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1.
Zhonghua Zhong Liu Za Zhi ; 46(7): 657-662, 2024 Jul 23.
Artigo em Chinês | MEDLINE | ID: mdl-39034801

RESUMO

Objectives: To explore the spatial distribution characteristics, trend changes, and spatial clustering of esophageal cancer among residents in China at the county (city, district) scale, a spatial epidemiological approach was used, with the aim of providing localized evidence for the prevention and treatment of esophageal cancer in China. Methods: The data source was the incidence (crude rate) and mortality (crude rate) of esophageal cancer from 2005 to 2016 in the 2008-2019 edition of China Cancer Registration Annual Report published by the National Cancer Center. The Joinpoint model was used for time trend analysis. The tumor registration area in 2016 was selected as the study area for spatial feature analysis, with a total of 487 counties (cities and districts), covering 27.6% of the national population. Spatial autocorrelation analysis was performed to reveal spatial distribution characteristics by using Arcgis 10.6 software, and spatial scanning statistics was used to analyze spatial clustering characteristics by using SaTScan 9.5 software. The log-likelihood ratio (LLR) and relative risk (RR) were calculated in different windows, and the region with the largest LLR value represented the most likely cluster. Results: From 2005 to 2016, the incidence and mortality rate of esophageal cancer in China showed a trend of increasing at first and then decreasing. The incidence and mortality rate of esophageal cancer in 2016 were characterized by spatial positive correlation. High incidence and high mortality were mainly concentrated in the areas through which the Huaihe River flowed. The primary clusters (taking high incidence rate as an example LLR=6 374.41, RR=2.37, P<0.001) were mainly distributed in Jiangsu, Anhui and Shandong in eastern China and eastern Henan and southern Hebei in central China, and secondary clusters (taking high incidence rate as an example LLR=1 971.19, RR=1.91, P<0.001) in Gansu, Ningxia Hui Autonomous Region, Shaanxi, Sichuan and other central and western regions. Conclusions: The incidence and mortality of esophageal cancer in China have decreased since 2010. The disease burden of esophageal cancer has obvious spatial differences, and measures should be taken according to local conditions in high-risk cluster areas such as the Huaihe River basin.


Assuntos
Neoplasias Esofágicas , Análise Espaço-Temporal , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Humanos , China/epidemiologia , Incidência , Análise por Conglomerados , Análise Espacial , Masculino
2.
Zhonghua Yi Xue Za Zhi ; 103(40): 3186-3192, 2023 Oct 31.
Artigo em Chinês | MEDLINE | ID: mdl-37879872

RESUMO

Objective: To investigate the oncological outcomes of active surveillance (AS) in patients showing thyroid nodules measuring≤1 cm with highly suspicious ultrasound features. Methods: A prospective single-center cohort study. A total of 534 patients with highly suspicious thyroid nodules (2015 American Thyroid Association Nodule Sonographic Patterns and Risk of Malignancy: High Suspicion) were enrolled in this study, the patients received AS at Peking Union Medical College Hospital between January 2017 and November 2022 to assess oncological outcomes (disease progression, recurrence/metastasis rate, etc). The patients were followed up every 6 months for physical examination and neck ultrasound examination. And the value of tumor volume changes in evaluating tumor enlargement was explored too. Results: There were 413 females and 121 males in this cohort, with a mean age of (42.6±11.8) years. During a median follow-up period of 45.6 months (ranged from 3.5 to 176.0 months), disease progression occurred in 26 patients (4.9%) with highly suspicious thyroid nodules, characterized by a minimum 3-mm increase in tumor diameter in 19 patients (3.6%) and lymph node metastases in 7 patients (1.3%). Forty-seven (8.8%) patients opted for delayed surgery, with 29 patients due to a change in preference. There was no significant differences in pathologic and follow-up outcomes between patients with disease progression and preference change. Patients aged≤40 years had a higher cumulative incidence of 5-year disease progression than those aged>40 years (4.9% vs 1.9%, P=0.060). No patients experienced distant metastases or deaths. Among the 595 high-risk thyroid nodules with continuous volume assessment results and an increase in nodule diameter of less than 3 mm (including all high-risk nodules in patients with single or multiple nodules), 184 (30.9%) and 79 (13.3%) nodules exhibited volume increases of more than 50% and 100%, respectively, in multiple measurements. Among the nodules with volume changes exceeding 50% and 100%, the proportion of nodules with a baseline tumor diameter of≤0.5 cm was significantly higher than those with a diameter of>0.5 cm, at 69.0% vs 31.0% (P<0.001) and 77.2% vs 22.8% (P<0.001), respectively. Conclusions: Active surveillance in patients with highly suspicious subcentimeter thyroid nodules has good short-term oncological outcomes and can be considered a safe alternative to surgery. Due to the large variability in the measurement results of tumor volume, it is not suitable as an indicator for evaluating tumor enlargement.


