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Citation Count: 52
Anti-proliferative, apoptotic and signal transduction effects of hesperidin in non-small cell lung cancer cells
(Springer, 2015) Cincin, Zeynep Birsu; Unlu, Miray; Kiran, Bayram; Bireller, Elif Sinem; Baran, Yusuf; Cakmakoglu, Bedia; Baran, Yusuf
Hesperidin, a glycoside flavonoid, is thought to act as an anti-cancer agent, since it has been found to exhibit both pro-apoptotic and anti-proliferative effects in several cancer cell types. The mechanisms underlying hesperidin-induced growth arrest and apoptosis are, however, not well understood. Here, we aimed to investigate the anti-proliferative and apoptotic effects of hesperidin on non-small cell lung cancer (NSCLC) cells and to investigate the mechanisms involved. The anti-proliferative and apoptotic effects of hesperidin on two NSCLC-derived cell lines, A549 and NCI-H358, were determined using a WST-1 colorimetric assay, a LDH cytotoxicity assay, a Cell Death Detection assay, an AnnexinV-FITC assay, a caspase-3 assay and a JC-1 assay, respectively, all in a time- and dose-dependent manner. As a control, non-cancerous MRC-5 lung fibroblasts were included. Changes in whole genome gene expression profiles were assessed using an Illumina Human HT-12v4 beadchip microarray platform, and subsequent data analyses were performed using an Illumina Genome Studio and Ingenuity Pathway Analyser (IPA). We found that after hesperidin treatment, A549 and NCI-H358 cells exhibited decreasing cell proliferation and increasing caspase-3 and other apoptosis-related activities, in conjunction with decreasing mitochondrial membrane potential activities, in a dose- and time-dependent manner. Through a GO analysis, by which changes in gene expression profiles were compared, we found that the FGF and NF-kappa B signal transduction pathways were most significantly affected in the hesperidin treated NCI-H358 and A549 NSCLC cells. Our results indicate that hesperidin elicits an in vitro growth inhibitory effect on NSCLC cells by modulating immune response-related pathways that affect apoptosis. When confirmed in vivo, hesperidin may serve as a novel anti-proliferative agent for non-small cell lung cancer.
Citation Count: 9
Bioactive sphingolipids in docetaxel-induced apoptosis in human prostate cancer cells
(Elsevier France-editions Scientifiques Medicales Elsevier, 2012) Bassoy, Esen Yonca; Baran, Yusuf; Baran, Yusuf
In this study, we examined the possible roles of ceramide/sphingosine-1-phosphate and ceramide/glucosyleceramide signaling in docetaxel-induced apoptosis by examining expression levels of the glucosyleceramide synthase and sphingosine kinase-1 and ceramide synthase gene family. As confirmed by isobologram analysis, docetaxel in combination with agents that increase intracellular ceramide levels increased the cytotoxic and apoptotic effects of docetaxel synergistically. More importantly, RT-PCR results revealed that expression levels of glucosyleceramide synthase and sphingosine kinase-1 were downregulated and ceramide synthase genes were upregulated in response to docetaxel. This study identifies mechanisms underlying the involvement of ceramide metabolizing genes in docetaxel-induced apoptosis in prostate cancer cells. (c) 2012 Elsevier Masson SAS. All rights reserved.
Citation Count: 16
Biodiversity, drug discovery, and the future of global health: Introducing the biodiversity to biomedicine consortium, a call to action
(Univ Edinburgh, Global Health Soc, 2017) Neergheen-Bhujun, Vidushi; Awan, Almas Taj; Baran, Yusuf; Bunnefeld, Nils; Chan, Kit; Edison Dela Cruz, Thomas; Kagansky, Alexander; Baran, Yusuf
[No Abstract Available]
Citation Count: 7
Comparative development of knowledge-based bioeconomy in the European Union and Turkey
(informa Healthcare, 2014) Ozan, Didem Celikkanat; Baran, Yusuf; Baran, Yusuf
Biotechnology, defined as the technological application that uses biological systems and living organisms, or their derivatives, to create or modify diverse products or processes, is widely used for healthcare, agricultural and environmental applications. The continuity in industrial applications of biotechnology enables the rise and development of the bioeconomy concept. Bioeconomy, including all applications of biotechnology, is defined as translation of knowledge received from life sciences into new, sustainable, environment friendly and competitive products. With the advanced research and eco-efficient processes in the scope of bioeconomy, more healthy and sustainable life is promised. Knowledge-based bioeconomy with its economic, social and environmental potential has already been brought to the research agendas of European Union (EU) countries. The aim of this study is to summarize the development of knowledge-based bioeconomy in EU countries and to evaluate Turkey's current situation compared to them. EU-funded biotechnology research projects under FP6 and FP7 and nationally-funded biotechnology projects under The Scientific and Technological Research Council of Turkey (TUBITAK) Academic Research Funding Program Directorate (ARDEB) and Technology and Innovation Funding Programs Directorate (TEYDEB) were examined. In the context of this study, the main research areas and subfields which have been funded, the budget spent and the number of projects funded since 2003 both nationally and EU-wide and the gaps and overlapping topics were analyzed. In consideration of the results, detailed suggestions for Turkey have been proposed. The research results are expected to be used as a roadmap for coordinating the stakeholders of bioeconomy and integrating Turkish Research Areas into European Research Areas.
