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1.
BMC Gastroenterol ; 23(1): 2, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36600208

RESUMO

BACKGROUND: Emerging evidence has shown the crucial roles of pleomorphic adenoma gene (PLAG) family genes in multiple cancers. However, their functions and mechanisms in pancreatic adenocarcinoma (PAAD) remain poorly understood. METHODS: We analyzed the expression levels of PLAG family genes in both The Cancer Genome Atlas (TCGA) database and a Gene Expression Omnibus (GEO) database, and confirmed the results in our three independent cohorts of 382 PAAD tissues and 362 adjacent nontumor pancreatic tissues. Integrated analyses were carried out to explore the function, mechanism and prognostic value of the selected PLAG family gene in PAAD patients. RESULTS: By analyzing the TCGA and GEO databases, PLAGL1 was identified to be downregulated in PAAD tissues, and its decreasing levels of both mRNA and protein were verified in our three independent PAAD cohorts. PLAGL1 expression was inversely correlated with clinicopathological factors including the Ki67+ cell rate and pathologic stage. Further GSEA of the TCGA-PAAD cohort demonstrated that multiple signaling pathways implicated in cell proliferation were enriched in the lower PLAGL1 expressing PAAD group. Moreover, we demonstrated that PLAGL1 expression was obviously negatively associated with patients' overall survival outcome in both the TCGA-PAAD cohort and our verification cohorts. Additionally, through MTS and BrdU assays, we further demonstrated in vitro that PLAGL1 had the impact of preventing the proliferation of pancreatic cancer cells. CONCLUSIONS: Our present study suggested that downregulated PLAGL1 might act as a biomarker in predicts poor prognosis and one of important factors in increasing cell proliferation in PAAD. This study provides us with a novel prognostic marker and therapeutic strategy for PAAD, which deserves further study.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Fatores de Transcrição , Proteínas Supressoras de Tumor , Humanos , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Prognóstico , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Neoplasias Pancreáticas
2.
HPB (Oxford) ; 24(5): 606-615, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34872867

RESUMO

BACKGROUND: Pancreatic fistula is a life-threatening complication of pancreaticoduodenectomy. Omega-like duct-to-mucosa pancreatojejunostomy is a novel technique which helps reduce the risk of fistulation. This study aimed to compare early postoperative outcomes of omega-like and conventional pancreatojejunostomy. METHODS: A retrospective single-centre cohort study comparing outcomes of adult patients who underwent open pancreatoduodenectomy with conventional (CDMP) or omega-like duct-to-mucosa pancreatojejunostomy (ODMP) between 1 January 2015 and 31 December 2019. The primary outcome measure was the pancreatic fistula rate. RESULTS: 440 patients were included in this study of whom 233 underwent CDMP and 207 ODMP. The rate of clinically relevant pancreatic fistula (grade B/C) was significantly higher after CDMP than ODMP (18.5% vs. 10.6%, P = 0.021). 153 patients in CDMP group and 99 patients in ODMP group developed one or more complications (65.7% vs. 47.8%, P = 0.004). The average hospitalization expenses were numerically decreased in ODMP group, although this was not statistically significant (120,000 ± 42,000 [Chinese Yuan] vs. 100,000 ± 40,000 [Chinese Yuan] or 18,581 ± 6503 [United States Dollar] vs. 15,484 ± 6194 [United States Dollar], P = 0.402). CONCLUSION: ODMP may reduce the incidence of pancreatic fistula and other early postoperative complications after pancreatoduodenectomy.


