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1.
Int J Clin Oncol ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31720994

RESUMO

OBJECTIVE: PBRM1, located on 3p21, functions as a tumor suppressor and somatic mutation of PBRM1 is frequent in clear cell renal cell carcinoma (ccRCC). This study aims to determine the influence of PBRM1 expression on the prognosis of patients with mRCC receiving tyrosine kinase inhibitor (TKI) treatment. METHODS: We identified 116 mRCC patients who were administered sunitinib or sorafenib as first-line therapy, between January 2006 and December 2016 at our institution. PBRM1 expression was assessed by immunohistochemistry. The Kaplan-Meier method was used to estimate the progression-free survival (PFS) and overall survival (OS), log-rank test was used to compare the survival outcomes between patients with low and high PBRM1 expression levels, and the Cox proportional hazard regression model was used to estimate the prognostic value. Prognostic accuracy was determined using Harrell concordance index, and nomograms were built to evaluate the prognosis of mRCC. RESULTS: Patients with low PBRM1 expression had significantly shorter median PFS (9 vs 26 months, P < 0.001) and OS (21 vs 44 months, P < 0.001) than those with high expression. Multivariate analysis showed that PBRM1 expression was an independent predictor of PFS (HR 1.975, P = 0.013) and OS (HR 2.282, P = 0.007). The model built by the addition of PBRM1 improved the C-index of PFS and OS to 0.72 and 0.82, respectively. CONCLUSIONS: The expression of PBRM1 could be a significant prognostic factor for mRCC patients treated with targeted therapy, and it increases the prognostic accuracy of the established prognostic model.

2.
Cell Death Differ ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570854

RESUMO

Metastasis is one of the main contributors to the poor prognosis of hepatocellular carcinoma (HCC). However, the underlying mechanism of HCC metastasis remains largely unknown. Here, we showed that TXNDC12, a thioredoxin-like protein, was upregulated in highly metastatic HCC cell lines as well as in portal vein tumor thrombus and lung metastasis tissues of HCC patients. We found that the enforced expression of TXNDC12 promoted metastasis both in vitro and in vivo. Subsequent mechanistic investigations revealed that TXNDC12 promoted metastasis through upregulation of the ZEB1-mediated epithelial-mesenchymal transition (EMT) process. We subsequently showed that TXNDC12 overexpression stimulated the nuclear translocation and activation of ß-catenin, a positive transcriptional regulator of ZEB1. Accordingly, we found that TXNDC12 interacted with ß-catenin and that the thioredoxin-like domain of TXNDC12 was essential for the interaction between TXNDC12 and ß-catenin as well as for TXNDC12-mediated ß-catenin activation. Moreover, high levels of TXNDC12 in clinical HCC tissues correlated with elevated nuclear ß-catenin levels and predicted worse overall and disease-free survival. In summary, our study demonstrated that TXNDC12 could activate ß-catenin via protein-protein interaction and promote ZEB1-mediated EMT and HCC metastasis.

4.
J Clin Lab Anal ; : e23017, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31441128

RESUMO

BACKGROUND: Thromboelastography (TEG) has been established as a sensitive method to assess the whole coagulation process. The aim of the study was to evaluate the diagnosis significance of TEG on hypercoagulability in patients suffering renal mass. METHODS: A total of 478 patients were diagnosed with renal tumor by histolopathologic examination and were assigned to three groups. Group A: 79 patients with benign renal tumor; Group B: 317 patients with renal cell carcinoma (RCC, Fuhrman grades I and II); Group C: 82 patients with high-risk RCC (Fuhrman grades III and IV). Subgroup analysis was performed in malignant renal tumor patients according to the TMN classification. The clinical data, whole blood TEG, and conventional coagulation tests were reviewed. RESULTS: There was no statistically significant difference between subgroups in respect to conventional coagulation tests. Hypercoagulablity was marked in Group C according to the TEG parameters. The elevated platelets and fibrinogen is linked with hypercoagulability in renal tumor. The positive correlation was between fibrinogen and MA value (r = .663, P < .05). The pathologic tumor stages were also associated with the TEG parameters. CONCLUSION: Patients suffering advanced RCC are hypercoagulable which can be identified by TEG. MA value could be potential diagnosis indicators for detecting high-grade RCC.