Assuntos
Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Estudos de Coortes , Estudos Prospectivos , Conduta Expectante , Ultrassonografia/métodos , Estudos Retrospectivos , Progressão da Doença
3.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(3): 272-276, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-34645172

RESUMO

Objective: To investigate the safety and feasibility of caudal-medial approach combined with "page-turning" middle lymphadenectomy in the laparoscopic right hemicolectomy. Methods: A descriptive cohort study was conducted. Clinical data of 35 patients who underwent laparoscopic radical right hemicolectomy using caudal-medial approach combined with "page-turning" middle lymphadenectomy at Department of Gastrointestinal Surgery, Guangdong Hospital of Chinese Medicine from April 2018 to May 2020 were retrospectively analyzed. All operations were performed consecutively by the same surgeon. The caudal-medial approach was used to dissect the right Toldt's fascia and the anterior pancreaticoduodenal space in a caudal-to-cranial and medial-to-lateral manner guided by the duodenum. The "page-turning" middle lymphadenectomy was used to dissect the mesocolon along the superior mesenteric vein with ileocolic vein, Henle's trunk and pancreas exposed preferentially. Results: All the 35 patients completed the operation successfully, and there was no damage and bleeding of superior mesenteric vessels and their branches. The operative time was (186.9±46.2) minutes, and the blood loss was 50 (10-200) ml. The first time to flatus was (2.1±0.6) days, and the time to fluid intake was (2.5±0.8) days. The postoperative hospital stay was 6 (3-18) d. The overall morbidity of postoperative complication was 8.6% (3/35), including grade II in 1 cases (2.8%) and grade IIIa in 2 case (5.7%) according to the Clavien-Dindo grading standard. The total number of lymph node dissected was 30.2±5.6, and the positive lymph node was 0 (0-7). Tumor staging revealed 5 cases of stage I, 18 cases of stage II, 11 cases of stage III, and 1 case of stage IVA. In this study, the median follow-up time was 15 (4-29) months. One patient died due to cerebrovascular accident 12 months after surgery, and no tumor recurrence or metastasis was observed in all other patients. Conclusions: Laparoscopic radical right hemicolectomy using caudal-medial approach combined with "page-turning" middle lymphadenectomy is safe and feasible. The anterior pancreaticoduodenal space is preferentially mobilized, which reduces the difficulty of central vascular dissection.


Assuntos
Neoplasias do Colo , Laparoscopia , Estudos de Coortes , Colectomia , Neoplasias do Colo/cirurgia , Humanos , Excisão de Linfonodo , Estudos Retrospectivos
4.
Zhonghua Xin Xue Guan Bing Za Zhi ; 49(8): 796-801, 2021 Aug 24.
Artigo em Chinês | MEDLINE | ID: mdl-34404189

RESUMO

Objective: To evaluate the efficiency of left cardiac sympathetic denervation (LCSD) in inherited arrhythmia patients with adrenergic activity-induced malignant ventricular arrhythmia, and observe exercise-stress test features before and after LCSD. Methods: This retrospective observational study included catecholaminergic polymorphic ventricular tachycardia(CPVT) and long QT syndromes(LQTS) patients who underwent video-assisted LCSD at Beijing Tsinghua Changgung Hospital and Peking University People's Hospital from September 2006 to May 2020. The indications for LCSD surgery were intolerant or refractory to beta-blocker medication. Clinical and exercise-stress tests data of included patients were collected before and 1 month after LCSD. Heart rate, exercise tolerance, atrial and ventricular arrhythmia, QTc interval and predictors for sudden cardiac death were analyzed. Patents were regularly followed up at 1, 3, 6, and 12 months after LCSD and then once every year thereafter. Cardiac events and medication adjustment records were collected. Results: Five patients (2 CPVT, 1 LQT1, and 2 LQT2)were included in the study. All patients experienced syncope as first symptom at the median age of 12(10, 16)years, and underwent LCSD at the median age of 21(16, 26)years, Baseline heart rate was similar before and after LCSD ((65.6±6.5) beats/min vs. (68.0±11.1) beats/min, P=0.57); while maximum workload tended to be lower after LCSD ((12.1±2.8) metabolic equivalents (METS) before surgery vs. (10.5±2.4) METS after surgery, P=0.07). Incidence of atrial and ventricular arrhythmia were significantly reduced post LCSD, and the ventricular arrhythmia score was decreased after LCSD in CPVT patients (4 points before LCSD vs. 3 points after LCSD in case 1;5 points before LCSD vs. 3 points after LCSD in case 2). QTc interval was shortened significantly in three LQTs patients (QTc interval at baseline heart rate: (546.6±72.3) ms before surgery vs. (493±61.1) ms after LCSD, P=0.047; QTc interval at maximal exercise heart rate: (516.3±73.7) ms before surgery vs. (486.7±64.2)ms after LCSD, P=0.035). Additionally, sudden cardiac death risk indicator ΔHRR1 (heart rate decreasing value within the first 1 min during recovery phase) decreased from (51.5±21.1) beats/min before surgery to (32.0±13.9) beats/min after surgery (P=0.035). During a median follow-up of 1(1, 4) year, all five patients were on low dosage of propranolol (37.0±21.7) mg/d. Cardiac events free survival was achieved in four out of 5 patients (80%) after sympathectomy, while 1 case suffered from sudden cardiac death after emotional stress. Conclusion: LCSD surgery can be safely and effectively performed in most hereditary arrhythmia patients with adrenergic activity-induced life-threatening cardiac events. Exercise stress test results show that LCSD could reduce malignant arrhythmias and improve sudden cardiac death risk indicators without decreasing heart rate.