Citation Count: 11
Cryopreservation of a cell-based biosensor chip modified with elastic polymer fibers enabling ready-to-use on-site applications
(Elsevier Advanced Technology, 2021) Ozsoylu, Dua; Isik, Tugba; Demir, Mustafa M.; Schoning, Michael J.; Wagner, Torsten; Demir, Mustafa
An efficient preservation of a cell-based biosensor chip to achieve a ready-to-use on-site system is still very challenging as the chip contains a living component such as adherent mammalian cells. Herein, we propose a strategy called on-sensor cryopreservation (OSC), which enables the adherent cells to be preserved by freezing (-80 degrees C) on a biosensor surface, such as the light-addressable potentiometric sensor (LAPS). Adherent cells on rigid surfaces are prone to cryo-injury; thus, the surface was modified to enhance the cell recovery for OSC. It relies on i) the integration of elastic electrospun fibers composed of polyethylene vinyl acetate (PEVA), which has a high thermal expansion coefficient and low glass-transition temperature, and ii) the treatment with O-2 plasma. The modified sensor is integrated into a microfluidic chip system not only to decrease the thermal mass, which is critical for fast thawing, but also to provide a precisely controlled micro-environment. This novel cryo-chip system is effective for keeping cells viable during OSC. As a proof-of-concept for the applicability of a ready-to-use format, the extracellular acidification of cancer cells (CHO-K1) was evaluated by differential LAPS measurements after thawing. Results show, for the first time, that the OSC strategy using the cryo-chip allows label-free and quantitative measurements directly after thawing, which eliminates additional post-thaw culturing steps. The freezing of the chips containing cells at the manufacturing stage and sending them via a cold-chain transport could open up a new possibility for a ready-to-use on-site system.
Citation Count: 34
Effect of Molecular Architecture on Cell Interactions and Stealth Properties of PEG
(Amer Chemical Soc, 2017) Ozer, Imran; Tomak, Aysel; Zareie, Hadi M.; Baran, Yusuf; Bulmus, Volga; Baran, Yusuf
PEGylation, covalent attachment of PEG to therapeutic biomolecules, in which suboptimal pharmacokinetic profiles limiting their therapeutic utility are of concern, is a widely applied technology. However, this technology has been challenged by reduced bioactivity of biomolecules upon PEGylation and immunogenicity of PEG triggering immune response and abrogating clinical efficacy, which collectively necessitate development of stealth polymer alternatives. Here we demonstrate that comb-shape poly[oligo(ethylene glycol) methyl ether methacrylate](POEGMA); a stealth polymer alternative, has a more compact structure than PEG and self-organize into nanoparticles in a molecular weight dependent manner. Most notably, we show that comb shape POEGMA promotes significantly higher cellular uptake and exhibits less steric hindrance imposed on the conjugated biomolecule than PEG. Collectively, comb-shape POEGMA offers a versatile alternative to PEG for stealth polymer-biomolecule conjugation applications.
