Browsing by Subject "Nucleotide sequence"

Now showing 1 - 8 of 8

Open Access
Choroid Plexus Papillomas in two siblings: Case report
(2009) Okay, O.; Dağlıoğlu, E.; Yakıcıer, Cengiz; Üren, Deniz; Dalgıç, A.; Ergüngör, F.
Choroid plexus papilloma (CPP) is a rare, benign epithelial brain tumor of the nervous system seen particularly in infants. Familial cases are extremely uncommon. Some other form of malignant tumors was noted in the relatives of patients with CPPs, and some genetic defects regarding this coincidence were reported in the literature. These neoplasms are occasionally bilateral and hydrocephalus is an associated sign in most of the cases. We report three lateral ventricle CPPs in two siblings, at the age of 7 month and 2 years respectively. All tumors were resected with parietotemporal craniotomy and a superior temporal sulcus approach to the lateral ventricle. To avoid a concomitant need of ventriculoperitoneal shunt insertion, external ventricular drainage was inserted for a week in the postoperative period relieving symptoms of hydrocephalus. Search for a hereditary defect in the p53 gene of the second infant (7 months old) revealed no mutation. Postoperative courses were uneventful and the patients were followed for three years without any recurrence. Bilateral CPPS are rare and unusual in two siblings. A genetic predisposition such as the p53 mutation should be investigated in bilateral CPPs in particular.
Open Access
MicroRNA-519a is a novel oncomir conferring tamoxifen resistance by targeting a network of tumour-suppressor genes in ER+ breast cancer
(John Wiley and Sons Ltd, 2014) Ward, A.; Shukla, K.; Balwierz, A.; Soons, Z.; König, R.; Sahin, O.; Wiemann, S.
Tamoxifen is an endocrine therapy which is administered to up to 70% of all breast cancer patients with oestrogen receptor alpha (ERα) expression. Despite the initial response, most patients eventually acquire resistance to the drug. MicroRNAs (miRNAs) are a class of small non-coding RNAs which have the ability to post-transcriptionally regulate genes. Although the role of a few miRNAs has been described in tamoxifen resistance at the single gene/target level, little is known about how concerted actions of miRNAs targeting biological networks contribute to resistance. Here we identified the miRNA cluster, C19MC, which harbours around 50 mature miRNAs, to be up-regulated in resistant cells, with miRNA-519a being the most highly up-regulated. We could demonstrate that miRNA-519a regulates tamoxifen resistance using gain- and loss-of-function testing. By combining functional enrichment analysis and prediction algorithms, we identified three central tumour-suppressor genes (TSGs) in PI3K signalling and the cell cycle network as direct target genes of miR-519a. Combined expression of these target genes correlated with disease-specific survival in a cohort of tamoxifen-treated patients. We identified miRNA-519a as a novel oncomir in ER+ breast cancer cells as it increased cell viability and cell cycle progression as well as resistance to tamoxifen-induced apoptosis. Finally, we could show that elevated miRNA-519a levels were inversely correlated with the target genes' expression and that higher expression of this miRNA correlated with poorer survival in ER+ breast cancer patients. Hence we have identified miRNA-519a as a novel oncomir, co-regulating a network of TSGs in breast cancer and conferring resistance to tamoxifen. Using inhibitors of such miRNAs may serve as a novel therapeutic approach to combat resistance to therapy as well as proliferation and evasion of apoptosis in breast cancer.
Open Access
Nicotine coregulates multiple pathways involved in protein modification/degradation in rat brain
(Elsevier, 2004) Kane, J. K.; Konu, Özlem; Ma, J. Z.; Li, M. D.