5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(6): 588-591, 2019 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-31055812

RESUMO

OBJECTIVE: To identify potential mutation in a child clinically diagnosed as Noonan syndrome and to provide genetic counseling and prenatal diagnosis for his family. METHODS: Genomic DNA was extracted from peripheral blood samples of the patient and his parents, and amniotic fluid was taken from the mother during the second trimester. Next generation sequencing (NGS) was used to screen potential mutations from genomic DNA. Suspected mutation was verified by Sanger sequencing. RESULTS: A heterozygous c.4A>G (p.Ser2Gly) mutation of the SHOC2 gene was identified in the patient but not among other family members including the fetus. CONCLUSION: The Noonan syndrome is probably caused by the c.4A>G mutation of the SHOC2 gene. NGS is helpful for the diagnosis of complicated genetic diseases. SHOC2 gene mutation screening is recommended for patient suspected for Noonan syndrome.


Assuntos
Síndrome de Noonan , Criança , Feminino , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Mutação , Gravidez , Diagnóstico Pré-Natal
6.
Cancer Res ; 79(13): 3220-3234, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31101763

RESUMO

Understanding the roles of noncoding RNAs (ncRNA) in tumorigenesis and metastasis would establish novel avenues to identify diagnostic and therapeutic targets. Here, we aimed to identify hepatocellular carcinoma (HCC)-specific ncRNA and to investigate their roles in hepatocarcinogenesis and metastasis. RNA-seq of xenografts generated by lung metastasis identified long noncoding RNA small nucleolar RNA host gene 10 (SNHG10) and its homolog SCARNA13 as novel drivers for the development and metastasis of HCC. SNHG10 expression positively correlated with SCARNA13 expression in 64 HCC cases, and high expression of SNHG10 or SCARNA13 was associated with poor overall survival. As SCARNA13 showed significant rise and decline after overexpression and knockdown of SNHG10, respectively, we hypothesized that SNHG10 might act as an upstream regulator of SCARNA13. SNHG10 and SCARNA13 coordinately contributed to the malignant phenotype of HCC cells, where SNHG10 served as a sponge for miR-150-5p and interacted with RPL4 mRNA to increase the expression and activity of c-Myb. Reciprocally, upregulated and hyperactivated c-Myb enhanced SNHG10 and SCARNA13 expression by regulating SNHG10 promoter activity, forming a positive feedback loop and continuously stimulating SCARNA13 expression. SCARNA13 mediated SNHG10-driven HCC cell proliferation, invasion, and migration and facilitated the cell cycle and epithelial-mesenchymal transition of HCC cells by regulating SOX9. Overall, we identified a complex circuitry underlying the concomitant upregulation of SNHG10 and its homolog SCARNA13 in HCC in the process of hepatocarcinogenesis and metastasis. SIGNIFICANCE: These findings unveil the role of a noncoding RNA in carcinogenesis and metastasis of hepatocellular carcinoma.

7.
Int J Biol Macromol ; 130: 117-124, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30807797

RESUMO

Nitrilase-catalyzed regioselective hydrolysis of 1-cyanocyclohexaneacetonitrile (1-CHAN) is a green and efficient approach for the preparation of 1-cyanocyclohexaneacetic acid (1-CHAA), a key precursor for the synthesis of gabapentin. Here, a mesoporous biosilica particles prepared by the ethyleneamine-mediated silicification have been used as carrier for the encapsulation of nitrilase from Acidovorax facilis (NitA). The silica-encapsulated NitA (NitA@silica) with triethylenetetramine as an initiator showed the highest immobilization efficiency (98.3%) and specific activity (672.6 U/g). Both free and encapsulated NitA were optimally active at 40 °C and pH 7.0, however, the encapsulated enzyme exhibited wider optimum temperature range, and enhanced thermal stability compared with the free enzyme. The kinetic parameters Km and Vmax for free and encapsulated NitA were calculated to be 141 mM and 9.97 mM min-1, and 280 mM and 9.02 mM min-1, respectively. The encapsulated NitA showed good reusability and retained about 94.2% of its initial activity even after 16 cycles of reaction. Also, the storage experiments revealed high activity maintenance of encapsulated NitA after 17-day storage at 4 °C. A preparative scale regioselective hydrolysis of 1-CHAN to 1-CHAA with encapsulated NitA as biocatalyst was carried out in a 2 L stirred bioreactor. The concentration of 1-CHAA reached 152 g/L after 8 h reaction and the conversion was 90.9%. These results showed that the encapsulation of NitA in ethyleneamine-mediated biosilica is an efficient and simple way for preparation of stable nitrilase and have a great potential for application in enzymatic production of carboxylic acids.


