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1.
Quant Imaging Med Surg ; 14(2): 1904-1915, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38415116

RESUMO

Background: The hepatocyte phase (HCP) in gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) plays an important role in the detection and characterization of liver lesions, treatment planning, and liver function evaluation. However, the imaging protocol is complicated and time-consuming. This cross-sectional study aimed to develop a convenient and reproducible protocol for the HCP acquisition in Gd-EOB-DTPA-enhanced MRI. Methods: A total of 107 patients were prospectively included and assigned to three groups based on Child-Pugh (CP) classification, with 37, 40, and 30 in the non-cirrhosis, CP A, and CP B groups, respectively. Dynamic HCPs were acquired every 5 min after the Gd-EOB-DTPA administration and ended in 25 min in non-cirrhosis patients and 40 min in cirrhotic patients. The HCP acquired 5 min after the initial visualization of the intrahepatic bile duct (IBD) was selected from the dynamic HCPs as the adequate HCP (HCPproposed) and the corresponding acquisition time was recorded as Timeproposed. In addition, according to the 2016 Expert Consensus (EC) on the definition of the adequate HCP from the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the adequate HCPEC and the corresponding TimeEC were also determined from the dynamic HCPs. The hepatic relative enhancement ratio (RER), the contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) of hepatic focal lesions in the HCPEC and HCPproposed images, as well as the TimeEC and Timeproposed were compared by the paired t-test for the three groups, respectively. Inter-observer agreement of the determination of the HCPEC and HCPproposed was compared by the χ2 test. Results: The RER, CNR, and SNR showed no significant difference between the HCPEC and HCPproposed in all three groups (all P>0.05). The paired differences between TimeEC and Timeproposed were 1.08±3.56 min (P=0.07), 2.88±4.22 min (P<0.001), and 5.83±5.27 min (P<0.001) in the three groups, respectively. Inter-observer agreement of the determination of the HCPEC and HCPproposed were 0.804 (86/107) and 0.962 (103/107), respectively (χ²=13.09, P=0.001). Conclusions: The adequate HCP could be acquired 5 min after the initial visualization of the IBD, which could serve as a convenient and reproducible protocol for the HCP imaging.

2.
Quant Imaging Med Surg ; 13(3): 1972-1982, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36915322

RESUMO

Background and Objective: Gadolinium ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) is widely used in clinical practice. Its unique hepatobiliary phase (HBP) has been used to improve the detection and identification of hepatic lesions and has also been used to evaluate hepatic function and fibrosis. At the early stage of its clinical practice, the HBP was typically collected empirically with a delay of 20 minutes after intravenous administration to image the liver with sufficient enhancement for diagnosis. However, numerous methods and consensus statements for optimizing HBP acquisition have been proposed. This review details the methods and consensus statements on optimizing HBP collection. Methods: The electronic literature search was performed using the databases PubMed, MEDLINE, Cochrane, and Embase without limit on publication period to identify published reports on optimizing HBP imaging in Gd-EOB-DTPA-enhanced MRI. Articles with low relevance to the topics were excluded. Key Content and Findings: Recently, an increasing number of investigations suggest that collecting HBP after 20 min is too drawn-out for patients with normal liver function but is too short for patients with cirrhosis. Previous studies demonstrated that liver enhancement is closely related to liver function in Gd-EOB-DTPA-enhanced MRI. Therefore several reports have proposed various HBP delay times at different liver function levels. These delay times could be evaluated by laboratory indicators, such as prothrombin (PT) activity, total bilirubin, direct bilirubin, and the model for end-stage liver disease. Other investigations have found that the initial visualization time of the intrahepatic bile duct (IHD) in Gd-EOB-DTPA-enhanced MRI to also be related to liver enhancement and function. Therefore, initial visualization of the IHD is considered necessary for adequate HBP and has been employed in HBP acquisition in recent reports. Conclusions: Optimizing HBP acquisition according to individual hepatic function is a good strategy and was followed in most of the investigations included in our review. Obtaining adequate HBP in the shortest possible time is the target condition in Gd-EOB-DTPA-enhanced MRI. However, a more concise and efficient HBP acquisition strategy is still expected to be developed in the future.

