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1.
Int J Ophthalmol ; 17(3): 473-479, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38721502

RESUMO

AIM: To establish a classification for congenital cataracts that can facilitate individualized treatment and help identify individuals with a high likelihood of different visual outcomes. METHODS: Consecutive patients diagnosed with congenital cataracts and undergoing surgery between January 2005 and November 2021 were recruited. Data on visual outcomes and the phenotypic characteristics of ocular biometry and the anterior and posterior segments were extracted from the patients' medical records. A hierarchical cluster analysis was performed. The main outcome measure was the identification of distinct clusters of eyes with congenital cataracts. RESULTS: A total of 164 children (299 eyes) were divided into two clusters based on their ocular features. Cluster 1 (96 eyes) had a shorter axial length (mean±SD, 19.44±1.68 mm), a low prevalence of macular abnormalities (1.04%), and no retinal abnormalities or posterior cataracts. Cluster 2 (203 eyes) had a greater axial length (mean±SD, 20.42±2.10 mm) and a higher prevalence of macular abnormalities (8.37%), retinal abnormalities (98.52%), and posterior cataracts (4.93%). Compared with the eyes in Cluster 2 (57.14%), those in Cluster 1 (71.88%) had a 2.2 times higher chance of good best-corrected visual acuity [<0.7 logMAR; OR (95%CI), 2.20 (1.25-3.81); P=0.006]. CONCLUSION: This retrospective study categorizes congenital cataracts into two distinct clusters, each associated with a different likelihood of visual outcomes. This innovative classification may enable the personalization and prioritization of early interventions for patients who may gain the greatest benefit, thereby making strides toward precision medicine in the field of congenital cataracts.

2.
Mater Today Bio ; 14: 100233, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35280330

RESUMO

Hemostatic materials are generally applied in surgical operations for cancer, but their effects on the growth and recurrence of tumors are unclear. Herein, three commonly used naturally derived hemostatic materials, gelatin sponge, Surgicel (oxidized regenerated cellulose), and biopaper (mixture of sodium hyaluronate and carboxymethyl chitosan), were cocultured with A549 human lung adenocarcinoma cells in vitro. Furthermore, the performance of hemostatic materials and the tumorigenicity of the materials with A549 â€‹cells were observed after subcutaneous implantation into BALB/c mice. The in vitro results showed that biopaper was dissolved quickly, with the highest cell numbers at 2 and 4 days of culture. Gelatin sponges retained their structure and elicited the least cell infiltration during the 2- to 10-day culture. Surgicel partially dissolved and supported cell growth over time. The in vivo results showed that biopaper degraded rapidly and elicited an acute Th1 lymphocyte reaction at 3 days after implantation, which was decreased at 7 days after implantation. The gelatin sponge resisted degradation and evoked a hybrid M1/M2 macrophage reaction at 7-21 days after implantation, and a protumor M2d subset was confirmed. Surgicel resisted early degradation and caused obvious antitumor M2a macrophage reactions. Mice subjected to subcutaneous implantation of A549 â€‹cells and hemostatic materials in the gelatin sponge group had the largest tumor volumes and the shortest overall survival (OS), while the Surgicel and the biopaper group had the smallest volumes and the longest OS. Therefore, although gelatin sponges exhibited cytotoxicity to A549 â€‹cells in vitro, they promoted the growth of A549 â€‹cells in vivo, which was related to chronic M2d macrophage reaction. Surgicel and biopaper inhibited A549 â€‹cell growth in vivo, which is associated with chronic M2a macrophage reaction or acute Th1 lymphocyte reaction.

3.
Lancet Digit Health ; 3(2): e88-e97, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33509389

RESUMO

BACKGROUND: Ocular changes are traditionally associated with only a few hepatobiliary diseases. These changes are non-specific and have a low detection rate, limiting their potential use as clinically independent diagnostic features. Therefore, we aimed to engineer deep learning models to establish associations between ocular features and major hepatobiliary diseases and to advance automated screening and identification of hepatobiliary diseases from ocular images. METHODS: We did a multicentre, prospective study to develop models using slit-lamp or retinal fundus images from participants in three hepatobiliary departments and two medical examination centres. Included participants were older than 18 years and had complete clinical information; participants diagnosed with acute hepatobiliary diseases were excluded. We trained seven slit-lamp models and seven fundus models (with or without hepatobiliary disease [screening model] or one specific disease type within six categories [identifying model]) using a development dataset, and we tested the models with an external test dataset. Additionally, we did a visual explanation and occlusion test. Model performances were evaluated using the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and F1* score. FINDINGS: Between Dec 16, 2018, and July 31, 2019, we collected data from 1252 participants (from the Department of Hepatobiliary Surgery of the Third Affiliated Hospital of Sun Yat-sen University, the Department of Infectious Diseases of the Affiliated Huadu Hospital of Southern Medical University, and the Nantian Medical Centre of Aikang Health Care [Guangzhou, China]) for the development dataset; between Aug 14, 2019, and Jan 31, 2020, we collected data from 537 participants (from the Department of Infectious Diseases of the Third Affiliated Hospital of Sun Yat-sen University and the Huanshidong Medical Centre of Aikang Health Care [Guangzhou, China]) for the test dataset. The AUROC for screening for hepatobiliary diseases of the slit-lamp model was 0·74 (95% CI 0·71-0·76), whereas that of the fundus model was 0·68 (0·65-0·71). For the identification of hepatobiliary diseases, the AUROCs were 0·93 (0·91-0·94; slit-lamp) and 0·84 (0·81-0·86; fundus) for liver cancer, 0·90 (0·88-0·91; slit-lamp) and 0·83 (0·81-0·86; fundus) for liver cirrhosis, and ranged 0·58-0·69 (0·55-0·71; slit-lamp) and 0·62-0·70 (0·58-0·73; fundus) for other hepatobiliary diseases, including chronic viral hepatitis, non-alcoholic fatty liver disease, cholelithiasis, and hepatic cyst. In addition to the conjunctiva and sclera, our deep learning model revealed that the structures of the iris and fundus also contributed to the classification. INTERPRETATION: Our study established qualitative associations between ocular features and major hepatobiliary diseases, providing a non-invasive, convenient, and complementary method for hepatobiliary disease screening and identification, which could be applied as an opportunistic screening tool. FUNDING: Science and Technology Planning Projects of Guangdong Province; National Key R&D Program of China; Guangzhou Key Laboratory Project; National Natural Science Foundation of China.