Assuntos
Acetonitrilos/química , Aminoidrolases/química , Aminoidrolases/metabolismo , Biocatálise , Cicloexanos/química , Nitrilos/química , Trientina/química , Acetonitrilos/metabolismo , Cápsulas , Cicloexanos/metabolismo , Estabilidade Enzimática , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Concentração de Íons de Hidrogênio , Hidrólise , Cinética , Nitrilos/metabolismo , Dióxido de Silício/química , Estereoisomerismo , Especificidade por Substrato , Temperatura Ambiente
8.
Water Sci Technol ; 78(8): 1802-1811, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30500804

RESUMO

A series of different ratios of Ag2S/ZnO/ZnS nanocomposites with visible light response were prepared by a microwave-assisted hydrothermal two-step method, whose composition, crystalline structure, morphology and surface physicochemical properties were well-characterized via X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), UV-vis diffuse reflectance spectroscopy (UV-vis/DRS), photoluminescence spectrum (PL), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HR-TEM) and N2 adsorption-desorption measurements. Results showed that as-composites mainly consisted of ZnS crystal phase, whose grain size increased obviously compared with non Ag2S samples. At the same time, due to the introduction of narrow band gap Ag2S, the synthesized composite can effectively increase the visible optical absorption of ZnO/ZnS composites. Among them, 1% Ag2S/ZnO/ZnS showed a mixed structure of nano-line and nano-particle, of which BET value increased significantly, and the morphology was more excellent. Photocatalytic activities of a series of Ag2S/ZnO/ZnS composites under different light sources were studied using methyl orange as a model molecule, and 1% Ag2S/ZnO/ZnS was taken as the best one. Meanwhile, 1% Ag2S/ZnO/ZnS also showed a good degradation effect on other dyes with different structures, and its degradation efficiency did not change significantly after three cycles, showing certain stability. In addition, composites with Ag2S loading of 1% possessed the highest hydrogen production ability of photolysis water, indicating that the introduction of Ag2S had significantly enhanced the catalytic performance.

9.
J Clin Lab Anal ; : e22660, 2018 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-30221396

RESUMO

BACKGROUND: Congenital heart disease (CHD) is a common birth defect originating from both environmental and genetic factors. An overabundance of copy number variations (CNVs) affecting cardiac-related genes has previously been detected in individuals with CHD. OBJECTIVE: To evaluate if the presence of CNVs in the 22q11.2 region, and to determine whether GATA4, NKX2-5, TBX5, BMP, and CRELD1 genes contributed toward the pathogenesis of isolated incidences of CHDs in southwest China. METHODS: In total 167 patients from southwest China with sporadic CHD were studied, including 121 patients with ventricular septal defect (VSD), 24 with atrial septal defect (ASD), 12 with tetralogy of fallot (TOF), six VSD cases with TOF, two cases with patent ductus arteriosus (PDA), and two VSD cases with ASD. 22q11.2, GATA4, NKX2-5, TBX5, BMP4, and CRELD1 regions were screened using MLPA and copy number variation sequencing (CNV-Seq). RESULTS: A 2.5-2.8 Mb deletion in the 22q11.2 region was identified in 5 patients with CHD. Two of these patients were diagnosed with VSD, while two had VSD and ASD, and the other had TOF. 5 patients correspond to the same classical DiGeorge syndrome. A 0.86 Mb duplication in the 22q11.2 region was identified in a PDA patient, whom was without extracardiac symptoms. CONCLUSION: These data suggest that copy number variation in the 22q11.2 region is common in CHD patients in southwest China. Regardless of the presence or absence of extracardiac symptoms, results also indicate that it is necessary to perform prenatal screening for CHD.

