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1.
World J Oncol ; 15(4): 695-710, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38993245

RESUMO

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors originating from the digestive system. Tertiary lymphoid structures (TLS), non-lymphoid tissues outside of the lymphoid organs, are closely connected to chronic inflammation and tumorigenesis. However, the detailed relationship between TLS and HCC prognosis remained unclear. In this study, we aimed to construct a TLS-related gene signature for predicting the prognosis of HCC patients. Methods: The Cancer Genome Atlas (TCGA) clinical data from 369 HCC tissues and 50 normal liver tissues were utilized to examine the differential expression of TLS-related genes. Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the prognostic model was constructed using the TCGA cohort and validated in the GSE14520 cohort and International Cancer Genome Consortium (ICGC) cohort. The Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves were employed to validate the predictive ability of the prognostic model. Furthermore, Cox regression analysis was applied to identify whether the TLS score could be employed as an independent prognosis factor. A nomogram was developed to predict the survival probability of HCC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for TLS-related genes. Genetic mutation analysis, the CIBERSORT algorithm, and single-sample gene set enrichment analysis (ssGSEA) were used to assess the tumor mutation landscape and immune infiltration. Finally, the role of the TLS score in HCC therapy was investigated. Results: Six genes were included in the construction of our prognostic model (CETP, DNASE1L3, PLAC8, SKAP1, C7, and VNN2), and we validated its accuracy. Survival analysis showed that patients in the high-TLS score group had a significantly better overall survival than those in the low-TLS score group. Univariate, multivariate Cox regression analysis and the establishment of a nomogram indicated that the TLS score could independently function as a potential prognostic marker. A significant association between TLS score and immunity was revealed by an analysis of gene alterations and immune cell infiltration. In addition, two subtypes of the TLS score could accurately predict the effectiveness of sorafenib, transcatheter arterial chemoembolization (TACE), and immunotherapy in HCC patients. Conclusion: In this research, we conducted and validated a prognostic model associated with TLS that may be helpful for predicting clinical outcomes and treatment responsiveness for HCC patients.

2.
Chemosphere ; 356: 141962, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38614399

RESUMO

The impact of shale gas extraction on surrounding environmental media remains unclear. In this study, the current state of contamination by polycyclic aromatic hydrocarbons (PAHs), which are high-frequency contaminants of shale gas, was investigated in the soil surrounding emerging shale gas development sites. The source analysis of PAHs was conducted in the soils of shale gas extraction sites using positive matrix factorization (PMF). The health risk assessment (HRA) was calculated for ingestion, dermal contact, and inhalation exposures, and the priority sources of PAHs in the soil were jointly identified by PMF and HRA to refine the contribution level of different individual PAHs to the carcinogenic risk. The results showed that both Sichuan and Chongqing mining site soils were contaminated to different degrees. Shale gas extraction has an impact on the surrounding soil, and the highest contributing source of PAHs in the mining site soil of Sichuan was anthropogenic activity, accounting for 31.6%, whereas that in the mining site soil of Chongqing was biomass combustion and mixed automobile combustion, accounting for 35.9%. At the two mining sites in Sichuan and Chongqing, none of the three exposure pathways (ingestion, dermal contact, and inhalation) posed a carcinogenic risk to children, whereas the dermal exposure pathway posed a carcinogenic risk to adults. Health risk assessments based on specific source assignments indicate that when managing soil pollution, the control of fossil fuel combustion and vehicular emissions should be prioritized.


Assuntos
Monitoramento Ambiental , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Solo , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes do Solo/análise , Medição de Risco , Humanos , Monitoramento Ambiental/métodos , Solo/química , China , Mineração , Gás Natural/análise
3.
Ecotoxicol Environ Saf ; 274: 116203, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38479313