Assuntos
Algoritmos , Simulação por Computador , Aprendizado Profundo , Doenças do Sistema Digestório/diagnóstico , Olho , Programas de Rastreamento/métodos , Modelos Biológicos , Adulto , Área Sob a Curva , China , Túnica Conjuntiva/diagnóstico por imagem , Doenças do Sistema Digestório/complicações , Olho/diagnóstico por imagem , Fundo de Olho , Humanos , Iris/diagnóstico por imagem , Fígado , Pessoa de Meia-Idade , Fotografação/métodos , Estudos Prospectivos , Curva ROC , Esclera/diagnóstico por imagem , Microscopia com Lâmpada de Fenda/métodos
4.
Nat Commun ; 12(1): 60, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397900

RESUMO

Long nanopore reads are advantageous in de novo genome assembly. However, nanopore reads usually have broad error distribution and high-error-rate subsequences. Existing error correction tools cannot correct nanopore reads efficiently and effectively. Most methods trim high-error-rate subsequences during error correction, which reduces both the length of the reads and contiguity of the final assembly. Here, we develop an error correction, and de novo assembly tool designed to overcome complex errors in nanopore reads. We propose an adaptive read selection and two-step progressive method to quickly correct nanopore reads to high accuracy. We introduce a two-stage assembler to utilize the full length of nanopore reads. Our tool achieves superior performance in both error correction and de novo assembling nanopore reads. It requires only 8122 hours to assemble a 35X coverage human genome and achieves a 2.47-fold improvement in NG50. Furthermore, our assembly of the human WERI cell line shows an NG50 of 22 Mbp. The high-quality assembly of nanopore reads can significantly reduce false positives in structure variation detection.


Assuntos
Nanoporos , Análise de Sequência de DNA , Linhagem Celular , Cromossomos Humanos/genética , Genoma Humano , Humanos , Retinoblastoma/genética , Software
5.
CNS Neurosci Ther ; 27(4): 449-463, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33314758

RESUMO

AIMS: Acyl-CoA synthetase long chain family member 4 (ACSL4) is closely related to tumor genesis and development in certain tissues. However, the function of ACSL4 in early brain injury (EBI) caused by subarachnoid hemorrhage (SAH) is unclear. In this study, we investigated the expression patterns and role of ACSL4 in SAH and post-SAH EBI using a rat model of SAH. METHODS: The rat model of SAH was induced by autologous blood injection into the prechiasmatic cistern of rats. We also used two specific inhibitors of ferroptosis (Ferrostatin-1 and Liproxstatin-1) to investigate the role of ferroptosis in EBI. RESULTS: We found that ACSL4 levels in brain tissue increased significantly in post-SAH EBI. Inhibiting the expression of ACSL4 using small interfering RNAs alleviated inflammation, blood-brain barrier (BBB) impairment, oxidative stress, brain edema, and behavioral and cognitive deficits, and increased the number of surviving neurons, after SAH. Similar effects were obtained by suppressing ferroptosis. CONCLUSIONS: ACSL4 exacerbated SAH-induced EBI by mediating ferroptosis. These findings may provide a theoretical basis for potential therapy aimed at alleviating post-SAH EBI.