Citation Count: 445
Flow cytometry: basic principles and applications
(Taylor & Francis Ltd, 2017) Adan, Aysun; Alizada, Gunel; Kiraz, Yagmur; Baran, Yusuf; Nalbant, Ayten; Baran, Yusuf
Flow cytometry is a sophisticated instrument measuring multiple physical characteristics of a single cell such as size and granularity simultaneously as the cell flows in suspension through a measuring device. Its working depends on the light scattering features of the cells under investigation, which may be derived from dyes or monoclonal antibodies targeting either extracellular molecules located on the surface or intracellular molecules inside the cell. This approach makes flow cytometry a powerful tool for detailed analysis of complex populations in a short period of time. This review covers the general principles and selected applications of flow cytometry such as immunophenotyping of peripheral blood cells, analysis of apoptosis and detection of cytokines. Additionally, this report provides a basic understanding of flow cytometry technology essential for all users as well as the methods used to analyze and interpret the data. Moreover, recent progresses in flow cytometry have been discussed in order to give an opinion about the future importance of this technology.
Citation Count: 7
HER2-Targeted, Degradable Core Cross-Linked Micelles for Specific and Dual pH-Sensitive DOX Release
(Wiley-v C H verlag Gmbh, 2022) Bayram, Nazende Nur; Ulu, Gizem Tugce; Topuzogullari, Murat; Baran, Yusuf; Isoglu, Sevil Dincer; Baran, Yusuf
Here, a targeted, dual-pH responsive, and stable micelle nanocarrier is designed, which specifically selects an HER2 receptor on breast cancer cells. Intracellularly degradable and stabilized micelles are prepared by core cross-linking via reversible addition-fragmentation chain-transfer (RAFT) polymerization with an acid-sensitive cross-linker followed by the conjugation of maleimide-doxorubicin to the pyridyl disulfide-modified micelles. Multifunctional nanocarriers are obtained by coupling HER2-specific peptide. Formation of micelles, addition of peptide and doxorubicin (DOX) are confirmed structurally by spectroscopical techniques. Size and morphological characterization are performed by Zetasizer and transmission electron microscope (TEM). For the physicochemical verification of the synergistic acid-triggered degradation induced by acetal and hydrazone bond degradation, Infrared spectroscopy and particle size measurements are used. Drug release studies show that DOX release is accelerated at acidic pH. DOX-conjugated HER2-specific peptide-carrying nanocarriers significantly enhance cytotoxicity toward SKBR-3 cells. More importantly, no selectivity toward MCF-10A cells is observed compared to HER2(+) SKBR-3 cells. Formulations cause apoptosis depending on Bax and Caspase-3 and cell cycle arrest in G2 phase. This study shows a novel system for HER2-targeted therapy of breast cancer with a multifunctional nanocarrier, which has higher stability, dual pH-sensitivity, selectivity, and it can be an efficient way of targeted anticancer drug delivery.
Citation Count: 58
Hierarchically Structured Metal Oxide/Silica Nanofibers by Colloid Electrospinning
(Amer Chemical Soc, 2012) Horzum, Nesrin; Munoz-Espi, Rafael; Glasser, Gunnar; Demir, Mustafa M.; Landfester, Katharina; Crespy, Daniel; Demir, Mustafa
We present herein a new concept for the preparation of nanofibrous metal oxides based on the simultaneous electrospinning of metal oxide precursors and silica nanoparticles. Precursor fibers are prepared by electrospinning silica nanoparticles (20 nm in diameter) dispersed in an aqueous solution of poly(acrylic acid) and metal salts. Upon calcination in air, the poly(acrylic acid) matrix is removed, the silica nanoparticles are cemented, and nanocrystalline metal oxide particles of 4-14 nm are nucleated at the surface of the silica nanoparticles. The obtained continuous silica fibers act as a structural framework for metal oxide nanoparticles and show improved mechanical integrity compared to the neat metal oxide fibers. The hierarchically nanostructured materials are promising for catalysis applications, as demonstrated by the successful degradation of a model dye in the presence of the fibers.
Citation Count: 39
Investigation of Oxygen Permeation through Composites of PMMA and Surface-Modified ZnO Nanoparticles
(Wiley-v C H verlag Gmbh, 2009) Hess, Sandra; Demir, Mustafa M.; Yakutkin, Vladimir; Baluschev, Stanislav; Wegner, Gerhard; Demir, Mustafa
oxygen permeabilities of nanocomposite films consisting of poly(methyl methacrylate) (PMMA) and different amounts of spherical zinc oxide (ZnO) nanoparticles were determined to investigate the barrier effect of this material with respect to particle content. A method was applied which is based on quenching of an excited phosphorescent dye by oxygen. Possible effects of the nanoparticles on the response of the dye molecules were investigated and were ruled out.
