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1.
Drug Dev Res ; 82(8): 1206-1216, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34056735

RESUMO

Bladder cancer is one of the most common types of urothelial carcinoma with a rising incidence rate worldwide. Circular RNAs (circRNAs) are involved in the development of numerous cancers, including bladder cancer. We aimed to uncover the role and associated mechanism of circMYLK in bladder cancer. The expression levels of circMYLK, miRNA-34a (miR-34a) and Cyclin D3 (CCND3) mRNA were investigated using real-time quantitative polymerase chain reaction. The protein level of CCND3 was investigated using western blot. In functional assays, flow cytometry assays were utilized for cell cycle analysis and cell apoptosis analysis. Transwell assays were used for cell migration and invasion analysis. Caspase-3 activity was examined to monitor cell apoptosis. The putative relationship between miR-34a and circMYLK or CCND3 was validated by dual-luciferase reporter assay and RNA immunoprecipitation assay. CircMYLK was highly expressed in bladder cancer tissues and cells. CircMYLK downregulation inhibited bladder cancer cell migration and invasion, and promoted cancer cell apoptosis and cell cycle arrest. MiR-34a, a target of circMYLK, was downregulated in bladder cancer tissues and cells. MiR-34a inhibition reversed the effects of circMYLK downregulation and then recovered bladder cell malignant behaviors. Further analysis showed that CCND3 was a downstream target of miR-34a, and CCND3 was upregulated in bladder cancer tissues and cells. MiR-34a overexpression blocked bladder cancer cell migration and invasion, and induced cell apoptosis and cycle arrest, while these effects were abolished by CCND3 overexpression. CircMYLK contributed to the malignant development of bladder cancer cells partly through the miR-34a/CCND3 regulatory network, showing the significance of circMYLK in bladder cancer pathogenesis.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Ciclina D3/genética , MicroRNAs/fisiologia , Quinase de Cadeia Leve de Miosina/genética , RNA Circular/fisiologia , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Regulação para Cima , Neoplasias da Bexiga Urinária/genética
2.
Am J Transl Res ; 13(4): 3555-3560, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017536

RESUMO

OBJECTIVE: To investigate the expression of metastasis-associated lung adenocarcinoma transcript 1 (Malat-1) in bladder carcinoma and its relationship with clinicopathological characteristics and prognosis. METHODS: Specimens were collected from 90 patients with bladder carcinoma who underwent urological surgery in our hospital. Twenty patients diagnosed with benign prostatic hyperplasia were selected as the negative control. The expression of Malat-1 was detected by real-time reverse transcription PCR, and its relationship with clinicopathological factors and prognosis was analyzed. RESULTS: The expression of Malat-1 in bladder carcinoma tissues (2.55±0.31) was higher than that in adjacent tissues (1.62±0.42) and normal bladder mucosa tissues (0.84±0.06); the differences were statistically significant (t=13.647 and 27.302, both P<0.001). The high expression rate of Malat-1 in bladder carcinoma tissues (86.67%) was significantly higher than that in adjacent tissues (22.22%) and normal bladder mucosa tissues (5.00%; P=0.000 and 0.000). The high expression rate of Malat-1 was correlated with age, tumor staging, degree of differentiation and lymph node metastasis (P=0.018, 0.000, 0.000, and 0.000). The median survival time and the 1-year, 3-year and 5-year survival rates of patients with high Malat-1 expression were lower than those with low expression of Malat-1 (P=0.006, 0.011, 0.000 and 0.002). High expression of Malat-1 is an independent risk factor for poor overall survival (OS) in bladder cancer patients. CONCLUSION: Overexpression of Malat-1 in bladder carcinoma tissues is associated with malignant biological characteristics and poor prognosis of patients.