Assuntos
Lesões Encefálicas/metabolismo , Coenzima A Ligases/biossíntese , Ferroptose/fisiologia , Hemorragia Subaracnóidea/metabolismo , Animais , Lesões Encefálicas/patologia , Masculino , Aprendizagem em Labirinto/fisiologia , Ratos , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/patologia
6.
World J Gastrointest Oncol ; 12(11): 1216-1236, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33250957

RESUMO

BACKGROUND: Programmed death ligand 1 (PD-L1) immunotherapy remains poorly efficacious in colorectal cancer (CRC). The recepteur d'origine nantais (RON) receptor tyrosine kinase plays an important role in regulating tumor immunity. AIM: To identify the patterns of RON and PD-L1 expression and explore their clinical significance in CRC. METHODS: Gene expression data from the Gene Expression Omnibus database (GEO; n = 290) and patients at the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZUSM; n = 381) were analyzed to determine the prognostic value of RON and PD-L1 expression within the tumor microenvironment of CRC. HT29 cell line was treated with BMS-777607 to explore the relationship between RON activity and PD-L1 expression. Signaling pathways and protein expression perturbed by RON inhibition were evaluated by cellular immunofluorescence and Western blot. RESULTS: In the GEO patient cohort, cut-off values for RON and PD-L1 expression were determined to be 7.70 and 4.3, respectively. Stratification of patients based on these cutoffs demonstrated that high expression of RON and PD-L1 was associated with a poor prognosis. In the FAHZUSM cohort, rates of high expression of RON in tumor cells, high PD-L1 expression in tumor cells and tumor infiltrating monocytes, and both high RON and high PD-L1 expression in the tumor microenvironment were 121 (32%), 43 (11%), 91 (24%), and 51 (13.4%), respectively. High expression of RON was significantly correlated with high expression of PD-L1 in the tumor cell compartment (P < 0.001). High expression of RON and that of PD-L1 were independent prognostic factors for poorer overall survival. Concurrent high expression of both RON and PD-L1 in the tumor microenvironment was significantly associated with a poor prognosis. In vitro, BMS-777607 inhibited the phosphorylation of RON, inhibited PD-L1 expression, and attenuated activation of the ERK1/2 and AKT signaling pathways in CRC cells. CONCLUSION: RON, PD-L1, and their crosstalk are significant in predicting the prognostic value of CRC. Moreover, phosphorylation of RON upregulates PD-L1 expression, which provides a novel approach to immunotherapy in CRC.

7.
Cancer Res Treat ; 52(3): 973-986, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32324988

RESUMO

PURPOSE: Triple-negative breast cancer (TNBC) is highly malignant and has poor prognosis and a high mortality rate. The lack of effective therapy has spurred our investigation of new targets for treating this malignant cancer. Here, we identified RON (macrophage-stimulating 1 receptor) and MET (MET proto-oncogene, receptor tyrosine kinase) as a prognostic biomarker and therapeutic targets for potential TNBC treatment. MATERIALS AND METHODS: We analyzed RON and MET expression in 187 primary TNBC clinical samples with immunohistochemistry. We validated the targeted therapeutic effects of RON and MET in TNBC using three tyrosine kinase inhibitors (TKIs): BMS-777607, INCB28060, and tivantinib. The preclinical therapeutic efficacy of the TKIs was mainly estimated using a TNBC xenograft model. RESULTS: Patients with TNBC had widespread, abnormal expression of RON and MET. There was RON overexpression, MET overexpression, and RON and MET co-overexpression in 63 (33.7%), 63 (33.7%), and 43 cases (23.0%), respectively, which had poor prognosis and short survival. In vivo, the TKI targeting RON ant MET inhibited the activation of the downstream signaling molecules, inhibited TNBC cell migration and proliferation, and increased TNBC cell apoptosis; in the xenograft model, they significantly inhibited tumor growth and shrank tumor volumes. The TKI targeting RON and Met, such as BMS-777607 and tivantinib, yielded stronger anti-tumor effects than INCB28060. CONCLUSION: RON and MET co-overexpression can be significant pathological characteristics in TNBC for poor prognosis. TKIs targeting RON and MET have stronger drug development potential for treating TNBC.


Assuntos
Biomarcadores Tumorais/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-met/genética , Receptores Proteína Tirosina Quinases/genética , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Front Oncol ; 9: 1377, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31867280

RESUMO

RON (recepteur d'origine nantais) and MET (hepatocyte growth factor receptor) are tyrosine kinase receptors. Various cancers have aberrant RON and MET expression and activation, which contribute to cancer cell proliferation, invasiveness, and metastasis. Here, we explored RON and MET expression in pancreatic cancer and their relationship with overall survival (OS) time, and evaluated their significance as therapeutic targets of tyrosine kinase inhibitors in pancreatic cancer. We enrolled 227 patients with pancreatic cancer in the study. RON and MET expression was analyzed by immunohistochemical staining. Four human pancreatic cancer cell lines expressing variable levels of RON or MET and four MET superfamily inhibitors (BMS777607, PHA665752, INCB28060, Tivantinib) were used. The effect of the four tyrosine kinase inhibitors on cell viability, migration, and apoptosis were determined using cell viability, scratch wound healing, and Caspase-Glo 3/7 assays. Cellular signaling was analyzed by immunoprecipitation and western blotting. The therapeutic efficacy of the tyrosine kinase inhibitors was determined with mouse xenograft pancreatic cancer models in vivo. There was wide aberrant RON and MET expression in the cancer tissues. In 227 pancreatic cancer samples, 33% had RON overexpression, 41% had MET overexpression, and 15.4% had RON and MET co-overexpression. RON and MET expression were highly correlated. RON and MET expression levels were significantly related to OS. Patients with RON and MET co-overexpression had poorer OS. BMS777607 and PHA665752 inhibited pancreatic cancer cell viability and migration, and promoted apoptosis by inhibiting RON and MET phosphorylation and further inhibiting the downstream signaling pathways in vitro. They also inhibited tumor growth and further inhibited phosphorylated (phosphor)-RON and phospho-MET expression in the mouse xenograft models in vivo effectively. INCB28060, which inhibits the MET signaling pathway alone, was not effective. RON and MET can be important indicators of prognosis in pancreatic cancer. Tyrosine kinase inhibitors targeting RON and MET in pancreatic cancer are a novel and potential approach for pancreatic cancer therapy.

