Browsing by Subject "unclassified drug"

Now showing 1 - 20 of 25

Unknown
3-Propionyl-thiazolidine-4-carboxylic acid ethyl esters: A family of antiproliferative thiazolidines
(Royal Society of Chemistry, 2015) Önen-Bayram F.E.; Buran, K.; Durmaz I.; Berk, B.; Cetin-Atalay, R.
Cancer results from unregulated cell growth. Reactivating the process of the programmed cell death, i.e. apoptosis, is a classical anticancer therapeutic strategy. The apoptosis-inducing property of the (2RS,4R)-2-phenyl-3-propionyl-thiazolidine-4-carboxylic acid ethyl ester (ALC 67) molecule has recently been discovered. We analyzed in this study the impact of the phenyl moiety of this molecule on its biological activity by synthesizing and evaluating analogues where this substituent was replaced by a series of aromatic and aliphatic groups. The results demonstrated that the molecule's antiproliferative property resisted such modifications. Thus, in addition to developing a family of thiazolidine compounds with promising anticancer properties; our investigation revealed that the second position of the thiazolidine ring can be used either to tune the physicochemical properties of ALC67 or to introduce a fluorescent tag to the structure in order to track it in cells and determine its exact molecular mechanism of action. © 2015 The Royal Society of Chemistry.
Unknown
4,5-dianilinophtalimide protects neuroendocrine cells against serum deprivation-induced stress and apoptosis
(2013) Ergin V.; Erdogan, M.; Karasu Ç.; Menevşe, A.
OBJECTIVE: The aim of this study was to reveal the effects of 4,5-dianilinophthalimide (DAPH), which inhibits amyloid β fibrillization, against serum deprivation (SD)-induced apoptosis and the possible mechanisms in differentiated PC12 neuron cells. METHODS: Firstly, we evaluated whether DAPH protects cell viability exposed to SD by MTT assay. Next, we examined the changes of phospho-p38 MAPK (Thr180/Tyr182), phospho-HSP27 (Ser82), phospho-c-JUN (Ser73) and cleaved-CASP3 (Asp175) profiles by immunoblotting, in PC12 cells exposed to SD. Intracellular reactive oxygen species (ROS) level was also measured. RESULTS: SD induced apoptosis accompanied by up-regulation of phospho-p38 MAPK (Thr180/Tyr182), phospho-HSP27 (Ser82), phospho-c-JUN (Ser73), cleaved-CASP3 (Asp175) and intracellular ROS content. Co-treatment with nontoxic doses of DAPH prevented apoptosis by the attenuation of activated proteins and reduction of ROS level. These results suggest that serum deprivation-induced apoptosis inhibited by DAPH administration. CONCLUSION: We have provided for the first evidence that DAPH has a neuroprotective effect on SD-caused stress, probably via contributing the reestablishment of redox homeostasis. © 2013 Neuroendocrinology Letters.
Unknown
Anti-cancer and anti-hepatitis C virus NS5B polymerase activity of etodolac 1,2,4-triazoles
(Taylor and Francis Ltd, 2015) Çikla-Süzgün P.; Kaushik-Basu, N.; Basu, A.; Arora P.; Talele, T.T.; Durmaz I.; Çetin-Atalay, R.; Küçükgüzel, S.G.
Arachidonic acid is an unsaturated fatty acid liberated from phospholipids of cell membranes. NSAIDs are known as targets of cyclooxygenase enzyme (COX-1, COX-2 and COX-3) in arachidonic acid metabolism. This mechanism of COX-2 in carcinogenesis causes cancer. In addition, COX-2 plays a role in the early stages of hepatocarcinogenesis. Hepatitis C virus (HCV) infection is cause of liver cirrhosis and hepatocellular carcinoma (HCC). The aim of our study was to improve effective agents against HCV. A novel series of new etodolac 1,2,4-triazoles derivatives (4a-h) have been synthesized and investigated for their activity against HCV NS5B polymerase. Compound 4a was found to be the most active with IC50 value of 14.8 M. In accordance with these results, compound 4a was screened for anti-cancer activity on liver cancer cell lines (Huh7, Mahlavu, HepG2, FOCUS). Compound 4a showed anti-cancer activity against Huh7 human hepatoma cell line with IC50 value of 4.29 M. Therefore, compound 4a could be considered as a new anti-cancer and anti-HCV lead compound. © 2015 Informa UK Ltd.
