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1.
Cancer Res ; 79(19): 4951-4964, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31409639

RESUMO

Lysyl oxidase-like 2 (LOXL2), a copper-dependent enzyme of the lysyl oxidase family and its nonsecreted, catalytically dead spliced isoform L2Δ13, enhance cell migration and invasion, stimulate filopodia formation, modulate the expression of cytoskeletal genes, and promote tumor development and metastasis in vivo. We previously showed that LOXL2 reorganizes the actin cytoskeleton in esophageal squamous cell carcinoma (ESCC) cells, however, the underlying molecular mechanisms were not identified. Here, using interactome analysis, we identified ezrin (EZR), fascin (FSCN1), heat shock protein beta-1 (HSPB1), and tropomodulin-3 (TMOD3) as actin-binding proteins that associate with cytoplasmic LOXL2, as well as with its L2Δ13 variant. High levels of LOXL2 and L2Δ13 and their cytoskeletal partners correlated with poor clinical outcome in patients with ESCC. To better understand the significance of these interactions, we focused on the interaction of LOXL2 with ezrin. Phosphorylation of ezrin at T567 was greatly reduced following depletion of LOXL2 and was enhanced following LOXL2/L2Δ13 reexpression. Furthermore, LOXL2 depletion inhibited the ability of ezrin to promote tumor progression. These results suggest that LOXL2-induced ezrin phosphorylation, which also requires PKCα, is critical for LOXL2-induced cytoskeletal reorganization that subsequently promotes tumor cell invasion and metastasis in ESCC. In summary, we have characterized a novel molecular mechanism that mediates, in part, the protumorigenic activity of LOXL2. These findings may enable the future development of therapeutic agents targeting cytoplasmic LOXL2. SIGNIFICANCE: LOXL2 and its spliced isoform L2Δ13 promote cytoskeletal reorganization and invasion of esophageal cancer cells by interacting with cytoplasmic actin-binding proteins such as ezrin.

2.
Brain Res ; 1720: 146304, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31233712

RESUMO

Lipocalin 2 (LCN2) is a member of the lipocalin family. Elevated expression of LCN2 has been observed in many human tumors, suggesting it might be a potential biomarker and/or therapeutic target in malignancies. In this study, we aimed to explore LCN2 interacting proteins through bioinformatics, as well as their biological functions. Protein-protein interaction networks (PPIN) were constructed using LCN2 and its interacting proteins as the core node. These PPINs were scale free biological networks in which LCN2 and its interacting proteins could connect or cross-talk with at least one partner protein. Both functional and KEGG pathway enrichment analyses identified the known and potential biological functions of the PPIN, such as cell migration and cancer-related pathways. Expression levels of the PPIN proteins, as well as their expression correlations, in five types of brain tumor, were analyzed and integrated into the PPIN to illustrate a dynamic change. A significant correlation was found between the survival time of glioblastoma patients and the expression level of 10 genes (LCN2, MMP9, MMP2, PDE4DIP, L2HGDH, HNRNPA1, DDX31, LOXL2, FAM60A and RNF25). Taken together, our results suggest that LCN2 and its interacting proteins are mostly differentially expressed and have a distinguishing co-expression pattern. They might promote proliferation and migration via cell migration signaling and cancer-related pathways. LCN2 and its interacting proteins might be potential biomarkers in glioblastoma.

3.
BMB Rep ; 52(4): 277-282, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30940322

RESUMO

Currently speaking, it is noted that radiofrequency ablation (RFA) has been the most widely used treatment for hepatocellular carcinoma (HCC) occurring in patients. However, accumulating evidence has demonstrated that the incidence of insufficient RFA (IRFA) may result in the identified rapid progression of residual HCC in the patient, which can greatly hinder the effectiveness and patient reported benefits of utilizing this technique. Although many efforts have been proposed, the underlying mechanisms triggering the rapid progression of residual HCC after IRFA have not yet been fully clarified through current research literature reviews. It was shown in this study that cell proliferation, migration and invasion of residual HepG2 and SMMC7721 cells were significantly increased after the IRFA was simulated in vitro. In other words, it is noted that IRFA could do this by enhancing the image of autophagy of the residual HCC cell via the HIF-1α/BNIP3 pathway. Consequently, the down-regulation of BNIP3 may result in the inhibition of the residual HCC cell progression and autophagy after IRFA. Our present study results suggest that IRFA could promote residual HCC cell progression in vitro by enhancing autophagy via the HIF-1α/BNIP3 pathway. For this reason, it is noted that the targeting of the BNIP3 may be useful in preventing the rapid growth and metastasis of residual HCC after IRFA. [BMB Reports 2019; 52(4): 277-282].