10.
Urol Int ; 101(4): 391-399, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30184524

RESUMO

OBJECTIVES: The purpose of this work was to investigate the effect of sorafenib or sunitinib as neoadjuvant therapy on the survival outcomes of renal cell carcinoma (RCC) with tumor thrombus. METHODS: A total of 92 RCC patients with tumor thrombus were included in this 2-center retrospective research from January 2007 to December 2014. Sorafenib and sunitinib were administered as neoadjuvant therapy in 9 patients and 14 patients, respectively, and 69 patients constituted non-neoadjuvant therapy groups. The Kaplan-Meier method was used to estimate the recurrence-free survival (RFS) and overall survival (OS). Log-rank test was used to compare the survival outcomes of patients with or without neoadjuvant therapy. RESULTS: The overall median RFS and OS time for all 92 patients were 28 months (95% CI 17-39 months) and 42 months (95% CI 30-54 months). Patients with neoadjuvant therapy had no significantly longer median RFS (30 vs. 28 months, p = 0.376) and OS (45 vs. 42 months, p = 0.702) than those without neoadjuvant therapy. CONCLUSIONS: Neoadjuvant therapy of sorafenib or sunitinib might not improve survival outcomes for high risk RCC patients with tumor thrombus. Thus, neoadjuvant therapy for RCC with tumor thrombus should be considered cautiously.

11.
Biosci Trends ; 12(2): 208-210, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29760360

RESUMO

Laparoscopic liver resection (LLR) has garnered attention as a new form of liver surgery. In China, many hepatobiliary surgeons are now encouraging the examination and assessment of LLC in order to improve its outcomes, and several young hepatobiliary surgeons recently shared their clinical experiences and the results of their research in presentations at the Akamon Forum as part of the 118th Annual Congress of the Japan Surgical Society, which was held April 5-7, 2018 in Tokyo, Japan. In China, LLR has gradually improved over the past 20 years, including both expanded indications and improved surgical approaches. However, China is a vast country, and the level of medical care varies nationwide. Medical facilities that can perform advanced laparoscopic techniques are currently limited to those in large cities. Moreover, additional clinical studies of the long-term oncological outcomes of LLR need to be performed in the future.


Assuntos
Hepatectomia/métodos , Laparoscopia/estatística & dados numéricos , Neoplasias Hepáticas/cirurgia , Cirurgiões , China , Congressos como Assunto , Hepatectomia/estatística & dados numéricos , Hepatectomia/tendências , Humanos , Laparoscopia/métodos , Laparoscopia/tendências , Tóquio , Resultado do Tratamento
12.
HPB (Oxford) ; 20(9): 795-802, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29779970

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignancy in liver. Transarterial chemoembolization (TACE) is recommended as an effective treatment in advanced HCC patients. Recent studies showed iodine-125 seed (a low-energy radionuclide) can provide long-term local control and increase survival for HCC patients. The aim of the study was to evaluate the outcome of TACE plus iodine-125 seed in comparison with TACE alone for HCC. METHODS: A comprehensive search of studies among PubMed, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews was conducted with published date from the earliest to January 10th, 2018. No language restrictions were applied, while only prospective randomized controlled trials (RCTs) or non-randomized controlled trials (non-RCTs) were eligible for a full-text review. The primary outcome was overall survival (OS), response rate (the rate of partial atrophy or complete clearance of the tumor lesion) and adverse events (AEs). The odds ratios (ORs) were combined using either fixed-effects model or random-effects model. All statistical analyses were performed using the Stata 12.0 software. RESULTS: 9 studies were included, involving 894 patients. Among them, 473 patients received combined therapy of TACE plus iodine-125 implantation, compared with 421 patients with TACE alone. Patients receiving combined therapy of TACE plus iodine-125 showed significantly improvement in 1-year OS (OR = 4.47, 95% confidence intervals (CI): 2.97-6.73; P < 0.001), 2-year OS (OR = 4.72, 95% CI: 2.63-8.47; P < 0.001). No significant publication bias was observed in any of the measured outcomes. CONCLUSIONS: Based on these findings, TACE plus iodine-125 implantation achieves better clinical efficacy compared with TACE alone in the treatment of HCC.

