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1.
Tumour Biol ; 36(3): 1983-91, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25394900

RESUMO

We previously demonstrated that microRNA (miR)-224 expression was significantly reduced in human prostate cancer (PCa) tissues and predicted unfavorable prognosis in patients. However, the underlying mechanisms of miR-224 have not been fully elucidated. In this study, calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) was identified as a target gene of miR-224. Then, we found that enforced expression of miR-224 could suppress PCa cell proliferation and cell cycle by regulating the expression of CAMKK2 in vitro. In addition, the expression levels of miR-224 in PCa tissues were negatively correlated with those of CAMKK2 mRNA significantly (Spearman's correlation: r = -0.66, P = 0.004). Moreover, combined low miR-224 expression and high CAMKK2 expression (miR-224-low/CAMKK2-high) was closely correlated with advanced clinical stage (P = 0.028). Furthermore, PCa patients with miR-224-low/CAMKK2-high expression more frequently had shorter overall survival than those in groups with other expression patterns of two molecules. In conclusion, our data offer the convincing evidence that miR-224 and its target gene CAMKK2 may synergistically contribute to the malignant progression of PCa. Combined detection of miR-224 and CAMKK2 expressions represents an efficient predictor of patient prognosis and may be a novel marker which can provide additional prognostic information in PCa.


Assuntos
Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/genética , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/patologia , RNA Mensageiro/genética
2.
BMC Urol ; 15: 90, 2015 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-26320076

RESUMO

BACKGROUND: The NIMA-related kinase 2 (NEK2) is a serine/threonine kinase that is involved in regulation of centrosome duplication and spindle assembly during mitosis. Dysregulation of these processes causes chromosome instability and aneuploidy, which are hallmark changes of many solid tumors. However, whether aberrant expression of NEK2 is associated with outcome of prostate cancer (PCa) patients remains to be determined. METHODS: Expression of NEK2 in human PCa cells and primary PCa tissues was assessed by quantitative RT-PCR. Expression of NEK2 in human PCa cells was depleted with siRNA. Effects of the depletion on cell proliferation, survival, and tumorigenicity were assessed both in vitro with cell cultures and in vivo with subcutaneous implantation of xenografts. In silico analyses of the online Taylor dataset were carried out to determine whether the expression level of NEK2 correlated with the clinicopathological characteristics of prostate cancer. RESULTS: Compared with benign human prostatic epithelial cells and tissues, the expression of NEK2 was elevated in human PCa cells and primary PCa tissues. Depleting NEK2 expression inhibited human PCa cell proliferation in vitro and xenograft growth in vivo. Expression level of NEK2 in PCa positively correlated with the Gleason score and pathologic stage of the patient. CONCLUSION: The results suggest that overexpression of NEK2 has the potential to serve as a biomarker for PCa prognosis. Further validation with large sample pool is warrant.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Idoso , Animais , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Nus , Quinases Relacionadas a NIMA , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco/métodos , Sensibilidade e Especificidade , Regulação para Cima
3.
Int J Cancer ; 135(3): 541-50, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24382668

RESUMO

Our previous microarray data showed that microRNA-224 (miR-224) was downregulated in human prostate cancer (PCa) tissues compared with adjacent benign tissues. However, the underlying mechanisms by which miR-224 is involved in PCa remain unclear. In this study, we identified TRIB1 as a target gene of miR-224. Forced expression of miR-224 suppressed PCa cell proliferation, invasion and migration, and promoted cell apoptosis by downregulating TRIB1. Moreover, the expression level of miR-224 in PCa tissues was negatively correlated with that of TRIB1. miR-224 downregulation was frequently found in PCa tissues with metastasis, higher PSA level and clinical stage, whereas TRIB1 upregulation was significantly associated with metastasis. Both miR-224 downregulation and TRIB1 upregulation were significantly associated with poor biochemical recurrence-free survival of patients with PCa. In conclusion, these findings reveal that the aberrant expression of miR-224 and TRIB1 may promote PCa progression and have potentials to serve as novel biomarkers for PCa prognosis.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MicroRNAs/genética , Próstata/metabolismo , Neoplasias da Próstata/genética , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Biomarcadores Tumorais/metabolismo , Western Blotting , Movimento Celular , Proliferação de Células , Progressão da Doença , Citometria de Fluxo , Humanos , Técnicas Imunoenzimáticas , Hibridização In Situ , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Próstata/patologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Análise Serial de Tecidos , Células Tumorais Cultivadas
4.
Mol Biol Rep ; 41(5): 2779-88, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24452717