3.
Oncotarget ; 8(28): 46468-46479, 2017 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28515349

RESUMO

Adenomatous polyposis coli (APC) promoter hypermethylation has been frequently observed in colorectal cancer (CRC). The association between APC promoter methylation and clinicopathological significance in CRC is under investigation. We performed a meta-analysis to quantitatively evaluate the significance of APC methylation in CRC. The study included a total of 24 articles and 2025 CRC patients. The frequency of APC promoter hypermethylation was significantly higher in colorectal adenoma than in normal colorectal tissue, OR was 5.76, 95% CI, 2.45-13.56; p<0.0001, I2=0%. APC promoter more frequently hypermethylated in CRC stage I compared to normal colorectal tissue, OR was 13.42, 95% CI, 3.66-49.20; p<0.0001, I2=31%. The risk of incidence of CRC was significantly correlated to APC promoter hypermethylation, pooled OR was 9.80, 95%CI, 6.07-15.81; p<0.00001, I2=43%. APC methylation was not associated with grade, stage of CRC as well as tumor location, patients' gender, and smoking behavior. The results indicate that APC promoter hypermethylation is an early event in carcinogenesis of CRC, could be a valuable diagnostic marker for early-stage CRC. APC methylation is not significantly associated with overall survival in patients with CRC. APC is a potential drug target for development of personalized treatment.


Assuntos
Proteína da Polipose Adenomatosa do Colo/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Metilação de DNA , Estudos de Associação Genética , Predisposição Genética para Doença , Biomarcadores Tumorais , Detecção Precoce de Câncer , Epigênese Genética , Feminino , Humanos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Razão de Chances , Regiões Promotoras Genéticas , Viés de Publicação , Fatores Sexuais
4.
Int J Pharm ; 513(1-2): 564-571, 2016 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-27613255

RESUMO

In this study, we have demonstrated gemcitabine (GEM)-conjugated amphiphilic biodegradable polymeric drug carriers. Our aim was to increase the chemotherapeutic potential of GEM in colon cancer by forming a unique polymer-drug conjugates. The polymer-drug conjugate micelles were nanosized with a typical spherical shape. The GEM-conjugated methoxy poly(ethylene glycol)-poly(lactic acid) (GEM-PL) exhibited a controlled release of drug in both the pH conditions. The developed GEM-PL efficiently killed the HT29 cancers cells in a typical time dependent manner. The clonogenic assay further confirmed the superior anticancer effect of GEM-PL which showed least number of colonies. GEM-PL formulation exhibited a significantly higher apoptosis of cancer cells (∼25%) when stained using Annexin-V/PI kit. Conjugation of GEM to the mPEG-PLA significantly enhanced the blood circulation potential in animal model compared to that of free GEM. GEM-PL could prevent quick elimination of the drug and can provide sufficient time for the greater accumulation of GEM at the tumor sites. GEM-PL showed a remarkable tumor regression effect as evident from the lowest tumor volume in HT-29 containing tumor model. Overall, mPEG-PLA/GEM conjugates showed the potential of polymer-based drug targeting and might hold significant clinical potential in the treatment of colon cancers.


Assuntos
Antimetabólitos Antineoplásicos , Desoxicitidina/análogos & derivados , Portadores de Fármacos , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/química , Antimetabólitos Antineoplásicos/farmacocinética , Antimetabólitos Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/química , Desoxicitidina/farmacocinética , Desoxicitidina/uso terapêutico , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/uso terapêutico , Liberação Controlada de Fármacos , Células HT29 , Humanos , Camundongos Nus , Micelas , Poliésteres/administração & dosagem , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/uso terapêutico , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/uso terapêutico , Ratos , Carga Tumoral/efeitos dos fármacos , Gencitabina
5.
World J Gastroenterol ; 21(36): 10367-74, 2015 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-26420963