Assuntos
Pancreaticoduodenectomia , Pancreaticojejunostomia , Adulto , Estudos de Coortes , Humanos , Mucosa , Fístula Pancreática/etiologia , Fístula Pancreática/prevenção & controle , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Pancreaticojejunostomia/efeitos adversos , Pancreaticojejunostomia/métodos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
3.
Am J Physiol Cell Physiol ; 320(5): C880-C891, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33502949

RESUMO

Renal cell carcinoma (RCC) has the highest mortality rate among urological cancers and tumor angiogenesis that plays a critical role in RCC progress. Epidermal growth factor-like domain multiple 7 (EGFL7) has been recently identified as a regulator in RCC tumor angiogenesis and progression. Long noncoding RNA (LncRNA) HOTAIR has been considered as a pro-oncogene in multiple cancers, but its precise mechanism of tumor angiogenesis has rarely been reported. MicroRNA-126 (miR-126) functions as a tumor suppressor in RCC. However, the underlying tumor angiogenesis mechanism of HOTAIR/miR-126 axis in RCC has not been studied. The proliferation, migration, angiogenesis, and expression of EGFL7 and related proteins in extracellular signal-regulated kinase (ERK)/activators of transcription 3 (STAT3) signal pathway were determined to examine the effect and mechanism of HOTAIR and miR-126 on RCC progress. The regulatory relationship of HOTAIR and miR-126, as well as miR-126 and EGFL7 were tested using dual-luciferase reporter assay. Aenograft RCC mice model was used to examine the effect of HOTAIR on RCC tumor growth and metastasis in vivo. HOTAIR knockdown and miR-126 overexpression suppressed the proliferation, migration, and angiogenesis of RCC cells. HOTAIR regulated EGFL7 expression by competitively binding to miR-126. Knockdown of HOTAIR significantly suppressed the RCC tumor progression and lung metastasis in vivo. These findings suggest that lncRNA HOTAIR regulate RCC angiogenesis through miR-126/EGFL7 axis and provide a new perspective on the molecular pathways of angiogenesis in RCC development, which might be potential therapeutic targets for RCC treatment.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma de Células Renais/metabolismo , Família de Proteínas EGF/metabolismo , Neoplasias Renais/metabolismo , MicroRNAs/metabolismo , Neovascularização Patológica , RNA Longo não Codificante/metabolismo , Animais , Proteínas de Ligação ao Cálcio/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Família de Proteínas EGF/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Densidade Microvascular , Pessoa de Meia-Idade , Invasividade Neoplásica , RNA Longo não Codificante/genética , Transdução de Sinais , Carga Tumoral
4.
Clin Endocrinol (Oxf) ; 92(4): 312-322, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31943312

RESUMO

BACKGROUND: Pancreatic neuroendocrine neoplasms (pNENs) are a group of endocrine tumours arising in the pancreas and deemed to be the most common neuroendocrine tumours. The pathogenesis of pNENs remains unknown. Long noncoding RNAs (lncRNAs) are aberrantly expressed in cancers. The functional roles of lncRNAs and lncRNA-mRNA expression profiles in pNENs are undefined. The aim of this study was to identify the lncRNA and mRNA expression profiles and explore the lncRNA-mRNA co-expression networks associated with the pNENs carcinogenesis. METHOD: Differentially expressed lncRNA and mRNA in pNENs tissues from adjacent tissues were detected using human lncRNA microarray V3.0 containing 30 586 lncRNA and 26 109 coding transcripts. Probable functions for lncRNAs and mRNAs were predicted according to lncRNA-mRNA network. RESULTS: The microarray identified 2080 lncRNAs and 1771 mRNAs in pNENs tumours differentially expressed compared with the adjacent tissues. The GO terms and KEGG pathway annotation data indicated that cell projection morphogenesis, cell adhesion molecules pathway, PI3K-AKT signalling pathway, focal adhesion pathway, neuroactive ligand-receptor interaction pathways and Ras signalling pathways were significantly associated with the pNENs tumorigenesis. Co-expression network analysis revealed the differential interactions between lncRNAs and mRNAs in pNENs tumours and adjacent tissues. The genes, situated at the important nodes of the co-expression network, include ICOSLG, ENST00000512077, FGF8 and ENST00000511918. CONCLUSIONS: There were significant differences in lncRNA and mRNA expression between pNEN tumours and adjacent tissues, and these differences were associated with tumorigenesis through multiple biological processes and signalling pathways. These results provided important insights regarding lncRNA in pNENs pathogenesis and provide potential therapeutic targets.