RESUMO

MicroRNA-30c (miR-30c) acts as a tumor suppressor or a tumor promoter in various human malignancies. However, the involvement of miR-30c in prostate cancer (PCa) is still unclear. The aim of this study was to investigate the molecular function and the clinical significance of miR-30c in PCa. Expression levels of miR-30c in PCa tissues and cells were detected by quantitative real-time-PCR (qRT-PCR). Additionally, the associations of miR-30c expression with clinicopathological features and prognosis in PCa patients were analyzed. The potential role of miR-30c in tumorigenesis of PCa cells was further evaluated by in vitro cell assays. MiR-30c was significantly down-regulated in PCa tissues and cells compared with the corresponding controls (P<0.05). In addition, the downregulation of miR-30c in PCa tissues was significantly associated with higher Gleason score (P=0.009), advanced pathological stage (P=0.016) and biochemical recurrence (P=0.034). Moreover, Kaplan-Meier survival analysis showed that the reduced expression of miR-30c was correlated with shorter biochemical recurrence-free survival (P=0.023). The multivariate analysis also identified miR-30c as an independent prognostic predictor for biochemical recurrence-free survival in patients with PCa. Furthermore, the enforced expression of miR-30c suppressed proliferation, migration and invasion of PCa cells in vitro. Our data indicated the involvement of miR-30c in PCa progression and suggested its potential role as an independent predictor of biochemical recurrence in PCa. On cellular level, miR-30c may function as a tumor suppressor for PCa cells by inhibiting tumor cell proliferation, migration and invasion.


Assuntos
Genes Supressores de Tumor , MicroRNAs/genética , Neoplasias da Próstata/genética , Adulto , Idoso , Movimento Celular/genética , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Curva ROC , Recidiva
5.
BMC Genomics ; 14: 757, 2013 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-24191917

RESUMO

BACKGROUND: Our recent study showed the global physiological function of the differentially expressed genes of prostate cancer in Chinese patients was different from that of other non-Chinese populations. microRNA are estimated to regulate the expression of greater than 60% of all protein-coding genes. To further investigate the global association between the transcript abundance of miRNAs and their target mRNAs in Chinese patients, we used microRNA microarray approach combined with bioinformatics and clinical-pathological assay to investigate the miRNA profile and evaluate the potential of miRNAs as diagnostic and prognostic markers in Chinese patients. RESULTS: A total of 28 miRNAs (fold change ≥ 1.5; P ≤ 0.05) were differentially expressed between tumor tissue and adjacent benign tissue of 4 prostate cancer patients.10 top Differentially expressed miRNAs were validated by qRT-PCR using all 20 tissue pairs. Compared to the miRNA profile of non-Chinese populations, the current study showed that miR-23b, miR-220, miR-221, miR-222, and miR-205 maybe common critical therapeutic targets in different populations. The integrated analysis for mRNA microarray and miRNA microarray showed the effects of specifically inhibiting and/or enhancing the function of miRNAs on the gene transcription level. The current studies also identified 15 specific expressed miRNAs in Chinese patients. The clinical feature statistics revealed that miR-374b and miR-19a have significant correlations with clinical-pathological features in Chinese patients. CONCLUSIONS: Our findings showed Chinese prostate cancer patients have a common and specific miRNA expression profile compared with non-Chinese populations. The miR-374b is down-regulated in prostate cancer tissue, and it can be identified as an independent predictor of biochemical recurrence-free survival.


Assuntos
Biomarcadores Tumorais/biossíntese , MicroRNAs/biossíntese , Recidiva Local de Neoplasia/genética , Neoplasias da Próstata/genética , Idoso , Povo Asiático , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica , Estudos de Associação Genética , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , RNA Mensageiro/genética
6.
Mol Cell Biochem ; 381(1-2): 51-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23666742