9.
Int J Ophthalmol ; 12(12): 1839-1847, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31850165

RESUMO

AIM: To study the change in ocular refraction in patients with pediatric cataracts (PCs) after lens extraction. METHODS: A total of 1258 patients who were undergoing cataract extraction with/without intraocular lens (IOL) implantation were recruited during preoperative examinations between Jan 2010 and Oct 2013. Patient ages ranged from 1.5mo to 14y. Follow-ups were conducted at 1wk, 1, and 3mo postoperatively and every 3mo in the first year, then 6mo thereafter. Ocular refraction [evaluated as spherical equivalent (SE)] and yearly myopic shift (YMS) were recorded and statistically analyzed among patients with age at surgery, baseline ocular refraction, gender, postoperative time and laterality (bilateral vs unilateral). RESULTS: By Dec 31st 2015, 1172 participants had been followed for more than 2y. The median follow-up period was 3y. The critical factors affecting the ocular refraction of PC patients were baseline ocular refraction, postoperative time for both aphakic and pseudophakic eyes. YMS grew most rapidly in young childhood and early adolescence. CONCLUSION: After lens surgeries, ocular refraction in PC patients shows an individual difference of change. Further concerns should be raising to monitor the rapid myopic shift at early adolescence of these patients.

10.
J Immunother Cancer ; 7(1): 250, 2019 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519211

RESUMO

BACKGROUND: Antibody-drug conjugates (ADCs) targeting the RON receptor, a tumorigenic factor contributing to cancer malignancy, has been considered as a novel strategy for cancer therapy. Here we describe a humanized antibody recognizing the RON plexin-semaphorin-integrin (PSI) domain with increased drug delivery capability for potential clinical application. METHOD: Monoclonal antibody PCM5B14 specific to the human and monkey RON PSI domain was generated and characterized by various immunological methods. Humanized antibody H5B14 was created by grafting PCM5B14 complementarity-determining regions into human IgG1/κ acceptor frameworks and conjugated with monomethyl auristatin E and duocarmycin to form two H5B14-based ADCs. Stability of H5B14-based ADCs in human plasma was measured using hydrophobic interaction chromatography. Various biochemical and biological assays were used to determine ADC- regulated RON internalization, cell viability, spheroid formation, and death of cancer stem-like cells. Efficacies of H5B14-based ADCs in vivo were validated using tumor xenograft models. Maximal tolerated doses of H5B14-based ADCs were established in mice. RESULTS: H5B14 was highly specific to the human RON PSI domain and superior over other anti-RON ADCs in induction of RON internalization in various cancer cell lines tested. H5B14-based ADCS had a drug to antibody ratio of ~ 3.70:1 and were stable in human plasma with a minimal dissociation within a 10-day period. Functionally, H5B14-mediated drug delivery decreased cell viability at early stages with an average IC50 at ~ 20 nM in multiple cancer cell lines examined. H5B14-based ADCs also inhibited spheroid formation and caused death of cancer stem-like cells with RON+/CD44+/ESA+ phenotypes. In vivo, H5B14-based ADCs in a single injection inhibited tumor xenograft growth mediated by multiple cancer cell lines. Tumoristatic concentrations calculated from xenograft tumor models were in the range of 0.63 to 2.0 mg/kg bodyweight. Significantly, H5B14-based ADCs were capable of eradicating tumors at variable levels across multiple xenograft models regardless their malignant statuses. Toxicologically, H5B14-based ADCs were well tolerated in mice up to 60 mg/kg. CONCLUSION: H5B14-based ADCs targeting the RON PSI domain are superior in inducing RON internalization, leading to robust drug delivery and overall inhibition and eradication of tumors in multiple xenograft models. These findings warrant H5B14-based ADCs for clinical trials in the future.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Imunoconjugados/administração & dosagem , Neoplasias/tratamento farmacológico , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Animais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/imunologia , Linhagem Celular Tumoral , Duocarmicinas/administração & dosagem , Duocarmicinas/imunologia , Feminino , Humanos , Imunoconjugados/imunologia , Dose Máxima Tolerável , Camundongos , Neoplasias/imunologia , Oligopeptídeos/administração & dosagem , Oligopeptídeos/imunologia , Domínios Proteicos/imunologia , Receptores Proteína Tirosina Quinases/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Int J Ophthalmol ; 10(12): 1835-1843, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29259901