Assuntos
Tumores Neuroendócrinos , RNA Longo não Codificante , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Tumores Neuroendócrinos/genética , Fosfatidilinositol 3-Quinases , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Transdução de Sinais/genética
5.
J Magn Reson Imaging ; 49(4): 1141-1148, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30230114

RESUMO

BACKGROUND: Robust parameters to evaluate pathological aggressiveness are needed to provide individualized therapy for cervical cancer patients. PURPOSE: To investigate the radiomics analysis of multiparametric MRI to evaluate tumor grade, lymphovascular space invasion (LVSI), and lymph node (LN) metastasis of cervical squamous cell carcinoma (CSCC). STUDY TYPE: Retrospective. SUBJECTS: Fifty-six patients with histopathologically confirmed CSCC. FIELD STRENGTH/SEQUENCE: 3T, axial T2 and T2 with fat suppression (FS), diffusion-weighted imaging (DWI) (multi-b values), axial dynamic contrast enhanced (DCE) MRI (8 sec temporal resolution). ASSESSMENT: Regions of interest were drawn around the tumor on each axial slice and fused to generate the whole tumor volume. Sixty-six radiomics features were derived from each image sequence, including axial T2 and T2 FS, ADC maps, and Ktrans , Ve , and Vp maps from DCE MRI. STATISTICAL TESTS: A univariate analysis was performed to assess each parameter's association with tumor grade and the presence of lymphovascular space invasion (LVSI) and lymph node (LN) metastasis. A principal component analysis was employed for dimension reduction and to generate new discriminative valuables. Using logistic regression, a discriminative model of each parameter was built and a receiver operating characteristic curve (ROC) was generated. RESULTS: The area under the ROC curve (AUC) of anatomical, diffusion, and permeability parameters in discriminating the presence of LVSI ranged from 0.659 to 0.814, with Ve showing the best discriminative value. The AUC in discriminating the presence of LN metastasis and distinguishing tumor grade ranged from 0.747 to 0.850, 0.668 to 0.757, with ADC and Ve showing the best discriminative value, respectively. DATA CONCLUSION: Functional maps exhibit better discriminative values than anatomical images for discriminating the pathological features of CSCC, with ADC maps showing the best discrimination performance for LN metastasis and Ve maps showing the best discriminative value for LVSI and tumor grade. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1141-1148.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Neoplasias do Colo do Útero/diagnóstico por imagem , Adulto , Idoso , Área Sob a Curva , Biópsia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos
6.
Eur Radiol ; 27(12): 5272-5279, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28534163

RESUMO

OBJECTIVES: To determine the diagnostic value of monoexponential, biexponential and stretched exponential models for identifying lymph nodes (LNs) in patients with cervical cancer. MATERIALS AND METHODS: Fifty female patients with cervical cancer underwent preoperative magnetic resonance imaging. The diffusion parameters of the LNs were calculated by fitting the values to monoexponential, biexponential and stretched exponential models and were compared between the metastatic and non-metastatic LN groups. RESULTS: A total of 157 LNs with high signal intensity on multi-b-value DWI were detected, 41 of which were pathologically shown to be metastatic. Metastatic LNs presented with higher pure water diffusion (D) values, lower perfusion fraction (f) values, higher diffusion heterogeneity (α) values, higher short diameter (Size-S), long diameter (Size-L) and short long diameter ratio (S/L Ratio) than non-metastatic LNs (P<0.05). The Size-S of LNs exhibited the highest diagnostic value, with an area under the curve of 0.844. CONCLUSIONS: Compared with the size parameters, the diffusion parameters derived from multi-b-value diffusion-weighted imaging cannot reliably discriminate metastatic from non-metastatic LNs in daily clinical routine due to limited sensitivity and specificity. KEY POINTS: • Biexponential and stretched exponential diffusion models can help to characterise LN status. • Metastatic LNs present with higher D and α values, lower f values. • Diffusion parameters were less reliable in discriminating LNs than size parameters.