RESUMO

PCDD/Fs are dioxins produced by waste incineration and pose risks to human health. We aimed to detail the health risks of airborne and soil PCDD/Fs near a municipal solid-waste incinerator (MSWI) for the surrounding population and develop a new model that improves upon existing methods. Thus, we conducted field sampling and then investigated a MSWI in the Pearl River Delta (2016-2018). Our results showed that the carcinogenic and non-carcinogenic risk values of PCDD/Fs exposed to residents in nearby areas were acceptable, with hazard index (HI) values lower than 1.0 and a total carcinogenic risk lower than 1.0E-6. Notably, the results raised concerns regarding higher non-carcinogenic risks in children than in adults. Comparative analysis of the frequency accumulation diagram, accumulated probability risk, and the absolute value of error (δ) between the 95% confidence interval (CI) and the 90% CI of the Monte Carlo stochastic simulation-triangular fuzzy number (MCSS-TFN) and the MCSS model, respectively, demonstrated that the MCSS-TFN exhibited less uncertainty than the MCSS model, regardless of the health risk value of PCDD/Fs in ambient air or in soil. This observation underscores the superiority of the MCSS-TFN model over other models in assessing the health risks associated with PCDD/Fs in situations with limited data. Our new method overcomes the limited dataset size and high uncertainty in assessing the health risks of dioxin substances, providing a more comprehensive understanding of their associated health risks than MCSS models.


Assuntos
Poluentes Atmosféricos , Dioxinas , Dibenzodioxinas Policloradas , Adulto , Criança , Humanos , Resíduos Sólidos , Monitoramento Ambiental/métodos , Dibenzodioxinas Policloradas/toxicidade , Dibenzodioxinas Policloradas/análise , Dibenzofuranos , Poluentes Atmosféricos/análise , Incineração , Dioxinas/toxicidade , Medição de Risco , Dibenzofuranos Policlorados/análise , Solo
4.
BMC Med Genomics ; 16(1): 189, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37592341

RESUMO

BACKGROUND: Wilms tumour (WT) is a mixed type of embryonal tumour that usually occurs in early childhood. However, our knowledge of the pathogenesis or progression mechanism of WT is inadequate, and there is a scarcity of beneficial therapeutic strategies. METHODS: High-throughput RNA sequencing was employed in this study to identify differentially expressed genes (DEGs) in clinical tumor samples and matching normal tissues. The STRING database was utilized to build a protein-protein interaction (PPI) network, and the Cytohubba method was used to identify the top 10 highly related HUB genes. Then, the key genes were further screened by univariate COX survival analysis. Subsequently, the XCELL algorithm was used to evaluate the tumour immune infiltration. RT-PCR, WB, and IF were used to verify the expression level of key genes in clinical tissues and tumour cell lines. Finally, the function of the key gene was further verified by loss-of-function experiments. RESULTS: We initially screened 1612 DEGs, of which 1030 were up-regulated and 582 were down-regulated. The GO and KEGG enrichment analysis suggested these genes were associated with 'cell cycle', 'DNA replication'. Subsequently, we identified 10 key HUB genes, among them CCNB1 was strongly related to WT patients' overall survival. Multiple survival analyses showed that CCNB1 was an independent indicator of WT prognosis. Thus, we constructed a nomogram of CCNB1 combined with other clinical indicators. Single gene GSEA and immune infiltration analysis revealed that CCNB1 was associated with the degree of infiltration or activation status of multiple immune cells. TIDE analysis indicated that this gene was correlated with multiple key immune checkpoint molecules and TIDE scores. Finally, we validated the differential expression level of CCNB1 in an external gene set, the pan-cancer, clinical samples, and cell lines. CCNB1 silencing significantly inhibited the proliferation, migration, and invasive capabilities of WIT-49 cells, also, promoted apoptosis, and in turn induced G2 phase cell cycle arrest in loss-of-function assays. CONCLUSION: Our study suggests that CCNB1 is closely related to WT progression and prognosis, and serves as a potential target.


Assuntos
Neoplasias Renais , Tumor de Wilms , Humanos , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células , Ciclina B1/genética , Neoplasias Renais/genética , Prognóstico , Tumor de Wilms/genética
5.
Int J Ophthalmol ; 16(2): 215-223, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36816206

