Mehmet Ozturk

Izmir Tinaztepe University

The transcription factor p73 is a member of the p53 tumor suppressor gene family and one of the key regulators of apoptosis. TP73 gene encodes two protein isoforms classes with diverse functions, TAp73 and DNp73, and TAp73 expression in tumor tissues is altered. Unlike the TP53 gene, TP73 is not mutated in cancers. Here, we sought to explore the ex...

AXL, a member of the TAM family, is a promising therapeutic target due to its elevated expression in advanced hepatocellular carcinoma (HCC), particularly in association with acquired drug resistance. Previously, RNA interference was used to study its role in cancer, and several phenotypic changes, including attenuated cell proliferation and decrea...

Purpose Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide with lack of effective systemic chemotherapy. In this study, we aimed to evaluate the value of ATPase family AAA domain-containing protein 2 (ATAD2) as a biomarker and potential therapeutic target for HCC. Methods The expression of ATAD2 was teste...

Purpose Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide with. lack of effective systemic chemotherapy. In this study, we aimed to evaluate the value of ATPase family AAA domain-containing protein 2 (ATAD2) as a biomarker and potential therapeutic target for HCC. Methods The expression of ATAD2 was test...

Aim: We wished to establish 3D organoid-like hepatocellular carcinoma (HCC) models from HCC cell lines. Methods: Hep3B, Huh7, HepG2, SNU398, SNU449, and SNU475 cell lines were inoculated into Matrigel and grown up to 9 days in hepatocyte specific or standard RPMI media. Spheroid formation was followed by light microscopy. Matrigel scaffolds were im...

Hepatocyte dedifferentiation is a major source of hepatocellular carcinoma (HCC), but its mechanisms are unknown. We explored the p73 expression in HCC tumors and studied the effects of transcriptionally active p73β (TAp73β) in HCC cells. Expression profiles of p73 and patient clinical data were collected from the Genomic Data Commons (GDC) data po...

Background : Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to a subgroup of coronaviruses rampant in bats for centuries. It caused the coronavirus disease 2019 (COVID-19) pandemic. Most patients recover, but a minority of severe cases experience acute respiratory distress or an inflammatory storm devastating many organs that...

Acetylcholinesterase (AChE), an enzyme responsible for degradation of acetylcholine, has been identified as a prognostic marker in liver cancer. Although in vivo Ache tumorigenicity assays in mouse are present, no established liver cancer xenograft model in zebrafish using an ache mutant background exists. Herein, we developed an embryonic zebrafis...

Chromone, imidazolidinedione, thiohydantoin and 2,4-thiazolidinedione structures are known to be cytotoxic to cancer cells. In this study, biological activities of previously synthesized 18 chromonyl-2,4-thiazolidinediones/imidazolidinediones/thiohydantoins were tested by sulforhodamine B assay in five liver and one breast cancer cell lines. It was...

Purpose: A new series of thiazolyl-2,4-thiazolidinedione / rhodanine compounds T1-T23 was synthesized and tested for their anticancer activities. Hepatocellular carcinoma cell lines were chosen due to their strong drug resistance to test the new compounds. Methods: All compounds were synthesized via Knoevenagel Condensation reaction and thiazoli...

New amide derivatives of (+)-dehydroabietylamine, tricyclic abietane diterpene amine, were prepared using Zhongping’s protocol. (+)-N-(2-phenyl-acetyl)-dehydroabietylamine derivative (11) demonstrated noticeable growth attenuation of hepatocellular carcinoma cell lines including PLC/PRF/5, SNU475, Hep3B-TR, and Huh7 with IC50 of 7.4 µM, 9.8 µM, 11....

H3.3 is a histone variant, which marks transcription start sites as well as telomeres and heterochromatic sites on the genome. H3.3 presence is thought to positively correlate with transcriptional status of its target genes. Using a conditional genetic strategy against H3.3B combined with short hairpin RNAs against H3.3A, we essentially depleted al...

Background The purpose of present work is to synthesize novel (+)-Dehydroabietylamine derivatives (DAAD) using N-acetyl-α-amino acid conjugates and determine its cytotoxic effects on hepatocellular carcinoma cells. Methods An analytical study was conducted to explore cytotoxic activity of DAAD on hepatocellular carcinoma cell lines. The cytotoxicit...

Development of drug resistance limits the efficacy of targeted therapies. Alternative approaches using different combinations of therapeutic agents to inhibit several pathways could be a more effective strategy for treating cancer. The effects of the approved epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (gefitinib) or a multi-t...

Hepatocellular carcinoma is a highly heterogeneous disease for different reasons. First, there are multiple and highly variable etiological factors including viruses with a DNA (HBV) or RNA (HCV) genome, chemicals (alcohol and aflatoxins), and inborn and acquired metabolic diseases. Second, these cancers might originate either from mature hepatocyt...

