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Assessment of the association between ZBTB20 rs9841504 polymorphism and gastric and esophageal cancer susceptibility: a meta-analysis.
Shi, J, Li, W, Ding, X
The International journal of biological markers. 2017;(1):e96-e101
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Abstract
BACKGROUND The protein encoded by ZBTB20 is a member of the POK family, whose members function as transcriptional repressors through interactions mediated by their conserved C2H2 Krüppel-type zinc finger and BTB/POZ domains. Polymorphisms in ZBTB20 appeared to be associated with gastric and esophageal cancer susceptibility in biological models, but the results of these studies were inconclusive. Therefore, we conducted a meta-analysis by pooling all available data to assess the exact association between the ZBTB20 rs9841504 polymorphism and gastric and esophageal cancer susceptibility. METHOD The meta-analysis was performed for homozygote comparison, heterozygote comparison, and dominant and recessive models by applying a fixed- or random-effects model. The pooled odds ratios (ORs) with the corresponding confidence intervals (CIs) were calculated. Moreover, the data were analyzed using the Stata 12.0 software(StataCorp). RESULT A total of 8 independent case-control studies comprising 9,994 cases and 10,258 controls were included. We found a significant association between the rs9841504 polymorphism and decreased gastric cancer susceptibility in the allelic, homozygous, dominant and recessive models (B vs. A:OR = 0.797, 95% CI 0.644-0.986, p = 0.036; BB vs. AA:OR = 0.601, 95% CI 0.366-0.988, p = 0.045; BA + BB vs. AA:OR = 0.789, 95% CI 0.627-0.992, p = 0.043; BB vs. BA + AA:OR = 0.635, 95% CI 0.405-0.997, p = 0.049). Conversely, no association between the rs9841504 polymorphism and esophageal cancer susceptibility was found. In subgroup analysis by ethnicity, we observed a significantly decreased susceptibility to gastric cancer in Asian populations in the allele contrast, homozygous and recessive models (B vs. A:OR = 0.791, 95% CI 0.628-0.996, p = 0.046; BB vs. AA:OR = 0.559, 95% CI 0.323-0.966, p = 0.037; BB vs. BA + AA:OR = 0.593, 95% CI 0.361-0.972, p = 0.038). CONCLUSIONS In summary, our work suggests that the ZBTB20 rs9841504 polymorphism is a protective factor for gastric cancer rather than esophageal cancer.
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Circulating semaphorin-4D and plexin-B1 levels in postmenopausal women with low bone mass: the 3-month effect of zoledronic acid, denosumab or teriparatide treatment.
Anastasilakis, AD, Polyzos, SA, Makras, P, Gkiomisi, A, Sakellariou, G, Savvidis, M, Papatheodorou, A, Kokkoris, P, Terpos, E
Expert opinion on therapeutic targets. 2015;(3):299-306
Abstract
OBJECTIVE The evaluation of circulating semaphorin-4D (sema4D) and plexin-B1 in postmenopausal women with low bone mass and the effect of antiresorptive or osteoanabolic treatment. METHODS Serum samples were obtained from postmenopausal women with low bone mass at baseline and 3 months after zoledronic acid infusion (n = 30), denosumab injection (n = 30) or teriparatide initiation (n = 28) and from controls matched for age, age at menopause and body mass index (n = 30) at the same time points. MAIN OUTCOME MEASURES Circulating sema4D and plexin-B1. RESULTS Circulating sema4D increased following denosumab (p = 0.026), whereas decreased following teriparatide (p = 0.013). Sema4D/plexin-B1 ratio increased following denosumab (p = 0.004). At baseline, sema4D and plexin-B1 levels were higher in patients pre-treated with bisphosphonates compared to naïve ones (p < 0.001 and p = 0.001, respectively). In bivariate correlations sema4D was inversely correlated with serum carboxyterminal telopeptide of type 1 collagen (rs -0.282, p = 0.002), intact parathyroid hormone (rs -0.388, p < 0.001) and 25(OH)D (rs -0.316, p < 0.001), whereas there was a trend towards correlation with lumbar spine bone mineral density (rs -0.191, p = 0.053). CONCLUSIONS Sema4D levels are independently associated with previous bisphosphonate treatment, intact parathyroid hormone and 25(OH)D levels. Denosumab and teriparatide seem to exert an opposite effect on circulating sema4D levels. Further studies are needed to evaluate whether sema4D mediates the coupling effect that occurs following both antiresorptive and osteoanabolic treatment.
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Effect of oral piperine on the swallow response of patients with oropharyngeal dysphagia.