Assuntos
Carcinoma Hepatocelular/terapia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/terapia , Proteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Ablação por Radiofrequência/métodos , Autofagia/efeitos da radiação , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Progressão da Doença , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Ablação por Radiofrequência/tendências , Transdução de Sinais
4.
Pathol Res Pract ; 215(6): 152406, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30967300

RESUMO

BACKGROUND: Cyclin-dependent kinase 8 (CDK8) as a Mediator complex-associated transcriptional regulator has been shown to play important role in the initiation and progression of various cancers. The present study aimed to explore miR-152-3p-modulated post-transcriptional repression of CDK8 in hepatic carcinogenesis. METHODS: Eighty-nine pairs of hepatocellular carcinoma (HCC) and adjacent non-tumor tissues were collected for molecular biological analysis. Cell viability and apoptosis assays were detected using CCK8 and Annexin V-fluorescein isothiocyanate/propidium iodide (Annexinv-FITC) double staining, respectively. Bioinformatics algorithms and luciferase reporter assay were performed to validate CDK8 as a direct target of miR-152-3p. Gene and protein expression levels were monitored using RT-qPCR, western blotting or immunohistochemical (IHC) staining. RESULTS: CDK8 expression levels were up-regulated and miR-152-3p was down-regulated in HCC tissues. The correlation analysis had documented a significant negative correlation between miR-152-3p and CDK8 in the HCC tissues. Both CDK8 and miR-152-3p could serve as the independent prognostic factors for predicting the OS and DFS in HCC patients. Bioinformatics and experimental measurement revealed that CDK8 was a direct target of miR-152-3p. After co-transfection with the miR-152-3p mimics and the CDK8 overexpressed plasmids, the anti-proliferative and pro-apoptotic roles of miR-152-3p were restricted by CDK8. CONCLUSION: The present results obtained forcefully proved that miR-152-3p exhibited an antineoplastic activity via targeting CDK8 and might be served as a potential therapeutic target for the treatment of HCC.

5.
Cell Signal ; 55: 8-16, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30557604

RESUMO

High level expression of lipocalin 2 (LCN2) usually indicates poor prognosis in esophageal squamous cell carcinoma (ESCC) and many other cancers. Our previous study showed LCN2 promotes migration and invasion of ESCC cells through a novel positive feedback loop. However, the key transcription activation protein (KTAP) in the loop had not yet been identified. In this study, we first predicted the most probable KTAPs by bioinformatic analysis. We then assessed the transcription regulatory regions in the human LCN2 gene by fusing deletions of its 5'-flanking region to a dual-luciferase reporter. We found that the region -720/-200 containing transcription factor 7-like 2 (TCF7L2) (-273/-209) and early growth response 1 (EGR1) (-710/-616) binding sites is crucial for LCN2 promoter activity. Chromatin immunoprecipitation (ChIP) experiments demonstrated that TCF7L2 and EGR1 bound directly to their binding sites within the LCN2 promoter as KTAPs. Mechanistically, overexpression of TCF7L2 and EGR1 increased endogenous LCN2 expression via the ERK signaling pathway. Treatment with recombinant human LCN2 protein enhanced activation of the ERK pathway to facilitate endogenous LCN2 expression, as well as increase the expression level of TCF7L2 and EGR1. Treatment with the MEK inhibitor U0126 inhibited the activation by TCF7L2 or EGR1 overexpression. Moreover, overexpression of TCF7L2 or EGR1 accelerated the migration and invasion of ESCC cells. A synergistic effect was observed between TCF7L2 and EGR1 in amplifying the induction of LCN2 and enhancing migration and invasion. Taken together, our study indicates that TCF7L2 and EGR1 are the KTAPs of LCN2, within a positive "LCN2 → MEK/ERK → LCN2" path, to promote the migration and invasion of ESCC cells. Based on their clinicopathological significance, LCN2 and its two expression regulators TCF7L2 and ERG1 might be therapeutic targets for ESCC.