RESUMO

AIM: To identify the risk factors for postoperative proliferative vitreoretinopathy (PVR) in patients with primary rhegmatogenous retinal detachment (RRD) and develop a nomogram for predicting postoperative PVR-free probability. METHODS: A total of 741 patients (741 eyes) diagnosed with primary RRD who underwent first surgery in the same hospital were retrospectively reviewed and randomly assigned with 521 to the training set and 220 to the validation set. Univariate and multivariate logistic regression analyses were performed in the training cohort to determine risk factors to construct a nomogram for predicting the 3-, 4-, 5-, and 6-month postoperative PVR-free probabilities. Nomogram performance was estimated by the concordance index (C-index), calibration plot, and the area receiver operating characteristic (ROC) curve. RESULTS: A nomogram was constructed based on the preoperative PVR, silicone oil tamponade time (SOTT), photocoagulation energy (PE), retinal tear size (RTS), and hypertension. In the training set, the C-index of the nomogram was 0.896, 0.936, 0.961, and 0.972 at 3, 4, 5, and 6mo, respectively. The C-index values in the validation set were 0.860, 0.936, 0.951, and 0.965 at 3, 4, 5, and 6mo, respectively. Decision-curve analysis indicated that only the 4-, 5-, and 6-month nomograms had significant net benefits over a large threshold probabilities interval. CONCLUSION: Preoperative PVR, SOTT, PE, RTS, and hypertension are significant risk factors for postoperative PVR formation in patients with primary RRD. The proposed nomogram can effectively predict the 4-, 5-, and 6-month PVR-free probabilities after surgery and assist in making clinical decisions during follow-up.

6.
Front Oncol ; 12: 1060574, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505780

RESUMO

Hepatocellular carcinoma (HCC) remains one of the most fatal malignancies with high morbidity and mortality rates in the world, whose molecular pathogenesis is incompletely understood. As an RNA-binding protein participating in the processing and modification of RNA, KIAA1429 has been proved to be implicated in the pathogenesis of multiple cancers. However, how KIAA1429 functions in alternative splicing is not fully reported. In the current study, multi-omics sequencing data were used to analyze and decipher the molecular functions and the underlying mechanisms of KIAA1429 in HCC samples. RNA sequencing data (RNA-seq) analysis demonstrated that in HCCLM3 cells, alternative splicing (AS) profiles were mediated by KIAA1429. Regulated AS genes (RASGs) by KIAA1429 were enriched in cell cycle and apoptosis-associated pathways. Furthermore, by integrating the RNA immunoprecipitation and sequencing data (RIP-seq) of KIAA1429, we found that KIAA1429-bound transcripts were highly overlapping with RASGs, indicating that KIAA1429 could globally regulate the alternative splicing perhaps by binding to their transcripts in HCCLM3 cells. The overlapping RASGs were also clustered in cell cycle and apoptosis-associated pathways. In particular, we validated the regulated AS events of three genes using clinical specimens from HCC patients, including the exon 6 of BPTF gene and a marker gene of HCC. In summary, our results shed light on the regulatory functions of KIAA1429 in the splicing process of pre-mRNA and provide theoretical basis for the targeted therapy of HCC.

7.
Sensors (Basel) ; 22(3)2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35161761

RESUMO

Gas sensing performance characterization systems are essential for the research and development of gas sensing materials and devices. Although existing systems are almost completely automatically operated, the accuracies of gas concentration control and of pressure control and the ability to simultaneously detect different sensor signals still require improvement. In this study, a high-precision gas sensing material characterization system is developed based on vacuum technology, with the objective of enabling the precise and simultaneous measurement of electrical responses. Because of the implementation of vacuum technology, the gas concentration control accuracy is improved more than 1600 times, whereas the pressure of the test ambient condition can be precisely adjusted between vacuum and 1.2 bar. The vacuum-assisted gas-exchanging mechanism also enables the sensor response time to be determined more accurately. The system is capable of performing sensitivity, selectivity, and stability tests and can control the ambient relative humidity in a precise manner. More importantly, the levels of performance of three different optical signal measurement set-ups were investigated and compared in terms of detection range, linearity, noise, and response time, based on which of their scopes of application were proposed. Finally, single-period and cyclical tests were performed to examine the ability of the system to detect optical and electrical responses simultaneously, both at a single wavelength and in a spectral region.