Assuntos
Adenocarcinoma/diagnóstico , Imagem de Difusão por Ressonância Magnética/métodos , Linfonodos/patologia , Estadiamento de Neoplasias/métodos , Neoplasias do Colo do Útero/diagnóstico , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adulto , Idoso , Feminino , Humanos , Histerectomia , Excisão de Linfonodo , Metástase Linfática/diagnóstico , Pessoa de Meia-Idade , Período Pré-Operatório , Estudos Prospectivos , Neoplasias do Colo do Útero/cirurgia
7.
J Comput Assist Tomogr ; 41(4): 592-598, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27997440

RESUMO

OBJECTIVE: The aims of this study were to evaluate the dependence of diffusion parameters on the b values adopted for intravoxel incoherent motion diffusion-weighted magnetic resonance imaging and to investigate the application value of multiple diffusion parameters obtained from monoexponential and biexponential models in subjects with a normal cervix and in cervical cancer patients. METHODS: A total of 120 female patients with cervical cancer and 21 female control subjects with a normal cervix underwent diffusion-weighted magnetic resonance imaging with 13 b values (0-2000 s/mm) at 3 T. The standard apparent diffusion coefficient (Dst), diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) were calculated by fitting with monoexponential and biexponential models at 2 different ranges of b values: 0 to 1000 and 0 to 2000 s/mm. A univariate analysis was performed to identify factors that could distinguish cervical carcinoma from normal cervical tissue. Parameters that correlated with the pathological grade and stage of cervical cancer were also evaluated. Receiver operating characteristic curves were used to evaluate the diagnostic efficiency of every parameter. RESULTS: All the tested parameters, except the D* of the 2 different ranges of b value groups, significantly differed between the patients with cervical carcinoma and control subjects (P < 0.01). D2000, Dst2000, and D1000 showed comparable diagnostic value, with an area under the curve of 0.923, 0.909, and 0.907, respectively. Dst2000, D2000, Dst1000, and D1000 differed significantly among the 3 degrees of cervical stromal infiltration depth (P < 0.05). CONCLUSIONS: D2000 and Dst2000 tended to outperform D1000 in terms of diagnostic efficiency, but there was no significant difference in their ability to differentiate cervical carcinoma from normal cervix. Cervical cancers with lower Dst and D values tended to have greater infiltration depth.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias do Colo do Útero/diagnóstico por imagem , Adulto , Idoso , Colo do Útero/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , Movimento (Física) , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
8.
Hepatobiliary Pancreat Dis Int ; 16(5): 537-544, 2017 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-28992887

RESUMO

BACKGROUND: Post-pancreaticoduodenectomy pancreatic fistula associated hemorrhage (PPFH) is one of the leading lethal complications. Our study was to analyze the risk factors and managements of hemorrhage associated with pancreatic fistula after pancreaticoduodenectomy, and to evaluate treatment options. METHOD: We analyzed 445 patients who underwent pancreaticoduodenectomy or pylorus-preserving pancreaticoduodenectomy and evaluated the relevance between clinical data and PPFH. RESULTS: The incidence of postoperative pancreatic fistula (POPF) was 27.42% (122/445), and the incidence of PPFH was 4.49% (20/445). Among the 20 patients with PPFH, 7 died and 13 were cured. Interventional angiographic therapy was performed for 10 patients and 5 were successfully treated. Relaparotomy was performed for 5 patients and 2 were successfully cured. Univariate logistic regression analysis indicated that several risk factors were related to PPFH: the nature of tumor (carcinoid/low-grade or high-grade malignancy), preoperative day 1 serum prealbumin, preoperative day 1 total bilirubin (TBIL), operative time, blood loss in the operation, operative method (vascular resection and revascularization), postoperative day 3 TBIL, biliary fistula, and the grade of POPF. The multivariate stepwise logistic regression analysis demonstrated that the nature of tumor and the grade of POPF were independently risk factors of PPFH. Receiver operating characteristic curve indicated that preoperative day 1 serum prealbumin level <173 mg/L and postoperative day 3 TBIL level ≥168 µmol/L were the risk factors of PPFH. CONCLUSIONS: The risk of PPFH was found to be increased with high potential malignancy and high grade of POPF. Angiography-embolization is one of the major and effective therapies for PPFH. Extraluminal-intraluminal PPFH is more serious and needs more aggressive treatments.