Open Access
Antiangiogenic response after 70% hepatectomy and its relationship with hepatic regeneration and angiogenesis in rats
(2010) Dogrul, A.B.; Colakoglu, T.; Kosemehmetoglu, K.; Birben, E.; Yaman, E.; Gedikoglu G.; Abbasoglu O.
Background: The aim of this study was to evaluate the antiangiogenic response and its relation to regeneration and angiogenesis after 70% hepatectomy in a rat model. Methods: Sixty-four Wistar albino rats were included in the study. Animals were allocated into 8 groups (n = 8). After a 70% hepatectomy, liver regeneration, angiogenesis, and antiangiogenic response were evaluated in the remnant liver on days 0, 1, 2, 3, 5, 7, 10, and 14. Regeneration and angiogenesis were determined with immunoreactivity to proliferating cell nuclear antigen and vascular endothelial growth factor. Antiangiogenic response was evaluated by detecting collagen 18 m RNA with reverse transcriptase polymerase chain reaction. Results: We showed that liver regeneration peaked at day 1, whereas angiogenesis in the periportal and perisinusoidal areas reached their peak values on days 3 and 7, respectively. Both regeneration and angiogenic activity around perisinusoidal hepatocytes returned to basal activity on the day 10. Antiangiogenic response first appeared on day 5, reached a peak on day 10, and returned to basal values on day 14. Conclusion: Collagen18 mRNA expression is present in the normal liver during the regenerative process. We suggest that the stimulus that causes the cessation of regeneration process may come from hepatocytes, and collagen 18 produced by hepatocytes may modulate this event by inhibiting the angiogenesis. © 2010 Mosby, Inc. All rights reserved.
Unknown
Benzothiazole derivatives as human DNA topoisomerase IIα inhibitors
(2013) Kaplan-Ozen, C.; Tekiner-Gulbas, B.; Foto, E.; Yildiz I.; Diril, N.; Aki, E.; Yalcin I.
Benzothiazole derivatives resembling the structure of DNA purine bases were tested to determine their topoisomerase inhibition activities. Based on DNA topoisomerase I and II relaxation assay results, all 12 derivatives acted as human topoisomerase IIα inhibitors, whereas only two compounds inhibited Calf thymus topoisomerase I. 3-amino-2-(2-bromobenzyl)-1,3-benzothiazol-3-ium 4-methylbenzensulfonate (BM3) was observed to be the most effective human topoisomerase IIα inhibitor with the lowest IC50 value of 39 nM. The mechanistic studies suggested that BM3 was neither a DNA intercalator nor a topoisomerase poison, it was only a DNA minor groove-binding agent. BM3 initially bound to the DNA topoisomerase IIα enzyme, then to DNA. As a result, the tested benzothiazole derivatives were obtained as strong topoisomerase IIα inhibitors. The benzothiazole tosylated salt form BM3 was found as the most effective topoisomerase IIα inhibitor. BM3's mechanisms of action might be its direct interaction with the enzyme. BM3's minor groove-binding property might also contribute to this action. Hence, BM3 could be a good candidate as a new anticancer agent. © 2013 Springer Science+Business Media New York.
Open Access
Coiled-Coil Domain Containing Protein 124 Is a Novel Centrosome and Midbody Protein That Interacts with the Ras-Guanine Nucleotide Exchange Factor 1B and Is Involved in Cytokinesis
(2013) Telkoparan P.; Erkek, S.; Yaman, E.; Alotaibi H.; Bayik, D.; Tazebay, U.H.
Cytokinetic abscission is the cellular process leading to physical separation of two postmitotic sister cells by severing the intercellular bridge. The most noticeable structural component of the intercellular bridge is a transient organelle termed as midbody, localized at a central region marking the site of abscission. Despite its major role in completion of cytokinesis, our understanding of spatiotemporal regulation of midbody assembly is limited. Here, we report the first characterization of coiled-coil domain-containing protein-124 (Ccdc124), a eukaryotic protein conserved from fungi-to-man, which we identified as a novel centrosomal and midbody protein. Knockdown of Ccdc124 in human HeLa cells leads to accumulation of enlarged and multinucleated cells; however, centrosome maturation was not affected. We found that Ccdc124 interacts with the Ras-guanine nucleotide exchange factor 1B (RasGEF1B), establishing a functional link between cytokinesis and activation of localized Rap2 signaling at the midbody. Our data indicate that Ccdc124 is a novel factor operating both for proper progression of late cytokinetic stages in eukaryotes, and for establishment of Rap2 signaling dependent cellular functions proximal to the abscission site. © 2013 Telkoparan et al.