5.
Eur Rev Med Pharmacol Sci ; 25(5): 2235-2244, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33755961

RESUMO

OBJECTIVE: Renal cell carcinoma (RCC) is the most common type of kidney cancer which could be mainly classified as kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP). KIRP ranks second in terms of morbidity rate which comprised 10%-15% of patients. Till now, there were few biomarkers could forecast the outcomes of KIRP. The aim of this study was to identify novel prognostic biomarkers to predict clinical outcomes for KIRP. MATERIALS AND METHODS: In this study, we firstly downloaded 326 miRNAs (35 controls vs. 291 patients), 321 mRNAs (33 controls vs. 288 patients) data and their corresponding clinical information from The Cancer Genome Atlas database. Then, we used DESeq2 analysis, univariate and multivariate Cox regression analysis, pathologic MNT correlation analysis, and specific prognostic model analysis to identify the potential prognosis biomarkers. RESULTS: We found 25 differential expression miRNAs (DEMs) and 7 differential expression genes (DEGs) were associated with the overall survival rates of KIRP patients. After multivariate Cox regression analysis, we established 2 prognostic prediction models and calculated the area under the 1-, 3-, and 5-year curve (AUC) values of DEMs and DEGs respectively. Among them, the prognostic index (PI) of DEMs and DEGs showed good predictive ability which was 0.8293/0.7205, 0.8148/0.7301 and 0.7776/0.6810 respectively. CONCLUSIONS: In this study, we found that 3 DEMs and 2 DEGs could be used as prognostic biomarkers to predict the outcome for KIRP. Our study was just a primary analysis based on high-throughput sequencing and clinical information.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Renais/genética , MicroRNAs/genética , Carcinoma de Células Renais/diagnóstico , Humanos , Neoplasias Renais/diagnóstico , Prognóstico
6.
Zhonghua Gan Zang Bing Za Zhi ; 28(9): 799-802, 2020 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-33053982

RESUMO

Aspirin, as a traditional non-steroidal anti-inflammatory drug, has therapeutic and preventive effects on gastrointestinal tumors. Hepatocellular carcinoma is one of the most common malignant tumors in the digestive tract, so it is necessary to find effective preventive and therapeutic measures. This article reviews the research progress and mechanism of aspirin on hepatocellular carcinoma with a view to provide references for future clinical treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Gastrointestinais , Neoplasias Hepáticas , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Humanos , Neoplasias Hepáticas/tratamento farmacológico
8.
Artigo em Chinês | MEDLINE | ID: mdl-31623049