3.
World J Radiol ; 14(6): 155-164, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35978977

RESUMO

BACKGROUND: In recent years, the detection rate of ground-glass nodules (GGNs) has been improved dramatically due to the popularization of low-dose computed tomography (CT) screening with high-resolution CT technique. This presents challenges for the characterization and management of the GGNs, which depends on a thorough investigation and sufficient diagnostic knowledge of the GGNs. In most diagnostic studies of the GGNs, morphological manifestations are used to differentiate benignancy and malignancy. In contrast, few studies are dedicated to the assessment of the hemodynamics, i.e., perfusion parameters of the GGNs. AIM: To assess the dual vascular supply patterns of GGNs on different histopathology and opacities. METHODS: Forty-seven GGNs from 47 patients were prospectively included and underwent the dynamic volume CT. Histopathologic diagnoses were obtained within two weeks after the CT examination. Blood flow from the bronchial artery [bronchial flow (BF)] and pulmonary artery [pulmonary flow (PF)] as well as the perfusion index (PI) = [PF/(PF + BF)] were obtained using first-pass dual-input CT perfusion analysis and compared respectively between different histopathology and lesion types (pure or mixed GGNs) and correlated with the attenuation values of the lesions using one-way ANOVA, student's t test and Pearson correlation analysis. RESULTS: Of the 47 GGNs (mean diameter, 8.17 mm; range, 5.3-12.7 mm), 30 (64%) were carcinoma, 6 (13%) were atypical adenomatous hyperplasia and 11 (23%) were organizing pneumonia. All perfusion parameters (BF, PF and PI) demonstrated no significant difference among the three conditions (all P > 0.05). The PFs were higher than the BFs in all the three conditions (all P < 0.001). Of the 30 GGN carcinomas, 14 showed mixed GGNs and 16 pure GGNs with a higher PI in the latter (P < 0.01). Of the 17 benign GGNs, 4 showed mixed GGNs and 13 pure GGNs with no significant difference of the PI between the GGN types (P = 0.21). A negative correlation (r = -0.76, P < 0.001) was demonstrated between the CT attenuation values and the PIs in the 30 GGN carcinomas. CONCLUSION: The GGNs are perfused dominantly by the PF regardless of its histopathology while the weight of the BF in the GGN carcinomas increases gradually during the progress of its opacification.

4.
Clin Hemorheol Microcirc ; 78(2): 139-149, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33554892

RESUMO

OBJECTIVE: To assess iliac blood vessels using conventional ultrasound (US) and contrast-enhanced ultrasonography (CEUS) before kidney transplantation (KT) and determine whether US findings related to post-transplant outcomes. METHODS: A total of 119 patients received US and CEUS before KT waiting-list acceptance. The preoperative iliac blood hemodynamics and vascular conditions were evaluated. The operative strategy and follow-up outcomes were recorded. Logistic regression and correlation analysis were used. The accuracy in determining the patency of iliac blood vessels was calculated before and after the injection of contrast materials. RESULTS: CEUS can help to significantly improve the visualization of the internal iliac artery, but there was no significant correlation with post-transplant outcomes. In terms of accuracy, there were significant differences in determining the patency of internal iliac arteries between conventional US and CEUS (60.5% and 100%, p < 0.001). The surgical strategy of one patient was regulated and two patients were excluded from KT according to US findings. CONCLUSIONS: Compared with conventional US, CEUS helps to improve the visualization of the internal iliac artery. Conventional US and CEUS have the potential to serve as effective methods to evaluate anatomy and hemodynamics of iliac vessels and have a potential value while defining clinical algorithms in surgery decision-making.


Assuntos
Meios de Contraste/química , Artéria Ilíaca/patologia , Veia Ilíaca/patologia , Nefropatias/patologia , Transplante de Rim/métodos , Cuidados Pré-Operatórios , Ultrassonografia/métodos , Adulto , Idoso , Algoritmos , Feminino , Humanos , Artéria Ilíaca/diagnóstico por imagem , Artéria Ilíaca/cirurgia , Veia Ilíaca/diagnóstico por imagem , Veia Ilíaca/cirurgia , Nefropatias/diagnóstico por imagem , Nefropatias/cirurgia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
Expert Rev Clin Immunol ; 17(2): 177-185, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33353450

RESUMO

OBJECTIVES: Methylation pattern of gene modification is essential for the differentiation of T regulatory cells (Tregs) and 5-Aza-2'-deoxycytidine is a common inhibitor of methylation. This study aimed to investigate the potential effects of Treg polarizing conditions and 5-Aza-2'-deoxycytidine treatment in the differentiation of naïve T cells during chronic hepatitis B virus (HBV) infection. METHODS: The frequency of Tregs in peripheral blood was determined by flow cytometry from patients with chronic hepatitis B (CHB) (n = 51), liver cirrhosis (LC) (n = 47), hepatocellular carcinoma (HCC) (n = 40) and healthy controls (HCs) (n = 17). Gene expression were detected by qRT-PCR and DNA methyltransferases (DNMT) Activity was also determined. RESULTS: The frequency of Tregs and Foxp3 expression in peripheral blood from 5-Aza-2'-deoxycytidine-treated groups were higher than that with acetic acid treatment as a control. Foxp3 mRNA and the frequency of Tregs derived from naïve CD4+T cells from peripheral blood of patients with HCC or LC were more pronounced compared with HCs. 5-Aza-2'-deoxycytidine may have induced a more pronounced upward trend of PD-1 expression in HBV patients. CONCLUSIONS: 5-Aza-2'-deoxycytidine mediated demethylation has potential effects on enhancing the differentiation of naïve T cells to Tregs in chronic HBV infection.