Unknown
Cyanide sensing via metal ion removal from a fluorogenic BODIPY complex
(Elsevier, 2009) Guliyev, R.; Buyukcakir, O.; Sozmen, F.; Bozdemir, O. A.
We report a highly selective and sensitive reversible cyanide sensor operating in the ‘turn-off-on’ mode via decomplexation of Cu(II) ions from a brightly fluorescent boradiazaindacene derivative. The sensor is reversible as the emission signal originates from the dynamic equilibration of dipicolylamine–Cu(II) and tetracyanocuprate complex ions.
Open Access
Cytotoxic activities of some benzothiazole-piperazine derivatives
(Taylor and Francis Ltd, 2015) Gurdal, E.E.; Durmaz I.; Cetin-Atalay, R.; Yarim, M.
Synthesis, characterization and cytotoxic activities of ten benzothiazole-piperazine derivatives were reported. In vitro cytotoxic activities of compounds were screened against hepatocellular (HUH-7), breast (MCF-7) and colorectal (HCT-116) cancer cell lines by sulphorhodamine B assay. Based on the GI50 values of the compounds, most of the benzothiazole-piperazine derivatives are active against HUH-7, MCF-7 and HCT-116 cancer cell lines. Compound 1d is highly cytotoxic against all tested cancer cell lines. Further investigation of compound 1d by Hoechst Staining and Fluorescence-Activated Cell Sorting Analysis (FACS) revealed that this compound causes apoptosis by cell cycle arrest at subG1 phase. © 2014 Informa UK Ltd. All rights reserved.
Open Access
GOPred: GO molecular function prediction by combined classifiers
(2010) Saraç Ö.S.; Atalay V.; Cetin-Atalay, R.
Functional protein annotation is an important matter for in vivo and in silico biology. Several computational methods have been proposed that make use of a wide range of features such as motifs, domains, homology, structure and physicochemical properties. There is no single method that performs best in all functional classification problems because information obtained using any of these features depends on the function to be assigned to the protein. In this study, we portray a novel approach that combines different methods to better represent protein function. First, we formulated the function annotation problem as a classification problem defined on 300 different Gene Ontology (GO) terms from molecular function aspect. We presented a method to form positive and negative training examples while taking into account the directed acyclic graph (DAG) structure and evidence codes of GO. We applied three different methods and their combinations. Results show that combining different methods improves prediction accuracy in most cases. The proposed method, GOPred, is available as an online computational annotation tool (http://kinaz.fen.bilkent.edu.tr/gopred). © 2010 Saraç et al.
Open Access
Identification of endogenous reference genes for qRT-PCR analysis in normal matched breast tumor tissues
(Cognizant Communication Corporation, 2009) Gur-Dedeoglu, B.; Konu, O.; Bozkurt, B.; Ergul, G.; Seckin, S.; Yulug, I. G.