RESUMO

Objective:To investigate the clinical characteristics, imaging features and treatment of neurogenic tumor in chilehood and to improve the experience in diagnosis and treatment for the disease. Method:The twenty-nine inpatients of histopathologically proven neurogenic tumor from January 2015 to December 2018 were retrospectively analyzed. The pathological types, clinical characteristics, imaging findings, and management were analyzed. Result: There were five cases of schwannoma aged from 9 years to 14 years, five cases of neurofibroma aged from 9 months to 9 years, and nineteen cases of neuroblastic tumor aged from 3 months to 5 years in our series. The chief manifestations were soft tissue masses, snore, and Honer syndrome. As the tumors had different components pathologically, on scans they presented as masses with heterogeneous density. Schwannoma showed as oval masses with clear margins, with the characteristic of"tail sign". The imaging findings of neurofibromas showed unclear boundaries and plexiform neurofibromas showed multiple clumps with visible separation. The ultrasonography of neuroblastic tumor was characterized by hypoechoic, heterogeneous and spotty calcification. All the cases underwent surgical resections. In 5 cases of schwannoma, it was confirmed that the tumors originated from the vagus nerve during the operation, which could be completely removed without postoperative complications. Two cases of neurofibromas were completely resected, 2 cases were only partially resected, and 1 case which located at the entrance of the esophagus was resected under supportive laryngoscopic for three times. Thirteen of 19 children with neuroblastogenic tumors underwent resection in our department after chemotherapy, and 2 patients with postoperative recurrence underwent another operation. Conclusion:Neuroblastoma is the most common neurogenic tumor in the head and neck of children. Most neurogenic tumors have their corresponding characteristics on imaging and should be differentiated. Schwannoma has clear boundary and intact capsule, so it is easier to complete resection. The neurofibroma is commonly difficult to remove with safety margin because of its unclear boundaries. Neuroblastoma should be treated according to the lesion range and stage. Most of the lesions are difficult to remove completely due to the wide range, peripheral blood vessels and important nerves. So preoperative chemotherapy is generally required.


Assuntos
Neoplasias de Cabeça e Pescoço , Neurilemoma , Neurofibroma , Criança , Humanos , Lactente , Recidiva Local de Neoplasia , Estudos Retrospectivos
10.
Transplant Proc ; 51(10): 3364-3368, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31358449

RESUMO

BACKGROUND: High hepatitis B virus (HBV) DNA level is strongly associated with hepatocellular carcinoma (HCC) development in chronic HBV infection. The aim of this study was to investigate the association between intrahepatic HBV DNA titer and post-liver transplantation (LT) prognosis for HBV-related HCC (HBV-HCC) patients. METHODS: A total of 60 patients with HBV-HCC who underwent LT were retrospectively studied. Using quantitative TaqMan fluorescent real-time polymerase chain reaction assay, HBV total DNA (tDNA) and covalently closed circular DNA (cccDNA) were both quantified in tumor tissue (TT) and adjacent non-tumor tissue (ANTT) from the explanted liver. RESULTS: The loads of tDNA and cccDNA in ANTT were associated with serum HBV DNA levels. Multivariate analysis showed that the presence of vascular invasion and cccDNA in TT were independent risk factors for tumor recurrence. The group of patients with cccDNA titers ≥31ogl0 copies/µg in TT had significantly higher cumulative recurrence rates than those with <31ogl0 copies/µg group. The cccDNA titers predicted the tumor recurrence with an area under the receiver operating characteristic curve of 0.664. CONCLUSIONS: Our findings would assist the clinical implementation of a more personalized therapy for tumor recurrence control and improve the prognosis of HBV-HCC patients.


Assuntos
Carcinoma Hepatocelular/virologia , DNA Viral/análise , Vírus da Hepatite B/genética , Neoplasias Hepáticas/virologia , Transplante de Fígado/efeitos adversos , Recidiva Local de Neoplasia/virologia , Complicações Pós-Operatórias/virologia , Adulto , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , DNA Circular/análise , Feminino , Hepatite B Crônica/complicações , Hepatite B Crônica/cirurgia , Hepatite B Crônica/virologia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Fatores de Risco
11.
Eur Rev Med Pharmacol Sci ; 23(9): 3569-3574, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31114980

RESUMO

OBJECTIVE: This work aims to study the influence of micro-ribonucleic acid (miR)-29 on the retinopathy in diabetic mice via the adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway. MATERIALS AND METHODS: A total of 24 C57BL/6 mice were randomly divided into normal group (n=12) and model group (n=12). Mice in the normal group were given to normal diet, and those in the model group were prepared for establishing diabetes mouse model. After animal procedures, electroretinogram was performed to detect the latent period and amplitude of b-wave. The expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected via immunohistochemistry. The protein levels of the phosphorylated AMPK (p-AMPK) and phosphorylated mammalian target of rapamycin (p-mTOR) were determined using Western blotting. Moreover, miR-29 expression and cell apoptosis were detected via quantitative Polymerase Chain Reaction (qPCR) and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL), respectively. RESULTS: Compared with those in the normal group, the latent period prolonged and amplitude of b-wave decreased in the model group (p<0.05). Immunohistochemistry showed that compared with normal group, mice in the model group exhibited increased Bax expression and decreased Bcl-2 expression (p<0.05). The Western blotting analysis showed that the protein levels of p-AMPK decreased and p-mTOR increased in the model group compared with those in the normal group (p<0.05). The qPCR revealed that compared with the normal group, the model group had notably decreased miR-29 expression (p<0.05). TUNEL detection displayed that the apoptotic rate was remarkably elevated in the model group compared with that in the normal group (p<0.05). CONCLUSIONS: Inhibition of miR-17-5p up-regulates the expression of VEGF-A and GDNF in MSCs, and promotes the repair of spinal cord injury by MSCs.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Experimental/metabolismo , MicroRNAs/metabolismo , Doenças Retinianas/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/patologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Estreptozocina/administração & dosagem
13.
Br J Oral Maxillofac Surg ; 56(2): 113-119, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29310844