Previously, we used cDNA microarrays to demonstrate that the phosphatidylinositol and MAP kinase signaling pathways are regulated by nicotine in different rat brain regions. In the present report, we show that, after exposure to nicotine for 14 days, ubiquitin, ubiquitin-conjugating enzymes, 20S and 19S proteasomal subunits, and chaperonin-containing TCP-1 protein (CCT) complex members are upregulated in rat prefrontal cortex (PFC) while being downregulated in the medial basal hypothalamus (MBH). In particular, relative to saline controls, ubiquitins B and C were upregulated by 33% and 47% (P<0.01), respectively, in the PFC. The proteasome beta subunit 1 (PSMB1) and 26S ATPase 3 (PSMC3) genes were upregulated in the PFC by 95% and 119% (P<0.001), respectively. In addition to the protein degradation pathway of the ubiquitin-proteasome complexes, we observed in the PFC an increase in the expression of small, ubiquitin-related modifiers (SUMO) 1 and 2 by 80% and 33%, respectively (P<0.001), and in 3 of 6 CCT subunits by up to 150% (P<0.0001). To a lesser extent, a change in the opposite direction was obtained in the expression of the same gene families in the MBH. Quantitative real-time RT-PCR was used to validate the microarray results obtained with some representative genes involved in these pathways. Taken together, our results suggest that, in response to systemic nicotine administration, the ubiquitin-proteasome, SUMO, and chaperonin complexes provide an intricate control mechanism to maintain cellular homeostasis, possibly by regulating the composition and signaling of target neurons in a region-specific manner.
Open Access
Oligonucleotide-based label-free detection with optical microresonators: strategies and challenges
(Royal Society of Chemistry, 2016) Toren, P.; Ozgur E.; Bayındır, Mehmet
This review targets diversified oligonucleotide-based biodetection techniques, focusing on the use of microresonators of whispering gallery mode (WGM) type as optical biosensors mostly integrated with lab-on-a-chip systems. On-chip and microfluidics combined devices along with optical microresonators provide rapid, robust, reproducible and multiplexed biodetection abilities in considerably small volumes. We present a detailed overview of the studies conducted so far, including biodetection of various oligonucleotide biomarkers as well as deoxyribonucleic acids (DNAs), ribonucleic acids (RNAs) and proteins. We particularly advert to chemical surface modifications for specific and selective biosensing.
Open Access
Regulation of Homer and group I metabotropic glutamate receptors by nicotine
(Wiley-Blackwell Publishing Ltd., 2005) Kane, J. K.; Hwang, Y.; Konu, O.; Loughlin, S. E.; Leslie, F. M.; Li, M. D.
The present study focuses on the nicotine-induced modulation of mRNA and protein expression of a number of genes involved in glutamatergic synaptic transmission in rat brain over different time periods of exposure. A subchronic (3 days) but not the chronic (7 or 14 days) administration of nicotine resulted in the up-regulation of Homer2a/b mRNA in the amygdala while in the ventral tegmental area (VTA) no change in expression of either Homer2a/b or Homer1b/c was observed. Although the increase in Homer2a/b mRNA was not translated into the protein level in the amygdala, a slight but significant up-regulation of Homer1b/c protein was observed in the same region at day 3. Both Homer forms were up-regulated at the protein level in the VTA at day 3. In the nucleus accumbens, 14 days of nicotine treatment up-regulated mRNA of Homer2b/c by 68.2% (P < 0.05), while the short form Homer1a gene was down-regulated by 65.0% at day 3 (P < 0.05). In regard to other components of the glutamatergic signalling, we identified an acute and intermittent increase in the mRNA and protein levels of mGluR1 and mGluR5 in the amygdala. In the VTA, however, the effects of nicotine on mGluR mRNA expression were long-lasting but rather specific to mGluR1. Nevertheless, mGluR1 protein levels in the VTA area were up-regulated only at day 3, as in the amygdala. These data provide further evidence for the involvement of nicotine in the glutamatergic neuronal synaptic activity in vivo, suggesting a role for the newly identified Homer proteins in this paradigm.
Open Access
Skewed X inactivation in an X linked nystagmus family resulted from a novel, p.R229G, missense mutation in the FRMD7 gene
(BMJ Group, 2008) Kaplan, Y.; Vargel, I.; Kansu, T.; Akin, B.; Rohmann, E.; Kamaci, S.; Uz, E.; Ozcelik, T.; Wollnik, B.; Akarsu, N. A.