Assuntos
Hemorragia/etiologia , Fístula Pancreática/complicações , Pancreaticoduodenectomia/efeitos adversos , Adulto , Idoso , Embolização Terapêutica , Feminino , Hemorragia/terapia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Pré-Albumina/análise , Fatores de Risco
9.
J Invest Surg ; 36(1): 2180115, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37733388

RESUMO

BACKGROUND: Our objective is to compare the early outcomes associated with passive (gravity) drainage (PG) and active drainage (AD) after surgery. METHODS: Studies published until April 28, 2022 were retrieved from the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science databases. RESULTS: Nine studies with 14,169 patients were identified. Two groups had the same intra-abdominal infection rate (RR: 0.55; P = 0.13); In subgroup analysis of pancreaticoduodenectomy, active drainage had no significant effect on postoperative pancreatic fistula (POPF) rate (RR: 1.21; P = 0.26) and clinically relevant POPF (CR-POPF) (RR: 1.05; P = 0.72); Active drainage was not associated with lower percutaneous drainage rate (RR: 1.00; P = 0.96), incidence of sepsis (RR: 1.00; P = 0.99) and overall morbidity (RR: 1.02; P = 0.73). Both groups had the same POPF rate (RR: 1.20; P = 0.18) and CR-POPF rate (RR: 1.20; P = 0.18) after distal pancreatectomy. There was no difference between two groups on the day of drain removal after pancreaticoduodenectomy (Mean difference: -0.16; P = 0.81) and liver surgery (Mean difference: 0.03; P = 0.99). CONCLUSIONS: Active drainage is not superior to passive drainage and both drainage methods can be considered.


Assuntos
Abdome , Pâncreas , Humanos , Abdome/cirurgia , Drenagem/efeitos adversos , Pancreatectomia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Pancreaticoduodenectomia/efeitos adversos
10.
Indian J Orthop ; 56(6): 983-995, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35669028

RESUMO

Objective: This meta-analysis evaluated surgical outcomes following endoscopic or conventional discectomy for recurrent lumbar disc herniation. Methods: Medline, Cochrane, EMBASE, and Google Scholar were search until October 16, 2016 using these terms: recurrent lumbar disc herniation, endoscopic surgery, and discectomy. Randomized controlled trials (RCTs), prospective, retrospective, and cohort studies were eligible for inclusion. Pooled difference in mean (PDM) with 95% confidence interval (CIs) or relative risks (RRs) were calculated using fixed-effects methods. Results: One RCT and 15 studies were included with a total of 820 patients. Patients received endoscopic surgery experienced shorter operation time than those received conventional surgery (PDM: -52.01, 95% CI: -76.84 to -27.18, P < 0.001). A significantly lower risk in complication was displayed in patients received endoscopic surgery compared to those received conventional surgery (RR: 0.209, 95% CI: 0.076-0.581, P = 0.003). No significant difference in the improvement in VAS (PDM: -2.19, 95% CI: -5.78 to 1.39, P = 0.231), length of stay (PDM: -6.44, 95% CI: -13.76 to 0.89, P = 0.085) and re-recurrence rate (PDM: 0.88, 95% CI: 0.22-3.50, P = 0.861) between groups. Conclusions: Endoscopic and conventional discectomy reduced patient pain comparably, but endoscopic discectomy had significantly lower operation time and lower risk in complications, which may impact other outcomes such as recovery and healthcare costs. More studies are needed to confirm our findings. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-022-00636-1.