RESUMO

AIM: To evaluate the efficacy of ursodeoxycholic acid (UDCA) as a chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC). METHODS: BALB/c nude mice were randomized into four groups 24 h before subcutaneous injection of hepatocarcinoma BEL7402 cells suspended in phosphate buffered saline (PBS) into the right flank. The control group (n = 10) was fed a standard diet while treatment groups (n = 10 each) were fed a standard daily diet supplemented with different concentrations of UDCA (30, 50 and 70 mg/kg per day) for 21 d. Tumor growth was measured once each week, and tumor volume (V) was calculated with the following equation: V = (L × W(2)) × 0.52, where L is the length and W is the width of the xenograft. After 21 d, mice were killed under ether anesthesia, and tumors were excised and weighed. Apoptosis was evaluated through detection of DNA fragmentation with gel electrophoresis and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the expression of apoptosis-related proteins BAX, BCL2, APAF1, cleaved caspase-9, and cleaved caspase-3. RESULTS: UDCA suppressed tumor growth relative to controls. The mean tumor volumes were the following: control, 1090 ± 89 mm(3); 30 mg/kg per day, 612 ± 46 mm(3); 50 mg/kg per day, 563 ± 38 mm(3); and 70 mg/kg per day, 221 ± 26 mm(3). Decreased tumor volumes reached statistical significance relative to control xenografts (30 mg/kg per day, P < 0.05; 50 mg/kg per day, P < 0.05; 70 mg/kg per day, P < 0.01). Increasing concentrations of UDCA led to increased DNA fragmentation observed on gel electrophoresis and in the TUNEL assay (control, 1.6% ± 0.3%; 30 mg/kg per day, 2.9% ± 0.5%; 50 mg/kg per day, 3.15% ± 0.7%, and 70 mg/kg per day, 4.86% ± 0.9%). Western blot analysis revealed increased expression of BAX, APAF1, cleaved-caspase-9 and cleaved-caspase-3 proteins, which induce apoptosis, but decreased expression of BCL2 protein, which is an inhibitor of apoptosis, following administration of UDCA. CONCLUSION: UDCA suppresses growth of BEL7402 hepatocellular carcinoma cells in vivo, in part through apoptosis induction, and is thus a candidate for therapeutic treatment of HCC.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Ácido Ursodesoxicólico/farmacologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Fatores de Tempo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Mol Med Rep ; 11(2): 1181-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25371216

RESUMO

Nemo­like kinase (NLK), a serine/threonine protein kinase, was previously reported to be associated with tumor proliferation and invasion. The present study aimed to evaluate whether NLK participates in the tumorigenesis and progression of colorectal cancer (CRC). NLK expression was examined using reverse transcription quantitative polymerase chain reaction (RT­qPCR) and western blot analysis in 50 paired CRC tissues as well as immunohistochemical analysis of 406 cases of primary CRC tissues and paired non­cancerous tissues. Correlations between NLK expression, the clinicopathological features of CRC patients and clinical outcome were then analyzed. NLK expression was found to be significantly higher in CRC tissues as well as associated with the depth of tumor invasion, lymph node metastasis, distant metastasis, histological differentiation, vascular invasion and advanced tumor stage. Patients with NLK­positive tumors demonstrated higher rates of recurrence and mortality than patients with NLK­negative tumors. Multivariate analyses revealed that NLK expression was an independent factor for overall survival [hazard ratio (HR)=0.035; 95% confidence interval (CI)=0.02­0.19; P<0.001] and disease­free survival (HR=0.033; 95% CI=0.007­0.09; P<0.001) in CRC patients. In conclusion, the results of the present study indicated that NLK may serve as a novel biomarker for tumor recurrence and survival for CRC patients.


Assuntos
Neoplasias Colorretais/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular/genética , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Proteínas Serina-Treonina Quinases/genética , Regulação para Cima
7.
Int J Clin Exp Pathol ; 7(10): 6616-25, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25400740