Rofes, L, Arreola, V, Martin, A, Clavé, P
Journal of gastroenterology. 2014;(12):1517-23
Abstract
BACKGROUND Oropharyngeal dysphagia (OD) is a major gastrointestinal motility disorder that causes severe nutritional and respiratory complications in elderly and neurological patients. In an earlier study, we found that stimulation of pharyngeal sensory neurons by capsaicinoids acting on transient receptor potential vanilloid 1 (TRPV1) improved the swallow response of dysphagic patients. The aim of this study was to explore the effect of piperine, a dual TRPV1/TRPA1 agonist, on the swallow response of dysphagic patients. METHODS A videofluoroscopic study was performed to assess the signs of impaired safety and efficacy of swallow and the swallow response of 40 dysphagic patients while swallowing one series of nectar control boluses and two series of nectar boluses supplemented with piperine. Patients were randomized into two groups: one group received 150 μM piperine and the other group received 1 mM. RESULTS Piperine improved the safety of swallow by: (a) reducing the prevalence of unsafe swallows by -34.48% (P = 0.004) at 150 μM and -57.19% (P < 0.001) at 1 mM, and the severity score of the penetration-aspiration scale from 3.25 ± 0.51 to 1.85 ± 0.27 (P = 0.003, 1 mM); and (b) shortening the time to laryngeal vestibule closure from 0.366 ± 0.024 to 0.270 ± 0.022 s with 150 μM piperine (P < 0.001) and from 0.380 ± 0.032 to 0.306 ± 0.028 s with 1 mM piperine (P < 0.05). CONCLUSIONS Supplementing the alimentary bolus with piperine speeds swallow response and strongly improves safety of swallow in patients with OD, with a maximal therapeutic effect at 1 mM. Our results suggest that activation of TRPV1/A1 in oropharyngeal sensory neurons is a very promising neurostimulation strategy for dysphagic patients.
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Experimental validation of 5 in-silico predicted glioma biomarkers.
Towner, RA, Jensen, RL, Vaillant, B, Colman, H, Saunders, D, Giles, CB, Wren, JD
Neuro-oncology. 2013;(12):1625-34
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Abstract
BACKGROUND Glioblastoma multiforme (GBM) is a high-grade glioma with poor prognosis. Identification of new biomarkers specific to GBM could help in disease diagnosis. We have developed and validated a bioinformatics method to predict proteins likely to be suitable as glioma biomarkers via a global microarray meta-analysis to identify uncharacterized genes consistently coexpressed with known glioma-associated genes. METHODS A novel bioinformatics method was implemented called global microarray meta-analysis, using approximately 16,000 microarray experiments to identify uncharacterized genes consistently coexpressed with known glioma-associated genes. These novel biomarkers were validated as proteins highly expressed in human gliomas varying in tumor grades using immunohistochemistry. Glioma gene databases were used to assess delineation of expression of these markers in varying glioma grades and subtypes of GBM. RESULTS We have identified 5 potential biomarkers-spondin1, Plexin-B2, SLIT3, fibulin-1, and LINGO1-that were validated as proteins highly expressed on the surface of human gliomas using immunohistochemistry. Expression of spondin1, Plexin-B2, and SLIT3 was significantly higher (P < .01) in high-grade gliomas than in low-grade gliomas. These biomarkers were significant discriminators in grade IV gliomas compared with either grade III or II tumors and also distinguished between GBM subclasses. CONCLUSIONS This study strongly suggests that this type of bioinformatics approach has high translational potential to rapidly discern which poorly characterized proteins may be of clinical relevance.
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Differential influences of gastric bypass and sleeve gastrectomy on plasma nesfatin-1 and obestatin levels in patients with type 2 diabetes mellitus.