Quantitative gene expression measurements from tumor tissue are frequently compared with matched normal and/or adjacent tumor tissue expression for diagnostic marker gene selection as well as assessment of the degree of transcriptional deregulation in cancer. Selection of an appropriate reference gene (RG) or an RG panel, which varies depending on cancer type, molecular subtypes, and the normal tissues used for interindividual calibration, is crucial for the accurate quantification of gene expression. Several RG panels have been suggested in breast cancer for making comparisons among tumor subtypes, cell lines, and benign/malignant tumors. In this study, expression patterns of 15 widely used endogenous RGs (ACTB, TBP, GAPDH, SDHA, HPRT, HMBS, B2M, PPIA, GUSB, YWHAZ2, PGK1, RPLP0, PUM1, MRPL19, and RPL41), and three candidate genes that were selected through analysis of two independent microarray datasets (IL22RA1, TTC22, ZNF224) were determined in 23 primary breast tumors and their matched normal tissues using qRTPCR. Additionally, 18S rRNA, ACTB, and SDHA were tested using randomly primed cDNAs from 13 breast tumor pairs to assess the rRNA/mRNA ratio. The tumors exhibited significantly lower rRNA/mRNA ratio when compared to their normals, on average. The expression of the studied RGs in breast tumors did not exhibit differences in terms of grade, ER, or PR status. The stability of RGs was examined based on two different statistical models, namely GeNorm and NormFinder. Among the 18 tested endogenous reference genes, ACTB and SDHA were identified as the most suitable reference genes for the normalization of qRTPCR data in the analysis of normal matched tumor breast tissue pairs by both programs. In addition, the expression of the gelsolin (GSN) gene, a well-known downregulated target in breast tumors, was analyzed using the two most suitable genes and different RG combinations to validate their effectiveness as a normalization factor (NF). The GSN expression of the tumors used in this study was significantly lower than that of normals showing the effectivity of using ACTB and SDHA as suitable RGs in this set of tumor–normal tissue panel. The combinational use of the best performing two RGs (ACTB and SDHA) as a normalization factor can be recommended to minimize sample variability and to increase the accuracy and resolution of gene expression normalization in tumor–normal paired breast cancer qRT-PCR studies.
Open Access
In vitro biocompatibility of plasma-aided surface-modified 316L stainless steel for intracoronary stents
(Institute of Physics Publishing, 2010) Bayram, C.; Mizrak, A.K.; Aktürk, S.; Kurşaklioǧlu H.; Iyisoy, A.; Ifran, A.; Denkbaş, E.B.
316L-type stainless steel is a raw material mostly used for manufacturing metallic coronary stents. The purpose of this study was to examine the chemical, wettability, cytotoxic and haemocompatibility properties of 316L stainless steel stents which were modified by plasma polymerization. Six different polymeric compounds, polyethylene glycol, 2-hydroxyethyl methacrylate, ethylenediamine, acrylic acid, hexamethyldisilane and hexamethyldisiloxane, were used in a radio frequency glow discharge plasma polymerization system. As a model antiproliferative drug, mitomycin-C was chosen for covalent coupling onto the stent surface. Modified SS 316L stents were characterized by water contact angle measurements (goniometer) and x-ray photoelectron spectroscopy. C1s binding energies showed a good correlation with the literature. Haemocompatibility tests of coated SS 316L stents showed significant latency (t-test, p < 0.05) with respect to SS 316L and control groups in each test. © 2010 IOP Publishing Ltd.
Open Access
Inflammasome induction and immunostimulatory effects of CpG-ODN loaded liposomes containing DC-cholesterol
(Turkish Society of Immunology, 2013) Bayyurt, B.; Gürsel I.
Objectives: This study aims to investigate the effects of cholesterol content and cationic property of liposomes on immune response. Materials and methods: Liposomes containing high amounts of 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol hydrochloride (DC-cholesterol) were prepared and loaded with K- and D-type CpG oligonucleotide (CpG-ODN) via dehydration-rehydration (DRV) method. After splenocytes and peritoneal exudate cells (PECs) primed with lipopolysaccharide (LPS) was incubated either with free or liposomal CpG-ODN counterparts, supernatants were collected and used in cytokine (IFN-g, IL-1γ and IL-1β) ELISA. Additionally, supernatants of PECs primed with LPS and stimulated with liposomes containing different doses of DC-cholesterol were collected and used in IL-1β ELISA assay. Results: Low-dose CpG-ODN loaded liposomal formulations induced higher immune activation than free CpG-ODN at the same dose. While high-dose liposomal CpG-ODN formulations decreased pro-inflammatory cytokine production in splenocytes, they increased the secretion of IL-1β. Inflammasome activation was increased in a dose dependent manner when PECs primed with LPS were incubated with only liposomes. Varying lipid molar ratios of DC-Cholesterol containing liposomes increased IL-1β production based on increasing lipid molar ratio. Conclusion: This study revealed that type and lipid ratio of liposomes may alter the cellular efficacy of the loaded immune-stimulatory agent and may initiate inflammasome activation. © 2014 Turkish Journal of Immunology.
Open Access
MST1 is a multifunctional caspase-independent inhibitor of androgenic signaling
(2011) Cinar, B.; Collak F.K.; Lopez, D.; Akgul, S.; Mukhopadhyay, N.K.; Kilicarslan, M.; Gioeli, D.G.; Freeman, M.R.