RESUMO

AIM: To compare visual prognoses and postoperative adverse events of congenital cataract surgery performed at different times and using different surgical approaches. METHODS: In this prospective, randomized controlled trial, we recruited congenital cataract patients aged 3mo or younger before cataract surgery. Sixty-one eligible patients were randomly assigned to two groups according to surgical timing: a 3-month-old group and a 6-month-old group. Each eye underwent one of three randomly assigned surgical procedures, as follows: surgery A, lens aspiration (I/A); surgery B, lens aspiration with posterior continuous curvilinear capsulorhexis (I/A+PCCC); and surgery C, lens aspiration with posterior continuous curvilinear capsulorhexis and anterior vitrectomy (I/A+PCCC+A-Vit). The long-term best-corrected visual acuity (BCVA) and the incidence of complications in the different groups were compared and analyzed. RESULTS: A total of 57 participants (114 eyes) with a mean follow-up period of 48.7mo were included in the final analysis. The overall logMAR BCVA in the 6-month-old group was better than that in the 3-month-old group (0.81±0.28 vs 0.96±0.30; P=0.02). The overall logMAR BCVA scores in the surgery B group were lower than the scores in the A and C groups (A: 0.80±0.29, B: 1.02±0.28, and C: 0.84±0.28; P=0.007). A multivariate linear regression revealed no significant relationships between the incidence of complications and long-term BCVA. CONCLUSION: It might be safer and more beneficial for bilateral total congenital cataract patients to undergo surgery at 6mo of age than 3mo. Moreover, with rigorous follow-up and timely intervention, the postoperative complications in these patients are treatable and do not compromise visual outcomes.

12.
Am J Cancer Res ; 6(12): 2816-2830, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28042502

RESUMO

Uveal melanoma (UM) is the most common primary ocular malignancy in adults. Currently, no beneficial systemic therapy is available; therefore, there is an urgent need for effective targeted therapeutic drugs. As verteporfin has shown anti-neoplastic activity in several types of cancers, here we hypothesized and investigated the efficacy of verteporfin against UM cells without light activation. MTS assay, flow cytometry analysis of apoptosis, Western blotting of relevant proteins, transwell migration and invasion assay, melanosphere culture, and measurement of ALDH+ populations, were used to evaluate the effects of verteporfin on UM cells. We found that verteporfin disrupted the interaction between YAP and TEAD4 in UM cells and decreased the expression of YAP targeted downstream genes. Verteporfin treatment decreased the cytoplasmic and nuclear levels of YAP and induced lysosome-dependent degradation of YAP protein. Verteporfin exhibited distinct inhibitory effect on the proliferation of four lines of UM cells (e.g., 92.1, Mel 270, Omm 1 and Omm 2.3), and induced apoptosis through the intrinsic pathway. Additionally, verteporfin suppressed migration and invasion of UM cells, impaired the traits of cancer stem-like cells (e.g., melanosphere formation capacity, and ALDH+ cell population). This study demonstrated the anti-neoplastic activity of verteporfin against UM cells in vitro, providing a rationale for evaluating this agent in clinical investigation.

13.
Proc Natl Acad Sci U S A ; 111(15): 5574-9, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24706897

RESUMO

The mammalian small ubiquitin-like modifiers (SUMOs) are actively involved in regulating differentiation of different cell types. However, the functional differences between SUMO isoforms and their mechanisms of action remain largely unknown. Using the ocular lens as a model system, we demonstrate that different SUMOs display distinct functions in regulating differentiation of epithelial cells into fiber cells. During lens differentiation, SUMO1 and SUMO2/3 displayed different expression, localization, and targets, suggesting differential functions. Indeed, overexpression of SUMO2/3, but not SUMO1, inhibited basic (b) FGF-induced cell differentiation. In contrast, knockdown of SUMO1, but not SUMO2/3, also inhibited bFGF action. Mechanistically, specificity protein 1 (Sp1), a major transcription factor that controls expression of lens-specific genes such as ß-crystallins, was positively regulated by SUMO1 but negatively regulated by SUMO2. SUMO2 was found to inhibit Sp1 functions through several mechanisms: sumoylating it at K683 to attenuate DNA binding, and at K16 to increase its turnover. SUMO2 also interfered with the interaction between Sp1 and the coactivator, p300, and recruited a repressor, Sp3 to ß-crystallin gene promoters, to negatively regulate their expression. Thus, stable SUMO1, but diminishing SUMO2/3, during lens development is necessary for normal lens differentiation. In support of this conclusion, SUMO1 and Sp1 formed complexes during early and later stages of lens development. In contrast, an interaction between SUMO2/3 and Sp1 was detected only during the initial lens vesicle stage. Together, our results establish distinct roles of different SUMO isoforms and demonstrate for the first time, to our knowledge, that Sp1 acts as a major transcription factor target for SUMO control of cell differentiation.