13.
Urol Oncol ; 36(6): 307.e15-307.e21, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29599070

RESUMO

PURPOSE: We examined the incidence of pulmonary thromboembolism (PE) and deep venous thromboembolism (DVT) in patients who underwent urologic tumor surgery. The aim of this study was to investigate the postoperative D-dimer for prediction of venous thromboembolism events (VTE), as well as to identify other risk factors associated with the occurrence of thromboembolisms. PATIENTS AND METHODS: This was a prospective observational cohort study, which included 1,269 patients who underwent major urologic tumor surgery, from August 2015 to February 2017, at our center. Data comprising age, sex, body mass index, Charlson comorbidity index, type of surgery, Caprini score, postoperative D-dimer levels, and other laboratory tests were collected for analyses. Lower limb venous ultrasound was performed before surgery and the day before hospital discharge to measure DVT. Computerized tomography or ventilation/perfusion lung scan was applied to detect PE. RESULTS: The overall incidence of VTE was 2.4% (31 cases) in 1,269 patients, consisting of 23 PE events and 9 DVT events. Patients undergoing radical cystectomy were most likely to suffer VTE (4.3%). The optimal cutoff value for postoperative D-dimer was 0.98µg/ml, according to the receiver operating characteristic curve analysis, with a sensitivity of 83.9%, and a specificity of 80.0%. On multivariate analysis, hypertension (odds ratio, OR = 2.5, 95% CI: 1.1-5.7; P = 0.026), Charlson comorbidity index ≥ 2 (OR = 5.6, 95% CI: 2.2-14.6; P<0.001), and D-dimer lever ≥ 1µg/ml on postoperative day 1 (OR = 12.52, 95% CI: 4.6-35.2; P<0.001) were independently associated with VTE after urologic tumor surgery. CONCLUSIONS: The overall incidence of urologic-tumor-surgery-associated VTE in an Asian population is similar to those reported in European and North American series. Elevated D-dimer early after operation is an independent predictor of VTE in patients undergoing urologic tumor surgery. In addition, hypertension and the Charlson comorbidity index are both important clinical risk factors. The Caprini score recommended by the guideline is inadequate in this study population. The postoperative D-dimer plasma level is a more reliable marker for identifying patients at high-risk of developing venous thromboembolisms.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Complicações Pós-Operatórias/diagnóstico , Neoplasias Urológicas/cirurgia , Procedimentos Cirúrgicos Urológicos/efeitos adversos , Tromboembolia Venosa/diagnóstico , Idoso , China/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Tromboembolia Venosa/sangue , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia
14.
Sci Rep ; 8(1): 5395, 2018 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-29599483

RESUMO

Hepatocellular carcinoma (HCC) is one of the most prevalent subtypes of liver cancer worldwide. LncRNAs have been demonstrated to be associated with the progression of HCC, but a systematic identification and characterization of their clinical roles and molecular mechanisms in HCC has not been conducted. In this study, the aberrantly expressed lncRNAs in HCC tissues were analyzed based on TCGA RNA-seq data. 1162 lncRNAs were found to be aberrantly expressed in HCC tissues, including 232 down-regulated lncRNAs and 930 up-regulated lncRNAs. The top 5 lncRNAs with the highest diagnostic accuracy were further analyzed to evaluate their clinical value and potential mechanism in HCC. Kaplan-Meier curves showed that higher expressions of DDX11-AS1 and AC092171.4 were in correlation with poorer survival in HCC patients. Significant difference was also observed when comparing the expression levels of DDX11-AS1 and SFTA1P in different clinical parameters (p < 0.05). GO analysis showed that genes regulated by the 5 lncRNAs were enriched in certain pathways, such as PI3K pathway. Moreover, GSEA analysis on the expression of DDX11-AS1 showed that DDX11-AS1 affected the gene expressions involved in HCC proliferation, differentiation and cell cycle, indicating an essential role of DDX11-AS1 in hepatocarcinogenesis.