8.
Acta Ophthalmol ; 100(4): e1024-e1030, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34403213

RESUMO

PURPOSE: To report the clinical outcomes and evaluate the efficacy of a novel bubble ultra-wide field viewing system for vitreoretinal surgery. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: One hundred and fifty-one eyes of 146 consecutive patients with proliferative diabetic retinopathy (PDR), vitreous haemorrhage originating from retinal vein occlusion (VH-RVO), epiretinal membrane (EM), macular hole (MH) or retinal detachment (RD) who underwent vitreoretinal surgery using the bubble ultra-wide field viewing system were included. METHODS: A standard phacoemulsification was performed on each patient. Core humour and mid-peripheral vitreous humour were removed using a planoconcave lens. A suitably sized bubble was infused to attach to the posterior capsule or the anterior chamber depending on the integrity of the posterior capsule. The planoconcave lens and the air bubble formed the wide-angle viewing system, through which peripheral vitrectomy was performed. MAIN OUTCOME MEASURES: Range of applications, field of view, model validation and complications were recorded. RESULTS: The new ultra-wide field viewing system was successfully applied in all eyes, including 34 with PDR, 28 VH-RVO, 28 EM, 25 MH and 36 RD. Peripheral vitrectomy, local or panretinal laser photocoagulation, and removal of the peripheral proliferative membrane were successfully performed while viewing through this system. Maximum peripheral retinal area observable during the procedure was positively correlated with pupil diameter. Model analysis results showed that when the pupil diameter was 6 mm, the maximum field of view was approximately 128.1- 148.0 degrees with this system. Of 142 eyes, the main intraoperative complication was iatrogenic retinal breaks (IRBs) in 8 eyes (5.3%) and posterior capsule injury by vitreous cutter during bubble removal in 6 eyes (4.2%). The postsurgery mean best-corrected visual acuity (BCVA) (0.48 ± 0.39 logMAR) was significantly improved compared with the preoperative mean BCVA (1.60 ± 1.08 logMAR, p < 0.001). No incidents of postoperative choroidal detachment, secondary glaucoma or endophthalmitis were recorded. CONCLUSIONS: For patients with lens excision or absence, vitreoretinal surgery can be successfully performed using the novel viewing system described here. The system is a safe, convenient and economical ultra-wide field viewing system with a wide range of applications.


Assuntos
Retinopatia Diabética , Membrana Epirretiniana , Descolamento Retiniano , Cirurgia Vitreorretiniana , Retinopatia Diabética/complicações , Membrana Epirretiniana/complicações , Membrana Epirretiniana/diagnóstico , Membrana Epirretiniana/cirurgia , Humanos , Complicações Pós-Operatórias/cirurgia , Estudos Prospectivos , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual , Vitrectomia/métodos , Cirurgia Vitreorretiniana/efeitos adversos
9.
Ying Yong Sheng Tai Xue Bao ; 32(12): 4370-4380, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34951278

RESUMO

Mechanisms underlying leaf photosynthetic acclimation in winter wheat under elevation of CO2 concentration ([CO2]) remain unclear. The aim of the study was to investigate the effects of source-sink variation on photosynthetic acclimation induced by drought under elevated [CO2]. A winter wheat (Triticum aestivum L. 'Zhengmai 9023') pot experiment was conducted in open top climate chambers with [CO2] of 400µmol·mol-1 or 600 µmol·mol-1 and soil water content at 80%±5% or 55%±5% of field capacity. The parameters of chlorophyll fluorescence, electron transport rate, photosynthetic curve, leaf nitrogen content, and grain yield were measured at the elongation and heading stages. Under drought condition, leaf PSⅡ photochemical efficiency was not affected by elevated [CO2], but the maximum electron transport rate and the ratio of electron partitioned to carboxylation reaction in Calvin cycle was increased at the elongation stage, and thus the Rubisco carboxylation rate and maximum photosynthetic rate were increased. Although the maximum electron transportation rate and partitioning ratio of electron to carboxylation reaction in Calvin cycle remained high at the heading stage, the PSⅡ photochemical efficiency, Rubisco carboxylation rate, and triose phosphate utilization rate were decreased by elevated [CO2], which consequently reduced the maximum photosynthetic rate for plant under drought stress. Under drought condition, elevated [CO2] increased wheat tiller biomass, kernel number, and kernel weight per ear, but decreased infertile kernel number, resulting in an overall increase in grain weight. In conclusion, the elevated [CO2]-induced increase in wheat grain yield per tiller under drought condition was mainly caused by enhanced photosynthetic performance at the elongation stage. The photosynthetic acclimation in source leaves during the heading stage under elevated [CO2] was mainly attributed to the reduction in PSⅡ photochemical efficiency and triose phosphate utilization rate, but not to the maximum electron transportation rate, ratio of electron partitioned to carboxylation in Calvin cycle or sink leaf strength.