Assuntos
Decitabina , Inibidores Enzimáticos , Hepatite B Crônica , Linfócitos T Reguladores , Adulto , Antígenos CD4/sangue , Antígenos CD4/imunologia , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/virologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Células Cultivadas , Decitabina/farmacologia , Inibidores Enzimáticos/farmacologia , Feminino , Fatores de Transcrição Forkhead/sangue , Fatores de Transcrição Forkhead/efeitos dos fármacos , Fatores de Transcrição Forkhead/genética , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/complicações , Hepatite B Crônica/imunologia , Hepatite B Crônica/patologia , Humanos , Tolerância Imunológica/genética , Tolerância Imunológica/imunologia , Cirrose Hepática/sangue , Cirrose Hepática/imunologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/virologia , Masculino , Metilação/efeitos dos fármacos , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/sangue , Receptor de Morte Celular Programada 1/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia
6.
Med Sci Monit ; 26: e927444, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33320844

RESUMO

BACKGROUND Alpha-fetoprotein (AFP) is widely used to screen for hepatocellular carcinoma (HCC). However, the use of this biomarker has been challenged due to its low sensitivity and high rate of false negatives. In this study, we evaluated the diagnostic capability of cyclin D2 (CCND2) promoter methylation in patients with HCC related to hepatitis B virus (HBV). MATERIAL AND METHODS Using methylation-specific PCR and quantitative real-time PCR, we measured methylation status and mRNA levels of CCND2 in plasma and peripheral blood mononuclear cells (PBMCs) from 275 subjects: 75 patients with chronic hepatitis B (CHB), 47 with liver cirrhosis (LC), 118 with HCC, and 35 healthy controls (HCs). RESULTS The methylation rate of the CCND2 promoter was significantly higher in HCC patients than in patients without HCC (P<0.001). Furthermore, advanced HCC (TNM III/IV) was associated with a significantly higher frequency of CCND2 methylation and lower CCND2 mRNA levels than early-stage disease (TNM I/II; P<0.05). Combined measurement of CCND2 methylation and AFP yielded significantly higher sensitivity and area under the curve (AUC) than AFP alone in distinguishing patients with HCC from subjects with LC and CHB (P<0.001). CONCLUSIONS CCND2 methylation may be useful for predicting HCC progression. In addition, combined measurement of CCND2 methylation and AFP could serve as a non-invasive diagnostic marker for patients with HBV-related HCC.


Assuntos
Carcinoma Hepatocelular , Ciclina D2/genética , Metilação de DNA , Hepatite B Crônica , Cirrose Hepática , Neoplasias Hepáticas , alfa-Fetoproteínas/análise , Área Sob a Curva , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Diagnóstico Diferencial , Progressão da Doença , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Humanos , Leucócitos Mononucleares/patologia , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Regiões Promotoras Genéticas , RNA Mensageiro/análise , Sensibilidade e Especificidade
7.
Int J Med Sci ; 17(18): 3190-3199, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173438

RESUMO

Objective: Hepatocellular carcinoma (HCC) accounts for approximately 85% of all cases of liver cancer. In China, chronic hepatitis B virus-related HCC (HBV-related HCC) is the most common type of HCC. However, the majority of HBV-related HCC patients are asymptomatic, and the best opportunities for treating these patients are missed. The precise diagnosis of HBV-related HCC is crucial. The main purpose of this study was to evaluate the diagnostic value of murine double minute-2 (MDM2) promoter methylation in HBV-related HCC patients. Methods: The methylation status of the MDM2 promoter was detected by methylation-specific PCR. The MDM2 expression levels were validated by quantitative real-time PCR. Enzyme-linked immunosorbent assay was used to determine the levels of interleukin-6 (IL-6) and tumor-necrosis factor-α (TNF-α) in plasma. Results: The methylation frequency of the MDM2 promoter was decreased in HBV-related HCC patients. The MDM2 mRNA levels of patients with HBV-related HCC were higher than those of patients with liver cirrhosis and chronic hepatitis B. The plasma levels of IL-6 and TNF-α were significantly higher in HBV-related HCC patients than that in liver cirrhosis and chronic hepatitis B patients. The TNF-α levels were higher in the unmethylated MDM2 promoter group than in the methylated MDM2 promoter group in HBV-related HCC patients. Moreover, the combination of MDM2 promoter methylation and alpha-fetoprotein (AFP) improved the diagnosis of HBV-related HCC. Conclusions: Our study indicates, for the first time, that MDM2 promoter hypomethylation is present in HBV-related HCC patients. The combination of MDM2 promoter methylation and AFP can greatly improve diagnostic efficiency in HBV-related HCC, which might provide a new method for HBV-related HCC diagnosis.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Hepatite B Crônica/diagnóstico , Neoplasias Hepáticas/diagnóstico , Proteínas Proto-Oncogênicas c-mdm2/genética , alfa-Fetoproteínas/análise , Adulto , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , Metilação de DNA , Diagnóstico Diferencial , Detecção Precoce de Câncer/métodos , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/genética , Hepatite B Crônica/virologia , Humanos , Fígado/patologia , Fígado/virologia , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/genética , Cirrose Hepática/virologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética
8.
Medicine (Baltimore) ; 99(20): e20326, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443384