6.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 34(10): 937-941, 2018 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30554588

RESUMO

Objective To investigate the diagnostic value of human papillomavirus (HPV) E6/E7 mRNA combined with P16/antigen KI-67(ki67) immunocytochemical double staining in the atypical squamous cells of undetermined significance (ASCUS). Methods A total of 272 patients were selected and the results of HPV E6/E7 and P16/ki67 immunocytochemical double staining in the remaining cytological specimens were retrospectively analyzed. HPV E6/E7 gene was detected by HPV E6/E7 gene detection kit and Panther molecular diagnostic instrument. P16/ki67 was detected by immunocytochemical staining and Ventana Benchmark Ultra immunohistochemical staining instrument. Then we analyzed the difference of positive rate between the two detection methods in the same grade of cervical epithelial lesions, explored the difference of the two detection methods and their combined detection in the diagnosis of high grade squamous intraepithelial lesions (HSIL), and finally evaluated the role of different detection methods in shunt diagnosis of ASCUS. Results Histopathological findings of cervical cytology ASCUS includes chronic cervicitis, low-grade squamous intraepithelial lesions (LSIL), HSIL and cervical cancer. The positive rate of simple molecular diagnosis or immunocytochemical staining increased with the severity of cervical lesions. In cervicitis and LSIL lesion group, the difference between the positive rates of the two methods was obvious, but in HSIL and cervical cancer lesion group, there was no significant difference between the positive rates of the two methods. The sensitivity, specificity, Yoden index, coincidence rate, positive predictive value and negative predictive value were 95.65%, 85.40%, 0.81, 87.13%, 57.14% and 98.97%, respectively. Conclusion The detection of HPV E6/E7 and P16/ki67 immunocytochemical staining has certain significance in ASCUS shunt diagnosis. The combined detection of HPV E6/E7 and P16/ki67 can significantly improve the sensitivity of shunt diagnosis and maintain a good specificity.


Assuntos
Células Escamosas Atípicas do Colo do Útero/virologia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Antígeno Ki-67/análise , Proteínas Oncogênicas Virais/análise , Proteínas E7 de Papillomavirus/análise , Infecções por Papillomavirus/diagnóstico , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/virologia , Feminino , Humanos , Imuno-Histoquímica , Papillomaviridae , RNA Mensageiro , Estudos Retrospectivos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia
7.
Oncol Lett ; 16(4): 5230-5236, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30250592

RESUMO

YC-1 is a synthetic compound, which serves as a hypoxia-inducible factor 1-α inhibitor or sensitizer to enhance the effect of chemotherapy. Previous studies have revealed the anti-cancer effects of YC-1 in various types of cancer, including hepatocellular carcinoma (HCC). ATPase inhibitory factor 1 (IF1) is upregulated in a number of human carcinomas and regulates mitochondrial bioenergetics and structure. However, whether IF1 is involved in the antitumor effects of YC-1 against HCC remains unclear. The present study examined the function of IF1 in HCC and its potential role in YC-1 effects within HCC cells. MTT, colony formation and Transwell assays revealed that IF1 overexpression promoted proliferation, colony formation and invasion of HCC cells, while IF1 downregulation had the opposite effects. Overexpression of IF1 reversed the inhibitory effects of YC-1 on Huh7 cell growth and invasion activities, while downregulation of IF1 increased the sensitivity of HCCLM3 cells to YC-1. YC-1 treatment of HCCLM3 and Huh7 cells reduced the levels of phosphorylated (p-) signal transducer and activator of transcription 3 (STAT3) and IF1, and increased the expression of E-cadherin. IF1 knockdown resulted in decreased p-STAT3 levels and increased E-cadherin expression, while IF1 overexpression increased p-STAT3 levels and reduced the expression of E-cadherin. The present study demonstrated that the inhibition of IF1 improves the antitumor effects of YC-1 in HCC cells. These findings support the clinical strategy of combining YC-1 and an IF1 inhibitor for the treatment of HCC.

