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Mertens F.,Catholic University of Leuven | Gremeaux L.,Catholic University of Leuven | Chen J.,Catholic University of Leuven | Chen J.,Huazhong University of Science and Technology | And 14 more authors.
Endocrine-Related Cancer | Year: 2015

Pituitary adenomas cause significant endocrine and mass-related morbidity. Little is known about the mechanisms that underlie pituitary tumor pathogenesis. In the present study, we searched for a side population (SP) in pituitary tumors representing cells with high efflux capacity and potentially enriched for tumor stem cells (TSCs). Human pituitary adenomas contain a SP irrespective of hormonal phenotype. This adenoma SP, as well as the purified SP (pSP) that is depleted from endothelial and immune cells, is enriched for cells that express 'tumor stemness' markers and signaling pathways, including epithelial-mesenchymal transition (EMT)-linked factors. Pituitary adenomas were found to contain self-renewing sphere-forming cells, considered to be a property of TSCs. These sphere-initiating cells were recovered in the pSP. Because benign pituitary adenomas do not grow in vitro and have failed to expand in immunodeficient mice, the pituitary tumor cell line AtT20 was further used.We identified a SP in this cell line and found it to be more tumorigenic than the non-SP 'main population'. Of the two EMTregulatory pathways tested, the inhibition of chemokine (C-X-C motif) receptor 4 (CXCR4) signaling reduced EMT-associated cell motility in vitro as well as xenograft tumor growth, whereas the activation of TGFb had no effect. The human adenoma pSP also showed upregulated expression of the pituitary stem cell marker SOX2. Pituitaries from dopamine receptor D2 knockout (Drd2K/K) mice that bear prolactinomas contain more pSP, Sox2C, and colony-forming cells than WT glands. In conclusion, we detected a SP in pituitary tumors and identified TSC-associated characteristics. The present study adds new elements to the unraveling of pituitary tumor pathogenesis and may lead to the identification of new therapeutic targets. © 2015 Society for Endocrinology Printed in Great Britain. Source

Lai K.,Zhejiang University | Cui J.,Zhejiang University | Ni S.,Zhejiang University | Zhang Y.,Zhejiang University | And 3 more authors.
PLoS ONE | Year: 2013

Background:Cataract is the leading cause of blindness worldwide. Many observational studies assessed the relationship between postmenopausal hormone replacement therapy (HRT) and risk of cataract development, but the reported results were controversial. The aim of present meta-analysis was to evaluate the association of postmenopausal hormone replacement therapy with risk of cataract development.Methods:The eligible observational studies, including cross-sectional, case-control and cohort studies, were identified by searching PubMed and Embase during March of 2013. Either a fixed- or a random-effects model was used to calculate the pooled odds ratio (OR) with its 95% confidence interval (95%CI). Subgroup analysis on cataract types was performed.Results:A total of four cohort and five case-control or cross-sectional studies were finally included into this meta-analysis. Overall, a significant decreased risk of developing any type of cataract was found in ever HRT group as compared with non-HRT group among cohort studies (OR 0.83; 95%CI: 0.71,0.97) and case-control or cross-sectional studies (OR 0.74; 95%CI: 0.59,0.93). Subgroup analysis on cataract types determined that the significantly decreased risk of nuclear cataract in current HRT group (OR 0.72; 95%CI: 0.61,0.85) and also a critically reduced risk of nuclear cataract in ever HRT group (OR 0.80; 95% CI: 0.64,1.01) were found among case-control or cross-sectional studies, as compared with non-HRT group. No association of HRT with risk of cortical and posterior subcapsular cataract was observed.Conclusions:The results of present meta-analysis indicate that postmenopausal hormone use may play a protective role in cataract development. © 2013 Lai et al. Source

Wu W.,Zhejiang University | Wu W.,Zhejiang Provincial Key Laboratory of Ophthalmology | Weng Y.,Zhejiang University | Weng Y.,Zhejiang Provincial Key Laboratory of Ophthalmology | And 5 more authors.
Investigative Ophthalmology and Visual Science | Year: 2016