RESUMO

The hypomethylation of the Cyclin D1 (CCND1) promoter induced by excess oxidative stress likely promotes the development of hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC). We aimed to evaluate methylation status of the CCND1 promoter as a new plasma marker for the detection of HBV-HCC.We consecutively recruited 191 participants, including 105 patients with HBV-HCC, 54 patients with chronic hepatitis B (CHB), and 32 healthy controls (HCs). Using methylation-specific polymerase chain reaction, we identified the methylation status of the CCND1 promoter in plasma samples. We analyzed the expression levels of the CCND1 mRNA in peripheral blood mononuclear cells by using quantitative real-time PCR. We assessed the plasma levels of superoxide dismutase, 8-hydroxydeoxyguanosine and malondialdehyde by using enzyme-linked immunosorbent assays.Patients with HBV-HCC (23.81%) presented a reduced methylation frequency compared with patients with CHB (64.81%) or HCs (78.13%) (P < .001). When receiver operating characteristic curves were plotted for patients with HBV-HCC versus CHB, the methylation status of the CCND1 promoter yielded diagnostic parameter values for the area under the curve of 0.705, sensitivity of 76.19%, and specificity of 64.81%, thus outperforming serum alpha-fetoprotein (AFP), which had an area under the curve of 0.531, sensitivity of 36.19%, and specificity of 90.74%. Methylation of the CCND1 promoter represents a prospective diagnostic marker for patients with AFP-negative HBV-HCC and AFP-positive CHB. The expression levels of CCND1 mRNA was increased in patients with HBV-HCC compared with patients with CHB (Z = -4.946, P < .001) and HCs (Z = -6.819, P < .001). Both the extent of oxidative injury and antioxidant capacity indicated by the superoxide dismutase, 8-hydroxydeoxyguanosine and malondialdehyde levels were increased in patients with HBV-HCC. Clinical follow up of patients with HBV-HCC revealed a worse overall survival (P = .012, log-rank test) and a decreased progression-free survival (HR = 0.109, 95%CI: 0.031-0.384) for the unmethylated CCND1 group than methylated CCND1 group.Our study confirms that oxidative stress appears to correlate with plasma levels of CCND1 promoter methylation, and the methylation status of the CCND1 promoter represents a prospective biomarker with better diagnostic performance than serum AFP levels.


Assuntos
Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/fisiopatologia , Ciclina D1/metabolismo , Hepatite B Crônica/complicações , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/fisiopatologia , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Idoso , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Metilação de DNA/fisiologia , Detecção Precoce de Câncer , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Regiões Promotoras Genéticas/fisiologia , Estudos Prospectivos , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Superóxido Dismutase/metabolismo , alfa-Fetoproteínas/análise
9.
Pathol Res Pract ; 216(5): 152914, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32147273

RESUMO

DNA methylation is one of the epigenetic mechanisms to regulate gene expression and frequently occurs in human cancer cells. T-cadherin (CDH13) is a new member of the cadherin superfamily and possesses multiple functions. Our study included 26 normal controls (NCs), 65 chronic hepatitis B patients (CHB), 14 liver cirrhosis patients (LC) and 157 hepatocellular carcinoma patients (HCC). We mainly focused on the mRNA expression and methylation status of CDH13 in peripheral blood mononuclear cells (PBMCs), which were detected by semi-quantitative real-time polymerase chain reaction (RT-qPCR) and methylation-specific polymerase chain reaction (MSP) respectively. The CDH13 mRNA level was lower in HCC, especially in early-stage of HCC than in NCs and CHB groups (p < 0.05). Methylation frequency of the CDH13 promoter was significantly higher in HCC patients than in the NCs and CHB groups (67.52 % vs 0.00 %, p < 0.001, 67.52 % vs 52.31 %, p < 0.05, respectively). CDH13 mRNA level was significantly and relatively lower in methylated groups than in unmethylated groups among the whole participants. The methylation level of CDH13 promoter in HCC might be influenced or partly influenced by some critical factors such as TBil, ALB and AFP (p < 0.05). As an important factor in signaling pathway regulating by CDH13 to promote carcinogenesis, JNK level was significantly higher in HCC which had a higher methylation frequency than in NCs, CHB and LC (p < 0.05). Furthermore, the combination of the methylated CDH13 level and AFP level showed a better score: AUC = 0.796 (SE = 0.031, 95 %CI 0.735-0.857; p < 0.001) in male and AUC = 0.832 (SE = 0.057, 95 %CI 0.721-0.944; p < 0.001) in female compared to AFP alone for diagnosing HCC from NCs, CHB and LC. The methylation of CDH13 promoter was an independent predictor for assessing the prognosis of HCC patients (r=-1.378 p < 0.05). In conclusion, hypermethylation of CDH13 in PBMCs was associated with the underexpression of mRNA and the high risk of HCC. The methylation status of the CDH13 promoter in PBMCs was a potential noninvasive biomarker to predict the prognosis of HCC patients.