Citation Count: 64
Mesenchymal stem cells ameliorate the histopathological changes in a murine model of chronic asthma
(Elsevier Science Bv, 2011) Firinci, Fatih; Karaman, Meral; Baran, Yusuf; Bagriyanik, Alper; Ayyildiz, Zeynep Arikan; Kiray, Muge; Karaman, Ozkan; Baran, Yusuf
Asthma therapies are effective in reducing inflammation but airway remodeling is poorly responsive to these agents. New therapeutic options that have fewer side effects and reverse chronic changes in the lungs are essential. Mesenchymal stem cells (MSCs) are promising for the development of novel therapies in regenerative medicine. This study aimed to examine the efficacy of MSCs on lung histopathology in a murine model of chronic asthma. BALB/c mice were divided into four groups: Group 1 (control group, n = 6), Group 2 (ovalbumin induced asthma only, n = 10), Group 3 (ovalbumin induced asthma + MSCs, n = 10), and Group 4 (MSCs only, n = 10). Histological findings (basement membrane, epithelium, subepithelial smooth muscle thickness, numbers of goblet and mast cells) of the airways and MSC migration were evaluated by light, electron, and confocal microscopes. In Group 3, all early histopathological changes except epithelial thickness and all of the chronic changes were significantly ameliorated when compared with Group 2. Evaluation with confocal microscopy showed that no noteworthy amount of MSCs were present in the lung tissues of Group 4 while significant amount of MSCs was detected in Group 3. Serum NO levels in Group 3, were significantly lower than Group 2. The results of this study revealed that MSCs migrated to lung tissue and ameliorated bronchial asthma in murine model. Further studies are needed to evaluate the efficacy of MSCs for the treatment of asthma. (C) 2011 Elsevier B.V. All rights reserved.
Citation Count: 3
Regulation of mRNA stability through a pentobarbital-responsive element
(Elsevier Science inc, 2007) Akgul, Bunyamin; Tu, Chen-Pei D.; Akgül, Bünyamin
Pentobarbital, a general anesthetic and non-genotoxic carcinogen, can induce gene expression by activating transcription. In the Drosophila glutathione S-transferase D21 (gstD21) gene, pentobarbital's regulatory influence extends to the level of mRNA turnover. Transcribed from an intronless gene, gstD21 mRNA is intrinsically very labile. But exposure to pentobarbital renders it stabilized beyond what can be attributed to transcriptional activation. We aim here to identify cis-acting element(s) of gstD21 mRNA as contributors to the molecule's pentobarbital-mediated stabilization. In the context of hsp70 5'UTR and the 3'UTR of act5C, gstD21 mRNA, minus its native UTRs, is stable. Maintaining the same context of heterologous UTRs, we can reconstitute using the full-length gstD21 sequence the inherent instability of gstD21 mRNA and its stabilization by pentobarbital. Transgenic flies that express these chimeric gstD21 mRNA exhibit decay intermediates lacking 3'UTR, which are not stabilized by PB treatment. The 3'UTR sequence, when inserted downstream from a reporter transcript, stabilizes it 1.6-fold under PB treatment. The analysis of the decay intermediates suggests a polysome-associated decay pattern. We propose a regulatory model that features a 59-nucleotide pentobarbital-responsive element (PBRE) in the 3'UTR of gstD21 mRNA. (c) 2006 Elsevier Inc. All rights reserved.