PURPOSE. We conducted a meta-analysis of individual studies reporting an association between serum vitamin D levels and AMD. METHODS. Relevant studies evaluating the association between serum vitamin D levels and AMD risk were identified by systematically searching four electronic literature databases (Ovid Medline, PubMed, EMBASE, and ISI Web of Science) censored by June 2015. Due to the heterogeneity of studies in categorizing serum vitamin D levels, all individual odds ratios (ORs) were recalculated and transferred for an increase of serum vitamin D levels by 10 ng/ ml. Summary ORs and 95% confidence intervals (CIs) of AMD risk per 10-unit increase of serum vitamin D were obtained using standard meta-analysis. Publication bias was evaluated using funnel plots and Kendall’s rank correlation tests. RESULTS. Ten individual studies were included and pooled in this meta-analysis. Meta-analysis of studies on AMD risk led to a pooled OR (95% CI) of 0.91 (0.69-1.22) for an increase of 25- hydroxy vitamin D by 10 ng/mL (P ¼ 0.12). No indication for publication bias was found, but substantial heterogeneity was obtained (I2 ¼ 79.7%, P < 0.01). Estimates from subgroup analyses also did not show statistically significant associations of serum vitamin D levels with different stages (early AMD, late AMD, and advanced AMD) and subtypes of AMD (neovascular AMD and nonneovascular AMD; P > 0.05). CONCLUSIONS. There is no evidence to indicate an inverse association between serum vitamin D levels and any stages and subtypes of AMD risk, but opposite results from the United States and Korea resulted in this nonsignificance. Potential difference across various study designs might exist, based on few studies reporting in heterogeneous manners so far. More studies are needed to further confirm the causality of vitamin D and AMD, especially longitudinal studies. © 2016, Association for Research in Vision and Ophthalmology Inc., All rights reserved. Source

Sun C.-B.,Zhejiang University | Sun C.-B.,Zhejiang Provincial Key Laboratory of Ophthalmology | Teng W.-Q.,Zhejiang University | Cui J.-T.,Zhejiang University | And 3 more authors.
Colloids and Surfaces B: Biointerfaces | Year: 2014

Migration and epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) are main causes of central posterior capsule opacification after cataract extraction combined with intraocular lens (IOL) implantation. In this study, commercially available hydrophobic acrylic IOLs were first pretreated with atmospheric pressure glow discharge plasma to produce plenty of negatively charged chemical groups onto IOL surface, then polyethylenimine was deposited onto IOL surfaces as a precursor monolayer, and then anti-TGF-β2 (anti-T) antibody and poly-l-lysine were sequentially deposited onto IOL surface for four cycles followed by another upmost monolayer of anti-T antibody via layer-by-layer self-assembly technique. After the fabrication of anti-T antibody multilayers on IOL surface, the surface characteristics of the anti-T antibody functionalized IOL, as well as its effect on LECs adhesion, proliferation, migration and EMT were then tested in this study. Our results revealed that anti-T antibody multilayers could be successfully immobilized onto IOL surfaces by plasma pretreatment and layer-by-layer self-assembly technique, and could keep stable for at least 3 months on IOL surface. The anti-T antibody immobilized in the multilayers on IOL surfaces showed good immunological activity by its specific antigen-antibody interaction with exogenous TGF-β2. Anti-T antibody functionalized IOL surface was as smooth and flat as the untreated IOL surface. No difference in optical or physical properties was found between the anti-T antibody functionalized IOLs and the untreated IOLs. Compared with the untreated IOLs, the anti-T antibody functionalized IOL greatly inhibited LECs from migration and EMT, yet showed only transient inhibition to LECs adhesion and no inhibition to LECs proliferation. With these data, we demonstrate a simple, inexpensive, and feasible method to fabricate surface functionalized IOL for in situ capture and neutralization of TGF-β2 in the capsular bag, which might be a possible solution to preventing posterior capsule opacification after cataract surgery. © 2013 Elsevier B.V. Source

Yu X.,Zhejiang University | Lyu D.,Zhejiang University | Dong X.,Zhejiang University | He J.,Zhejiang University | And 2 more authors.
PLoS ONE | Year: 2014

Background: Cataract is the major cause of blindness across the world. Many epidemiologic studies indicated that hypertension might play an important role in the development of cataract, while others not. We therefore conducted this metaanalysis to determine the relationship between risk of cataract and hypertension. Methods: Retrieved studies on the association of hypertension with cataract risk were collected from PubMed, Web of Science and the Cochrane Library during June 2014 and were included into the final analysis according to the definite inclusion criteria. Odds ratio (OR) or risk ratio (RR) were pooled with 95% confidence interval (CI) to evaluate the relationship between hypertension and cataract risk. Subgroup analyses were carried out on the basis of cataract type, race and whether studies were adjusted for main components of metabolic syndrome (MS). Results: The final meta-analysis included 25 studies (9 cohort, 5 case-control and 11 cross-sectional) from 23 articles. The pooled results showed that cataract risk in populations with hypertension significantly increased among cohort studies (RR 1.08; 95% CI: 1.05-1.12) and case-control or cross-sectional studies (OR 1.28;95% CI: 1.12-1.45). This association was proved to be true among both Mongolians and Caucasians, and the significance was not altered by the adjustment of main components of MS. Subgroup analysis on cataract types indicated that an increased incidence of posterior subcapsular cataract (PSC) resulted among cohort studies (RR 1.22; 95% CI: 1.03-1.46) and cross-sectional/ case-control studies (OR 1.23; 95% CI: 1.09-1.39). No association of hypertension with risk of nuclear cataract was found. Conclusions: The present meta-analysis suggests that hypertension increases the risk of cataract, especially PSC. Further efforts should be made to explore the potential biological mechanisms. © 2014 Yu et al. Source

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