Assuntos
Biomarcadores Tumorais/genética , Caderinas/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/virologia , Metilação de DNA , Progressão da Doença , Feminino , Hepatite B Crônica/complicações , Humanos , Leucócitos Mononucleares , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas
10.
J Cell Biochem ; 121(1): 524-533, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31318098

RESUMO

Renal ischemia-reperfusion injury (IRI) is one of the most common causes of acute kidney injury (AKI), which is closely related to high morbidity and mortality. However, the pathogenesis underlying renal IRI is complex and not fully defined. N6-methyladenosine (m6A) was recently found to be an abundant modification in mammalian messenger RNAs. It is implicated in various biological processes, while the role of m6A in IRI is not illustrated. Here we show that the m6A-methylated RNA level and its methyltransferase METTL14 are elevated in human AKI renal tissues and IRI HK-2 cells. Moreover, METTL14 knockdown protects the kidney against IRI in vitro and in vivo. Mechanistically, we identified that YAP1 is a direct target of METTL14 in AKI progression. Inhibition of YAP1-TEAD signaling by peptide 17 abrogates the protective effect of METTL14 against IRI in vitro and in vivo. Taken together, these results reveal that the N6-methyladenosine mRNA methylase METTL14 promotes the renal IRI via suppressing YAP1. The discovery of the METTL14-YAP1 pathway provides an important new perspective for understanding AKI and is conducive to revealing new therapeutic strategies and targets.


Assuntos
Injúria Renal Aguda/patologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/metabolismo , Metilação de DNA , Metiltransferases/metabolismo , Metiltransferases/fisiologia , Traumatismo por Reperfusão/patologia , Fatores de Transcrição/metabolismo , Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenosina/análogos & derivados , Adenosina/química , Animais , Proteínas de Ciclo Celular/genética , Progressão da Doença , Humanos , Masculino , Metiltransferases/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Substâncias Protetoras , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Proteínas de Sinalização YAP
11.
Oncogene ; 38(9): 1448-1460, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30275562

RESUMO

X-linked inhibitor of apoptosis protein (XIAP) possesses a critical role in promotion of cell survival and maintenance of cellular homeostasis. In cancer, elevated XIAP expression has been associated with malignancy, poor prognosis, and treatment resistance. However, the underlying mechanisms of these effects remain unclear. XIAP has previously been proposed to promote tumor growth through suppression of autophagy. In this study, we examined the expression of XIAP and p62, two critical mediators of autophagy, in breast and colon cancer. We observed a negative correlation between XIAP and p62 expression in normal and cancer tissues of breast and colon, and that the ratio of XIAP and p62 expression determines the cancer phenotype. In vitro, we observed that XIAP interacted with p62 and also that XIAP depletion resulted in increased expression of p62. XIAP functioned as an ubiquitination E3 ligase towards p62 and suppressed p62 expression through ubiquitin-proteasomal degradation. Furthermore, XIAP enhanced cancer cell proliferation, viability, and colony formation in vitro via suppression of p62. In addition, we demonstrated that XIAP-enhanced tumor growth is dependent on depletion of p62 in vivo. Herein, we have therefore delineated a novel mechanism by which XIAP contributes to development and progression of breast and colon carcinoma.


Assuntos
Neoplasias da Mama/genética , Neoplasias do Colo/genética , Proteínas de Ligação a RNA/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Animais , Apoptose/genética , Autofagia/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias do Colo/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Proteólise , Ubiquitina-Proteína Ligases/genética , Ubiquitinação/genética , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Sci Rep ; 7(1): 8108, 2017 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-28808280

RESUMO

Three kinds of Al-TiO2 samples and pure TiO2 samples were synthesized via a modified polyacrylamide gel route using different aluminum salts, including Al2(SO4)3∙18H2O, AlCl3, and Al(NO3)3∙9H2O under identical conditions. The influence of different aluminum salts on the phase purity, morphologies, thermal stability of anatase and photocatalytic properties of the as-prepared Al-TiO2 nanoparticles were studied. The energy gap (Eg) of Al-TiO2 nanoparticles decreases due to Al ion doping into TiO2. The photocatalytic activities of the Al-TiO2 samples were investigated by the degradation of acid orange 7 dye in aqueous solution under simulated solar irradiation. The Al-TiO2 nanoparticles prepared from Al(NO3)3∙9H2O exhibit the best photocatalytic activity among the four kinds of samples, followed in turn by the Al-TiO2 nanoparticles prepared with AlCl3, Al2(SO4)3∙18H2O and pure TiO2. The different performances are attributed to complex effects of Eg, particle size, surface morphology, phase purity and the defect sites of the Al-TiO2 nanoparticles.