RESUMO

Suppressors of cytokine signaling (SOCS) proteins have been identified as negative feedback regulators of cytokine-mediated signaling in various tissues, and demonstrated to play critical roles in tumorigenesis and tumor development of different cancers. The involvement of SOCSs in human prostate cancer (PCa) has not been fully elucidated. Thus, the aim of this study is to investigate the expression patterns and the clinical significance of SOCSs in PCa. The expression changes of SOCSs at mRNA and protein levels in human PCa tissues compared with adjacent benign prostate tissues were, respectively, detected by using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) and immunohistochemistry analyses. The associations of SOCSs expression with clinicopathological features and clinical outcome of PCa patients were further statistically analyzed. Among SOCSs, both QRT-PCR and immunohistochemistry analyses found that SOCS2 expression was upregulated (at mRNA level: change ratio = 1.98, P = 0.031; at protein level: 5.12 ± 0.60 vs. 2.68 ± 0.37, P = 0.016) and SOCS6 expression was downregulated (at mRNA level: change ratio = -1.65, P = 0.008; at protein level: 3.03 ± 0.32 vs. 4.0.72 ± 0.39, P = 0.004) in PCa tissues compared with those in non-cancerous prostate tissues. In addition, the upregulation of SOCS2 in PCa tissues was correlated with the lower Gleason score (P < 0.001), the absence of metastasis (P < 0.001) and the negative PSA failure (P = 0.009); the downregulation of SOCS6 tended to be found in PCa tissues with the higher Gleason score (P = 0.016), the advanced pathological stage (P = 0.007), the positive metastasis (P = 0.020), and the positive PSA failure (P = 0.032). Furthermore, both univariate and multivariate analyses showed that the downregulation of SOCS2 was an independent predictor of shorter biochemical recurrence-free survival. Our data offer the convincing evidence for the first time that the dysregulation of SOCS2 and SOCS6 may be associated with the aggressive progression of PCa. SOCS2 may be potential markers for prognosis in PCa patients.


Assuntos
Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Próstata/metabolismo , Próstata/patologia
7.
Int J Cancer ; 130(2): 300-8, 2012 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-21328337

RESUMO

Novel molecular markers that are associated with prostate cancer (PCa) progression will provide valuable information in the diagnosis and treatment of the disease. Extracellular matrix metalloproteinase inducer (CD147) has been demonstrated to be involved in tumor invasion, metastasis, growth and survival. In our study, we examined whether the expression of CD147 can be used as a prognostic marker for predicting PCa progression. Tissue samples from 240 patients who received radical prostatectomy for PCa were obtained. CD147 expression in these samples was evaluated using immunohistochemical staining with a monoclonal antibody specifically against CD147. Increased expression of CD147 was correlated with higher Gleason scores (GS), positive surgical margin, prostate-specific antigen (PSA) failure, metastasis and reduced overall survival. Both univariate Cox regression analysis and multivariate analysis including competing biological variables demonstrated that increased CD147 expression was associated with increased risk for reduced PSA failure-free, metastasis-free and overall survival. Kaplan-Meier survival curves showed that the CD147 overexpression was a significant predictor for the PSA failure-free, metastasis-free and the overall survival in both pT2 and pT3 PCa patients. More significantly, higher expression of CD147 can serve as an independent prognostic predictor for PSA failure-free survival in PCa patients when they are stratified by GS. Our study results demonstrate the involvement of CD147 in PCa progression and suggest its potential role as an independent predictor of biochemical recurrence, development of metastasis and reduced overall survival in PCa.


Assuntos
Basigina/biossíntese , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Progressão da Doença , Intervalo Livre de Doença , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prostatectomia , Neoplasias da Próstata/cirurgia , Resultado do Tratamento
8.
BMC Cancer ; 12: 248, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-22703285

RESUMO

BACKGROUND: SOX genes play an important role in a number of developmental processes. Potential roles of SOXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the involvement of SOXs in the progression and prognosis of human prostate cancer (PCa). METHODS: The gene expression changes of SOXs in human PCa tissues compared with non-cancerous prostate tissues was detected using gene expression microarray, and confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. The roles of these genes in castration resistance were investigated in LNCaP xenograft model of PCa. RESULTS: The microarray analysis identified three genes (SOX7, SOX9 and SOX10) of SOX family that were significantly dis-regulated in common among four PCa specimens. Consistent with the results of the microarray, differential mRNA and protein levels of three selected genes were found in PCa tissues by QRT-PCR analysis and immunohistochemistry. Additionally, we found that the immunohistochemical staining scores of SOX7 in PCa tissues with higher serum PSA level (P = 0.02) and metastasis (P = 0.03) were significantly lower than those with lower serum PSA level and without metastasis; the increased SOX9 protein expression was frequently found in PCa tissues with higher Gleason score (P = 0.02) and higher clinical stage (P < 0.0001); the down-regulation of SOX10 tend to be found in PCa tissues with higher serum PSA levels (P = 0.03) and advanced pathological stage (P = 0.01). Moreover, both univariate and multivariate analyses showed that the down-regulation of SOX7 and the up-regulation of SOX9 were independent predictors of shorter biochemical recurrence-free survival. Furthermore, we discovered that SOX7 was significantly down-regulated and SOX9 was significantly up-regulated during the progression to castration resistance. CONCLUSIONS: Our data offer the convince evidence that the dis-regulation of SOX7, SOX9 and SOX10 may be associated with the aggressive progression of PCa. SOX7 and SOX9 may be potential markers for prognosis in PCa patients. Interestingly, the down-regulation of SOX7 and the up-regulation of SOX9 may be important mechanisms for castration-resistant progression of PCa.