Assuntos
Secas , Triticum , Aclimatação , Dióxido de Carbono , Fotossíntese , Folhas de Planta
10.
Otol Neurotol ; 41(9): 1280-1287, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32925861

RESUMO

OBJECTIVE: To test the feasibility of image-guided Baha Attract implant surgery with mixed reality (MR) in the form of the HoloLens to visualize critical structures and facilitate precise Baha implant placement. METHODS: A cadaveric case study of bilateral Baha Attract implant approaches was conducted using Star Atlas MR three-dimensional (3D) medical interaction system guidance at the Otolaryngology Department of PUMCH, Beijing, China. The accuracy of visual surface registration was determined by the target registration error (TRE) between the predefined points on the preoperative 3D holographic Baha Attract implant model and the postoperatively reconstructed 3D model. RESULTS: Bilateral Baha Attract implantation was completed successfully for all four cadaveric heads using the Star Atlas MR 3D medical interaction system with the HoloLens. The preoperative 3D digital model characteristics (including bone quality and thickness and avoidance of cranial vessels, air cells, and cranial sutures) corresponded well with the 3D model of the actual implantation reconstructed postoperatively. The median TRE of our system was 2.97 mm (ranging from 1.98 to 4.58 mm) in terms of distance and 2.76 degrees (ranging from 0.59 to 6.4 degrees) in terms of angle. CONCLUSIONS: Applying MR technology in the form of the HoloLens in Baha Attract implant surgery is feasible and could improve the accuracy of the surgery. The described MR system for Baha Attract implantation has the potential to improve the surgeon's confidence, as well as the surgical safety, efficiency, and precision.


Assuntos
Realidade Aumentada , Cirurgia Assistida por Computador , China , Humanos , Próteses e Implantes , Tecnologia
11.
Aging (Albany NY) ; 12(6): 5479-5499, 2020 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-32213661

RESUMO

It is crucial to grasp the characteristics of tumour immune microenvironment to improve effects of immunotherapy. In this study, the immune and stromal scores of 371 cases were calculated for quantitative analysis of immune and stromal cell infiltration in the tumour microenvironment of hepatocellular carcinoma (HCC). The weighted gene co-expression network analysis and protein-protein interaction network were analysed to identify immune microenvironment-related genes. The results showed that patients with high immune scores had a higher 4-year recurrence-free rate. TP53, CTNNB1, and AXIN1 mutations significantly varied with immune scores. In immune score-related modules analysis, Kyoto encyclopaedia of genes and genomes pathways and gene ontology terms were closely related to immune processes, tumorigenesis, and metastasis. Twelve new immune microenvironment-related genes were identified and had significantly positive correlations with seven immune checkpoint genes. In prognostic analysis, eleven immune microenvironment-related genes exhibited high expression, nine of which were validated in the GSE62232 dataset and were significantly associated with a good prognosis. Our findings suggest that calculating immune score and stromal score could help to determine tumour purity and immune cell infiltration in the tumour microenvironment. Nine immune microenvironment-related genes identified in this study had potential as prognostic markers for HCC.


Assuntos
Biomarcadores Tumorais/imunologia , Carcinoma Hepatocelular/imunologia , Perfilação da Expressão Gênica/métodos , Neoplasias Hepáticas/imunologia , Fígado/citologia , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/imunologia , Prognóstico , Mapas de Interação de Proteínas , Células Estromais , Microambiente Tumoral/genética
12.
Onco Targets Ther ; 11: 7947-7953, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30519036

RESUMO

BACKGROUND: The survival outcomes between supracricoid partial laryngectomy (SCPL) and total laryngectomy (TL) were compared in the groups of matched-pair patients with T3 laryngeal squamous cell carcinoma (LSCC). METHODS: Patients with T3 LSCC were matched based on prognostic factors. The Kaplan-Meier curve and the Cox proportional hazards model were used for analysis on survival. RESULTS: A total of 212 patients with T3 LSCC were included after matching (106 underwent SCPL and 106 underwent TL). Multivariable analysis showed no differences in overall survival (hazard risk [HR]=1.15; 95% CI: 0.79-1.67; P=0.47), disease-specific survival (HR=1.11; 95% CI: 0.69-1.80; P=0.66), and recurrence-free survival (HR=1.07; 95% CI: 0.68-1.68; P=0.77) between the SCPL group and TL group. CONCLUSION: SCPL provides reliable therapeutic outcomes and can be used to avoid a TL surgery in some patients with advanced primary laryngeal cancer.