13.
Biosci Rep ; 37(4)2017 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-28667103

RESUMO

The present study explores the correlation of human epidermal growth factor receptor-2 (HER-2) protein expression with sentinel lymph node (SLN) metastasis and prognosis of breast cancer. The breast cancer tissues and adjacent tissues were obtained from patients with primary breast cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the mRNA level of HER-2. Spearman correlation analysis was used to analyze the correlation of HER-2 expression with SLN metastasis. The disease-free survival (DFS) and overall survival (OS) of breast cancer patients were investigated. Univariate and multivariate analyses were performed to explore factors influencing SLN metastasis and prognosis of breast cancer. Compared with adjacent tissues, HER-2 expression was significantly up-regulated in breast cancer tissues. HER-2 expression was correlated with the pathological type, tumor node metastasis (TNM) staging, histological grade, blood vessel invasion, SLN metastasis, estrogen receptor (ER), and progesterone receptor (PR). The expression level of HER-2 was positively related to the SLN metastasis (r=0.548). Median DFS and OS were longer in patients with negative HER-2 expression than in patients with positive HER-2 expression. TNM staging, SLN metastasis, and expression levels of HER-2 and ER were independent factors for DFS of breast cancer patients, while TNM staging, blood vessel invasion, histological grade, SLN metastasis, and expression levels of HER-2 and PR were independent factors for OS of breast cancer patients. Our study suggests that high expression of HER-2 promoted SLN metastasis. HER-2 expression and SLN metastasis were the independent factors for the prognosis of breast cancer.


Assuntos
Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Linfonodo Sentinela/patologia , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Estatística como Assunto , Fatores de Tempo
14.
Chin Med J (Engl) ; 124(8): 1189-92, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21542994

RESUMO

BACKGROUND: The morbidity and mortality of prostate cancer have been increasing rapidly in recent China. There were few studies investigating prostate-specific antigen (PSA) values ranges in the healthy Chinese population. We performed this study to determine the distribution of serum PSA in a large healthy Chinese population. METHODS: From January 2001 to May 2008, 11 150 healthy Chinese men aged 30 - 79 years came to our hospital for routine health check-up. All subjects without a previous diagnosis of prostate cancer, a history of prostate surgery, or urogenital tract infection were proposed to undergo systematic serum PSA measurement and digital rectal examination (DRE). Men with normal DRE and PSA ≤ 4.0 ng/ml and those PSA > 4.0 ng/ml or abnormal DRE but without adverse findings on prostate biopsy were included (n = 9358). Age and serum PSA concentration were recorded and correlated through Logistic regression analysis. RESULTS: The 95th percentile serum PSA concentration was 1.89 ng/ml for men aged 30 to 39 years, 2.19 ng/ml for men aged 40 to 49 years, 2.88 ng/ml for men aged 50 to 59 years, 4.42 ng/ml for men aged 60 to 69 years, and 6.52 ng/ml for men aged 70 to 79 years. The serum PSA concentration correlated with age (P < 0.0001) with an annual increase of 0.97% for men in 40 years, 1.58% for men in 50 years, 3.04% for men in 60 years, and 3.99% for men in 70 years. CONCLUSIONS: The serum PSA level correlates directly with age in Chinese men older than 40 years, not in Chinese men younger than 40 years old. Chinese men have lower PSA level compared with white men above 60 years of age, not in those under 60 years of age.


Assuntos
Antígeno Prostático Específico/sangue , Adulto , Fatores Etários , Idoso , Povo Asiático , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia
15.
Eur J Radiol ; 73(1): 96-101, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19008065

RESUMO

OBJECTIVE: To examine CT patterns of intraductal papillary mucinous neoplasm (IPMN), analyze their correlation with pathologic classification, and discuss the value of CT in the diagnosis and differential diagnosis of IPMN. METHODS: CT patterns of 39 IPMN patients, whose clinical data were complete and whose diagnosis was confirmed by surgery and pathology, were classified into three types: (1) simple main pancreatic duct (MPD) dilation type, (2) MPD dilation with pancreatic cystic lesion type, and (3) simple pancreatic cystic lesion type. Correlations between the three CT types and Takada pathologic classification (MPD type, furcation type and mixture type) were analyzed. The 39 IPMN cases were pathologically classified as the benign group and the malignant/borderline group. CT characteristics including the presence or absence of mural nodules, intrafocal partitions, focal size and the degree of MPD and common bile duct (CBD) dilation were analyzed statistically. RESULTS: A correlation was found between the CT simple MPD dilation type and the pathological MPD type, between the MPD dilation with pancreatic cystic lesion type and the furcation and mixture types, and between the simple cystic lesion type and the furcation type (p<0.001). The benign rate was 92% in patients without intrafocal mural nodules, and 42% in patients with intrafocal mural nodules. The difference between the two groups was statistically significant (p=0.003). The presence or absence of intrafocal partitions was not correlated with benignancy or malignancy (p=0.793). The maximum diameter of malignant/borderline lesions was bigger than that of benign ones (p=0.016). There was no significant difference in MPD and CBD diameters between the benign and malignant/borderline groups. Regardless of pathological classification, the MPD diameter was larger than the CBD diameter in all cases (p=0.02). CONCLUSION: The three CT types of IPMN well correlated with the pathologic classification, which is helpful for analyzing CT manifestations and improving the accuracy of diagnosis. MPD dilation is usually larger than CBD dilation in IPMN patients, which is also helpful in the diagnosis and differential diagnosis of IPMN in the context of other related findings.