Aim: To investigate the expression of DNA repair genes and the impact of BRCA1 on chemoresistance of hepatocellular carcinoma (HCC). Methods: Microarray gene expression datasets were analyzed using the gene set enrichment analysis method. BRCA1 protein was tested by western blotting. Response of HCC cells to interstrand cross-links (ICL) was inv...

Background: Hepatocellular carcinoma is the second deadliest cancer with limited treatment options. Loss of PTEN causes the P13K/Akt pathway to be hyperactive which contributes to cell survival and resistance to therapeutics in various cancers, including the liver cancer. Hence molecules targeting this pathway present good therapeutic strategies f...

Introduction/Aim: In the last century, identifying of new small molecules that stop tumor growth has become very popular for anticancer drug discovery. However, because of multi-disease nature of cancer, the cells become resistant against approved anticancer drugs. Therefore scientists still work on finding more potent chemical structure to cure th...

Introduction/Aim: Before the clinical trials, drug candidates should pass through in vitro cytotoxicity experiments in cancer cell lines. Due to multi disease nature of cancer, usage of more than one cancer cells is suggested. We basically used hepatocellular carcinoma (HCC), one of the most resistant tumor types against anticancer agents, as a mod...

Hepatocellular carcinoma (HCC) is one of the most deadly cancers with a 5-year survival rate below 15% [1]. The treatment of HCC has been a challenge so far because of its unusual resistance to chemotherapeutic agents. Sorafenib is the only drug approved by FDA (Food and Drug Administration, United States) for targeted HCC treatment, but its effect...

To determine the mutation status of human telomerase reverse transcriptase gene (TERT) promoter region in hepatocellular carcinoma (HCC) from different geographical regions. We analyzed the genomic DNA sequences of 59 HCC samples comprising 15 cell lines and 44 primary tumors, collected from patients living in Asia, Europe and Africa. We amplified...

Oleanolic acid (3 β -hydroxy-olean-12-en-28-oic acid; OA-01), a pentacyclic triterpene, exhibit a wide range of pharmacological ad biological activities. We have isolated oleanolic acid from methanolic extract of Periploca aphylla, collected from surroundings of Karachi in the month of February. Furthermore, four known and two new C-28 amino acid c...

Epigenetic alterations, such as the deacetylation of histones, are known to contribute to cellular transformation by silencing critical genes. Histon deacetylase inhibitors (HDACIs) promote or enhance several different anticancer mechanisms, such as apoptosis, cell cycle arrest and cellular differentiation, and therefore are in evidence as potentia...

Deregulated histone acetylation caused by aberrant activity of histone deacetylase enzymes has been linked to tumorigenesis. Thus, histone deacetylase inhibitors are great anticancer drug candidates, especially for the tumors that are resistant to conventional therapies. In this study, a new series of benzamido / acetic acid / acetic acid ethyl est...

Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become "immortal") by inactivating growth control genes such as TP53 and CDKN2A. They also reac...

Patient demographic data, diagnosis and disease etiology of clinical samples used for gene signature validation test. (XLSX)

Microarray gene expression data and literature review of 15 classifier genes. (XLSX)

Gene Set Enrichment Analysis (GSEA) results of gene expression data from Huh7 clones (immortal and senescent) and diseased liver tissues (cirrhosis and HCC). “C2_All” curated gene sets of the MSig Database were analyzed. Commonly enriched gene sets in senescent/cirrhosis, immortal/cirrhosis, immortal/HCC, senescent/HCC groups are provided. The fina...

Introduction: Hepatocellular carcinoma (HCC) is one of the most deadly cancers with a 5- year survival rate below 15% [1]. Treatment of HCC has been a challenge so far because of its unusual resistance to chemotherapeutic agents. Sorafenib is the only drug approved by FDA (Food and Drug Administration, United States) for targeted HCC treatment, but...

Background One-third of breast cancers display amplifications of the ERBB2 gene encoding the HER2 kinase receptor. Trastuzumab, a humanized antibody directed against an epitope on subdomain IV of the extracellular domain of HER2 is used for therapy of HER2-overexpressing mammary tumors. However, many tumors are either natively resistant or acquire...

Interaction between anti-HER2 antibodies and tumor necrosis factor-α. MDA-MB-361 cells were partially sensitive to anti-HER2 antibodies, but highly sensitive to TNF-α (top). MCF-7 cells were resistant to anti-HER2 antibodies, but highly sensitive to TNF-α (middle). T47D cells were resistant to both anti-HER2 antibodies and TNF-α (bottom). Growth me...

In vitro molecular responses of SK-BR-3 cells to tumor necrosis factor-α. SK-BR-3 cells were treated up to 24 h with TNF-α (1000 U/ml). Cell lysates were prepared from cells harvested at indicated times (hr, hours) and the expressions of phospho-HER2 (pHER2), phospho-Akt (pAkt), total Akt (Akt), phospho-ERK1/phospho-Erk2 (pErk1/2), total Erk1/Erk2...