Lee, WJ, Chen, CY, Ser, KH, Chong, K, Chen, SC, Lee, PC, Liao, YD, Lee, SD
Current pharmaceutical design. 2013;(32):5830-5
Abstract
OBJECTIVE The mechanisms by which bariatric surgeries, including gastric bypass (GB) and sleeve gastrectomy (SG), achieve remission of type 2 diabetes mellitus (T2DM) and sustained weight reduction are unknown. We hypothesized that the novel anorexic hormone nesfatin-1 and another new hormone obestatin might contribute to the marked improvement in glycemic homeostasis and weight loss in diabetics after GB and SG. METHODS A hospital-based, prospective study was conducted. Overnight fasting plasma concentrations of nesfatin-1 and obestatin were analyzed in T2DM patients before surgery, and at 3 and 12 months after laparoscopic GB (n =12) and SG (n = 6). RESULTS At 12 months, reductions of body mass index (BMI), fasting blood glucose, and glycated hemoglobin were similar between GB and SG groups (P all > 0.05). Plasma nesfatin-1 levels in patients undergoing GB or SG significantly decreased after surgeries (P both < 0.05). In contrast, plasma obestatin concentrations significantly increased in patients after SG (P < 0.05) but without any alteration after GB. The alterations of plasma nesfatin-1 were significantly and negatively associated with the reduction of fasting blood glucose (P <0.05) at 12 months after GB and SG. In the SG group, the reduction of nesfatin-1 significantly and positively correlated with the decrease of BMI (P < 0.05). CONCLUSIONS GB and SG produce differential influences with regards to circulating nesfatin-1 and obestatin levels in non-morbidly obese, T2DM patients. Circulating nesfatin-1 may modulate glucose homeostasis in two surgical procedures, and participate in regulating body weight in SG.
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Association between DPP6 polymorphism and the risk of progressive multiple sclerosis in Northern and Southern Europeans.
Brambilla, P, Esposito, F, Lindstrom, E, Sorosina, M, Giacalone, G, Clarelli, F, Rodegher, M, Colombo, B, Moiola, L, Ghezzi, A, et al
Neuroscience letters. 2012;(2):155-60
Abstract
BACKGROUND In this study, we investigated the role of the dipeptidyl-peptidase-6 (DPP6) gene in the etiopathogenesis of progressive forms of multiple sclerosis (PrMS). This gene emerged as a candidate gene in a genome-wide association study (GWAS) performed in an Italian sample of PrMS and controls in which two SNPs located in the gene (rs6956703 and rs11767658) showed evidence of association (nominal p-value<10(-4)) (Martinelli-Boneschi et al.) [18]. Moreover, the gene is highly expressed in the central nervous system, and it has been found to be associated with sporadic cases of amyotrophic lateral sclerosis which shares some feature with PrMS. METHODS We genotyped 19 SNPs selected using a direct and tagging approach in 244 Italian PrMS and 225 controls, and we measured the expression levels of the gene in 13 PrMS cases and 25 controls. RESULTS Five out of 19 SNPs were found to be associated with the disease (adjusted p<0.05), and they have been tested in an independent sample of 179 primary progressive MS and 198 controls from Northern Europe. None of the SNPs was replicated, but combined analysis confirmed the presence of association for rs2046748 (p=2.5×10(-3),OR=1.82, 95%CI=1.24-2.69). CONCLUSIONS These results, inflated by the limited sample size determined by the rarity of this condition, suggest a possible role of this gene in the susceptibility to PrMS, at least in Southern Europeans. Moreover, DPP6 was over-expressed in PrMS patients compared to controls.
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Role of TRPM8 and TRPA1 for cold allodynia in patients with cold injury.
Namer, B, Kleggetveit, IP, Handwerker, H, Schmelz, M, Jorum, E
Pain. 2008;(1):63-72
Abstract
Local cold injury often induces hypersensitivity to cold and cold allodynia. Sensitisation of TRPM8 or TRPA1 could be the underlying mechanisms. This was evaluated by psychophysics and axon-reflex-flare induction following topical menthol and cinnamaldehyde application in cold injury patients and healthy subjects. The patients had no signs of neuropathy except cold allodynia. We applied 20% cinnamaldehyde and 40% menthol solutions in the cold-allodynic area of the patients and in a corresponding area in healthy subjects and obtained sensory ratings during application. Thermotesting and Laser Doppler Imaging were performed before and after exposure to the compounds. Menthol did not induce axon-reflex-erythema in patients or in controls. After menthol cold pain threshold was decreased in healthy subjects; however, no further sensitisation was observed in the patients moreover in some patients an amelioration of their cold allodynia was observed. Cinnamaldehyde-induced pain sensation did not differ between patients and controls. Heat pain thresholds following cinnamaldehyde were lowered to a similar extent in patients and controls (43-39.8 and 44-39 degrees C) and also the axon-reflex-flare responses were comparable. No evidence for sensitisation of responses to TRPM8 or TRPA1-stimulation was found in patients with cold injury-induced cold allodynia. The lack of TRPM8 induced axon-reflex indicates that also de-novo expression of TRPM8 on mechano-insensitive C-nociceptors does not underlie cold allodynia in these patients. We conclude from these data that the mechanisms for the induction of cold allodynia in the patients with cold injury are independent of TRPM8 or TRPA1 and differ therefore from neuropathic pain patients.