Assuntos
Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/patologia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como Assunto
16.
Zhonghua Gan Zang Bing Za Zhi ; 17(1): 38-41, 2009 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-19203450

RESUMO

OBJECTIVES: To study the inhibitory effect of HBx antisense oligodeoxynucleotide on the formation of transplanted hepatocellular carcinoma in nude mice. METHOD: 50 nude mice were randomly divided into 5 groups: 1 control group and 4 experimental groups. Log-phase Hep3B cells endogenously expressing HBX were injected subcutaneously in nude mice. From the second day, the PAGE purified AS1, AS2, AS3 and AS4 HBx antisense oligodeoxynucleotides were injected intraperitoneally into the 4 experimental groups, respectively, on alternate days for 5 times, and distilled water was injected into the control group. Growth information of subcutaneous transplantation tumor in nude mice was recorded for 30 days. Incidence rate of transplanted tumor in different groups was compared and analyzed by survival analysis. Statistics software SPSS12.0 was used to analyze the data. RESULTS: Incidence rate of transplanted tumor was 100% in AS1, AS2, AS3 and control groups, and 90% in AS4 group (x2 = 3.995, P = 1.0). The median latency period for transplanted tumor formation was 19 days (17.48-20.52), 12 days (9.93-14.07), 11 days (9.45 to 12.55), 21 days (19.48 to 22.52), and 10 days (8.99 to 11.01) in AS1, AS2, AS3, AS4 and control group, respectively. The latency period for tumor formation was prolonged by treatment of mice with AS1 and AS4 antisense oligodeoxynucleotide (P less than 0.01). CONCLUSION: Antisense oligodeoxynucleotide targeting to the appropriate sites of HBx gene can prolong the latency period of subcutaneously transplanted tumor in nude mice, however, the formation of transplanted tumor can not be completely blocked by limited treatment with these antisense oligos. In addition, our results suggest that peritoneal injection may be an effective way to deliver antisense oligodeoxynucleotide to living organisms.


Assuntos
Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Vírus da Hepatite B/genética , Neoplasias Hepáticas Experimentais/patologia , Oligodesoxirribonucleotídeos Antissenso/farmacologia , Transativadores/metabolismo , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas Experimentais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Oligodesoxirribonucleotídeos Antissenso/administração & dosagem , Oligodesoxirribonucleotídeos Antissenso/genética , Distribuição Aleatória , Transativadores/genética , Proteínas Virais Reguladoras e Acessórias , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Zhonghua Yi Xue Za Zhi ; 88(14): 943-7, 2008 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-18756963

RESUMO

OBJECTIVE: To evaluate the diagnostic value of CT in pancreas intraductal papillary mucinous neoplasm (IPMN) by analyzing its CT feature and pathological findings. METHODS: The clinical and CT data was analyzed among 39 patients with IPMN whose diagnosis was confirmed by pathology. The CT manifestations were classified into 3 types: simple main pancreatic duct enlargement; main pancreatic duct enlargement combined with pancreatic cystic lesion; and simple pancreatic cystic lesion. The correlation between the CT types and Takada pathological types (main duct type, branch type, and mixed type) was analyzed. All the cases were pathologically classified into benign and malignant/boundary groups. Statistical tests of the difference of CT features (mural nodule, septa, size, caliber of main pancreatic duct and common bile duct) between the 2 groups were performed. RESULTS: The CT type I matched the main duct type, the CT type II mainly matched the branch type and mixed type, and the CT type III matched the branch type (P < 0.001). The probability of benign lesion was 92% with no mural nodule in the lesion, while the probability of benign lesion was only 42% with mural nodule presented (P = 0.003). In terms of the septa, there was no significant difference between benign and malignant lesions (P = 0.793). The size of malignant/boundary lesions exceeded that of benign lesions (P = 0.016). There were no significant difference in calibers of main pancreatic duct and common bile duct between the benign and malignant/ boundary groups. Without considering pathological grouping the caliber of main pancreatic duct exceeded that of the common bile duct in all the cases (P = 0.02). CONCLUSION: CT typing of IPMN well matches the pathological typing which benefits the CT diagnosis of IPMN. The caliber of main pancreatic duct usually exceeds that of common bile duct in IPMN. This feature contributes to its diagnosis.


Assuntos
Carcinoma Ductal Pancreático/patologia , Pâncreas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
18.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 27(2): 205-10, 2005 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-15960267