15.
Medicine (Baltimore) ; 97(8): e0033, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29465544

RESUMO

The aim of this study was to evaluate different surgical therapies for hepatic alveolar echinococcosis in different clinical stages.We analyze the clinical data of 115 patients who received surgical treatment in West China Hospital from January 2004 to June 2016. Among these patients, 77 cases underwent radical hepatic resection (group A, n = 77); 17 cases underwent palliative resection (group B, n = 17), and 21 cases underwent liver transplantation (group C, n = 21) with 12 cases of orthotopic liver transplantation and 9 cases of liver autotransplantation.The postoperative complication rate of radical hepatic resection group was 13.0% (10/77), which is statistically significant (P < .05) than the rate of palliative resection group 29.4% (5/17) or liver transplantation group 23.8% (5/21). The follow-up period ranged from 1 to 72 months. The overall median survival rate of radical resection was 72/77, higher than the rate of palliative group (12/17) or transplantation group (17/21), which was also statistically significant (P < .01).In our study, we believe in that all stages of hepatic alveolar echinococcosis should take active surgical interventions, and radical hepatic resection should be considered as the first-choice treatment for early stage of alveolar echinococcosis, while palliative surgery is still helpful to relieve symptoms and improve the life quality for advanced patients. Liver transplantation might also be an alternative option for the late-stage hepatic alveolar echinococcosis.


Assuntos
Equinococose Hepática/cirurgia , Hepatectomia/efeitos adversos , Transplante de Fígado/efeitos adversos , Cuidados Paliativos/métodos , Complicações Pós-Operatórias/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Feminino , Hepatectomia/métodos , Humanos , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
16.
J Cancer Res Clin Oncol ; 144(1): 39-52, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28993942

RESUMO

PURPOSE: Renal cell carcinoma (RCC) is the most common malignancy of urogenital system, and patients with RCC may face a poor prognosis. However, limited curable therapeutic options are currently available. The aim of this study is to investigate the role of Cannabinoid receptor 2 (CB2) in RCC progression. METHODS: Immunohistochemistry was to investigate the expression pattern of CB2 in 418 RCC tissues and explore its prognostic function in RCC patients. Furthermore, the role of used CB2 si-RNA knockdown and inhibited by AM630, a CB2 inverse agonist, on cell proliferation, migration, and cell cycle of RCC cell lines in vitro was also investigated. RESULTS: We observed that CB2 was up-regulated in RCC tissues, and presented as an independent prognostic factor for overall survival of RCC patients and higher CB2 expression tends to have poor clinical outcomes in survival analyses. Moreover, we also observed that CB2, incorporated with pN stage, pathological grade, and recurrence or distant metastasis after surgery, could obviously enhance their prognostic accuracy in a predictive nomogram analysis. In addition, knockdown or inhibition by AM630 for the expression of CB2 in vitro could significantly decreased cell proliferation and migration, and obviously induced cell cycle arrest in G2/M of RCC cells. CONCLUSIONS: CB2 expression is functionally related to cellular proliferation, migration, and cell cycle of RCC cells. Our data suggest that CB2 might be a potential therapeutic target for RCC.


Assuntos
Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Receptor CB2 de Canabinoide/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Progressão da Doença , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Indóis/farmacologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Prognóstico , Receptor CB2 de Canabinoide/antagonistas & inibidores , Receptor CB2 de Canabinoide/deficiência , Receptor CB2 de Canabinoide/genética , Adulto Jovem
17.
BMC Cancer ; 17(1): 900, 2017 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-29282004