Citation Count: 24
Role of autophagy in the progression and suppression of leukemias
(Elsevier Science inc, 2012) Ekiz, Huseyin Atakan; Can, Geylani; Baran, Yusuf; Baran, Yusuf
Autophagy is a physiological process in which cellular components are degraded by the lysosomal machinery. Thereby, organelles are recycled and monomers are produced in order to maintain energy production. Current studies indicate autophagy might suppress or augment survival of cancer cells. Therefore, by elucidating the role of autophagy in cancer pathogenesis, novel therapeutic intervention points may be revealed. Leukemia therapy has advanced in recent years; but a definitive cure is still lacking. Since autophagy often is deregulated in this particular type of cancer, it is clear that future findings will have clinical implications. This review will discuss the current knowledge of autophagy in blood cancers. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
Citation Count: 12
The roles of macromolecules in imatinib resistance of chronic myeloid leukemia cells by Fourier transform infrared spectroscopy
(Elsevier France-editions Scientifiques Medicales Elsevier, 2013) Baran, Yusuf; Ceylan, Cagatay; Camgoz, Aylin; Baran, Yusuf
Imatinib is a first generation tyrosine kinase inhibitor, which is used for the treatment of chronic myeloid leukemia. However, resistance to imatinib is an important problem. Different mechanisms have been explained for imatinib resistance. In this study, we examined the roles of macromolecules in imatinib resistance in K562 cells at the molecular level using Fourier Transform Infrared (FT-IR) spectroscopy. An amount of 3 mu M imatinib resistant cells were generated by our group and named as K562/IMA-3 cells. Changes in macromolecules in parental and resistant cells were studied by FT-IR spectroscopy. Imatinib resistance caused changes, which indicated decreases in the level of glycogen and increases in the membrane order. The amount of unsaturated lipids increased in the imatinib resistant cells indicating lipid peroxidation. Imatinib resistance caused changes in the lipid/protein ratio. The relative protein content increased with respect to nucleic acids indicating higher transcription and protein expression and structural/organizational changes in the nucleus were evident as revealed by frequency changes in the nucleic acid bands. Changes in the amide bands revealed changes in the proteome of the resistant cells. Protein secondary structural changes indicated that the antiparallel beta sheet's structure increased, however the alpha helix structure, beta sheet structure, random coil structure and turns decreased in the resistant cells. These results indicate that the FT-IR technique provides a suitable method for analyzing drug resistance related structural changes in leukemia and other cancer types. (C) 2013 Elsevier Masson SAS. All rights reserved.
Citation Count: 66
Sorption Efficiency of Chitosan Nanofibers toward Metal Ions at Low Concentrations
(Amer Chemical Soc, 2010) Horzum, Nesrin; Boyaci, Ezel; Eroglu, Ahmet E.; Shahwan, Talal; Demir, Mustafa M.; Demir, Mustafa
Chitosan fibers showing narrow diameter distribution with a mean of 42 nm were produced by electrospinning and utilized for the sorption of Fe(III), Cu(II), Ag(I), and Cd(II) ions from aqueous solutions. The ion concentrations in the supernatant solutions were determined using inductively coupled plasma-mass spectrometry (ICP-MS). The filtration efficiency of the fibers toward these ions was studied by both batch and microcolumn methods. High efficiency in sorption of the metal ions was obtained in the both methods. The effects of sorbent amount (0.10-0.50 mg), shaking time (15-120 min), initial metal ion concentration (10.0-1000.0 mu g.L-1), and temperature (25 and 50 degrees C) on the extent of sorption were examined. The sorbent amount did not significantly alter the efficiency of sorption; however, shaking time, temperature, and metal ion concentration were found to have a strong influence on sorption. By virtue of its mechanical integrity, the applicability of the chitosan mat in solid phase extraction under continuous flow looks promising.
Citation Count: 12
STAT pathway in the regulation of zoledronic acid-induced apoptosis in chronic myeloid leukemia cells
(Elsevier France-editions Scientifiques Medicales Elsevier, 2013) Kiper, Hatice Demet; Kaymaz, Burcin Tezcanli; Gokbulut, Aysun Adan; Selvi, Nur; Avci, Cigir Biray; Kosova, Buket; Saydam, Guray
In this study, we aimed to evaluate the cytotoxic and apoptotic effects of zoledronic acid on K562 chronic myeloid leukemia (CML) cells and to examine the roles of STAT genes on zoledronic acid-induced apoptosis. The results showed that zoledronic acid decreased proliferation, and induced apoptosis in K562 cells in a dose- and time-dependent manner. mRNA and protein levels of STAT3, -5A and -5B genes were significantly reduced in zoledronic acid-treated K562 cells. These data indicated that STAT inhibition by zoledronic acid may be therapeutic in CML patients following the confirmation with clinical studies. (C) 2013 Elsevier Masson SAS. All rights reserved.