Assuntos
Diferenciação Celular/fisiologia , Células Epiteliais/fisiologia , Regulação da Expressão Gênica/fisiologia , Cristalino/crescimento & desenvolvimento , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Fator de Transcrição Sp1/metabolismo , Sumoilação/fisiologia , Animais , Western Blotting , Imunoprecipitação da Cromatina , Primers do DNA/genética , Ensaio de Desvio de Mobilidade Eletroforética , Fatores de Crescimento de Fibroblastos/metabolismo , Imuno-Histoquímica , Imunoprecipitação , Cristalino/citologia , Camundongos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 20(6): 1389-91, 2012 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-23257439

RESUMO

This study was aimed to explore the significance of the bone marrow biopsy for the diagnosis of multiple myeloma. Bone marrow smears and bone marrow biopsy originated from 279 cases of multiple myeloma were detected and compared in term of bone marrow hyperplasia, bone marrow plasma cell infiltration, proliferation mode, pathological changes in the bone marrow stroma and myelofibrosis. The results indicated that the levels of proliferation in bone marrow biopsy was significantly higher than that in bone marrow smears. Plasma cell proliferation mode in bone marrow biopsy was not completely consistent with the proportion of plasma cells in bone marrow smears. The myelofibrosis level displayed influence on the consistency of the proliferation between bone marrow smears and biopsies. It is concluded that as compared with bone marrow smears the bone marrow biopsy can more accurately reflect the levels of bone marrow hyperplasia and bone marrow plasma cell infiltration, proliferation mode and so on. Bone marrow biopsy is valuable for multiple myeloma diagnosis.


Assuntos
Biópsia/métodos , Exame de Medula Óssea/métodos , Medula Óssea/patologia , Mieloma Múltiplo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Int J Ophthalmol ; 5(5): 638-40, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23166878

RESUMO

AIM: To investigate the relationship between China's first Western-style eye hospital development and the prevention of blindness in China and determine the main factor influencing eye health today. METHODS: Data about eye health, blindness and cataract surgery rate of China from public website of World Health Organization (WHO), ORBIS International, Ministry of Health (MOH) of China, Pubmed center and Historical Archives of Zhongshan Ophthalmic Center (ZOC) were reviewed and analyzed. RESULTS: ZOC is China's first Western-style eye hospital. In 2012, the ORBIS Flying Eye Hospital has chosen ZOC once again as one of its destinations, 30 years after ORBIS expanded internationally to train eye care professionals and treat underserved patients in developing countries in 1982. During the past 30 years, cataract surgery rate and public awareness of blindness prevention were improved greatly in China, in which ZOC plays a very important role. CONCLUSION: ZOC, as China's first Western-style eye hospital, has improved in the prevention of blindness. Eye health has become everyone's responsibility.

16.
Chin Med J (Engl) ; 124(12): 1784-9, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21740833

RESUMO

BACKGROUND: Pseudoaneurysms (PAs) are common vascular abnormalities predominantly arising from a disruption in the integrity of the arterial wall. The potential complications of PAs are usually unpredictable and carry high rates of morbidity and mortality. This paper presents our experience with various treatment strategies for PAs. METHODS: Fifty-four patients with 55 PAs were diagnosed by non-invasive imaging examination. The etiology of PAs included trauma (33/55), infection (5/55), iatrogenic (6/55), and idiopathic (11/55). Different procedures including ultrasound (US)-guided compression, endovascular treatment, and surgery were performed depending on the location of PAs, size of the sac and neck, and characteristics of the donor artery. The methods of endovascular treatment included embolization of parent artery, the PA sac, or implantation of a stent-graft. Follow-up was performed using US or CT and ranged from 1 day to 24 months (average 16.7 months). RESULTS: In all 54 patients, 3 patients with superficial PAs were treated by US-guided compression, while 44 patients with 45 PAs located in the head and neck (n = 20), viscera (n = 10) or extremities (n = 15) were treated by endovascular treatment. Nine patients with PAs located in the head and neck (n = 2) or extremities (n = 7) were treated by surgery. Among them, one patient underwent endovascular treatment combined with surgery and 1 was treated by surgery after unsuccessful US-guided compression. In the 3 patients treated with US-guided compression, 2 were successfully treated while the remaining patient required additional surgery. Primary technical success of endovascular management was 97.7% (43/44) and the cure rate was 95.5% (42/44). In the surgery group, 4 patients recovered well, 1 patient was cured by endovascular treatment combined with surgery, 2 cases underwent amputation, 1 patient died of multi-organ failure and 1 patient was paralysed. CONCLUSIONS: Minimally invasive interventional techniques are established treatment methods for PA with favorable success rates and minimal morbidity. The therapeutic options should be tailored to the location, size and rupture risk of PA, condition of the donor artery and existing comorbidity.


Assuntos
Falso Aneurisma/terapia , Adulto , Falso Aneurisma/diagnóstico , Falso Aneurisma/etiologia , Embolização Terapêutica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Zhonghua Yan Ke Za Zhi ; 47(4): 298-302, 2011 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-21612677