Assuntos
Neoplasias da Próstata/genética , Fatores de Transcrição SOX/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Progressão da Doença , Perfilação da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Orquiectomia , Prognóstico , Hiperplasia Prostática , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Reprodutibilidade dos Testes , Fatores de Transcrição SOX/metabolismo , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Fatores de Transcrição SOXE/genética , Fatores de Transcrição SOXE/metabolismo , Fatores de Transcrição SOXF/genética , Fatores de Transcrição SOXF/metabolismo
9.
Zhonghua Nan Ke Xue ; 18(8): 692-6, 2012 Aug.
Artigo em Zh | MEDLINE | ID: mdl-22934513

RESUMO

OBJECTIVE: To investigate the effects of the expression of the PPAR-gamma gene on the proliferation and glycolysis metabolism of prostate cancer cells. METHODS: Using RNAi, we constructed lowly--expressed shRNA-PPARgamma adenoviruses and transfected them to PC3 prostate cancer cells, with blank vectors as controls. Then we detected the proliferation and apoptosis of the cells, glycolysis metabolism related genes and lactate accumulation by CCK-8 kit, and compared the results between the two groups. RESULTS: Compared with the control group, the PPAR-gamma gene expression was obviously inhibited by RNAi in the PC3 cells, and its protein expression was reduced to (26.00 +/- 4.06)%. The proliferation inhibition rate was (39.5 +/- 4.92)% on the 2nd day, and the apoptosis rate was as high as (21.03 +/- 3.08)%. The glycolysis metabolism related gene products (Myc and Glut-1) were significantly decreased, and the lactate concentration was reduced to 69.71% of that of the controls on the 4th day. There were statistically significant differences in the above findings as compared with the control group (P < 0.01). CONCLUSION: PPAR-gamma gene knockdown is expected to be a new way to treat prostate cancer.


Assuntos
Glicólise , PPAR gama/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Interferência de RNA , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Vetores Genéticos , Transportador de Glucose Tipo 1/metabolismo , Humanos , Masculino , PPAR gama/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Interferente Pequeno , Transfecção
10.
Zhonghua Yi Xue Za Zhi ; 91(34): 2407-10, 2011 Sep 13.
Artigo em Zh | MEDLINE | ID: mdl-22321786

RESUMO

OBJECTIVE: To explore the relationship between smoking and bladder cancer in China. METHODS: A multicenter case-control study was conducted from September 2005 to June 2008. A total of 432 bladder cancer patients, matched with 392 control cases, received a questionnaire including the type of exposure (active vs. passive smoking), the age of beginning and/or quitting smoking, smoking amount and time and depth of smoke inhalation. RESULTS: Both active smoking and passive smoking increased the incidence of bladder cancer (P < 0.05). Bladder cancer risk increased 1.89 times in active smokers and 1.88 times in passive smokers compared to non-smokers (P < 0.05). Smoke amount and time were significantly correlated with bladder cancer risk (P < 0.05). But the age of beginning smoking did not affect the bladder cancer risk (P > 0.05). Inhaling smoke into mouth or throat was also a risk factor for bladder cancer (P < 0.05). CONCLUSION: There is a strong association between smoking and bladder cancer. Active and passive smoking, smoke amount and time, and the depth of smoke inhalation are risk factors for bladder cancer. The best way of preventing bladder cancer is never smoking.


Assuntos
Fumar , Neoplasias da Bexiga Urinária , Estudos de Casos e Controles , China , Humanos , Fatores de Risco , Fumar/epidemiologia , Poluição por Fumaça de Tabaco , Neoplasias da Bexiga Urinária/epidemiologia
11.
J Surg Res ; 160(2): 260-7, 2010 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-19286191