13.
Cell Physiol Biochem ; 51(1): 301-314, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30453302

RESUMO

BACKGROUND/AIMS: This study aims to examine the effect of long noncoding RNA HOST2 (LncRNA HOST2) on epithelial-mesenchymal transition (EMT), proliferation, invasion and migration of hepatocellular carcinoma (HCC) cells via activation of the JAK2-STAT3 signaling pathway. METHODS: HCC and para-cancerous tissues were collected from 136 HCC patients. Immunohistochemistry was used to detect the expression of JAK2 and STAT3. HCC SMMC7721 cells were grouped into blank, negative control (NC), HOST2 mimic and HOST2 inhibitor groups. The mRNA and protein expression levels of HOST2, JAK2, STAT3, E-cadherin, vimentin, Snail, Slug, Twist and Zeb1 in tissues and cells were determined by reverse transcription -quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. An MTT assay, scratch test and Transwell assay were applied to measure cell proliferation, migration and invasion, respectively. RESULTS: The levels of JAK2, STAT3 and vimentin were higher in HCC tissues, while the expression of E-cadherin was lower in HCC tissues compared with para-cancerous tissues. The silencing of HOST2 significantly decreased cell proliferation, migration and invasion, reduced the levels of HOST2, JAK2, STAT3 and vimentin, and elevated the expression of E-cadherin. HOST2 silencing also decreased the levels of Snail, Slug and Twist but increased the level of Zeb1 protein, while the opposite findings were observed in the HOST2 mimic group. CONCLUSION: These results reveal a possible mechanism in HCC in which LncRNA HOST2 may increase EMT and enhance proliferation, invasion and metastasis of HCC cells via activation of the JAK2-STAT3 signaling pathway.


Assuntos
Proliferação de Células , Transição Epitelial-Mesenquimal , Janus Quinase 2/metabolismo , RNA Longo não Codificante/metabolismo , Fator de Transcrição STAT3/metabolismo , Adulto , Idoso , Caderinas/genética , Caderinas/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Feminino , Humanos , Janus Quinase 2/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Fator de Transcrição STAT3/genética , Transdução de Sinais , Vimentina/genética , Vimentina/metabolismo
14.
Biomed Pharmacother ; 97: 809-817, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29112934

RESUMO

OBJECTIVE: To explore the core mechanism of long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) in the regulation of multidrug resistance of pancreatic cancer cells. METHODS: mRNA levels of GAS5, miR-181c-5p and Hippo pathway related genes were detected by quantitative real-time PCR (qRT-PCR). Protein levels of MDR-1, MST1, YAP and TAZ were measured by western blot. Cell viability was detected by MTT assay. The combination between GAS5 and miR-181c-5p was confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assay. We also established pancreatic cancer-bearing mice model and analyzed tumor volumes. RESULTS: Our data showed GAS5 expression was significantly down-regulated, miR-181c-5p expression was significantly up-regulated in pancreatic cancer cells. Besides, Overexpresson of GAS5 obviously inhibited cell viability, while GAS5 knockdown showed the opposite outcome. Additionally, we also found that GAS5 negatively regulated miR-181c-5p, and miR-181c-5p dramatically promoted pancreatic cancer cell chemoresistance through inactivating the Hippo signaling. GAS5 regulated chemoresistance and Hippo pathway of pancreatic cancer cells via miR-181c-5p/Hippo. Finally, we confirmed that overexpression of GAS5 inhibited tumor growth in pancreatic cancer-bearing mice model. CONCLUSION: GAS5 regualtes Hippo signaling pathway via miR-181c-5p to antagonize the development of multidrug resistance in pancreatic cancer cells.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , Neoplasias Pancreáticas/genética , RNA Longo não Codificante/genética , Animais , Western Blotting , Linhagem Celular Tumoral , Sobrevivência Celular , Regulação para Baixo , Resistência a Múltiplos Medicamentos , Feminino , Regulação Neoplásica da Expressão Gênica , Via de Sinalização Hippo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/patologia , Proteínas Serina-Treonina Quinases/genética , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Cell Biosci ; 7: 66, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29225772