11.
Cell Death Discov ; 7(1): 390, 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34907162

RESUMO

Pancreatic cancer is a highly lethal malignancy due to failures of early detection and high metastasis in patients. While certain genetic mutations in tumors are associated with severity, the molecular mechanisms responsible for cancer progression are still poorly understood. Synaptotagmin-8 (SYT8) is a membrane protein that regulates hormone secretion and neurotransmission, and its expression is positively regulated by the promoter of the insulin gene in pancreatic islet cells. In this study, we identified a previously unknown role of SYT8 in altering tumor characteristics in pancreatic cancer. SYT8 levels were upregulated in patient tumors and contributed towards increased cell proliferation, migration, and invasion in vitro and in vivo. Increased SYT8 expression also promoted tumor metastasis in an in vivo tumor metastasis model. Furthermore, we showed that SYT8-mediated increase in tumorigenicity was regulated by SIRT1, a protein deacetylase previously known to alter cell metabolism in pancreatic lesions. SIRT1 expression was altered by orphan nuclear receptor ERRα and troponin-1 (TNNI2), resulting in cell proliferation and migration in an SYT8-dependent manner. Together, we identified SYT8 to be a central regulator of tumor progression involving signaling via the SIRT1, ERRα, and TNNI2 axis. This knowledge may provide the basis for the development of therapeutic strategies to restrict tumor metastasis in pancreatic cancer.

12.
Gland Surg ; 10(3): 1104-1117, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33842254

RESUMO

BACKGROUND: Pancreatic cancer (PC) is one of the most invasive and metastatic neoplasms among the fatal malignancies of the digestive system. Abnormal expression of genes and long non-coding RNAs (lncRNAs) are reportedly linked to multiple cancers. However, the lncRNA-mRNA expression profiles and their molecular mechanisms in PC progression are poorly known. This study aimed to map the hub genes and lncRNAs which might play core roles in the development of PC. METHODS: This study used microarray expression analysis to screen for both differentially expressed genes (DEGs) and differentially expressed lncRNAs (DElncRNAs) between PC and matched adjacent non-tumor (AN) tissues. In order to clarify the functional classification of DEGs, we conducted GO and KEGG pathway enrichment analyses via the Enrichr database. LncRNA-mRNA co-expressed networks were also constructed to explore the probable core regulating DEGs and DElncRNAs. Subsequently, the hub genes and lncRNAs were validated via the ONCOMINE and GEPIA databases and the co-expressed networks. RESULTS: By analyzing an mRNA-lncRNA microarray, we identified 943 mRNAs and 1,138 lncRNAs differentially expressed in PC tumors compared with the matched AN tissues. GO analysis confirmed that both up-regulated and down-regulated DEGs were enriched in multiple terms. The KEGG pathways enrichment analyses revealed that DEGs were mostly enriched in the focal adhesion and glutathione metabolism pathways, amongst others. Co-expressed networks were established to reveal the differential interactions between DEGs and DElncRNAs, and to indicate the core regulatory factors located at the core nodes of the co-expressed networks. The expression levels of potential core-regulating DEGs were validated by the GEPIA and ONCOMINE databases, and the relationship between overall survival and tumor stage and the potential core-regulating DEGs was analyzed using the GEPIA database. As a result, five genes and sixteen lncRNAs were finally considered as the hub transcripts in PC. CONCLUSIONS: This study identified DEGs and DElncRNAs between PC tumors and matched AN tissues, and these transcripts were connected with malignant phenotypes in PC through different BPs and signaling pathways. Furthermore, five hub genes and sixteen lncRNAs were identified, which are expected to represent candidate diagnostic biomarkers or potential therapeutic targets for PC.