RESUMO

OBJECTIVE: To compare the amounts of intraocular lens (IOL) decentration and tilt, the anterior chamber depth (ACD) and the degree of posterior capsule opacification (PCO) using the Pentacam Scheimpflug System after cataract surgery between eyes with 1-piece acrylic IOL and 3-piece acrylic IOL. METHODS: It was a perspective study. Fifty-one patients with bilateral senile cataract had implantation of a 1-piece SA60AT IOL in one eye and a 3-piece MA60BM IOL in the contralateral eye. The amount of IOL decentration, tilt, the ACD, and the degree of PCO was measured using the Pentacam Scheimpflug System 1 day and 1, 6, 12 and 24 months postoperatively. RESULTS: There were no significant changes during the 24 m follow-up period in the decentration (0.37 ± 0.16, 0.36 ± 0.15, 0.36 ± 0.16, 0.37 ± 0.15, 0.38 ± 0.16), tilt (3.59 ± 0.91, 3.64 ± 0.92, 3.61 ± 0.90, 3.63 ± 0.90, 3.70 ± 0.89) or PCO (22.20 ± 3.99, 21.96 ± 4.00, 22.40 ± 4.03, 22.53 ± 4.00, 22.95 ± 3.87) in the 1-piece SA60AT group (F = 1.938, 0.785, 1.814; P > 0.05) or in the 3-piece MA60BM group (0.34 ± 0.14, 0.33 ± 0.14, 0.34 ± 0.14, 0.35 ± 0.14, 0.36 ± 0.14), (3.55 ± 0.90, 3.57 ± 0.92, 3.63 ± 0.88, 3.61 ± 0.88, 3.65 ± 0.89), (21.14 ± 3.88, 20.98 ± 3.87, 21.23 ± 3.83, 21.59 ± 3.82, 21.65 ± 3.87) (F = 1.004, 0.525, 1.963; P > 0.05). There was no significant difference between the two groups in IOL decentration (t = 0.802, 0.701, 0.588, 0.898, 0.631), tilt (t = 0.199, 0.337, 0.094, 0.121, 0.248) or PCO (t = 1.214, 1.119, 1.334, 1.082, 1.517) at any time points (P > 0.05). The ACD did not change after the surgery in the 1-piece group (3.90 ± 0.99, 3.88 ± 1.07, 3.91 ± 1.01, 3.90 ± 1.02, 3.92 ± 1.02) (F = 1.333, P > 0.05) but was significantly deeper in the 3-piece group (4.37 ± 1.02, 3.90 ± 0.98, 3.95 ± 0.99, 3.93 ± 0.96, 3.97 ± 0.99) (F = 92.757, P < 0.05) one day after the operation. The ACD was more shallow in the 1-piece SA60AT group than in the 3-piece MA60BM group at all time points. However, the difference was statistically significant only at 1 day after surgery (t = 102.944, P < 0.05). CONCLUSIONS: The degrees of IOL decentration, tilt, ACD and PCO in eyes with a 1-piece acrylic IOL with flexible haptics implanted in the capsular bag were similar to those in eyes with a 3-piece acrylic IOL with rigid PMMA haptics. But the 1-piece acrylic IOL provides a better stability than the 3-piece acrylic IOL in the early stage postoperatively.


Assuntos
Resinas Acrílicas/uso terapêutico , Cápsula do Cristalino/cirurgia , Implante de Lente Intraocular/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Lentes Intraoculares , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Resultado do Tratamento
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 19(1): 202-6, 2011 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-21362252

RESUMO

The aim of study was to explore the influence of the number of megakaryocytes in bone marrow smear and trephine biopsy on clinical outcome of idiopathic thrombocytopenic purpura (ITP). The clinical outcome of 115 patients with ITP was compared by different clinical subtype, number of blood platelet, number of megakaryocyte in bone marrow smear and trephine biopsy. The results showed that: (1) the clinical outcome of acute ITP was better than that of chronic ITP, the short clinical outcome of acute ITP and chronic ITP were 86.6% vs 60.4% respectively (p < 0.01), the long clinical outcome of them were 82.5% vs 68.9% respectively (p < 0.05); (2) different number of blood platelet at occurrence of diseases had no obviously influence on clinical outcome of patients with ITP; (3) all cases were subgrouped according to number of megakaryocyte in bone marrow smear, the number of megakaryocyte in bone marrow smear less than 7/4.5 cm(2) was defined as group I, the number of megakaryocyte between 7/4.5 cm(2) to 35/4.5 cm(2) was defined as group II, and the number of megakaryocyte in bone marrow smear greater than 35/4.5 cm(2) was defined as group III. The effective rates of 3 groups in short term treatment were 53.3%, 73.8% and 86.2% respectively, and there were statistical difference between these 3 groups (p < 0.01), the effective rates of these 3 groups in long term treatment were 42.8%, 84.6% and 85.5% respectively, and there was no statistical different between group II and group III (p > 0.05), but both had statistical difference, as compared with group I (p < 0.01). (4) all cases were subgrouped by the number of megakaryocyte in trephine biopsy on time of disease occurrence, the number of megakaryocyte in bone marrow smear less than 8/mm(2) was defined as group I, the number of megakaryocyte between 8/mm(2) to 15/mm(2) was defined as group II, the number of megakaryocyte greater than 15/mm(2) was defined as group III. The effective rate of these 3 groups in short term treatment were 53.8%, 85.0% and 90.3% respectively, group II and III had no statistical difference each other (p > 0.05), but both groups had statistical difference as compared with group I (p < 0.01). Effective rate of these 3 groups in long term treatment were 33.3%, 63.1% and 87.9% respectively, and there were statistical difference between them (p < 0.01). (5) the number of blood platelet at time of disease occurrence was not related to number of megakaryocyte in bone marrow smear and in trephine biopsy section(r = 0.31, p > 0.05; r = 0.41, p > 0.05). The number of megakaryocyte in bone marrow smear had positive correlation to that in trephine biopsy slides (r = 0.52, p < 0.01). In case to use single factor Logistic regression, the results showed that number of megakaryocyte in bone marrow smear and trephine biopsy had obvious influence on long term treatment of ITP. It is concluded that the number of megakaryocyte in trephine biopsy can be used as a available supplement method for bone smear, and can forecast the therapeutic effect of patients with ITP.