RESUMO

BACKGROUND: Long non-coding RNA growth arrest-specific transcript 5 (lncRNA GAS5) is a well-known tumor suppressor in the pathogenesis of a variety of human cancers. The precise role of GAS5 in pancreatic cancer (PC) progression is currently unknown, so the aim of this study was to explore the functional participation of GAS5 in PC metastasis. METHODS: The expression changes of GAS5, miR-32-5p and PTEN in human PC specimens and cell lines were compared by means of molecular biology methods. Transfection of the recombinant plasmid was applied to modulate the expression levels of the target genes. RIP and RNA pull-down assays were designed to investigate the interaction between GAS5 and miR-32-5p. The effect of GAS5 and miR-32-5p on PC progression was assessed with cell proliferation, migration, invasion and apoptosis in vitro. RESULTS: GAS5 and PTEN protein were decreased in human PC tissues and cells, but miR-32-5p was increased. GAS5 induction greatly inhibited the proliferation, migration and invasion of PC cells PANC-1 and BxPC-3 in vitro and simultaneously induced cell apoptosis. Moreover, GAS5 positively regulated the expression of PTEN through miR-32-5p. Furthermore, GAS5 suppressed the proliferation, migration and invasion of PC cells through regulating miR-32-5p/PTEN axis. Additionally, this finding was further supported by the results of in vivo experiments. CONCLUSION: GAS5 could positively regulate PTEN-induced tumor-suppressor pathway via miR-32-5p, thereby suppressing PC metastasis.

16.
Yi Chuan ; 39(3): 250-262, 2017 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-28420621

RESUMO

Platinum-based chemotherapy is an important treatment for non-small cell lung cancer. However, the effectiveness of the treatment varies among the patients. We investigated the association between DNA polymorphisms of the autophagy pathway and responses of such treatment among 1004 Chinese patients. Ninety-nine SNPs located on 13 genes of the autophagy pathway were genotyped and assessed for their association with clinical benefit, progression-free survival (PFS) and overall survival (OS). The results showed that rs7953348 (G>A) (P=0.017, OR: 0.67, 95%CI: 0.49-0.93) and rs12303764 (A>C) (P=0.009, OR: 0.63, 95%CI: 0.45-0.89) at the ULK1 gene, and rs17742719 (C>A) (P=0.002, OR: 1.83, 95%CI: 1.26-2.66), rs8003279 (A>G) (P=0.006, OR: 1.65, 95%CI: 1.16~2.35) and rs1009647 (G>A) (P=0.002, OR: 1.70, 95%CI: 1.22-2.37) at the ATG14 gene were associated with clinical benefit. Polymorphisms at rs7955890 (G>A) (P=0.004, HR: 0.63; 95%CI: 0.46-0.86) and rs17032060 (G>A) (P=0.006, HR: 0.65, 95%CI: 0.48-0.88) at the DRAM gene, and rs13082005 (G>A) (P=0.012, HR: 1.27, 95%CI: 1.05-1.53) at the ATG3 gene were significantly associated with PFS. We also found that rs7953348 (G>A) (P=0.011, HR: 0.74, 95%CI: 0.58-0.93) at the ULK1 gene and rs1864183 (G>A) (P=0.016, HR: 0.42, 95%CI: 0.21-0.85) at the ATG10 gene were associated with OS. Thus, the study demonstrated that the autophagy pathway might play important role(s) in platinum-based chemotherapy. DNA polymorphisms in its component genes can potentially be predictors for clinical responses of platinum-based chemotherapy among the patients with non-small lung cancer.