RESUMO

BACKGROUND: CD147/extracellular matrix metalloproteinase inducer (EMMPRIN) expressed by tumor cells stimulates peri-tumorous fibroblasts to produce matrix metalloproteinases (MMPs), thus contributing to tumor invasion and metastasis. To assess its suitability as a potential therapeutic target, as well as its association with the clinicopathologic features and the prognosis of patients, the expression of CD147/EMMPRIN in neoplastic tissues of the genitourinary system were analyzed. METHODS: CD147/EMMPRIN expression in 52 patients with renal carcinoma, 58 patients with bladder carcinoma, 101 patients with prostate carcinoma, 17 patients of penis carcinoma, and 17 patients of testis carcinoma were examined by immunostaining on paraffin-embedded tumor specimens using monoclonal antibodies. Then, the association of its expression with clinicopathologic characteristics to the patients' prognosis was analyzed. The RNA interference approach was used to silence CD147/EMMPRIN expression in the human prostate carcinoma cell line LNCAP and human bladder carcinoma cell line J82. The in vitro proliferative ability of CD147/EMMPRIN-deficient cells was determined by a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay. RESULTS: CD147/EMMPRIN was expressed in neoplastic tissues, but not in normal tissues. Positive expression was shown in 42 of 52 (80.77%) of the patients with renal carcinoma, 41 of 58 (70.69%) of the patients with bladder carcinoma, 67 of 101 (66.34%) of the patients with prostate carcinoma, 16 of 17 (94.12%) of the patients with penis carcinoma and testis carcinoma. Positive CD147/EMMPRIN staining was significantly associated with TNM stages and histological subtypes of patients with various urinary carcinomas (P < 0.05). In all five groups, for different expression levels of CD147/EMMPRIN, the patients with a highly positive expression of CD147/EMMPRIN had the poorest prognosis. The siRNA-treated cells exhibited significantly decreased growth ability compared with control cells in vitro. CONCLUSION: These results may assist in defining the suitability of CD147/EMMPRIN as a therapeutic target and as a method for predicting a poor outcome in patients with various urinary carcinomas.


Assuntos
Basigina/genética , Basigina/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Urogenitais , Adulto , Idoso , Divisão Celular/fisiologia , Linhagem Celular Tumoral , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Neoplasias Penianas/metabolismo , Neoplasias Penianas/mortalidade , Neoplasias Penianas/patologia , Valor Preditivo dos Testes , Prognóstico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , RNA Interferente Pequeno , Fatores de Risco , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Neoplasias Urogenitais/metabolismo , Neoplasias Urogenitais/mortalidade , Neoplasias Urogenitais/patologia
12.
Mol Med ; 15(11-12): 363-70, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19707524

RESUMO

Overexpression of elongation factor-1alpha (EF-1alpha) has been reported to contribute to the development and progression of various cancers. However, its role in prostate cancer (PCa) still remains poorly understood. In the present study, we investigate the influence of EF-1alpha in Du145, a high-grade metastatic PCa cell line, and demonstrate that EF-1alpha plays an essential role in cellular properties associated with tumor progression, namely cell proliferation, invasion, and migration. In this study, EF-1alpha expression in human PCa cell line Du145 was reduced by RNA interference (RNAi) technology, and the proliferation, invasion, and migration of EF-1alpha-reduced Du145 cells were examined. We also detected an EF-1alpha expression pattern in 20 pairs of primary PCa samples and their corresponding normal tissues. Expression of EF-1alpha was detectable in four PCa cell lines (22RV1, LnCap, Du145, and PC3), indicating its possible role in pathogenesis of PCa. RNAi-mediated knockdown of EF-1alpha expression in Du145 cells, which expressed the highest level of EF-1alpha among four PCa cell lines, led to a decrease in proliferation. Similarly, suppression of EF-1alpha inhibited Du145 cell migration and invasion through a basement membrane substitute. Furthermore, we found that the normal prostate tissues showed a relatively low level of EF-1alpha expression, whereas PCa tissues demonstrated significantly higher expression levels of EF-1alpha (P < 0.001). Taken together, these findings support the hypothesis that EF-1alpha affects multiple processes involved in tumor progression, and identify EF-1alpha as a potential therapeutic target.