RESUMO

Our aim was to improve the accuracy of measurement of the angulation and the shortening of the height of the ramus in fractures of the mandibular condyle using modified methods. We analysed spiral computed tomography (CT) of 67 unilateral fractures with the OsiriX v 5.0 (©Pixmeo Sarl) and Mimics 19.0 (©2016 Materialise NV, Belgium) and analysed them with SPSS (version 24.0, IBM® SPSS®). Angulation was measured using both the traditional method and our modified method. The results showed significant difference (p = 0.0001), and the values measured with the traditional method were lower, which is consistent with geometric analysis. We repositioned the condylar fragment with computer-aided surgical simulation and measured the shortened ramus. We were unable to find a significant difference between these values and those measured with our modified method (p = 0.053), so the accuracy of the modified method is acceptable. The measurement of the height of the ramus by our modified method is applicable to patients with unilateral, and those with bilateral, fractures. The accuracy in measurement of the major variables of condylar fractures is acceptable in both theory and practice. On the basis of such accurate measurement, more prospective clinical study is needed to find out the most appropriate treatment for condylar fractures.


Assuntos
Côndilo Mandibular/diagnóstico por imagem , Côndilo Mandibular/lesões , Fraturas Mandibulares/classificação , Fraturas Mandibulares/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Interpretação de Imagem Radiográfica Assistida por Computador
14.
Pharmacogenomics J ; 18(3): 450-459, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-28696419

RESUMO

As a common chemotherapy drug, methotrexate (MTX) has achieved remarkable clinical success. However, high inter-individual variability and unpredictable toxicity continue to challenge its use in clinical practices. Some studies suggest this variation is associated with a methylenetetrahydrofolate reductase (MTHFR) gene polymorphism, but results remain unclear. In this meta-analysis, we include 14 studies that focus on MTHFR C677T and A1298C polymorphisms in pediatric patients with malignancy. We found significant associations of the MTHFR C677T polymorphism with hepatotoxicity (grade ⩾2; CC vs CT/TT: risk ratio (RR): 0.82, 95% confidence interval (CI): 0.67-0.99; P=0.04), hematological toxicity (grade 3-4; CC vs CT/TT: RR: 0.65, 95% CI: 0.44-0.97; P=0.03) in a dominant genetic model and mucositis (grade ⩾3) in all models (CC vs CT/TT: RR: 0.18, 95% CI: 0.04-0.87; P=0.03; CC/CT vs TT: RR: 0.10, 95% CI: 0.03-0.32; P⩽0.0001; CC vs TT: RR: 0.10, 95% CI: 0.02-0.50; P=0.005). No significant association was found with the MTHFR A1298C polymorphism. For children with malignancy, genotyping of the MTHFR C677T polymorphism is expected to be a useful tool in reducing toxicity and improving outcome in personalized MTX therapy.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Metotrexato/efeitos adversos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Neoplasias/tratamento farmacológico , Criança , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Metotrexato/uso terapêutico , Neoplasias/genética , Neoplasias/patologia , Pediatria , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
15.
Oncogene ; 36(47): 6509-6517, 2017 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-28759036

RESUMO

Vaccinia H1-related phosphatase (VHR/DUSP3) is a member of the dual-specificity phosphatase family. Deregulation of VHR is observed in various malignant diseases. We identified focal adhesion kinase (FAK) as a VHR-interacting molecule. Over-expression of VHR decreased tyrosine phosphorylation of FAK and decreasing VHR promoted FAK tyrosine phosphorylation. In vitro assays proved that recombinant VHR directly dephosphorylated FAK and paxillin. VHR-knockout mice did not have obvious abnormality; however, VHR-knockout cells showed decreased expression of integrins and FAK but stronger FAK and paxillin phosphorylation upon attachment to fibronectin. Additionally, VHR-knockout fibroblast and lung epithelial cells had elevated ligand-induced epidermal growth factor receptor (EGFR) phosphorylation. Inducible expression of VHR suppressed directional cell migration, and VHR deficiency resulted in a higher cell migratory ability. VHR-knockout cells have stronger FAK phosphorylation in cell adhesions, long-lasting trailing ends and slower turnover of focal adhesions. These collective data indicate that VHR is a FAK phosphatase and participates in regulating the formation and disassembly of focal adhesions.