Assuntos
Células da Medula Óssea/patologia , Megacariócitos/patologia , Púrpura Trombocitopênica Idiopática/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Células da Medula Óssea/citologia , Contagem de Células , Criança , Feminino , Humanos , Masculino , Megacariócitos/citologia , Pessoa de Meia-Idade , Adulto Jovem
19.
J Vasc Interv Radiol ; 22(4): 525-8, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21354822

RESUMO

Percutaneous vertebroplasty (PVP) has been used widely to treat pain caused by osteolytic spinal lesions, whereas vertebroplasty for osteoblastic spinal lesions is less known. The purpose of this study is to describe PVP as a highly effective miniinvasive procedure to treat painful osteoblastic metastatic spinal lesions. Four patients with painful osteoblastic metastatic spinal lesions were treated by PVP in the authors' department, and immediately relief of pain was achieved in all of them. The findings from this study may encourage more studies of PVP in palliative treatment of patients with osteoblastic lesions.


Assuntos
Osteoblastos/patologia , Dor/prevenção & controle , Neoplasias da Coluna Vertebral/terapia , Vertebroplastia/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoblastos/diagnóstico por imagem , Dor/etiologia , Medição da Dor , Cuidados Paliativos , Radiografia Intervencionista , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/secundário , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vertebroplastia/efeitos adversos
20.
Chin Med J (Engl) ; 123(18): 2562-7, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21034628

RESUMO

BACKGROUND: Dislocation of posterior chamber intraocular lens is one of the most common complications of intraocular lens implantation. Lens exchange is an effective solution to this unsatisfactory status. This study was conducted to analyze the possible predisposing factors for out-of-the-bag posterior chamber intraocular lens dislocation and to study the outcomes of lens exchange surgery. METHODS: Thirty-six consecutive patients (36 eyes) with out-of-the-bag intraocular lens dislocation who underwent posterior chamber intraocular lens exchange in Zhongshan Ophthalmic Center of Sun Yat-sen University (Guangdong, China) from January 2003 to October 2009 were included. A 6-month follow-up was completed. The causes for out-of-the-bag intraocular lens dislocation and visual outcomes of posterior chamber intraocular lens exchange were analyzed. The out-of-the-bag intraocular lens dislocation was diagnosed on the basis of the findings from slit-lamp microscope and B-ultrasound. The dislocated intraocular lens was explanted. Reimplantation of a new posterior chamber intraocular lens was performed in each case using standardized surgical procedures. RESULTS: In this study, a total of thirty-six consecutive patients (36 eyes) with out-of-the-bag intraocular lens dislocation underwent posterior chamber intraocular lens exchange surgery. Causes for out-of-the-bag intraocular lens dislocation included posterior capsule rupture during the initial cataract extraction procedure (23 eyes, 63.8%), trauma (5 eyes, 13.9%),neodymium-doped yttrium aluminium garnet (Nd:YAG) laser-induced dislocation (2 eyes, 5.6%), the status after vitrectomy (2 eyes, 5.6%) and unidentifiable etiology (4 eyes, 11.1%). Symptoms of these patients mainly included decrease in visual acuity (17 cases, 47.2%), blurred vision (16 cases, 44.4%), glare (1 case, 2.8%), diplopia (1 case, 2.8%), and halo (1 case, 2.8%). Intraocular lens dislocation into the posterior vitreous cavity (29 eyes, 80.5%), anterior chamber (1 eye, 2.8%) and anterior vitreous cavity (6 eyes, 16.7%) was found in this series. The foldable intraocular lenses (acrylic or silicone) were explanted from 27 eyes (75%) and rigid intraocular lenses (poly methyl methacrylate, PMMA) from 9 eyes (25%). The most common explanted intraocular lens material was single-piece acrylic (13 pieces, 36.1%), followed by 3-piece acrylic (9 pieces, 25%), single-piece PMMA (9 pieces, 25%), and 3-piece silicone (5 pieces, 13.9%). Uncorrected visual acuity postoperatively improved in 29 eyes (81%), unchanged in 4 eyes (11%), and worsened in 3 eyes (8%) in comparison to that before exchange operation (P = 0.006). Best corrected visual acuity tended to improve, but the improvement was not significant (P = 0.206). Complications related to lens exchange surgery were mainly intraocular lens redislocation (1 eye), retinal detachment (1 eye), vitreous hemorrhage (1 eye), and cystoid macular edema (1 eye). CONCLUSIONS: Out-of-the-bag intraocular lens dislocation was mainly caused by posterior capsule rupture during the initial cataract extraction procedure and the foldable lens was the most common dislocated intraocular lens. In most cases, posterior chamber intraocular lens exchange surgery could provide satisfied final visual outcomes.


Assuntos
Implante de Lente Intraocular/efeitos adversos , Subluxação do Cristalino/etiologia , Subluxação do Cristalino/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Adulto Jovem
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