Citation Count: 32
Therapeutic applications of bioactive sphingolipids in hematological malignancies
(Wiley, 2010) Ekiz, Huseyin Atakan; Baran, Yusuf; Baran, Yusuf
Sphingolipids are sphingosine-based lipid molecules that have important functions in cellular signal transduction and in a variety of cellular processes including proliferation, differentiation, programmed cell death (apoptosis) and responses to stressful conditions. Ceramides, dihydroceramide, sphingosine and sphingosine-1-phosphate are examples of those bioactive sphingolipids. They have a major impact on determination of the cell fate by contributing to the cell survival or cell death through apoptosis. Despite the number of carbon atoms in the fatty acid chain changes the physiological role; ceramides generally exert suppressive roles on the cell proliferation. There have been several enzymes identified in this pathway that are responsible for the conversion of ceramide into other sphingolipid derivatives. Those,derivatives also have differential roles on those cellular process. Sphingosine-1-phosphate is an example of such sphingolipid derivatives which has antiapoptotic effects. As they have significant impacts particularly on the cell death and survival, bioactive sphingolipids have a great potential to be targets in cancer therapy. Increasing number of studies indicates that sphingolipid derivatives are important in the progression of hematological malignancies, and they are also involved in the resistance to current chemotherapeutic options. This review compiles the current knowledge in this area for enlightening the therapeutic potentials of bioactive sphingolipids in various leukemias.
Citation Count: 68
Toward Transparent Nanocomposites Based on Polystyrene Matrix and PMMA-Grafted CeO₂ Nanoparticles
(Amer Chemical Soc, 2011) Parlak, Onur; Demir, Mustafa M.; Demir, Mustafa
The association of transparent polymer and nanosized pigment particles offers attractive optical materials for various potential and existing applications. However, the particles embedded into polymers scatter light due to refractive index (RI) mismatch and reduce transparency of the resulting composite material. In this study, optical composites based on polystyrene (PS) matrix and poly(methyl methacrylate) (PMMA)-grafted CeO2 hybrid particles were prepared. CeO2 nanoparticles with an average diameter of 18 +/- 8 nm were precipitated by treating Ce(NO3)center dot 6H(2)O with urea in the presence of a polymerizable surfactant, 3-methacyloxypropyltrimethoxy silane. PMMA chains were grafted on the surface of the nanoparticles upon free radical in situ solution polymerization. While blending of unmodified CeO2 particles with PS resulted in opaque films, the transparency of the composite films was remarkably enhanced when prepared by PMMA-grafted CeO2 hybrid particles, particularly those having a PMMA thickness of 9 nm. The improvement in transparency is presumably due to the reduction in RI mismatch between CeO2 particles and the PS matrix when using PMMA chains at the interface.
Citation Count: 12
An update on molecular biology and drug resistance mechanisms of multiple myeloma
(Elsevier Science inc, 2015) Mutlu, Pelin; Kiraz, Yagmur; Gunduz, Ufuk; Baran, Yusuf; Baran, Yusuf
Multiple myeloma (MM), a neoplasm of plasma cells, is the second most common hematological malignancy. Incidance rates increase after age 40. MM is most commonly seen in men and African-American population. There are several factors to this, such as obesity, environmental factors, family history, genetic factors and monoclonal gammopathies of undetermined significance (MGUS) that have been implicated as potentially etiologic. Development of MM involves a series of complex molecular events, including chromosomal abnormalities, oncogene activation and growth factor dysregulation. Chemotherapy is the most commonly used treatment strategy in MM. However, MM is a difficult disease to treat because of its marked resistance to chemotherapy. MM has been shown to be commonly multidrug resistance (MDR)-negative at diagnosis and associated with a high incidence of MDR expression at relapse. This review deals with the molecular aspects of MM, drug resistance mechanisms during treatment and also possible new applications for overcoming drug resistance. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Citation Count: 81
An update on molecular biology of thyroid cancers
(Elsevier Science inc, 2014) Omur, Ozgur; Baran, Yusuf; Baran, Yusuf
Differentiated thyroid cancer (DTC) is the most common endocrinological malignancy. There are several histological variants such as papillary and follicular thyroid carcinoma. Many patients with well-differentiated subtypes of DTC are cured by surgery alone or with radioiodine, while poorly differentiated types usually have a worse prognosis. The aggressiveness of thyroid tumors is closely linked to specific gene alterations. Several diagnostic and prognostic molecular markers such as BRAF and RAS point mutations; RET/PTC and PAX8/PPAR gamma gene rearrangements; MAPK, PI3K, p53, Wnt-beta catenin, HIF1 alpha and NF-kappaB signaling pathways; microRNA profiles and aberrant methylation have been demonstrated in more than 70% of DTC. Diagnostic use of these molecular markers may be optimized for identifying higher risks of mortality, tumor recurrence and metastatic potential. Understanding the molecular biology of thyroid cancers can be an important avenue for diagnosis and treatment of radioiodine-refractory or inoperable DTC patients with novel molecular targeted therapeutic agents. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

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