Assuntos
Adesão Celular , Movimento Celular , Fosfatase 3 de Especificidade Dupla/fisiologia , Quinase 1 de Adesão Focal/metabolismo , Animais , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Adesões Focais/metabolismo , Técnicas de Inativação de Genes , Humanos , Integrinas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Paxilina/metabolismo , Fosforilação/fisiologia , Tirosina/metabolismo
16.
Zhonghua Wai Ke Za Zhi ; 55(8): 592-598, 2017 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-28789509

RESUMO

Objective: To investigate the related factors for lymph node metastasis (LNM), especially for high volume LNM (>5 metastatic lymph nodes) in papillary thyroid carcinoma (PTC). Methods: The medical records of 2 073 consecutive PTC patients who underwent lobectomy, near-total thyroidectomy or total thyroidectomy with ipsilateral or bilateral central lymph node dissection in Department of General Surgery, Peking Union Medical College Hospital from November 2013 to October 2014 were reviewed. Clinical and pathological features were collected. Univariate and multivariate analysis were performed to identify the related factors for LNM/high volume LNM. Results: In all 2 073 patients, LNM and high volume LNM were confirmed in 936 (45.15%) cases and 254 (12.25%) cases respectively. In univariate analysis, large tumor size, young patients (<40 years), male were associated with both LNM and high volume LNM. In multivariate analysis, tumor size >2.0 cm, young patients (<40 years), male were independent related factors of LNM (OR=5.262, 95% CI: 3.468 to 7.986; OR=2.447, 95% CI: 2.000 to 2.995; OR=1.988, 95% CI: 1.593 to 2.480, respectively, all P=0.000) and high volume LNM (OR=6.687, 95% CI: 4.477 to 9.986; OR=2.975, 95% CI: 2.224 to 3.980; OR=2.354, 95% CI: 1.737 to 3.191, respectively, all P=0.000). In 1 414 PTMC patients, a similar result was also demonstrated.Compared with young patients (<40 years), old patients (≥60 years) had lower incidence of LNM (25.47% vs. 52.24%, χ(2)=62.903, P=0.000) and high volume LNM (1.89% vs. 13.18%, χ(2)=37.341, P=0.000). Additionally, old patients also had lower risk of both LNM (OR=0.316, 95% CI: 0.194 to 0.517, P=0.000) and high volume LNM (OR=0.142, 95% CI: 0.034 to 0.599, P=0.000). Conclusions: The tumor size was the main related factor for both LNM and high volume LNM in PTC. The treatment should be more active in patients with tumor size >2 cm with consideration of higher incidence and risk for LNM and high volume LNM. Young patient was another important related factor for LNM and high volume LNM. In PTMC, old patients had lower incidence and risk for both LNM and high volume LNM. Dynamic observation or less surgical extent could be an option for these patients.


Assuntos
Metástase Linfática , Neoplasias da Glândula Tireoide , Adulto , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
17.
Oncogene ; 36(38): 5369-5381, 2017 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-28504721