The MST1 serine - threonine kinase, a component of the RASSF1-LATS tumor suppressor network, is involved in cell proliferation and apoptosis and has been implicated in cancer. However, the physiologic role of MST1 in prostate cancer (PCa) is not well understood. Here, we investigated the possibility of a biochemical and functional link between androgen receptor (AR) and MST1 signaling. We showed that MST1 forms a protein complex with AR and antagonizes AR transcriptional activity as shown by coimmunoprecipitation (co-IP), promoter reporter analysis, and molecular genetic methods. In vitro kinase and site-specific mutagenesis approaches indicate that MST1 is a potent AR kinase; however, the kinase activity of MST1 and its proapoptotic functions were shown not to be involved in inhibition of AR. MST1 was also found in AR - chromatin complexes, and enforced expression of MST1 reduced the binding of AR to a well-characterized, androgen-responsive region within the prostate-specific antigen promoter. MST1 suppressed PCa cell growth in vitro and tumor growth in mice. Because MST1 is also involved in regulating the AKT1 pathway, this kinase may be an important new link between androgenic and growth factor signaling and a novel therapeutic target in PCa. ©2011 AACR.
Open Access
Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: A novel gene related to nuclear envelopathies
(Elsevier Ltd, 2014) Kayman-Kurekci G.; Talim, B.; Korkusuz P.; Sayar, N.; Sarioglu, T.; Oncel I.; Sharafi P.; Gundesli H.; Balci-Hayta, B.; Purali, N.; Serdaroglu-Oflazer P.; Topaloglu H.; Dincer P.
We performed genome-wide homozygosity mapping and mapped a novel myopathic phenotype to chromosomal region 1q25 in a consanguineous family with three affected individuals manifesting proximal and distal weakness and atrophy, rigid spine and contractures of the proximal and distal interphalangeal hand joints. Additionally, cardiomyopathy and respiratory involvement were noted. DNA sequencing of torsinA-interacting protein 1 (TOR1AIP1) gene encoding lamina-associated polypeptide 1B (LAP1B), showed a homozygous c.186delG mutation that causes a frameshift resulting in a premature stop codon (p.E62fsTer25). We observed that expression of LAP1B was absent in the patient skeletal muscle fibres. Ultrastructural examination showed intact sarcomeric organization but alterations of the nuclear envelope including nuclear fragmentation, chromatin bleb formation and naked chromatin. LAP1B is a type-2 integral membrane protein localized in the inner nuclear membrane that binds to both A- and B-type lamins, and is involved in the regulation of torsinA ATPase. Interestingly, luminal domain-like LAP1 (LULL1)-an endoplasmic reticulum-localized partner of torsinA-was overexpressed in the patient's muscle in the absence of LAP1B. Therefore, the findings suggest that LAP1 and LULL1 might have a compensatory effect on each other. This study expands the spectrum of genes associated with nuclear envelopathies and highlights the critical function for LAP1B in striated muscle. © 2014 Elsevier B.V.
Open Access
De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder
(Elsevier, 2014) Dong, S.; Walker, M.F.; Carriero, N.J.; DiCola, M.; Willsey, A.; Ye, A.Y.; Waqar, Z.; Gonzalez L.E.; Overton J.D.; Frahm, S.; Keaney J.F.; III, Teran, N.A.; Dea J.; Mandell J.D.; HusBal V.; Sullivan, C.A.; DiLullo, N.M.; Khalil, R.O.; Gockley J.; Yuksel, Z.; Sertel, S.M.; Ercan-Sencicek, A.G.; Gupta, A.R.; Mane, S.M.; Sheldon, M.; Brooks, A.I.; Roeder, K.; Devlin, B.; State, M.W.; Wei L.; Sanders, S.J.
Whole-exome sequencing (WES) studies have demonstrated the contribution of de novo loss-of-function single-nucleotide variants (SNVs) to autism spectrum disorder (ASD). However, challenges in the reliable detection of de novo insertions and deletions (indels) have limited inclusion of these variants in prior analyses. By applying a robust indel detection method to WES data from 787 ASD families (2,963 individuals), we demonstrate that de novo frameshift indels contribute to ASD risk (OR= 1.6; 95% CI= 1.0-2.7; p= 0.03), are more common in female probands (p= 0.02), are enriched among genes encoding FMRP targets (p= 6× 10-9), and arise predominantly on the paternal chromosome (p< 0.001). On the basis of mutation rates in probands versus unaffected siblings, we conclude that de novo frameshift indels contribute to risk in approximately 3% of individuals with ASD. Finally, by observing clustering of mutations in unrelated probands, we uncover two ASD-associated genes: KMT2E (MLL5), a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release. © 2014 The Authors.