Assuntos
Fator 1 de Elongação de Peptídeos/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação para Baixo , Humanos , Imuno-Histoquímica , Masculino , Invasividade Neoplásica , Fator 1 de Elongação de Peptídeos/genética , Neoplasias da Próstata/genética , Interferência de RNA , RNA Interferente Pequeno/genética , Reprodutibilidade dos Testes
13.
Cancer Invest ; 27(7): 788-93, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19548138

RESUMO

AIM: To investigate the clinicopathologic characteristics of extracellular matrix (ECM) metalloproteinase inducer (CD147) and vascular endothelial growth factor (VEGF) expression in advanced renal cell carcinoma (RCC), and to evaluate the clinical significance of these two markers in the prognosis of advanced RCC. METHODS: CD147 and VEGF expression in paraffin-embedded specimens gathered from 53 patients with advanced RCC and 12 healthy controls were detected by the method of immunohistochemistry. The Spearman correlation was calculated between the expression levels of CD147 and VEGF in advanced RCC tissues. The association of CD147 and VEGF expression with the clinicopathologic features and prognosis of advanced RCC was subsequently assessed. RESULTS: CD147 and VEGF were positively expressed in 47/53 (88.7%) and 45/53 (84.9%) of patients with advanced RCC, respectively. Positive expression of CD147 (p= 0.02) and VEGF (p< 0.01) was significantly correlated with TNM stage of advanced RCC. A significant correlation was found between the expression of CD147 and VEGF in advanced RCC (r= 0.629, p= 0.04). Additionally, tumor CD147 and tumor VEGF expressions were significantly associated with the prognosis of advanced RCC patients. The survival rate of the patients with CD147-/VEGF- expression was the lowest (p< 0.01), and conjoined expressions of CD147-/VEGF- and CD147+/VEGF+ were independent prognostic indicators of advanced RCC (both p< 0.01). CONCLUSION: The expression of CD147 or VEGF may be an important feature of advanced RCC. A combined detection of CD147/VEGF coexpression may benefit us in the prediction of the prognosis of advanced RCC.


Assuntos
Basigina/fisiologia , Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Proteínas de Neoplasias/fisiologia , Fator A de Crescimento do Endotélio Vascular/fisiologia , Idoso , Basigina/análise , Carcinoma de Células Renais/química , Carcinoma de Células Renais/patologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/química , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Estadiamento de Neoplasias , Prognóstico , Fator A de Crescimento do Endotélio Vascular/análise
14.
Med Oncol ; 26(3): 303-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19003546

RESUMO

To investigate the expressions of PIM-1 and hK2 mRNA in normal prostate, benign prostatic glandular hyperplasia (BPH), and prostate cancer (PCa), and to explore the association of PIM-1 and hK2 expressions with PCa progression. The samples were harvested from 37 patients with BPH, 23 patients with PCa, and three with normal prostate tissues. Total RNA was extracted from their prostate tissues and analyzed for PIM-1 and hK2 mRNA levels using SYBR green I-based quantitative real-time RT-PCR (QRT-PCR) assays and Southern blot analysis. The differences of gene expressions were calculated based on standard curve. Quantitative expressions of PIM-1 and hK2 mRNA in normal prostate, BPH, and PCa were 1.05 +/- 0.04, 2.57 +/- 0.74, 4.45 +/- 0.63, and 1.02 +/- 0.03, 2.264 +/- 0.46, 5.905 +/- 0.78, respectively. PIM-1 and hK2 were expressed higher in PCa than those in BPH and normal prostate tissues, the differences among which had statistic significance (P < 0.05). Our results support the hypothesis that PIM-1 and hK2 play a significant role in the growth of PCa and the detection of PIM-1 and hK2 mRNA expressions by QRT-PCR provided more reliable and helpful information on diagnosis, treatment, and prognosis of PCa.


Assuntos
Biomarcadores Tumorais/genética , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-pim-1/genética , RNA Mensageiro/biossíntese , Calicreínas Teciduais/genética , Idoso , Benzotiazóis , Biomarcadores Tumorais/biossíntese , Distribuição de Qui-Quadrado , Diaminas , Expressão Gênica , Humanos , Masculino , Compostos Orgânicos/química , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas c-pim-1/biossíntese , Quinolinas , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Calicreínas Teciduais/biossíntese
15.
Zhonghua Yi Xue Za Zhi ; 89(26): 1844-6, 2009 Jul 14.
Artigo em Zh | MEDLINE | ID: mdl-19953931

RESUMO

OBJECTIVE: To investigate the expression of CD147 in prostate cancer and discuss its diagnostic value in prostate cancer. METHODS: The method of immunohistochemical SP was employed to detect the expression of CD147 in 101 cases of prostate cancer, 90 cases of benign prostatic hyperplasia, 36 cases of normal prostate and 15 cases of embryonic prostate by so as to evaluate its clinical significance in the histological classification and prognosis of prostate cancer. RESULTS: The CD147 expression was positively expressed in 67/101 (66.3%) of prostate cancer, 21/90 (23.3%) of benign prostatic hypertrophy, 2/36 (5.6%) of normal prostate and 0/15 (0.0) of embryonic prostate respectively. A positive expression of CD147 was dramatically associated with TNM stage (P < 0.001), the depth of prostatic capsule invasion (P = 0.002) and histological grade (P = 0.006). CONCLUSIONS: The detection of CD147 is helpful to raise the early diagnosis rate of prostate cancer. It will become a tumor marker of reflecting the malignant degree and predicting the prognosis of prostate cancer.