Aims: This study aimed to identify the underlying genetic defect of a large Turkish X linked nystagmus (NYS) family. Methods: Both Xp11 and Xq26 loci were tested by linkage analysis. The 12 exons and intron-exon junctions of the FRMD7 gene were screened by direct sequencing. X chromosome inactivation analysis was performed by enzymatic predigestion of DNA with a methylation-sensitive enzyme, followed by PCR of the polymorphic CAG repeat of the androgen receptor gene. Results: The family contained 162 individuals, among whom 28 had NYS. Linkage analysis confirmed the Xq26 locus. A novel missense c.686C>G mutation, which causes the substitution of a conserved arginine at amino acid position 229 by glycine (p.R229G) in exon 8 of the FRMD7 gene, was observed. This change was not documented in 120 control individuals. The clinical findings in a female who was homozygous for the mutation were not different from those of affected heterozygous females. Skewed X inactivation was remarkable in the affected females of the family. Conclusions: A novel p.R229G mutation in the FRMD7 gene causes the NYS phenotype, and skewed X inactivation influences the manifestation of the disease in X linked NYS females.
Open Access
SOX1 antibodies are markers of paraneoplastic Lambert-Eaton myasthenic syndrome
(Lippincott Williams & Wilkins, 2008) Sabater, L.; Titulaer, M.; Saiz, A.; Verschuuren, J.; Güre, A. O.; Graus, F.
BACKGROUND/OBJECTIVE: We reported that 43% of patients with Lambert-Eaton myasthenic syndrome (LEMS) and small cell lung cancer (SCLC) had an antibody called anti-glial nuclear antibody (AGNA), defined by the immunoreaction with the nuclei of the Bergmann glia of the cerebellum. This study was undertaken to identify the antigen recognized by AGNA and to confirm the association with paraneoplastic LEMS in a larger series. METHODS: We probed a fetal brain cDNA library with AGNA-positive sera. The presence of antibodies against the isolated antigen was detected by immunoblot of phage plaques from two positive clones. We studied 105 patients with LEMS (55 with SCLC), 50 with paraneoplastic neurologic syndromes, SCLC, and Hu antibodies, and 50 with only SCLC. RESULTS: Probing of the fetal brain expression library with AGNA sera resulted in the isolation of SOX1, a highly immunogenic tumor antigen in SCLC. IgG eluted from SOX1 clones produced the same cerebellar immunoreactivity as of AGNA sera. SOX1 antibodies were present in 64% of patients with LEMS and SCLC but in none of the 50 with idiopathic LEMS (p < 0.0001). Compared with paraneoplastic LEMS, the frequency of SOX1 antibodies was significantly lower in patients with Hu antibodies (32%, p = 0.002) and in those with only SCLC (22%). CONCLUSIONS: SOX1 is the antigen recognized by anti-glial nuclear antibody-positive sera. The detection of SOX1 antibodies in patients with Lambert-Eaton myasthenic syndrome (LEMS) predicts the presence of small cell lung cancer and may be used to follow more closely those LEMS patients with no evidence of cancer at the initial workup.
Open Access
TP53 mutations in familial breast cancer: Functional aspects
(John Wiley & Sons, Inc., 2003) Gasco, M.; Yulug, I. G.; Crook, T.
Mutation in p53 (TP53) remains one of the most commonly described genetic events in human neoplasia. The occurrence of mutations is somewhat less common in sporadic breast carcinomas than in other cancers, with an overall frequency of about 20%. There is, however, evidence that p53 is mutated at a significantly higher frequency in breast carcinomas arising in carriers of germ-line BRCA1 and BRCA2 mutations. Some of the p53 mutants identified in BRCA1 and BRCA2 mutation carriers are either previously undescribed or infrequently reported in sporadic human cancers. Functional characterization of such mutants in various systems has revealed that they frequently possess properties not commonly associated with those occurring in sporadic cases: they retain apoptosis-inducing, transactivating, and growth-inhibitory activities similar to the wild-type protein, yet are compromised for transformation suppression and also possess an independent transforming phenotype. The occurrence of such mutants in familial breast cancer implies the operation of distinct selective pressures during tumorigenesis in BRCA-associated breast cancers.