RESUMO

OBJECTIVE: To study the relationship between the expression of dipeptidyl peptidase IV (DPP IV) gene and malignant behavior of cells of ovarian carcinoma. METHODS: The differences of the malignant behavior of A2780, SKOV-3, HO-8910 and HO-8910PM cell lines were examined by drawing cell proliferative curves, adhesive test, assay of incursion and chemotaxis. The expression of DPP IV among the cell lines and its relationship with the malignant behavior of ovarian carcinoma cell were detected by techniques of DPP IV activity assay, cytometry and reverse transcription polymerase chain reaction. RESULTS: Among all cell lines, the ability of proliferation, adhesion, incursion and chemotaxis of HO-8910PM were the highest, while those of A2780 were the lowest. The transcription of mRNA in A2780, SKOV-3, HO-8910 and HO-8910PM cell lines were 0.7512 +/- 0.0012, 0.5596 +/- 0.0015, 0.3369 +/- 0.0009, and 0.2777 +/- 0.0006, respectively. The activity of DPP IV were 0.79 +/- 0.02, 0.64 +/- 0.03, 0.21 +/- 0.02, and 0.18 +/- 0.01, respectively; and the protein expression of DPP IV gene were 657.83 +/- 1.14, 538.53 +/- 5.29, 130.50 +/- 1.46, and 33.14 +/- 0.47, respectively, as assayed by cytometry. The correlation coefficients of the transcription of DPP IV gene and the adhesive, incursive and migratory ability of ovarian carcinoma cells were -0.987, -0.983, and -0.991, respectively; the correlation coefficients of the expression of DPP IV and those ability of cells were -0.959, -0.988, and -0.968; the correlation coefficients of the activity of DPP IV and those ability of cells were -0.952, -0.868, and -0.983. CONCLUSION: There is a negative correlation between the expression of DPP IV gene and the adhesive and incursive capability of cells of ovarian carcinoma.


Assuntos
Dipeptidil Peptidase 4/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Adesão Celular , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cistadenocarcinoma/genética , Cistadenocarcinoma/patologia , Dipeptidil Peptidase 4/biossíntese , Feminino , Humanos , Invasividade Neoplásica , Metástase Neoplásica , RNA Mensageiro/biossíntese , RNA Mensageiro/genética
19.
Zhonghua Liu Xing Bing Xue Za Zhi ; 24(9): 822-6, 2003 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-14521778

RESUMO

OBJECTIVE: To explore the relation of angiotensin-converting enzyme (ACE) gene polymorphism, angiotensin II type I receptor (ATIR) gene polymorphism and other factors on cerebral infarction. METHODS: One thousand three hundred fifty-one subjects from Tangshan coalmine were enrolled with study method of cluster sampling. Face to face interviews were conducted to fill in questionnaires by trained interviewers. ACE gene, ATIR gene and inflammation factors including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-8, IL-10, C reactive protein (CRP), fibrinogen (Fg), fibrin monome polymerized velocity (FMPV), absorbance maximum (A(max)), FMPV/A(max), were measured. RESULTS: No different prevalence rates of ACE genotype were found on cerebral infarction. The distributions of AA genotype of ATIR gene in the cerebral infarction was higher than that of the controls. The prevalence of AA genotype was higher than other groups, but the prevalence of combined genotype did not show much difference. Under the existence of factors that related to cerebral infarction, AA genotype frequencies were higher than those of non-smoking and with hypertension. IL-6, ATIR gene polymorphism, sex, FMPV/A(max) were strongly related to cerebral infarction. The level of IL-6 was higher than the normal ones. CONCLUSIONS: The prevalence of cerebral infarction obviously increased in the hypertensive groups having AA genotype of ATIR gene. In the cerebral infarction groups, the level of IL-6 was higher than that in the normal population, indicating that these can be resulted from local inflammation and immunity reactivity. Environmental and genetic factors in the pathogenesis of cerebral infarction might have coordinating functions.


Assuntos
Infarto Cerebral/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Receptor Tipo 1 de Angiotensina/genética , Idoso , Estudos Transversais , Feminino , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade
20.
Zhonghua Yi Xue Za Zhi ; 83(14): 1274-7, 2003 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-12930647

RESUMO

OBJECTIVE: To construct the tumor-specific expression vector driven by human telomerase reserve transcriptase gene promotor. METHODS: The fragment of the enhanced green fluorescent protein (EGFP) gene was PCR amplified from the pEGFP-N1 plasmid and cloned into the multiple cloning site of pLNCX vector, and the recombinant was named as pLNCX-EGFP. The fragment of human telomerase reserve transcriptase gene promoter was amplified from the human genome by using the human telomerase reserve transcriptase gene specific primers, and cloned into the pLNCX-EGFP vector, where the cytomegalovirus promoter was previously removed using restriction enzymes, in sense orientation relative to the green fluorescent protein coding sequence. Then the expression vector pLNT-EGFP under the control of the human telomerase reserve transcriptase gene promoter, containing green fluorescent protein reporter gene, was successfully constructed. To detect the transcriptional activity of the human telomerase reserve transcriptase gene promoter, transient transfection of this specific expression vector into HLF cell lines with high telomerase activity and WI38 cell lines without telomerase activity was performed. RESULTS: The expression vector proven by restriction enzymes digestion and sequencing was in correspondence with the design. The results of transient transfection showed that the pLNT-EGFP vector could highly expressed green fluorescent protein reporter gene in telomerase-positive cells, but not in telomerase-negative cells. CONCLUSION: A tumor-specific expression vector driven by human telomerase reserve transcriptase gene promotor has been successfully constructed.


Assuntos
Vetores Genéticos , Regiões Promotoras Genéticas , Telomerase/genética , Citomegalovirus/genética , DNA Antissenso/análise , DNA Complementar/análise , Proteínas de Ligação a DNA , Terapia Genética , Humanos , Neoplasias/metabolismo , Neoplasias/patologia
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