Assuntos
Basigina/metabolismo , Próstata/metabolismo , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Humanos , Masculino , Estadiamento de Neoplasias , Prognóstico , Próstata/patologia , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/patologia
16.
Oncology ; 75(3-4): 230-6, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18852494

RESUMO

AIM: CD147 and MMPs have been demonstrated to be involved in tumor invasion and angiogenesis. The aim of this study was to analyze the clinicopathological significance of CD147, MMP-1, MMP-2 and MMP-9 expression in human prostate cancer (PCa) and to evaluate their involvement in the progression of PCa. METHODS: CD147, MMP-1, MMP-2 and MMP-9 expression was assessed in paraffin-embedded specimens collected from 62 cases of PCa and 15 cases of benign prostatic hyperplasia (BPH) by immunohistochemistry. Spearman's correlation was applied to determine possible relationships between CD147, MMP-1, MMP-2 and MMP-9 expression and PCa. The association of CD147 and MMP-2 protein expression with the clinicopathological characteristics and the prognosis of PCa was subsequently assessed. RESULTS: CD147was expressed in 51/62 (82.3%) PCa patients and in 2/15 (13.3%) BPH cases. MMP-1, MMP-2 and MMP-9 expression was significantly higher in PCa tissue than in BPH tissue. Using Spearman analysis, a significant positive correlation between CD147 and MMP-1, MMP-2 and MMP-9 expression was found (p <0.05). CD147 and MMP-2 expression was correlated with TMN grade and Gleason score. Patients with concurrent expression of CD147+ and MMP-2+ had the lowest survival (p <0.01). CONCLUSION: The results suggest that concurrent expression of CD147 and MMP may be an important characteristic of PCa which may help in the prediction of PCa progression.


Assuntos
Basigina/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias da Próstata/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Próstata/metabolismo , Próstata/patologia , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Hiperplasia Prostática/cirurgia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia
17.
Clin Invest Med ; 31(4): E212-7, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18682045

RESUMO

PURPOSE: To investigate the protective effect of ganoderan on renal damage in rat models with chronic glomerulonephritis induced by adriamycin. METHODS: 48 healthy Sprague-Dawley rats were randomly divided into three groups: control, nephritic model and ganoderan treatment groups. Changes of the following indices in the three groups were observed 6 weeks after treatment: 24-hour urine protein, albumen, serum creatinine, cholesterol. Histopathological observations of the renal cortex were made by light and electron microscopy. RESULTS: Compared with controls, levels of 24-hour urine protein (9.60+/-0.57 mg/d vs. 82.50+/-3.18 mg/d), serum creatinine (35.25+/-2.63 micromol/L vs. 44.75+/-8.06 micromol/L) and cholesterol (1.15+/-0.10 mmol/L vs. 4.02+/-0.25 mmol/L) of rats in the nephritic model group were increased (P < 0.05), and the concentration of albumen was decreased (35.98+/-1.34 g/L vs. 19.05+/-0.62 g/L, P < 0.05). Ganoderan administration decreased 24-hour urine protein (82.50+/-3.18 mg/d vs. 45.01+/-3.94 mg/d, P < 0.05). Following ganoderan, the pathological changes in kidney tissue were improved compared with those in the nephritic model group. CONCLUSION: Ganoderan exerts protective effects in rats with chronic glomerulonephritis induced by ADR. Ganoderan reduced 24-hour urine protein, serum creatinine, cholesterol, improving renal function and reducing the severity of renal injury.