Open Access
PATZ1 is a DNA damage-responsive transcription factor that inhibits p53 function
(American Society for Microbiology, 2015) Keskin, N.; Deniz, E.; Eryilmaz J.; Un, M.; Batur, T.; Ersahin, T.; Atalay, R.C.; Sakaguchi, S.; Ellmeier W.; Erman, B.
Insults to cellular health cause p53 protein accumulation, and loss of p53 function leads to tumorigenesis. Thus, p53 has to be tightly controlled. Here we report that the BTB/POZ domain transcription factor PATZ1 (MAZR), previously known for its transcriptional suppressor functions in T lymphocytes, is a crucial regulator of p53. The novel role of PATZ1 as an inhibitor of the p53 protein marks its gene as a proto-oncogene. PATZ1-deficient cells have reduced proliferative capacity, which we assessed by transcriptome sequencing (RNA-Seq) and real-time cell growth rate analysis. PATZ1 modifies the expression of p53 target genes associated with cell proliferation gene ontology terms. Moreover, PATZ1 regulates several genes involved in cellular adhesion and morphogenesis. Significantly, treatment with the DNA damage-inducing drug doxorubicin results in the loss of the PATZ1 transcription factor as p53 accumulates. We find that PATZ1 binds to p53 and inhibits p53-dependent transcription activation. We examine the mechanism of this functional inhibitory interaction and demonstrate that PATZ1 excludes p53 from DNA binding. This study documents PATZ1 as a novel player in the p53 pathway. © 2015, American Society for Microbiology.
Open Access
PTPRD is homozygously deleted and epigenetically downregulated in human hepatocellular carcinomas
(Mary Ann Liebert Inc., 2015) Acun, T.; Demir, K.; Oztas, E.; Arango, D.; Yakicier, M.C.
PTPRD (protein tyrosine phosphatase, receptor type, D) is a tumor suppressor gene, frequently inactivated through deletions or epigenetic mechanisms in several cancers with importance for global health. In this study, we provide new and functionally integrated evidence on genetic and epigenetic alterations of PTPRD gene in hepatocellular carcinomas (HCCs). Importantly, HCC is the sixth most common malignancy and the third most common cause of cancer-related mortality worldwide. We used a high throughput single nucleotide polymorphism (SNP) microarray assay (Affymetrix, 10K2.0 Assay) covering the whole genome to screen an extensive panel of HCC cell lines (N=14 in total) to detect DNA copy number changes. PTPRD expression was determined in human HCCs by Q-RT-PCR and immunohistochemistry. Promoter hypermethylation was assessed by combined bisulfite restriction analysis (COBRA). DNA methyl transferase inhibitor 5-azacytidine (5-AzaC) and/or histone deacetylase inhibitor Trichostain A (TSA) were used to restore the expression. We identified homozygous deletions in Mahlavu and SNU475 cells, in the 5′UTR and coding regions, respectively. PTPRD mRNA expression was downregulated in 78.5% of cell lines and 82.6% of primary HCCs. PTPRD protein expression was also found to be lost or reduced in HCC tumor tissues. We found promoter hypermethylation in 22.2% of the paired HCC samples and restored PTPRD expression by 5-AzaC and/or TSA treatments. In conclusion, PTPRD is homozygously deleted and epigenetically downregulated in HCCs. We hypothesize PTPRD as a tumor suppressor candidate and potential cancer biomarker in human HCCs. This hypothesis is consistent with compelling evidences in other organ systems, as discussed in this article. Further functional assays in larger samples may ascertain the contribution of PTPRD to hepatocarcinogenesis in greater detail, not to forget its broader importance for diagnostic medicine and the emerging field of personalized medicine in oncology. © Copyright 2015, Mary Ann Liebert, Inc. 2015.
Open Access
A ranking-based meta-analysis reveals let-7 family as a meta-signature for grade classification in breast cancer
(Public Library of Science, 2015) Oztemur, Y.; Bekmez, T.; Aydos, A.; Yulug I.G.; Bozkurt, B.; Dedeoglu, B.G.