Antibody binding to endogenously expressed HER2 protein as tested by immunoprecipitation-western blot assay. T47D-derived lysates were subjected to immunoprecipitation with different anti-HER2 antibodies. Antigen-antibody complexes were captured onto Protein G-conjugated beads, eluted and subjected to western blot assay using CB11 antibody. Blots w...

Anti-HER2 antibodies did not react with EGFR. Mice were immunized with SK-BR-3 cells, followed by a recombinant protein composed of extracellular domain of HER2 fused to human IgG1 Fc domain (HER2 ECD). ELISA plates that have been coated with either HER2 ECD or EGFR ECD were incubated with antibody-containing hybridoma supernatants, followed by alk...

Epitope mapping of anti-HER2 antibodies using combined immunoprecipitation-western blot assay. Huh7 cells were transfected in 6-well plates using a set of mammalian expression plasmids encoding full-length or N-terminally truncated HER2 protein. Transfected cells were cultivated for 48 h; cell lysates were subjected to immunoprecipitation with diff...

The serine/threonine kinase Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K), is involved in cell survival and anti-apoptotic signaling. Akt has been shown to be constitutively expressed in a variety of human tumors including hepatocellular carcinoma (HCC). In this report we analyzed the status of Akt pathway in three HCC cell lin...

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensi...

BACKGROUND & AIMS Escape from senescence plays a crucial remains elusive. we investigated the hepatocelluf ar carcinoma (HCC), METHODS I ! role in rodent tumors. Its role in human tumors i refevance of senescence escape to hurnan we compared gene expression profiles of senescence-arrested and senescence-esca ped HCC cells, as well as liver cirrhosi...

Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths. Aflatoxins, which may play a causative role in 5-28% of HCCs worldwide, are activated in liver cells and induce principally G→T mutations, including the TP53 codon 249(G→T) hotspot mutation. The DNA damage checkpoint response acts as an antitumour mechanism against genotoxic agents...

Introduction: Doxorubicin (DOX, adriamycin) is an anti-cancer drug commonly used in treatment of several human solid cancers including unresectable hepatocellular carcinoma (HCC). Therapeutic effects of DOX have been linked to DNA intercalation and topoisomerase inhibition as well as oxidative stress induction. As DNA damage and oxidative stress ha...

Targets of E2F transcription factors effectively regulate the cell cycle from worms to humans. Furthermore, the dysregulation of E2F transcription modules plays a highly conserved role in cancers of human and zebrafish. Studying E2F target expression under a given cellular state, such as quiescence, might lead to a better understanding of the conse...

The Wnt signaling pathway is involved in many differentiation events during embryonic development and can lead to tumor formation after aberrant activation of its components. beta-catenin, a cytoplasmic component, plays a major role in the transduction of canonical Wnt signaling. The aim of this study was to identify novel genes that are regulated...

Di(2-ethylhexyl)-phthalate (DEHP) is the most abundantly used phthalate derivative, inevitable environmental exposure of which is suspected to contribute to the increasing incidence of testicular dysgenesis syndrome in humans. Oxidative stress and mitochondrial dysfunction in germ cells are suggested to contribute to phthalate-induced disruption of...

Unlabelled: Senescence induction could be used as an effective treatment for hepatocellular carcinoma (HCC). However, major senescence inducers (p53 and p16(Ink4a)) are frequently inactivated in these cancers. We tested whether transforming growth factor-beta (TGF-beta) could serve as a potential senescence inducer in HCC. First, we screened for H...

STR analysis data that shows the authenticity of breast cancer cell lines used in this study. (1.50 MB XLS)

p16Ink4a expression in colonies obtained from breast cancer cell lines. There was no correlation between p16Ink4a expression and progenitor subtype. (3.39 MB TIF)

Co-staining experiments indicate that SABG staining is associated with p21Cip1, but with p16Ink4a expression in SCP cells. Colonies were generated from T47D and MB-MDA-231 cells and subjected to SABG staining, followed by p21Cip1 or p16Ink4a immunoperoxidase (brown) staining. MDA-MB-231 cells were used as negative control. (2.74 MB TIF)

Effect of estrogen receptor-overexpression on the production of BrdU-negative terminally arrested cell progeny. ER-overexpressing (ER-5, ER-7, ER-26) and control (C-8, C-10, C-11) stable clones were established from T47D cells. Following transfection with ER expression and control vectors, colonies were generated from respective cell lines, labeled...

Unsupervised hierarchical clustering of breast tumor and cell line gene expression data that is described in Fig. 7A. Dendrogram shown here includes tumor and cell line sample IDs. (1.05 MB TIF)