8.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 30(5): 477-480, 2018 May.
Artigo em Chinês | MEDLINE | ID: mdl-29764555

RESUMO

OBJECTIVE: Human infection with avian influenza A (H7N9) is an acute contagious respiratory disease. Acute respiratory distress syndrome (ARDS) is a common complication in patients with severe avian influenza A (H7N9), for whom mechanical ventilation (MV) is an important supportive method. A patient, suffered from severe avian influenza A (H7N9) and complicated with ARDS, was admitted to the Second Affiliated Hospital of Guizhou Medical University in January 2017. With very intensive care for oxygenation, respiration and consciousness, and monitoring, she was successfully cured by comprehensive managements, among which noninvasive mechanical ventilation (NIV) was the major respiratory support method. The result demonstrate that, in patients with conscious state, satisfied expectoration ability and relatively good cooperation, and with close observation of oxygenation and respiratory rate, NIV may be accepted as an effective method for patient with ARDS caused by severe avian influenza A (H7N9).


Assuntos
Influenza Humana , Síndrome do Desconforto Respiratório do Adulto , Feminino , Humanos , Subtipo H7N9 do Vírus da Influenza A , Ventilação não Invasiva , Respiração Artificial
9.
Br J Cancer ; 118(11): 1476-1484, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29765149

RESUMO

BACKGROUND: Oesophageal squamous cell carcinoma (ESCC) is one of the most malignant cancers worldwide. Treatment of ESCC is in progress through accurate staging and risk assessment of patients. The emergence of potential molecular markers inspired us to construct novel staging systems with better accuracy by incorporating molecular markers. METHODS: We measured H scores of 23 protein markers and analysed eight clinical factors of 77 ESCC patients in a training set, from which we identified an optimal MASAN (MYC, ANO1, SLC52A3, Age and N-stage) signature. We constructed MASAN models using Cox PH models, and created MASAN-staging systems based on k-means clustering and minimum-distance classifier. MASAN was validated in a test set (n = 77) and an independent validation set (n = 150). RESULTS: MASAN possessed high predictive accuracies and stratified ESCC patients into three prognostic groups that were more accurate than the current pTNM-staging system for both overall survival and disease-free survival. To facilitate clinical utilisation, we also constructed MASAN-SI staging systems based on staining indices (SI) of protein markers, which possessed similar prognostic performance as MASAN. CONCLUSION: MASAN provides a good alternative staging system for ESCC prognosis with a high precision using a simple model.

10.
Oncol Lett ; 15(6): 9353-9360, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29805660

RESUMO

5-lipoxygenase (5-LO) catalyzes the first step of arachidonic acid metabolism to inflammatory mediator leukotrienes. The present study assessed 5-LO expression in esophageal squamous cell carcinoma (ESCC) tissue specimens for associations with clinicopathological and survival data from patients, then explored 5-LO activity in ESCC cells in vitro. 5-LO expression was detected in tissue microarrays containing 297 ESCC samples using immunohistochemistry. Kaplan-Meier curves were used to analyze the survival significance of 5-LO expression and relative risk was evaluated using the multivariate Cox proportional hazards model. Cultured tumor cells were subjected to gene transfection, western blotting, and cell migration and proliferation assays. 5-LO protein was primarily expressed in normal cell cytoplasm and/or membrane, and never in the whole cytoplasm, whereas 5-LO was expressed diffusely in ESCC tissues with nearly homogeneous whole-cytoplasm staining. 5-LO expression was significantly associated with tumor regional lymph node metastasis (P=0.013) and pTNM stage (P=0.004). 5-LO expression was associated with poor overall survival (P=0.029). Multivariate analysis demonstrated that 5-LO overexpression was an independent prognostic factor for ESCC patients (P=0.041). Furthermore, the inhibition of 5-LO expression reduced ESCC cell viability and migration in vitro. These data provide further evidence that the upregulation of 5-LO expression is associated with advanced stages of disease and poor ESCC prognosis, and that 5-LO expression may independently predict overall survival in patients with ESCC. The inhibition of 5-LO expression reduced ESCC malignant behavior in vitro.