RESUMO

BACKGROUND AND AIMS: Endoscopic Interventional Treatment is of little trauma and less complications in the treatment of gastric schwannoma and leads to faster recovery and fewer days of hospitalization. This study was aimed to investigate the safety and efficacy of endoscopic interventional therapy for gastric schwannoma, including endoscopic submucosal excavation, non-laparoscopic-assisted endoscopic full-thickness resection, endoscopic tunneling submucosal resection, and so on. METHODS: Six patients of gastric schwannoma diagnosed by pathology examination were retrospectively analyzed ranging from Oct 2011 to Feb 2014 at Shandong Provincial Hospital affiliated to Shandong University. Five of the six patients accepted endoscopic interventional therapy. RESULTS: Among the five patients, there were four males and one female, aged from 48 to 65 years old (the average age was 58 ± 6.4). The lesions located at the fundus, the fundus-cardia, gastric body or gastric antrum, respectively, with the diameters ranged from 8 to 25 millimeter (the average was 17.1 ± 7.8 mm). All the patients were performed endoscopic interventional therapy successfully. Among five patients, one patient was treated by endoscopic tunneling submucosal resection, two by endoscopic submucosal excavation, and the other two were given endoscopic full-thickness resection. Operation duration was about 43 to 83 minutes (the average was 57.6 ± 16.1 minutes). The mass were completely removed, with limited bleeding. During the operation, perforation and pneumoperitoneum occurred in two patients, who finally recovered by endoscopic and conservative treatment. No bleeding, inflammation or infection occurred in these patients. The average follow-up time was (7.4 ± 4.4) months. Neither recurrence nor metastasis was found during follow-up. CONCLUSION: Endoscopic interventional therapy is a safe and effective treatment for gastric schwannoma.


Assuntos
Dissecação/métodos , Gastrectomia/métodos , Gastroscopia/métodos , Neurilemoma/cirurgia , Neoplasias Gástricas/cirurgia , Idoso , Perda Sanguínea Cirúrgica , China , Dissecação/efeitos adversos , Endossonografia , Feminino , Gastrectomia/efeitos adversos , Gastroscopia/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Neurilemoma/patologia , Duração da Cirurgia , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Fatores de Tempo , Resultado do Tratamento
8.
Tumour Biol ; 35(1): 339-43, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24014085

RESUMO

Methylenetetrahydrofolate reductase (MTHFR) is one of the most important enzymes for folate metabolism which plays a key role in cell metabolism. MTHFR rs1801131 (A1298C) polymorphism can decrease in vitro MTHFR enzyme activity and has been hypothesized to be associated with liver cancer risk. This study aimed to quantify the strength of the association between MTHFR rs1801131 polymorphism and liver cancer risk by performing a meta-analysis. We searched the PubMed and Wanfang databases for studies relating on the association between MTHFR rs1801131 polymorphism and risk of liver cancer. Seven studies with 2,030 cases of liver cancer and 3,096 controls were finally included into the meta-analysis. Meta-analysis of a total of seven studies showed that the homozygote genotype CC of MTHFR rs1801131 polymorphism was significantly associated with decreased risk of liver cancer (for CC versus AA: odds ratio (OR) = 0.65, 95% confidence interval (CI) 0.47-0.89, P = 0.007; for CC versus AA + AC: OR = 0.65, 95% CI 0.48-0.89, P = 0.006). Subgroup by race showed that the homozygote genotype CC of MTHFR rs1801131 polymorphism was significantly associated with decreased risk of liver cancer in Asians (CC versus AA: OR = 0.64, 95% CI 0.46-0.90, P = 0.010; for CC versus AA + AC: OR = 0.63, 95% CI 0.45-0.88, P = 0.007). However, the association in Caucasians was still unclear owing to the limited data available now. Thus, Asian individuals with the homozygote genotype CC of MTHFR rs1801131 polymorphism are significantly associated with decreased risk of liver cancer. The association in Caucasians needs further studies.