13.
Front Genet ; 12: 650090, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249081

RESUMO

Pancreatic cancer (PCa) is one of the most aggressive lethal malignancies, and cancer metastasis is the major cause of PCa-associated death. F-box/LRR-repeat protein 7 (FBXL7) regulates cancer metastasis and the chemosensitivity of human pancreatic cancer. However, the clinical significance and biological role of FBXL7 in PCa have been rarely studied. In this study, we found that the expression of FBXL7 was down-regulated in PCa tissues compared with tumor-adjacent tissues, and the low expression of FBXL7 was positively associated with cancer metastasis. Functionally, overexpression of FBXL7 attenuated PANC1 cell invasion, whereas FBXL7 silencing promoted BxPC-3 cell invasion. Forced expression of FBXL7 upregulated the expression of epithelial markers (e.g., E-cadherin) and repressed the expression of mesenchymal markers (e.g., N-cadherin and Vimentin), indicating that FBXL7 negatively regulated the epithelial-mesenchymal transition (EMT) of PCa cells. Furthermore, we identified that FBXL7 repressed the expression of Snail1, a crucial transcription factor of EMT. Mechanistically, FBXL7 bound to Snail1 and promoted its ubiquitination and proteasomal degradation. In vivo studies demonstrated that FBXL7 inhibition promotes PCa metastasis. Taken together, our findings demonstrate that FBXL7 knockdown could efficiently enhance PCa metastasis by regulating Snail1-dependent EMT.

14.
Endocr Relat Cancer ; 26(7): 643-658, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31117050

RESUMO

Pancreatic neuroendocrine neoplasms (pNENs) are endocrine tumors arising in pancreas and is the most common neuroendocrine tumors. Mounting evidence indicates lncRNA H19 could be a determinant of tumor progression. However, the expression and mechanism of H19 and the relevant genes mediated by H19 in pNENs remain undefined. Microarray analysis was conducted to identify the differentially expressed lncRNAs in pNENs. H19 expression was analyzed in 39 paired pNEN tissues by qPCR. The biological role of H19 was determined by functional experiments. RNA pulldown, mass spectroscopy and RNA immunoprecipitation were performed to confirm the interaction between H19 and VGF. RNA-seq assays were performed after knockdown H19 or VGF. H19 was significantly upregulated in pNEN tissues with malignant behaviors, and the upregulation predicted poor prognosis in pNENs. In vitro and in vivo data showed that H19 overexpression promoted tumor growth and metastasis, whereas H19 knockdown led to the opposite phenotypes. H19 interacted with VGF, which was significantly upregulated in pNENs, and higher VGF expression was markedly related to poor differentiation and advanced stage. Furthermore, VGF was downregulated when H19 was knocked down, and VGF promoted cell proliferation, migration and invasion. Mechanistic investigations revealed that H19 activated PI3K/AKT/CREB signaling and promoted pNEN progression by interacting with VGF. These findings indicate that H19 is a promising prognostic factor in pNENs with malignant behaviors and functions as an oncogene via the VGF-mediated PI3K/AKT/CREB pathway. In addition, our study implies that VGF may also serve as a candidate prognostic biomarker and therapeutic target in pNENs.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Fatores de Crescimento Neural/metabolismo , Tumores Neuroendócrinos/metabolismo , Neoplasias Pancreáticas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo , Adulto , Idoso , Animais , Progressão da Doença , Feminino , Humanos , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Transdução de Sinais , Células Tumorais Cultivadas
15.
Front Microbiol ; 8: 1577, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28871243

RESUMO

Canine piroplasmosis is a significant disease in dogs caused by Babesia and Theileria parasites. The clinical manifestations range from mild illness to serious disease depending on the parasite species and the physical condition of the infected dog. Canine piroplasmosis has been reported to be prevalent in China. However, no molecular evidence of the disease has been reported in pet dogs from Wuhan. In this study, 118 blood samples were randomly collected from pet dogs in veterinary clinics. The blood samples were subjected to both microscopic examination and reverse line blot (RLB) hybridization assays to detect piroplasm infection. Parasites were observed in 10 blood samples via microscopic examination, whereas there were 14 Babesia gibsoni-positive RLB tests. Phylogenetic analysis was performed after the 18S rRNA and ITS gene sequences from the 14 positive samples were cloned and sequenced. The results confirmed the existence of B. gibsoni in this area. This is the first molecular report of canine babesiosis in pet dogs from Wuhan, China. Pet dogs are companion animals, and the prevalence of babesiosis will be of concern in daily life. This study will help veterinarians better understand the prevalence of canine babesiosis and provide a guide for disease control in pet dogs.