11.
J Med Case Rep ; 12(1): 77, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29540219

RESUMO

BACKGROUND: More and more cases of human infections with avian influenza A H7N9 have been reported since it was first mentioned in 2013 in China, but concurrence of influenza A H7N9 with Mycoplasma pneumoniae, however, has never been described. Here, we reported the case of a woman co-infected by influenza A H7N9 and Mycoplasma pneumoniae, whose treatment process was a little bit longer and a little bit complicated as well. CASE PRESENTATION: Our patient was an 80-year-old Chinese woman who presented with fever, cough, chest tightness, and shortness of breath. A computed tomography scan showed obvious infiltrations at lower parts of both lungs. Arterial blood gas analysis confirmed a severe respiratory failure (type I). Her sputum and throat swabs were checked for nucleic acid of influenza A and the result was positive for influenza A H7N9. She was diagnosed as having severe influenza A H7N9 and acute respiratory distress syndrome, and was admitted to an intensive care unit. She was given comprehensive treatment, including oseltamivir, methylprednisolone, immunoglobulin, gastric protection, and noninvasive mechanical ventilation. Her condition improved 4 days later. However, some symptoms exacerbated again 2 days later with ground-glass changes appearing in upper area of right lung and the titer of antibody to Mycoplasma pneumoniae rising from 1:80 to 1:640. She was reasonably considered to be infected with Mycoplasma pneumoniae as well, and azithromycin and moxifloxacin were added to her treatment. Oseltamivir was discontinued because of three consecutive negative results of nucleic acid for influenza A H7N9, but anti-Mycoplasma treatment was continued. Although her symptoms and abnormal changes on computed tomography scan slowly went away, she finally recovered from the mixed infection after a total of 33 days of management. CONCLUSION: In patients with confirmed influenza A H7N9 infection whose condition worsens again, especially with new infiltration or lung ground-glass infiltration, one should suspect infection by other pathogens such as Mycoplasma pneumoniae.


Assuntos
Coinfecção/complicações , Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Influenza Humana/complicações , Mycoplasma pneumoniae/isolamento & purificação , Pneumonia por Mycoplasma/complicações , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Feminino , Fluoroquinolonas/uso terapêutico , Humanos , Imunoglobulinas/uso terapêutico , Influenza Humana/diagnóstico , Influenza Humana/tratamento farmacológico , Metilprednisolona/uso terapêutico , Moxifloxacina , Oseltamivir/uso terapêutico , Pneumonia por Mycoplasma/diagnóstico , Pneumonia por Mycoplasma/tratamento farmacológico
12.
Bioorg Chem ; 77: 429-435, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29433092

RESUMO

The free fatty acid receptor 1 (FFA1) plays an important role in amplifying insulin secretion in a glucose dependent manner. We have previously reported a series of FFA1 agonists with thiazole scaffold exemplified by compound 1, and identified a small hydrophobic subpocket partially occupied by the methyl group of compound 1. Herein, we describe further structure optimization to better fit the small hydrophobic subpocket by replacing the small methyl group with other hydrophobic substituents. All of these efforts resulted in the identification of compound 6, a potent FFA1 agonist (EC50 = 39.7 nM) with desired ligand efficiency (0.24) and ligand lipophilicity efficiency (4.7). Moreover, lead compound 6 exhibited a greater potential for decreasing the hyperglycemia levels than compound 1 during an oral glucose tolerance test. In summary, compound 6 is a promising FFA1 agonist for further investigation, and the structure-based study promoted our understanding for the binding pocket of FFA1.

13.
World J Gastroenterol ; 23(39): 7077-7086, 2017 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-29093616

RESUMO

Recent studies have shown that radiofrequency (RF) ablation therapy is a safe, feasible, and effective procedure for hepatic hemangiomas, even huge hepatic hemangiomas. RF ablation has the following advantages in the treatment of hepatic hemangiomas: minimal invasiveness, definite efficacy, high safety, fast recovery, relatively simple operation, and wide applicability. It is necessary to formulate a widely accepted consensus among the experts in China who have extensive expertise and experience in the treatment of hepatic hemangiomas using RF ablation, which is important to standardize the application of RF ablation for the management of hepatic hemangiomas, regarding the selection of patients with suitable indications to receive RF ablation treatment, the technical details of the techniques, therapeutic effect evaluations, management of complications, etc. A final consensus by a Chinese panel of experts who have the expertise of using RF ablation to treat hepatic hemangiomas was reached by means of literature review, comprehensive discussion, and draft approval.