Assuntos
Neoplasias Hepáticas/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Alelos , Estudos de Casos e Controles , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Neoplasias Hepáticas/etnologia , Razão de Chances , Viés de Publicação , Risco
9.
PLoS One ; 8(7): e68588, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23935875

RESUMO

BACKGROUND: Previous studies have focused on the association of miR-34 family members with carcinogenesis of many cancers, including hepatocellular carcinoma (HCC). It has been suggested that miR-34b/c polymorphism (rs4938723) is associated with susceptibility to HCC. In the present study, we performed a meta-analysis to systematically summarize the possible association between rs4938723 and the risk for HCC. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a search of case-control studies on the associations of rs4938723 with susceptibility to HCC in PubMed, EMBASE, ISI Web of Science, Cochrane Central Register of Controlled Trials, ScienceDirect, Wiley Online Library, Wangfang database in China, and Chinese National Knowledge Infrastructure databases. Data from eligible studies were extracted for meta-analysis. HCC risk associated with rs4938723 was estimated by pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). 3 studies on rs4938723 were included in our meta-analysis. Our results showed that neither allele frequency nor genotype distribution of the rs4938723 was associated with risk for HCC in all genetic models. CONCLUSIONS/SIGNIFICANCE: This meta-analysis suggests that rs4938723 is not associated with the risk of HCC. Well-designed studies with larger sample size and more ethnic groups are required to further validate the results.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Modelos Genéticos , Razão de Chances , Fatores de Risco
10.
Tumour Biol ; 34(6): 3483-90, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23794112

RESUMO

Interleukin-18 (IL-18) is a key cytokine responsible for immune response and involved in the process of cancer development. The association of -137G>C polymorphism in the promoter region of IL-18 with cancer risk is still elusive based on current genetic association studies. We performed this meta-analysis to determine whether the -137G>C polymorphism is associated with cancer risk. A comprehensive search was conducted for databases of PubMed, EMBASE, and China National Knowledge Infrastructure. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association strength. Publication bias was detected by Egger's and Begg's test. Twenty-one eligible studies including 3,498 cancer patients and 5,222 controls were identified and analyzed. In the overall analysis, no significant association between -137G>C polymorphism and cancer risk was observed. In the sub-group analyses of ethnicities, the -137G>C polymorphism significantly increased cancer risk in Asian population (GC/CC vs. GG: OR = 1.313, 95% CI = 1.053-1.638, heterogeneity P < 0.001) but not in Caucasian population. Further stratified analyses showed that the variant -137C allele was significantly associated with increased risk of nasopharyngeal carcinoma (C vs. G: OR = 1.484, 95% CI = 1.193-1.847, heterogeneity P = 0.213). No publication bias was detected. We provide evidence that the -137G>C polymorphism in IL-18 promoter region significantly increases cancer risk in Asian population but not in Caucasian population, and the variant -137C allele is associated with increased risk of nasopharyngeal carcinoma.


Assuntos
Predisposição Genética para Doença/genética , Interleucina-18/genética , Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/etnologia , Neoplasias Nasofaríngeas/genética , Neoplasias/etnologia , Fatores de Risco , População Branca/genética , Adulto Jovem
11.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 30(1): 72-5, 2010 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-20353039

RESUMO

OBJECTIVE: To explore the mechanism of Wenfei Huayin Recipe (WHR) in treating chronic obstructive pulmonary diseases (COPD). METHODS: The COPD model was induced by modified fumigating method and intra-tracheal instillation of lipopolysaccharide. Then reformed COPD model of cold-phlegm retention in Fei syndrome type. All the model rats were randomly divided into two groups, the model group and the treated group, treated respectively with WHR and saline for 14 successive days. Besides, a blank group without any intervention was set up for control. The general condition, weight growth rate, pathological changes of lung tissue under light microscope, ultrastructure under electron microscope, arterial blood gas analysis and levels of interleukin 4 (IL-4), interleukin 8 (IL-8), tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in lung homogenate by radio-immunity assay were observed. RESULTS: In the treated group, as compared with the control group, the symptoms of aversion to cold, swarming, wheezing, the degree of epithelial cell degeneration and necrosis, the inflammatory cell infiltration and the volume of cilia lodging, sloughing, and bullae of lung were lessened and weight growth rate was higher (P<0.01). Moreover, the treated group was superior to the control group in decreasing levels of PaCO2, IL-4, IL-8, TNF-alpha and increasing PaO2, IFN-gamma and IFN-gamma/IL-4 ratio (P<0.01 or P<0.05). CONCLUSION: WHR can correct the Th1/Th2 imbalance and inhibit the inflammatory reaction, displaying an important role in improving the airway function and structure in COPD rats.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Fitoterapia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/metabolismo , Animais , Modelos Animais de Doenças , Interferon gama/metabolismo , Interleucina-4/metabolismo , Interleucina-8/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
12.
Hepatogastroenterology ; 57(102-103): 1196-202, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21410058