RESUMO

BACKGROUND: This study provides a comprehensive examination of the histological features of non-neoplastic parenchyma in renal cell carcinoma (RCC). We prospectively collected radical nephrectomy (RN) specimens, to analyze the histological changes within peritumoral and distant parenchyma. METHODS: Data of patients who underwent RN and had no known history of diabetes, hypertension, hyperlipidemia, or chronic kidney disease etc., were prospectively collected. Tumor pseudo-capsule (PC), and parenchyma within 2 cm from tumor margin, were pathologically assessed. The parenchyma beyond PC or tumor margin was divided into 20 subsections of 1 mm in width. Histological changes, including chronic inflammation, glomerulosclerosis, arteriosclerosis and nephrosclerosis, were given scores of 0, 1, 2 or 3 for each subsection of each specimen, according to their severity. The 20 subsections of each specimen were further divided into four groups according to the distance from the tumor edge (group 1: 0-2 mm; group 2: 2-5 mm; group 3: 5-10 mm; group 4: 10-20 mm), to better compare the peritumoral parenchyma with the distant parenchyma. RESULTS: In total, 53 patients were involved in this study. All tumors were confirmed RCCs (clear cell vs. papillary vs. chromophobe were 83% vs. 5.7% vs. 11.3%, respectively), with a mean size of 5.6 cm. Histological changes were more severe in peritumoral parenchyma close to PC or tumor edge (0-5 mm), and less common within parenchyma more distant from the tumor (5-20 mm) (p < 0.001). chronic inflammation and nephrosclerosis were the most common changes especially in peritumoral parenchyma (0-2 mm). PC was present in 49 tumors (92.5%), and PC invasion occurred in 5 cases (10.2%). Mean PC thickness was 0.7 mm. PCs were more likely to be present in clear cell RCC or papillary RCC than in chromophobe RCC (100% vs. 100% vs. 33.3%, respectively; p < 0.001). CONCLUSIONS: Most RCCs have a well-developed PC, especially clear cell RCC. Histological changes mainly occur in peritumoral parenchyma, being rather uncommon in distant parenchyma. A compression band filled with severe histological changes was typically observed in renal parenchyma close to the tumor. Its preservation while performing an enucleation margin may not be entirely necessary.


Assuntos
Carcinoma Papilar/patologia , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Rim/patologia , Nefrectomia/métodos , Tecido Parenquimatoso/patologia , Carcinoma Papilar/cirurgia , Carcinoma de Células Renais/cirurgia , Feminino , Seguimentos , Humanos , Rim/cirurgia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Tecido Parenquimatoso/cirurgia , Prognóstico , Estudos Prospectivos
18.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(11): 1150-1154, 2017 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-29132460

RESUMO

OBJECTIVE: To study the gene mutation profile of primary carnitine deficiency (PCD) in neonates, and to provide a theoretical basis for early diagnosis and treatment, genetic counseling, and prenatal diagnosis of PCD. METHODS: Acylcarnitine profile analysis was performed by tandem mass spectrometry using 34 167 dry blood spots on filter paper. The SLC22A5 gene was sequenced and analyzed in neonates with free carnitine (C0) levels lower than 10 µmol/L as well as their parents. RESULTS: In the acylcarnitine profile analysis, a C0 level lower than 10 µmol/L was found in 10 neonates, but C0 level was not reduced in their mothers. The 10 neonates had 10 types of mutations at 20 different sites in the SLC22A5 gene, which included 4 previously unreported mutations: c.976C>T, c.919delG, c.517delC, and c.338G>A. Bioinformatics analysis showed that the four new mutations were associated with a risk of high pathogenicity. CONCLUSIONS: Tandem mass spectrometry combined with SLC22A5 gene sequencing may be useful for the early diagnosis of PCD. Identification of new mutations enriches the SLC22A5 gene mutation profile.