Assuntos
Autofagia/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Platina/uso terapêutico , Polimorfismo Genético/genética , Adulto , Idoso , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Proteínas Relacionadas à Autofagia/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Feminino , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Enzimas de Conjugação de Ubiquitina/genética , Proteínas de Transporte Vesicular/genética
17.
Int J Clin Exp Pathol ; 10(9): 10102-10111, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-31966901

RESUMO

BACKGROUND: Thyroglossal duct carcinoma (TDCa) is a rare malignancy. Thus, we summarized the clinical characteristics of TDCa to explore the strategy of diagnosis, surgical treatment, and prognosis of patients with papillary TDCa. CASE PRESENTATION: A retrospective study was conducted about the medical records of cases with TDCa. General information including the diagnosis, surgical treatment, and prognosis of patients were obtained and analyzed. A total of 480 patients with thyroglossal duct anomalies were treated in our hospital during 1981 to 2011. Nine patients were identified as papillary TDCa and Sistrunk procedure was performed in these patients. Total thyroidectomy and selected neck dissection were performed in 3 TDCa patients with additional multiple thyroid nodules at presentation, of whom one was diagnosed as papillary thyroid carcinoma and another was found to have lymph node metastases. With a median follow-up of 119 months, all patients were alive with no recurrences or metastases. CONCLUSIONS: Although the incidence of TDCa is very low, early diagnosis and surgical operation of TDCa should be performed as soon as possible. Besides, the pathological examination is the only way to confirm the diagnosis, and surgery, especially Sistrunk's procedure, is the prior choice of the treatments. In the presence of thyroid lesions or cervical lymphadenopathy, total thyroidectomy and neck dissection should be considered.

18.
Head Neck ; 38 Suppl 1: E1562-7, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26929189

RESUMO

BACKGROUND: Reconstruction of the internal carotid artery (ICA) is an operative challenge for lesions involving the lateral skull base because of excessive blood loss, intraoperative cranial nerve injury, and difficulties in cerebral protection. METHODS: Between January 2010 and October 2014, 9 patients with vascular lesions at the lateral skull base were treated with a "pre-reconstruction" technique, which means reconstruction of the ICA in advance of excising the lesions. RESULTS: All operations were technically successful with no mortality or strokes. The mean blood loss was 921 ± 210 mL. The mean total clamping time was 18 ± 5 minutes. Among the 5 patients without invasion of specific cranial nerves, no long-term sequelae occurred during the follow-up period ranging from 11 to 54 months. CONCLUSION: With less blood loss, slighter cranial nerve injuries, and shorter clamping time, the "pre-reconstruction" technique was safe and effective for the treatment of vascular lesions at the lateral skull base. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1562-E1567, 2016.


Assuntos
Artéria Carótida Interna/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Base do Crânio/cirurgia , Adolescente , Adulto , Perda Sanguínea Cirúrgica , Artéria Carótida Interna/patologia , Traumatismos dos Nervos Cranianos/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço , Base do Crânio/patologia , Adulto Jovem
19.
Int J Neurosci ; 126(11): 989-95, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26514341

RESUMO

AIMS: To assess the effectiveness of delayed surgery and follow-up observation in managing severe Bell's palsy after two months of onset. METHODS: Forty-one Bell's palsy patients with severe facial paralysis were treated after two months of onset. Eighteen patients in group I underwent decompression operations between two and three months after onset, and eight patients in group II underwent surgery after three months of onset; 15 patients in group III were managed with follow-up observation. All patients were followed up at the end of 3rd, 6th and 12th months, and surgical outcomes were compared with follow-up observations using House-Brackmann score and Facial Clinimetric Evaluation (FaCE) scale. RESULTS: Between groups I and III, the difference in the proportion of the patients with fair or poor recoveries was statistically significant (p < 0.05) at the three-month follow-up visit. There was no significant difference in the distribution of complete, fair or poor recoveries at the 12-month follow-up visits among the three groups (p < 0.05). The total FaCE score and five individual domains were significantly improved at the end of the follow-up period in groups I and III (p < 0.05). However, in group I, the lacrimal control scores were significantly decreased at the end of the follow-up period compared to scores before surgery (p < 0.05). After surgery, four patients had sensorineural hearing loss, three patients had tinnitus and no patients had vertigo. CONCLUSION: Patients with severe Bell's palsy after two months of onset would not benefit from delayed decompression surgery.


Assuntos
Paralisia de Bell/cirurgia , Descompressão Cirúrgica/métodos , Avaliação de Resultados em Cuidados de Saúde , Adulto , Descompressão Cirúrgica/normas , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem
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