RESUMO

BACKGROUND/AIMS: Ursodeoxycholic acid (UDCA), a natural component of bile, has been synthesized to treat cholestatic liver diseases such as primary biliary cirrhosis. Broad biochemical changes in UDCA-treated patients suggest beneficial effects of UDCA beyond stimulating hepatobiliary secretion and possible efficacy of the medicine in treating cirrhosis of other causes. The aim was to explore the potential benefit of UDCA in controlling immune-mediated hepatic fibrosis. METHODOLOGY: We applied the rat experimental model of liver fibrosis induced by intraperitoneal injection of porcine serum. UDCA was administered orally during the course of the serum injections. RESULTS: Compared with the untreated group, the rats treated with UDCA ended with significantly higher body weight, lower liver weight, and lower spleen weight. The treated groups also demonstrated less severe liver fibrosis, with significantly lowered hepatic expression of type I and type III collagens, in terms of both mRNA and proteins. Moreover, serum levels of hyaluronic acid (HA), laminin (LN), type IV collagen (C IV), and type III procollagen (PC III) were also lower in the UDCA-treated animals. CONCLUSION: UDCA deters development of immune-mediated liver fibrosis by inhibiting the expression of collagen and other extracelluar matrix components.


Assuntos
Cirrose Hepática Experimental/prevenção & controle , Ácido Ursodesoxicólico/uso terapêutico , Animais , Colágeno Tipo I/análise , Colágeno Tipo II/análise , Feminino , Fígado/patologia , Fígado/ultraestrutura , Cirrose Hepática Experimental/imunologia , Cirrose Hepática Experimental/patologia , Masculino , Microscopia Eletrônica , Ratos , Ratos Wistar , Suínos
14.
Chin Med J (Engl) ; 122(10): 1209-13, 2009 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-19493473

RESUMO

BACKGROUND: Hepatic fibrosis is the key stage of the pathological progress from hepatic injury to cirrhosis. Ursodeoxycholic acid (UDCA) has been known as having significant clinical therapeutic effects on chronic liver diseases. Our research aimed to study the effect of UDCA on the signaling pathway of transforming growth factor beta1 (TGFbeta1)/Smad and discuss its possible molecular mechanisms of inhibiting hepatic fibrosis. METHODS: Rat hepatic stellate cells were cultured in vitro and randomly assigned to 4 groups. Group A was control group, with only DMEM culture medium applied, and groups B, C, D were experimental groups, with different doses of UDCA (1.0 mmol/L, 0.5 mmol/L and 0.25 mmol/L respectively) added into their DMEM culture medium for further culture of 24 hours and 48 hours. The protein expressions of TGFbeta1, TGF type I receptor, Smad3, Smad4 and Smad7 were measured by Western blotting, as well as the expressions of TGFbeta1, Smad3, Smad7 and cAMP response element (CREB) binding protein (CBP) mRNA by real-time PCR. SPSS 11.5 statistical package was adopted for data analyses. RESULTS: Compared with control group, the mRNA expressions of TGFbeta1 in the high and middle UDCA dose groups for 24 hours and 48 hours significantly decreased (P < 0.05), the protein expressions of TGFbeta1 in the two above groups for 48 hours and in the high dose group for 24 hours significantly decreased (P < 0.05). The protein and mRNA expressions of Smad3 in each UDCA dose group for 24 hours and 48 hours significantly decreased, with significant difference among different UDCA dose groups and between that of 24 hours and 48 hours observed (P < 0.05). The protein and mRNA expressions of Smad7 in the high and middle UDCA dose groups for 24 hours and 48 hours significantly increased. The CBP mRNA expression in each UDCA dose group for 24 hours and 48 hours significantly decreased (P < 0.05), with significant difference among different UDCA dose groups observed (P < 0.05). CONCLUSION: UDCA could curb the development of hepatic fibrosis through affecting the signaling pathway of TGFbeta1/Smad by inhibiting the expressions of TGFbeta1, Smad3 and CBP and increasing the expression of Smad7.