Breast cancer is one of the most important causes of cancer-related deaths worldwide in women. In addition to gene expression studies, the progressing work in the miRNA area including miRNA microarray studies, brings new aspects to the research on the cancer development and progression. Microarray technology has been widely used to find new biomarkers in research and many transcriptomic microarray studies are available in public databases. In this study, the breast cancer miRNA and mRNA microarray studies were collected according to the availability of their data and clinical information, and combined by a newly developed ranking-based meta-analysis approach to find out candidate miRNA biomarkers (meta-miRNAs) that classify breast cancers according to their grades and explain the relation between miRNAs and mRNAs. This approach provided meta-miRNAs specific to breast cancer grades, pointing out let-7 family members as grade classifiers. The qRTPCR studies performed with independent breast tumors confirmed the potential biomarker role of let-7 family members (meta-miRNAs). The concordance between the meta-mRNAs and miRNA target genes specific to tumor grade (common genes) supported the idea of mRNAs as miRNA targets. The pathway analysis results showed that most of the let-7 family miRNA targets, and also common genes, were significantly taking part in cancer-related pathways. The qRT-PCR studies, together with bioinformatic analyses, confirmed the results of meta-analysis approach, which is dynamic and allows combining datasets from different platforms. © 2015 Oztemur et al.
Open Access
Resveratrol affects histone 3 lysine 27 methylation of vessels and blood biomarkers in DOCA salt-induced hypertension
(Kluwer Academic Publishers, 2015) Han, S.; Uludag, M.O.; Usanmaz, S.E.; Ayaloglu-Butun F.; Akcali, K.C.; Demirel-Yilmaz, E.
Hypertension is a risk factor for the cardiovascular diseases. Although, several drugs are used to treat hypertension, the success of the antihypertensive therapy is limited. Resveratrol decreases blood pressure in animal models of hypertension. This study researched the mechanisms behind the effects of resveratrol on hypertension. Hypertension was induced by using the deoxycorticosterone acetate (DOCA)-induced (15 mg/kg twice per week, subcutaneously) salt-sensitive hypertension model of Wistar rats. Hypertension caused a decrease in endothelium-dependent relaxations of the isolated thoracic aorta. Resveratrol treatment (50 mg/l in drinking water) prevented DOCA salt-induced hypertension, but did not improve endothelial dysfunction. Plasma nitric oxide (NO), asymmetric dimethylarginine (ADMA), total antioxidant capacity (TAC) and hydrogen sulfide (H2S) levels were not changed by DOCA salt application. However, treatment of resveratrol significantly decreased ADMA and increased TAC and H2S levels. NO level in circulation was not significantly changed by resveratrol. DOCA salt application and resveratrol treatment also caused an alteration in the epigenetic modification of vessels. Staining pattern of histone 3 lysine 27 methylation (H3K27me3) in the aorta and renal artery sections was changed. These results show that preventive effect of resveratrol on DOCA salt-induced hypertension might due to its action on the production of some blood biomarkers and the epigenetic modification of vessels that would focus upon new aspect of hypertension prevention and treatment. © 2014, Springer Science+Business Media Dordrecht.
Open Access
A role for LYNX2 in anxiety-related behavior
(2009) Tekinay, A.B.; Nong, Y.; Miwa J.M.; Lieberam I.; Ibanez-Tallon I.; Greengard P.; Heintz, N.
Anxiety disorders are the most prevalent mental disorders in developed societies. Although roles for the prefrontal cortex, amygdala, hippocampus and mediodorsal thalamus in anxiety disorders are well documented, molecular mechanisms contributing to the functions of these structures are poorly understood. Here we report that deletion of Lynx2, a mammalian prototoxin gene that is expressed at high levels in anxiety associated brain areas, results in elevated anxiety-like behaviors. We show that LYNX2 can bind to and modulate neuronal nicotinic receptors, and that loss of Lynx2 alters the actions of nicotine on glutamatergic signaling in the prefrontal cortex. Our data identify Lynx2 as an important component of the molecular mechanisms that control anxiety, and suggest that altered glutamatergic signaling in the prefrontal cortex of Lynx2 mutant mice contributes to increased anxiety-related behaviors.