Assuntos
Ablação por Cateter , Hemangioma/cirurgia , Neoplasias Hepáticas/cirurgia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/mortalidade , China , Consenso , Hemangioma/mortalidade , Hemangioma/patologia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Resultado do Tratamento
14.
Oncotarget ; 8(31): 52006-52011, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28881707

RESUMO

BACKGROUND: Traditionally, open hepatic resection is the first choice of treatment for symptomatic enlarging hepatic hemangiomas, which requires a large abdominal incision and is associated with substantial recovery time and morbidity. Minimally invasive laparoscopic resection has been used recently in liver surgery for treating selected hepatic hemangiomas. However, laparoscopic liver surgery poses the significant technical challenges and high rate of conversion. Radiofrequency (RF) ablation has been proved feasible in the treatment of hepatic hemangiomas with a size range of 5.0-9.9 cm. It is controversial to treat giant hepatic hemangiomas (≥10.0 cm) by means of RF ablation, due to the low technique success rate and high incidence of ablation-related complications. We aimed to assess the safety and efficacy of combined laparoscopic resection with intratumoral RF-induced coagulation for giant hepatic hemangiomas. METHODS: We treated 2 patients with giant subcapsular hepatic hemangioma (12.0 cm and 13.1 cm in diameters respectively) by laparoscopic resection following intratumoral coagulation of the tumor with RF ablation. RESULTS: Blood loss during resection was 100 ml (case 1) and 300ml (case 2) respectively. No blood transfusion and dialysis were needed during perioperative period. The two patients were discharged 6 days (case 1) and 12 days (case 2) after surgery without any complications, respectively. Postoperative contrast-enhanced CT follow up showed there was no residual tumor. CONCLUSIONS: It is feasible to treat giant subcapsular hepatic hemangioma by laparoscopic tumor resection boosted by intratumoral coagulation using RF ablation, which may open a new avenue for treating giant hemangioma.

15.
Hum Pathol ; 66: 115-125, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28603065

RESUMO

Our previous studies have highlighted the importance of ezrin in esophageal squamous cell carcinoma (ESCC). Here our objective was to explore the clinical significance of ezrin-interacting proteins, which would provide a theoretical basis for understanding the function of ezrin and potential therapeutic targets for ESCC. We used affinity purification and mass spectrometry to identify PDIA3, CNPY2, and STMN1 as potential ezrin-interacting proteins. Confocal microscopy and coimmunoprecipitation analysis further confirmed the colocalization and interaction of ezrin with PDIA3, CNPY2, and STMN1. Tissue microarray data of ESCC samples (n=263) showed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower for the CNPY2 (OS, P=.003; DFS, P=.011) and STMN1 (OS, P=.010; DFS, P=.002) high-expression groups compared with the low-expression groups. By contrast, overexpression of PDIA3 was significantly correlated with favorable survival (OS, P<.001; DFS, P=.001). Cox regression demonstrated the prognostic value of PDIA3, CNPY2, and STMN1 in ESCC. Furthermore, decision tree analysis revealed that the resulting classifier of both ezrin and its interacting proteins could be used to better predict OS and DFS of patients with ESCC. In conclusion, a signature of ezrin-interacting proteins accurately predicts ESCC patient survival or tumor recurrence.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteínas do Citoesqueleto/metabolismo , Técnicas de Apoio para a Decisão , Árvores de Decisões , Neoplasias Esofágicas/metabolismo , Isomerases de Dissulfetos de Proteínas/metabolismo , Estatmina/metabolismo , Biópsia , Western Blotting , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Linhagem Celular Tumoral , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago , Feminino , Imunofluorescência , Humanos , Imuno-Histoquímica , Imunoprecipitação , Estimativa de Kaplan-Meier , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Fosforilação , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Ligação Proteica , Estudos Retrospectivos , Fatores de Tempo , Análise Serial de Tecidos
16.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 29(5): 473-476, 2017 May.
Artigo em Chinês | MEDLINE | ID: mdl-28524040

RESUMO

OBJECTIVE: One confirmed diagnosis case of severe human infection by avian influenza H7N9 admitted to intensive care unit (ICU) of the Second Affiliated Hospital of Guizhou Medical University on January 12th, 2017 was reported. The patient was treated with the sepsis bundle, and recovered finally, including a series of comprehensive treatments, such as respiratory support, circulation support, antiviral, anti-inflammation, immunization enhancement, critical nursing, fluid management, nutritional support and treatment of complications. The critical patient was admitted on January 27th, and the treatment was successful. It has important significance to rescue the severe human infection from avian influenza H7N9 by the sepsis bundle.