Assuntos
Colagogos e Coleréticos/farmacologia , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Ácido Ursodesoxicólico/farmacologia , Animais , Western Blotting , Células Cultivadas , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Humanos , Reação em Cadeia da Polimerase , Ratos , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismo , Proteína Smad4/metabolismo , Proteína Smad7/metabolismo
15.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 26(11): 984-7, 2006 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-17186726

RESUMO

UNLABELLED: To observe the clinical effect of drug cupping therapy (DCT, cupping therapy with pingchuan ointment made by the authors themselves in the cups) on chronic asthmatic bronchitis (CAB) during the protracted period, and explore its effect on immune function. METHODS: Seventy-seven patients were randomly divided into two groups:the treated group (n=40) treated by orally taken Liuwei Dihuang Pill (LDP) and DCT and the control group (n=37) with LDP and common cupping therapy without drug in cups. The changes of T-lymphocyte subset, levels of interferon-gamma (IFN-gamma), interleukin (IL), immunoglobulin (Ig), complement 3 and 4 (C3 and C4) were detected before and after treatment. RESULTS: The total effective rate was higher in the treated group than that in the control group (90.0% vs. 59.5%, P < 0.01). The levels of CD4+, CD4+ /CD8+, IL-2, IFN-gamma, C3, C4, IgA, IgG and IgM increased, while the levels of IgE, IL-4, IL-10 and CD8+ decreased after treatment in both groups (P < 0.05 or P < 0.01), the improvements were better in the treated group than that in the control group (P < 0.05). CONCLUSION: DCT shows better curative effects than that of common cupping therapy without drug, it could improve the cellular and humoral immunity in CAB patients.


Assuntos
Asma/terapia , Bronquite/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Adolescente , Adulto , Idoso , Asma/imunologia , Bronquite/imunologia , Antígenos CD4/análise , Relação CD4-CD8 , Terapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Citometria de Fluxo , Humanos , Interferon gama/análise , Interleucina-10/análise , Interleucina-2/análise , Masculino , Pessoa de Meia-Idade , Fitoterapia/métodos , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia
16.
Zhonghua Zhong Liu Za Zhi ; 28(12): 924-7, 2006 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-17533745

RESUMO

OBJECTIVE: To assess the clinical diagnostic value of 18F-FDG imaging by coincidence circuit SPECT with low-dose CT in differential diagnosis of pulmonary lesions and mediastinal lymph node involvement, which can not be definitely diagnosed based on regular CT image in patients with non-small-cell lung cancer (NSCLC). METHODS: By using GE-Millennium VG with Hawkeye, 18F-FDG imaging was carried out in 48 patients with suspected lung cancer. Clinical value of 18F-FDG imaging for diagnosing malignancy was evaluated through comparison with the final pathological results. Mediastinal lymph node involvement was also assessed through lesion-by-lesion comparison with pathologic results in 74 lymph node regions from 24 patients. RESULTS: Final pathologic diagnoses of these patients were 36 malignancies consisting of 20 adenocarcinomas, 12 squamous cell carcinomas, 3 small cell carcinomas and I large cell carcinoma; 12 benign tumors including 6 pneumonias, 2 tuberculosis, 2 hamatomas, 1 cyst and 1 neurofibroma. Of 48 patients, uptake of 18F-FDG in the chest was found to be abnormal in 40. Correct diagnosis were made in 34 malignancies and 6 false positive lesions were excluded based on morphology and 18F-FDG uptake status of the lesion. There were 6 false positive and 2 false negative cases. Furthermore, extrathoracic metastases which were not showed on previous CT image in 4 patients including one in the adrenal gland and 3 in the bone were detected by 18F-FDG imaging. The sensitivity, specificity and accuracy of the 18F-FDG imaging for differentiating malignant tumor from benign was 94.4%, 50.0% and 83.3%, respectively. Squamous cell carcinoma was found to uptake more FDG than adenocarcinoma. For determination of mediastinal lymph node involvement, the sensitivity, specificity and accuracy of 18F-FDG imaging was 57.9% , 90.9% and 82.4%, respectively through lesion-by-lesion comparison; whereas, which was 61.5%, 81.8% and 70.8%, respectively, based on case-by-case comparison. CONCLUSION: 18F-FDG imaging by coincidence circuit SPECT with low-dose CT is quite helpful in differential diagnosis for patient with undetermined lesion on regular CT image, but it is limited for staging of lung cancer in the patients with non-small cell lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico , Pneumonia/diagnóstico , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonia/diagnóstico por imagem , Cuidados Pré-Operatórios , Doses de Radiação , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/diagnóstico por imagem
17.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 22(5): 332-4, 2002 May.
Artigo em Chinês | MEDLINE | ID: mdl-12584827