RESUMO

Exosomes are carriers of pro-tumorigenic factors that participate in glioblastoma (GBM) progression, and many fusion genes are strong driver mutations in neoplasia and are involved in tumorigenesis. However, the ability of fusion genes to be transduced by exosomes is unknown. We characterized exosomes from GBM cells harbouring and not harbouring PTPRZ1-MET fusion (ZM fusion). We also determined the effect of the exosomes from ZM fusion cells (ZM exosomes) on pro-oncogenic secretions and showed that ZM exosomes are internalized by the recipient cells. In addition, we studied the effect of ZM exosome-mediated intercellular communication in the GBM microenvironment. MET proto-oncogene expression was higher in ZM exosomes. Moreover, phosphorylated MET was detected only in ZM exosomes and not in exosomes released by non-ZM fusion GBM cells. ZM exosomes transferred to non-ZM fusion GBM cells and normal human astrocytes altered gene expression and induced epithelial-mesenchymal transition. The uptake of ZM exosomes also induced an exosome-dependent phenotype defined by GBM cell migration and invasion, neurosphere growth and angiogenesis. In addition, ZM exosomes conferred temozolomide resistance to the GBM cells, and exosome-derived ZM fusion network proteins targeted multiple pro-oncogenic effectors in recipient cells within the GBM microenvironment. Our findings show that exosomes mediate the aggressive character of GBM and demonstrate the role of ZM fusion in the exacerbation of this effect. These findings have possible implications for the foundation of gene fusion-based therapy for managing GBM.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Dacarbazina/análogos & derivados , Exossomos/metabolismo , Glioblastoma/tratamento farmacológico , Proteínas de Fusão Oncogênica/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/metabolismo , Animais , Comunicação Celular , Linhagem Celular Tumoral , Dacarbazina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas de Fusão Oncogênica/genética , Fenótipo , Fosforilação , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/genética , Temozolomida
18.
Zhonghua Xin Xue Guan Bing Za Zhi ; 45(4): 277-282, 2017 Apr 24.
Artigo em Chinês | MEDLINE | ID: mdl-28545277

RESUMO

Objective: To evaluate the effect of the ischemic post-conditioning (IPC) on the prevention of the cardio-renal damage in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI). Methods: A total of 251 consecutive STEMI patients underwent PPCI in the heart center of Tianjin Third Central Hospital from January 2012 to June 2014 were enrolled in this prospective, randomized, control, single-blinded, clinical registry study. Patients were randomly divided into IPC group (123 cases) and control group (128 cases) with random number table. Patients in IPC group underwent three times of inflation/deflation with low inflation pressure using a balloon catheter within one minute after culprit vessel blood recovery, and then treated by PPCI. Patients in control group received PPCI procedure directly. The basic clinical characteristics, incidence of reperfusion arrhythmia during the procedure, the rate of electrocardiogram ST-segment decline, peak value of myocardial necrosis markers, incidence of contrast induced acute kidney injury(CI-AKI), and one-year major adverse cardiovascular events(MACE) which including myocardial infarction again, malignant arrhythmia, rehospitalization for heart failure, repeat revascularization, stroke, and death after the procedure were analyzed between the two groups. Results: The age of IPC group and control group were comparable((61.2±12.6) vs. (64.2±12.1) years old, P=0.768). The incidence of reperfusion arrhythmia during the procedure was significantly lower in the IPC group than in the control group(42.28% (52/123) vs. 57.03% (73/128), P=0.023). The rate of electrocardiogram ST-segment decline immediately after the procedure was significantly higher in the IPC group than in the control group (77.24% (95/123) vs. 64.84% (83/128), P=0.037). The peak value of myocardial necrosis markers after the procedure were significantly lower in the IPC group than in the control group(creatine kinase: 1 257 (682, 2 202) U/L vs. 1 737(794, 2 816)U/L, P=0.029; creatine kinase-MB: 123(75, 218)U/L vs.165(95, 288)U/L, P=0.010). The rate of CI-AKI after the procedure was significantly lower in the IPC group than in the control group(5.69%(7/123) vs. 14.06%(18/128), P=0.034). The rate of the one-year MACE was significantly lower in the IPC group than in the control group(7.32%(9/123) vs. 15.63% (20/128), P=0.040). Conclusion: The IPC strategy performed eight before PPCI can reduce myocardial ischemia- reperfusion injury, decline the rates of CI-AKI and one-year MACE significantly in STEMI patients, thus has a significant protective effect on heart and kidney in STEMI patients. Clinical Trial Registration Chinese Clinical Trials Registry, ChiCTR-ICR-15006590.


Assuntos
Injúria Renal Aguda/prevenção & controle , Infarto Miocárdico de Parede Anterior , Pós-Condicionamento Isquêmico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Idoso , Biomarcadores , Creatina Quinase Forma MB , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Estudos Prospectivos
19.
Zhonghua Liu Xing Bing Xue Za Zhi ; 38(3): 320-325, 2017 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-28329932