Assuntos
Glomerulonefrite/tratamento farmacológico , Falência Renal Crônica/tratamento farmacológico , Polissacarídeos/uso terapêutico , Proteinúria/urina , Albuminúria/urina , Animais , Colesterol/sangue , Creatinina/sangue , Glomerulonefrite/patologia , Glomerulonefrite/prevenção & controle , Imuno-Histoquímica , Falência Renal Crônica/patologia , Falência Renal Crônica/prevenção & controle , Testes de Função Renal , Microscopia Eletrônica , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Fatores de Tempo
18.
Chin Med J (Engl) ; 120(17): 1491-3, 2007 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-17908456

RESUMO

BACKGROUND: Pim-1 plays an important role in the apoptosis, proliferation, differentiation of cancer cells and progression of cancer. In this study we detected the expression of pim-1 mRNA in normal prostate, benign prostatic hyperplasia (BPH), and prostate cancer (PCa) and explored its diagnostic value for PCa. METHODS: The prostate tissues were collected from 23 patients with PCa, 37 patients with BPH, and 3 healthy volunteers. Pim-1 mRNA expression levels in these samples were determined by the quantitative real-time PCR (QRT-PCR). The differences of expression were calculated based on a standard curve. RESULTS: The ratio of pim-1 mRNA to beta-actin in the normal prostate, BPH, and PCa were 1.05 +/- 0.04, 2.57 +/- 0.74 and 4.45 +/-0.63, respectively. The differences among PCa, BPH and NT were significant (P < 0.05, respectively). CONCLUSION: Detecting pim-1 mRNA expression by QRT-PCR provides a reliable metric for the diagnosis of PCa.


Assuntos
Neoplasias da Próstata/diagnóstico , Proteínas Proto-Oncogênicas c-pim-1/genética , RNA Mensageiro/análise , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/metabolismo , Sensibilidade e Especificidade
19.
Zhonghua Yi Xue Za Zhi ; 87(36): 2544-6, 2007 Sep 25.
Artigo em Zh | MEDLINE | ID: mdl-18067829

RESUMO

OBJECTIVE: To investigate the value of special fluorescence spectrum in the early diagnosis of bladder cancer. METHODS: Hematoporphyrin monomethyl ether (HMME) of the concentrations of 10, 100, and 200 microg/ml, as photosensitizer, was added into the sample vessels of bladder cancer tissue to be incubated for 1 - 3 h. A detecting system consisting of solid state ultraviolet laser with the wavelength of 355 nm was used to measure the fluorescence spectrum. RESULTS: The laser-induced auto-fluorescence (LIAF) of the bladder cancer tissue had characteristic double peaks at 445 - 490 nm. There was a remarkable characteristic peak, drug peak, located at 628.25 nm in the laser-induced drug-fluorescence (LIDF) of the bladder cancer tissue soaked by HMME. CONCLUSION: Photosentisizer raise the sensitivity and specificity of fluorescence spectrum in diagnosis of bladder cancer. Stable, and with high strength and visible drug peak, the LIDF is may help improve the early diagnosis of bladder cancer.


Assuntos
Espectrometria de Fluorescência/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Éter de Diematoporfirina/química , Diagnóstico Precoce , Humanos , Técnicas In Vitro , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/química
20.
Int J Clin Exp Med ; 8(3): 4186-94, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26064329

RESUMO

Dual-specificity phosphatase 5 (DUSP5), which specifically inactivates the extracellular signal-regulated kinase (ERK) 1/2 within the mitogen-activated protein kinase (MAPK) signaling, has recently been considered to be a tumor suppressor. However, its role in prostate cancer is still elusive. In this study, we performed immunohistochemistry analysis on human tissue microarray (TMA) to detect the DUSP5 protein expression pattern. The results indicated that DUSP5 was down-regulated in the human prostate cancer relative to the adjacent benign tissues (IRS: PCa = 4.29 ± 1.72 versus Benign = 4.89 ± 1.58, P = 0.04). In addition, when we linked the DUSP5 protein levels to the clinicopathological features of the patients, we found that the downregulation of DUSP5 was significantly associated with advanced pathological stage (P = 0.004) and high Gleason score (P = 0.009). Moreover, we attempted to validate these findings and investigate the prognostic value of DUSP5 in a publicly available microarray-based Taylor Dataset. Statistic analysis demonstrated that the downregulation of DUSP5 was closely correlated with high Gleason score (P = 0.011), positive metastasis (P < 0.001) and biochemical recurrence (BCR) (P = 0.016). More importantly, Kaplan-Meier analysis revealed that significant differences between patients with high and low DUSP5 expression level in regard to the BCR-free survival of overall (P = 0.009), non-metastatic (P = 0.006) and patients with Gleason score 7 (P = 0.044). Multivariate analysis by Cox regression indicated that DUSP5 could be an independent predictor for the risk of BCR (HR: 0.41, 95% CI: 0.2-0.82; P = 0.012). In summary, our findings disclose that DUSP5 may be an important tumor suppressor that inhibits the progression of PCa. The downregulation of DUSP5 may accurately predict poor prognosis in PCa patients.

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