Assuntos
Subtipo H7N9 do Vírus da Influenza A , Antivirais , China , Humanos , Influenza Humana , Sepse
17.
Cancer Med ; 6(7): 1707-1719, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28556501

RESUMO

Current staging is inadequate for predicting clinical outcome of esophageal squamous cell carcinoma (ESCC). Aberrant expression of LOXL2 and actin-related proteins plays important roles in ESCC. Here, we aimed to develop a novel molecular signature that exceeds the power of the current staging system in predicting ESCC prognosis. We found that LOXL2 colocalized with filamentous actin in ESCC cells, and gene set enrichment analysis (GSEA) showed that LOXL2 is related to the actin cytoskeleton. An ESCC-specific protein-protein interaction (PPI) network involving LOXL2 and actin-related proteins was generated based on genome-wide RNA-seq in 15 paired ESCC samples, and the prognostic significance of 14 core genes was analyzed. Using risk score calculation, a three-gene signature comprising LOXL2, CDH1, and FN1 was derived from transcriptome data of patients with ESCC. The high-risk three-gene signature strongly correlated with poor prognosis in a training cohort of 60 patients (P = 0.003). In mRNA and protein levels, the prognostic values of this signature were further validated in 243 patients from a testing cohort (P = 0.001) and two validation cohorts (P = 0.021, P = 0.007). Furthermore, Cox regression analysis revealed that the signature was an independent prognostic factor. Compared with using the signature or TNM stage alone, the combined model significantly enhanced the accuracy in evaluating ESCC prognosis. In conclusion, our data reveal that the tumor-promoting role of LOXL2 in ESCC is mediated by perturbing the architecture of actin cytoskeleton through its PPIs. We generated a novel three-gene signature (PPI interfaces) that robustly predicts poor clinical outcome in ESCC patients.


Assuntos
Actinas/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Regulação Neoplásica da Expressão Gênica , Mapas de Interação de Proteínas , Aminoácido Oxirredutases/genética , Aminoácido Oxirredutases/metabolismo , Biomarcadores Tumorais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Linhagem Celular , Biologia Computacional/métodos , Citoesqueleto , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Estadiamento de Neoplasias , Prognóstico , Mapeamento de Interação de Proteínas , Curva ROC , Reprodutibilidade dos Testes
18.
Medicine (Baltimore) ; 95(49): e5472, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27930527

RESUMO

This retrospective cohort study investigated the feasibility of radiofrequency (RF) ablation as an alternative to surgical intervention in patients with huge multiloculated pyogenic liver abscesses (PLAs).From August 2010 to April 2016, 83 patients with PLA were admitted to Beijing Chao-Yang Hospital, China. Four of these patients had huge multiloculated PLAs and underwent RF ablation plus antibiotics. The inclusion criteria for RF ablation were as follows: multiloculated PLA confirmed by computed tomography (CT) or magnetic resonance imaging (MRI), widest diameter of the PLA ≥5 cm, failure to respond to or not suitable to treatment with percutaneous drainage (PD), and patient refusal of surgery. The safety and effectiveness of RF ablation were initially assessed. All patients were commenced on antibiotics on admission to our hospital. CT-guided percutaneous catheter drainage was attempted in one patient but was unsuccessful. The main organism isolated from cultures of these patients' blood or abscess samples was Klebsiella pneumoniae (3/4). RF ablation was performed as soon as eligibility according to the above criteria was established.RF ablation was technically successful in all 4 study patients, all PLAs being completely eradicated. The median duration of fever after RF ablation was 4.5 days. No abscesses recurred; thus, this strategy for managing PLA was 100% successful (4/4). No procedure-related deaths or major complications occurred. One patient had an asymptomatic right pleural effusion that resolved with conservative treatment including albumin infusion and diuretics.Our preliminary data indicate that RF ablation is a safe, feasible, and effective treatment for huge multiloculated PLAs. It should be considered as an alternative treatment for patients who fail to respond to or not suitable for PD plus antibiotics and refuse surgical intervention.