RESUMO

Objective: To grope for an ideal immune strategy in grown-ups via comparison of immunological effects under 4 different vaccination schemes. Methods: Study population was selected by stratified random cluster sampling. A total of 4 different vaccination proposals, including Strategy A (3 doses, 10 µg, administrated repeatedly into the unilateral deltoid muscle at 0-1-6 months), Strategy B (2 doses, 20 µg, administrated into the bilateral deltoid muscles simultaneously), Strategy C (3 doses, 10 µg, administrated repeatedly into the unilateral deltoid muscle at 0-1-2 months) and Strategy D (2 doses, 10 µg, administrated to the bilateral deltoid muscles at the same time), were conducted in Liangzhou, Minqin Gulang, and the Tianzhu Tibetan Autonomic county respectively, in Wuwei city, Gansu province. Under 4 different strategies, post-vaccination immunological effectiveness was evaluated when blood samples of participants collected in the eighth months, post-first injection and in the third year, and tested by enzyme-linked immunoassays and electro-chemiluminescence immunoassay. Chi-squared test and Fisher exact test were used to evaluate the immunological differences between the 4 strategies. Wilcoxon' s signed rank test and Kruskal-Waillis H test were conducted to compare the differences of the geometric mean titers (GMTs) of antibody against HBV surface antigen (anti-HBs) titers. Results: A total of 1 621 eligible participants aged 16 to 60 years old, were recruited for the study. Numbers of administration and gender were testified as the presuming factors for influencing immune effectiveness. The vaccination completion rates were 53.97% and 79.82% in Strategy A and C, respectively, and the difference statistically significant (P<0.05). In the first year, the protective antibody sero-conversion rates (standardization rate) were 89.21%, 54.88%, 92.11%, and 41.63%, in Strategy A, B, C and D, respectively, and the significant statistically differences emerged (P<0.05) if Strategy B, C and D were compared with Strategy A (as the gold standard). Over a 3-year follow-up period, the levels of GMTs on protective antibody declined from 179.2 IU/L, 51.6 IU/L, 277.1 IU/L and 10.1 IU/L to 61.3 IU/L, 21.2 IU/L, 31.8 IU/L and 6.0 IU/L in Strategy A, B, C and D, respectively, and the differences of declination on GMTs showed statistically significant differences (P<0.05) when compared within or between the 4 strategies. Conclusion: The 0-1-2 months' prophylactic schedules (Strategy C) seemed superior to the others, in terms of effectively inducing the protective antibody, with shorter duration of vaccination, persisting longer immunity and having higher rate of completive vaccination, so is worth to be recommended as a feasible immune programme for adults, especially for migrants from the rural regions.


Assuntos
Anticorpos Anti-Hepatite B/imunologia , Vacinas contra Hepatite B/imunologia , Hepatite B/imunologia , População Rural , Adulto , Esquema de Medicação , Feminino , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Humanos , Técnicas Imunoenzimáticas , Masculino , Fatores de Tempo , Vacinação/métodos
20.
Transplant Proc ; 48(4): 1059-62, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27320556

RESUMO

BACKGROUND: Recipient hepatectomy can be complicated by severe bleeding during caudate lobe dissection in living-donor liver transplantation (LDLT), especially when the inferior vena cava is encased or with dense adhesions from prior interventions. Total hepatic vascular exclusion (TVE) including total hepatic inflow (Pringle maneuver) and occlusion of supra- and infra-hepatic inferior vena cava during the partial hepatectomy has been studied well, but it has not been mentioned regarding recipient hepatectomy in LDLT. The aim of this study is to evaluate hemodynamic impact and surgical outcome by using the technique of TVE in LDLT. METHODS: From April 2010 to June 2010, 30 consecutive LDLT recipients at Kaohsiung Chang Gung Memorial Hospital with TVE (TVE group, n = 14) or without TVE (non-TVE group, n = 16) for the caudate lobe dissection were analyzed retrospectively. RESULTS: The TVE group had a mean decrease in systolic blood pressure and cardiac index of 21% and 41% during caudate dissection in recipient hepatectomy, respectively. The TVE group had shorter time for caudate mobilization and less blood loss compared with the non-TVE group (3904 mL vs. 5650 mL, P = .461). Two patients in the non-TVE group were shifted to TVE as a salvage procedure to control bleeding. Three patients in the non-TVE group underwent relaparotomy for homeostasis. CONCLUSIONS: Short-term TVE is a technically feasible procedure and should be considered during recipient hepatectomy with difficult caudate lobe dissection in LDLT to create a bloodless surgical field. Most patients tolerated the TVE without hemodynamic impact under anesthetic management.


Assuntos
Dissecação/métodos , Procedimentos Endovasculares/métodos , Hepatectomia/métodos , Veias Hepáticas/cirurgia , Transplante de Fígado/métodos , Adulto , Perda Sanguínea Cirúrgica/prevenção & controle , Pressão Sanguínea , Feminino , Hepatectomia/efeitos adversos , Veias Hepáticas/fisiopatologia , Humanos , Fígado/irrigação sanguínea , Fígado/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Veia Cava Inferior/cirurgia
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