RESUMO

OBJECTIVE: To explore the clinical effect and therapeutic mechanism of Kangxian Baogan Decoction (KXBGD) on liver fibrosis caused by chronic hepatitis B. METHODS: Eight-one patients with chronic hepatitis B were divided into two groups randomly. The 54 patients in the treated group were treated by KXBGD and the 27 patients in the control group were treated by conventional liver protecting treatment. Serum levels of hyaluronic acid (HA), procollagen type III (PC III), collagen type IV (C-IV), laminin (LN), transforming growth factor beta 1 (TGF beta 1) and tumor necrosis factor-alpha (TNF-alpha) were measured before and after treatment, meanwhile, liver function and pathological changes of liver tissues were observed. RESULTS: The total effective rate in the treated group was significantly higher than that in the control group. Serum levels of HA, PC III, C-IV, LN, TGF beta 1 and TNF-alpha in the treated group obviously reduced after treatment, and the liver function got better with significant difference as compared with those in the control group (P < 0.05 or P < 0.01). Pathological examination of liver biopsy showed that the fibrous tissue in the liver reduced. CONCLUSION: KXBGD has a definite effect of anti-liver fibrosis.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Ácido Hialurônico/sangue , Cirrose Hepática/tratamento farmacológico , Fitoterapia , Adulto , Idoso , Colágeno Tipo III/sangue , Colágeno Tipo IV/sangue , Feminino , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade
18.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 22(6): 435-6, 2002 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-12585189

RESUMO

OBJECTIVE: To investigate the effect of Tongxinluo capsule (TXLC) on the patients with unstable angina pectoris (UAP). METHODS: Patients of UAP were divided into two groups, the treated group (n = 60) was treated with TXLC and the Danshen group (n = 30) was treated with composite Danshen tablet. The plasma endothelin (ET) and calcitonin gene related peptide (CGRP) were measured before and after treatment. Data were compared between the two groups and also compared with those measured in 20 healthy subjects for control. RESULTS: ET level was higher and CGRP level lower significantly in UAP patients than that in healthy subjects significantly (P < 0.05). After TXLC treatment, ET significantly lowered (P < 0.01) and CGRP increased (P < 0.05). But in the Danshen group after treatment, the former decreased (P < 0.05), while the latter remained unchanged (P > 0.05). The effect of TXLC was better than that of composite Danshen tablet. CONCLUSION: TXLC is an effective drug for UAP treatment, which could efficiently regulate the ET and CGRP metabolism and ameliorate the degree of myocardial ischemia damage.


Assuntos
Angina Instável/tratamento farmacológico , Peptídeo Relacionado com Gene de Calcitonina/sangue , Medicamentos de Ervas Chinesas/uso terapêutico , Endotelinas/sangue , Fitoterapia , Adulto , Idoso , Angina Instável/sangue , Cápsulas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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