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Reversed diurnal variation in depression: associations with a differential antidepressant response, tryptophan: large neutral amino acid ratio and serotonin transporter polymorphisms.
Joyce, PR, Porter, RJ, Mulder, RT, Luty, SE, McKenzie, JM, Miller, AL, Kennedy, MA
Psychological medicine. 2005;(4):511-7
Abstract
BACKGROUND Although diurnal variation of mood is a widely recognized symptom of depression, the clinical, neurobiological and psychopharmacological significance of this symptom has not previously been reported. METHOD A total of 195 depressed out-patients underwent a detailed clinical and neurobiological assessment, and were then randomized to treatment with either fluoxetine or nortriptyline. RESULTS Of the 195 depressed patients, 62 had a pattern of reversed diurnal variation (i.e. worse in the evening). Those with reversed diurnal variation had a poorer response to a serotonergic anti-depressant, were less likely to have bipolar II disorder, had a higher tryptophan: large neutral amino acid ratio and had different allele frequencies of the polymorphisms in the promoter region of the serotonin transporter. CONCLUSIONS These findings raise the possibility of serotonergic influence on diurnal variation, and that the symptom of reversed diurnal variation is of relevance to antidepressant prescribing.
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Dopamine transporter gene polymorphism, spect imaging, and levodopa response in patients with Parkinson disease.
Contin, M, Martinelli, P, Mochi, M, Albani, F, Riva, R, Scaglione, C, Dondi, M, Fanti, S, Pettinato, C, Baruzzi, A
Clinical neuropharmacology. 2004;(3):111-5
Abstract
OBJECTIVES To assess the potential association between dopamine transporter (DAT) genotype, single photon emission CT (SPECT) measures using [123I]-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane ([123I]-FP-CIT) of striatal dopaminergic function, and oral levodopa response pattern in a cohort of patients with Parkinson disease. METHODS Thirty-six patients at different disease stages enrolled in the study. Each patient was examined by [123I]-FP-CIT SPECT and a standardized oral levodopa test on 2 separate days in a randomized order within 3 weeks. The main outcome variables were the specific-to-nonspecific tracer uptake ratio in the contralateral putamen for SPECT analysis; latency, duration, and magnitude of the motor effect; and presence of dyskinesias for the levodopa test. The variable number of tandem repeat (VNTR) polymorphisms of the gene coding for DAT were detected for each patient by standard methods. RESULTS Contralateral putamen [123I]-FP-CIT uptake ratios were similar in the patients carrying the 9-copy allele (n=20) of the DAT VNTR compared with 10-repeat homozygotes (n=16). No significant difference was found in levodopa main outcome variables and dyskinesia incidence between the two groups of patients stratified by DAT VNTR polymorphism. CONCLUSIONS The study did not identify clinically relevant in vivo DAT neurochemical function phenotypes or levodopa response patterns associated with the DAT polymorphism.
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Brain serotonin transporter availability predicts treatment response to selective serotonin reuptake inhibitors.
Kugaya, A, Sanacora, G, Staley, JK, Malison, RT, Bozkurt, A, Khan, S, Anand, A, Van Dyck, CH, Baldwin, RM, Seibyl, JP, et al
Biological psychiatry. 2004;(7):497-502
Abstract
BACKGROUND Few studies have investigated the predictive value of central serotonin transporter (SERT) availability for treatment response to serotonin reuptake inhibitors (SSRIs). This study used brain imaging to examine the relationship between pretreatment brain SERT availability and transporter occupancy by SSRIs with treatment response in two independent depressed populations. METHODS Study 1: Twenty-three patients with major depression underwent a single photon emission computed tomography (SPECT) measurement of brain SERT availability using [123I]beta-CIT ([123I]methyl 3beta-(4-iodophenyl) tropane-2beta-carboxylate. The SERT availability was correlated with treatment response to fluoxetine (20 mg/day) assessed with weekly Hamilton Depression Rating Scale (HDRS) for 6 weeks. Study 2: The second group included 10 depressed patients who received 6 weeks of paroxetine treatment (20 mg/day) and serial SPECT scans (baseline, during, and after the treatment). RESULTS In Study 1, higher pretreatment diencephalic SERT availability significantly predicted better treatment response 4 weeks later. Similar results were found in Study 2 and supported Study 1 findings. The data showed that greater occupancy of diencephalic transporters by paroxetine correlated with better treatment response. CONCLUSIONS Higher pretreatment availability and greater occupancy of SERT in diencephalon may predict better treatment course in response to SSRIs.