Assuntos
Cardiomiopatias/genética , Carnitina/deficiência , Hiperamonemia/genética , Doenças Musculares/genética , Mutação , Membro 5 da Família 22 de Carreadores de Soluto/genética , Cardiomiopatias/diagnóstico , Carnitina/genética , Biologia Computacional , Aconselhamento Genético , Humanos , Hiperamonemia/diagnóstico , Recém-Nascido , Doenças Musculares/diagnóstico , Espectrometria de Massas em Tandem
19.
Biosci Trends ; 11(4): 389-398, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28904327

RESUMO

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the second leading cause of cancer-related mortality worldwide. In this review, we made a review on current guidelines published from January 2001 to June 2017 worldwide with a focus on the clinical management of HCC. The electronic databases MEDLINE, the Chinese SinoMed, and the Japanese CiNii were systematically searched. A total of 18 characteristic guidelines for HCC management were finally included, including 8 guidelines from Asia, 5 from Europe, and 5 from the United States of America (USA). If guidelines were published in multiple versions, the most recent update was included, and surveillance, diagnosis, and treatment were compared. The composition of and recommendations in current guidelines on HCC varied, so these guidelines were regrouped and diagnostic and treatment algorithms were summarized graphically to provide the latest information to clinicians. The diagnostic criteria were grouped into 2 categories of a "Size-based pathway" and a "Non-size-based pathway." The treatment criteria were divided into 4 categories: i) Criteria based on the Barcelona Clinic Liver Cancer staging system; ii) Criteria based on the modified Union of International Cancer Control staging system; iii) Criteria based on the Child-Pugh class of liver function; and iv) Criteria based on tumor resectability. Findings from comparison of current guidelines might help target and concentrate efforts to improve the clinical management of HCC. However, further studies are needed to improve the management and outcomes of HCC. More straightforward or refined guidelines would help guide doctors to make better decisions in the treatment of HCC in the future.


Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Guias de Prática Clínica como Assunto , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Fatores de Risco
20.
Int Urol Nephrol ; 49(11): 1955-1963, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28889323

RESUMO

OBJECTIVE: Prognostic nutritional index (PNI) is a recognized indicator of both immune and nutritional status. It was firstly used as a preoperative prognostic indicator, and its role in the prognosis of patients with metastatic renal cell carcinoma (mRCC) has not yet been investigated in large-scale study. The purpose of this work was to investigate the prognostic role of pretreatment PNI in patients with mRCC with sorafenib or sunitinib as first-line targeted therapy. METHOD: In this retrospective single-center research, the Kaplan-Meier method was used to estimate the progression-free survival (PFS) and overall survival (OS) of 178 mRCC patients who received first-line therapy of sorafenib or sunitinib. Log-rank test was used to compare the survival outcomes of patients with low pretreatment PNI (PNI < 51.62) and high pretreatment PNI (PNI ≥ 51.62), and Cox proportional hazard regression model was used to compare PFS and OS between these two groups. Prognostic accuracy was determined using Harrell concordance index. RESULTS: The overall median PFS and OS time for all 178 patients were 11 months (95% CI 9-12 months) and 24 months (95% CI 19-33 months), respectively. Patients with low pretreatment PNI both had significantly shorter median PFS (7 vs 19 months, P < 0.001) and OS (14 vs 50 months, P < 0.001) than those with high PNI. Multivariate analysis showed that pretreatment PNI was an independent predictor of OS (HR 1.658, 95% CI 1.040-2.614, P = 0.033) and an independent predictor of PFS as well (HR 1.842, 95% CI 1.226-2.766, P = 0.003). The model built by the addition of pretreatment PNI improved predictive accuracy of PFS and OS compared with the International Metastatic Renal Cell Carcinoma Database Consortium Model (Heng model) (c-index: 0.68 and 0.70). Comparing to NLR (neutrophil-to-lymphocyte ratio) (0.69 and 0.72), PNI might be a preciser factor to predict PFS and OS (0.71 and 0.73). CONCLUSIONS: Low pretreatment PNI could be a significant risk factor for mRCC patients who received tyrosine kinase inhibitors as first-line target therapy and increase the accuracy of established prognostic model.


Assuntos
Carcinoma de Células Renais/terapia , Indóis/uso terapêutico , Neoplasias Renais/terapia , Niacinamida/análogos & derivados , Estado Nutricional , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirróis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/secundário , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Nefrectomia , Neutrófilos , Niacinamida/uso terapêutico , Período Pré-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Sorafenibe , Sunitinibe , Taxa de Sobrevida , Adulto Jovem
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