Assuntos
Abscesso Hepático Piogênico/cirurgia , Adulto , Idoso , Antibacterianos/administração & dosagem , Ablação por Cateter , Estudos de Coortes , Infecções por Escherichia coli/diagnóstico por imagem , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Infecções por Klebsiella/diagnóstico por imagem , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/cirurgia , Laparoscopia , Abscesso Hepático Piogênico/diagnóstico por imagem , Abscesso Hepático Piogênico/tratamento farmacológico , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Biomed Res Int ; 2016: 1256384, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27610364

RESUMO

Data of HPV genotype including 16 high-risk HPV (HR-HPV) and 4 low-risk HPV from 38,397 women with normal cytology, 1341 women with cervical cytology abnormalities, and 223 women with ISCC were retrospectively evaluated by a hospital-based study. The prevalence of high-risk HPV (HR-HPV) was 6.51%, 41.83%, and 96.86% in women with normal cytology, cervical cytology abnormalities, and ISCC, respectively. The three most common HPV types were HPV-52 (1.76%), HPV-16 (1.28%), and HPV-58 (0.97%) in women with normal cytology, whereas the most prevalent HPV type was HPV-16 (16.85%), followed by HPV-52 (9.55%) and HPV-58 (7.83%) in women with cervical cytology abnormalities. Specifically, HPV-16 had the highest frequency in ASC-H (24.16%, 36/149) and HSIL (35.71%, 110/308), while HPV-52 was the most common type in ASC-US (8.28%, 53/640) and LSIL (16.80%, 41/244). HPV-16 (75.78%), HPV18 (10.31%), and HPV58 (9.87%) were the most common types in women with ISCC. These data might contribute to increasing the knowledge of HPV epidemiology and providing the guide for vaccine selection for women in Shantou.


Assuntos
Alphapapillomavirus/genética , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Genótipo , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Idoso , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , China/epidemiologia , Estudos Transversais , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/virologia , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Invasividade Neoplásica , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
20.
J Laparoendosc Adv Surg Tech A ; 26(7): 560-6, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27285103

RESUMO

AIMS: To evaluate the technical and clinical outcomes of early laparoscopic radiofrequency (RF) ablation for spontaneously ruptured hepatocellular carcinoma (HCC). METHODS: From April 2005 to July 2015, ten patients with spontaneously ruptured HCC treated by laparoscopic RF ablation in our hospital were included in the study. The post treatment outcomes were recorded and analyzed. RESULTS: The mean size of the 10 HCCs was 6.6 ± 2.2 cm (4.0-10.1 cm) in the maximal dimension. Procedures of laparoscopic RF ablation were performed successfully for all patients. Complete ablation was achieved in 60.0% patients (6/10). Four patients with incompletely ablated tumors received repeated RF ablation to achieve complete ablation. During clinical follow-up, 3 (30.0%) patients developed minor complications and no patient had peritoneal recurrence. As of March 2016 (with a mean follow-up of 32.9 months), 3 patients (30.0%) were alive and 7 (70.0%) died. Of the 10 patients, the 1- and 3-year survival rates were 90.0% and 70.0%, respectively. CONCLUSION: Early laparoscopic RF ablation therapy is an effective treatment measure for spontaneously ruptured HCC in selected patients, which presents an advantage of achieving simultaneous hemostasis, tumor elimination, and rinsing of peritoneal cavity to minimize the risk of peritoneal metastasis.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Idoso , Carcinoma Hepatocelular/complicações , Ablação por Cateter , Árvores de Decisões , Feminino , Humanos , Laparoscopia , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/complicações , Complicações Pós-Operatórias , Estudos Retrospectivos , Ruptura Espontânea/etiologia , Ruptura Espontânea/cirurgia , Taxa de Sobrevida , Resultado do Tratamento
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