Epigenetics: we are using conditional knock-out mouse models for histone variants made available by Stefan Dimitrov (Institute Albert Bonniot, France) combined with “Sleeping Beauty transposon system based liver tumor models (in collaboration with Kasim Diril, iBG-izmir). Selected histone variant genes are deleted specifically in liver cells using a liver-specific promoter associated with 4OH-tamoxifen induction. We will examine the effects of histone variant gene ablations on liver development, regeneration, and carcinogenesis.

3- Cell surface proteins: Proteins that are aberrantly expressed on the surface of hepatocellular cancers will be explored by.

RESEARCH HIGHLIGHTS

Our most recent findings concern senescence-related events associated with hepatocellular cancer cell immortalization. We used genome-wide expression analysis to identify sets of genes whose expression is associated with either senescence and cirrhosis or immortality and hepatocellular carcinoma. Surprisingly, a large number of gene sets were affected (Ozturk et al., PNAS 2006, Yildiz et al. PLoS ONE, 2013). We identified a gene signature that allowed us to differentiate HCC from cirrhosis (Yildiz et al. PLoS ONE 2013). More interestingly, we also identified another gene signature with an excellent prediction of patient survival (PATENT PENDING PCT/EP2014/058293).

Selected Publications

Senem Demir, Cigdem Özen, Meltem Ceylan‐Ünlüsoy, Mehmet Öztürk, Oya Bozdağ‐Dündar. Novel Furochromone Derivatives: Synthesis and Anticancer Activity Studies. Journal of Heterocyclic Chemistry. 2019 Feb doi:10.1002/jhet.3508.

Ozen C, Ceylan-Unlusoy M, Ozturk M, Bozdag-Dundar O. A novel chromonyl thiohydantoin with anti-proliferative action on primary hepatocellular carcinoma cells. Med Chem Res. 2018 Jan ; 27 (1): 153-160. doi:10.1007/s00044-017-2037-0.

Keziban Oral, Mert Akan, Sevda Özkardeşler, Nilay Boztaş, Bekir Uğur Ergür, Mehmet Ensari Güneli, Çimen Olguner, Hatice Fidan. Comparison of Direct and Remote Ischaemic Preconditioning of Renal Ischaemia Reperfusion Injury in Rats. Turkish Journal of Anaesthesiology and Reanimation. 2018 Dec ; 46 (6): 453-461. doi:10.5152/TJAR.2018.07992 .

Avci ME, Keskus AG, Targen S, Isilak ME, Ozturk M, Atalay RC, Adams MM, Konu O. Development of a novel zebrafish xenograft model in ache mutants using liver cancer cell lines. Scientific Reports. 2018 Jan ; 8 (1): 1570. doi:10.1038/s41598-018-19817-w.

Özge Kuzgun, Sevda Özkardeşler, Şule Özbilgin, Mert Akan, Bekir Uğur Ergür, Gonca Kamacı, Mehmet Ensari Güneli, Nazire Ateş , Ali Rıza Şişman , Reci Meseri Dalak. Effects of Dexmedetomidine on Renal Ischaemia Reperfusion Injury in Streptozotocin-Induced Diabetic Rats. Turkish Journal of Anaesthesiology and Reanimation. 2018 Dec ; 46 (6): 462-469. doi:10.5152/TJAR.2018.07992.

Ozbilgin S, Yurtlu DA, Kucukoztas B, Kamaci, et al. Evaluation of the Effectiveness of Sugammadex for Digoxin Intoxication: An Experimental Study. CARDIOVASCULAR TOXICOLOGY. 2018 Oct ; 18 (5): 400-406. doi:10.1007 /s1201 2-018-9 450-6.

Fatma Ilknur Ulugun, Aydin Sanli,Ensari Guneli,Duygu Gurel. The Effect of Ozone Treatment to the Inflammatory Response in Lung Contusion. Journal of Basic and Clinical Health Sciences. 2018 ; 2 (3): . doi:10.3062 1/jbachs .2018.4 32.

Serkan YILDIZ, Zahide ÇAVDAR, Gülgün OKTAY, Sülen SARIOĞLU, Ensari GÜNELI, Osman YILMAZ, Taner ÇAMSARI. The Effects of Doxycycline on Peritoneal Fibrosis Induced by Chemical Peritonitis in Rats. Turkish Journal of Nephrology. 2018 ; 27 (1): 49-56. doi:10.5262 /tndt.20 17.1003 .25 .

Karaman M, Baltacioglu G, Kolatan HE, Celik A, Yilmaz O and Guneli E. Effect of Cross-Fostering on a Variety of Viral Agents in Conventionally Bred Rats. Journal of Animal Research and Nutrition . 2017 Aug ; 2 (2): 1-5. doi:10.2176 7/2572- 5459.10 0032 .

Gumustekin M, Arici A, Cilaker Micili S, Karaman M. , Guneli ME, Tekmen I. HGF/c-Met Pathway has a role in testicular Damage in Diabetes Induced by Streptozotocin. ACTA ENDOCRINOLOGICA (BUC). 2017 Mar ; 13 (1): 17-22. doi:10.4183 /aeb.20 17.17.

Ors A, Papin C, Favier B, Roulland Y, Dalkara D, Ozturk M, Hamiche A, Dimitrov S, Padmanabhan K. Histone H3.3 regulates mitotic progression in mouse embryonic fibroblasts. Biochem Cell Biol. 2017 Aug ; 95 (4): 491-499. doi:10.1139/bcb-2016-0190.

Ozturk M, Batur T, Ekin U, Erdogan A, İscan E, Keles U, Oz O, Ozen C.. Molecular Pathogenesis of Liver Cancer. J Gastrointest Cancer. 2017 Jul doi:10.1007/s12029-017-9957-2.

Balci C, Akan M, Boztas, N, Ozkardesler, et al. Protective effects of dexmedetomidine and remote ischemic preconditioning on renal ischemia reperfusion injury in rats. ULUSAL TRAVMA VE ACIL CERRAHI DERGISI-TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY. 2017 Jul ; 23 (4): 279-286. doi:10.5505 /tjtes.20 16.4910 3 .

Cavdar Z, Ural C, Celik, A, Arslan, et al. Protective effects of taurine against renal ischemia/reperfusion injury in rats by inhibition of gelatinases, MMP-2 and MMP-9, and p38 mitogen-activated protein kinase signaling. BIOTECHNIC & HISTOCHEMISTRY. 2017 Sep ; 92 (7): 524-535. doi:10.1080 /10520 295.201 7.13670 33 .

Cigdem Ozen, Meltem Ceylan Unlusoy, Nazanin Aliary, Mehmet Ozturk, Oya Bozdag Dundar.. Thiazolidinedione or Rhodanine: A Study on Synthesis and Anticancer Activity Comparison of Novel Thiazole Derivatives. J Pharm Sci. 2017 Nov ; 20 (1): 415-427. doi:10.18433/J38P9R.

Contact

Ozturk Lab. on Cancer Mechanisms and Theranostics

Prof.Dr. Mehmet ÖZTÜRK
mehmet.ozturk@ibg.edu.tr
+90 232 299 41 00 (5211 / 1000)
+90 232 299 41 71