16.
Int J Clin Exp Pathol ; 8(9): 11747-52, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26617921

RESUMO

Immunoglobulin G4-related disease (IgG4-RD) is a recently described inflammatory disease involving multiple organs. Prostate involvement with IgG4-RD is very rare. In this report, we describe a case of IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy. This patient was present with urine retention symptoms. MRI and CT examination revealed the prostatic enlargement and the multiple lymphadenopathy. Serum IgG4 levels were elevated. Prostatic tissue samples resected both this time and less than 1 year earlier showed the same histological type of prostatitis with histopathologic and immunohistochemical findings characteristic of IgG4-RD. The right submandibular lymph nodes excised 2 years earlier were eventually proven to be follicular hyperplasia-type IgG4-related lymphadenopathy. This is the first case of IgG4-RD that began as localized IgG4-related lymphadenopathy and progressed into a systemic disease involving prostate and multiple lymph nodes. This patient showed a good response to steroid therapy. This leads us to advocate a novel pathogenesis of prostatitis, and a novel therapeutic approach against prostatitis. Pathologists and urologists should consider this disease entity in the patients with elevated serum IgG4 levels and the symptoms of prostatic hyperplasia to avoid ineffective medical or unnecessary surgical treatment.


Assuntos
Imunoglobulina G/imunologia , Doenças Linfáticas/imunologia , Doenças Linfáticas/patologia , Prostatite/imunologia , Prostatite/patologia , Idoso , Progressão da Doença , Humanos , Masculino
17.
Int J Surg ; 13: 84-89, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25481836

RESUMO

BACKGROUND: Postoperative pancreatic fistula (POPF) remains a leading cause of morbidity and mortality after pancreaticoduodenectomy (PD). Thus, a number of technical modifications regarding the pancreatoenteric anastomosis after PD have been proposed to reduce POPF rate. In this article we focused on evaluating whether the double layer continuous suture technique was better than the double layer interrupted suture technique in pancreatic-enteric anastomosis after PD. MATERIAL AND METHODS: From 2012 to 2013, 114 patients (67 men and 47 women) underwent a pancreatic-enteric anastomosis after PD were analysed. There were 79 patients using the double layer continuous suture technique and 35 patients were using the double layer interrupted suture technique. The operation time, intraoperative blood loss, initial postoperative day of oral feeding, postoperative hospital stay and the presence of main early complications (pancreatic fistulas) were evaluated by chi-square test or unpaired t-test in this study. RESULTS: Pancreatic fistulas occurred in patients with double layer continuous suture was 17.14%(6/35), and in those with interrupted suture was 39.24%(31/79) (p<0.05). Grade A of POPF was found in 4 patients (4/35, 11.43%) of the double layer continuous suture group and in 5 patients (5/79, 6.33%) of the double layer interrupted suture group. Grade B of POPF was identified only in 1 patients (1/35, 2.83%) of the double layer continuous suture group and in 23 patients (23/79, 29.11%) of the double layer interrupted suture group. The presence of Grade C pancreatic fistulas was only documented in one patient in the double layer continuous suture group and 3 patients in the interrupted suture group. No operative or in-hospital deaths occurred. CONCLUSIONS: The double-layer continuous suturing after PD is safe, reliable, rapid, favorable and associated with a lower risk of pancreatic fistula than the double layer interrupted suture.


Assuntos
Pâncreas/cirurgia , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/métodos , Pancreaticojejunostomia/efeitos adversos , Técnicas de Sutura/efeitos adversos , Adulto , Idoso , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Perda Sanguínea Cirúrgica , Distribuição de Qui-Quadrado , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Pancreatectomia/efeitos adversos , Período Pós-Operatório , Estudos Retrospectivos , Medição de Risco
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