RESUMEN
PURPOSE: We studied the efficacy of B vitamins as a treatment for hyperhomocysteinemia and endothelial dysfunction in renal transplant recipients in the Chinese population. MATERIALS AND METHODS: A total of 36 stable renal transplant recipients with hyperhomocysteinemia were randomly assigned to folate treatment (5 mg folic acid per day, 50 mg vitamin B6 per day and 1,000 microg vitamin B12 per day) or to the control group (placebo only) for 6 months. All subjects underwent tests for creatinine, creatinine clearance rate, average blood pressure, total cholesterol, triglyceride and fasting homocysteine. Endothelial function was evaluated using high resolution vascular ultrasound. RESULTS: Homocysteine significantly decreased in those with folate treatment after intervention compared with baseline (12.6 +/- 3.9 vs 20.1 +/- 5.4 micromol/l, t = 5.3, p <0.01), whereas no significant changes were observed in controls. In the folate treatment group endothelium dependent and independent vasodilatation responses significantly increased after intervention (12.2% +/- 4.6% vs 8.8% +/- 5.2%, t = 2.9, p <0.01 and 17.6% +/- 3.9% vs 12.2% +/- 4.7%, t = 3.4, p <0.01, respectively). However, no significant changes were observed in controls. Endothelium dependent and independent vasodilatation responses were significantly lower in controls compared to levels in the folate group after treatment (8.7% +/- 6.3%, t = 2.8, p <0.01 and 12.2% +/- 5.3%, t = 3.5, p <0.01, respectively). CONCLUSIONS: Based on these data B vitamin supplementation may decrease blood homocysteine and improve endothelial function in renal transplant recipients with hyperhomocysteinemia.
Asunto(s)
Hiperhomocisteinemia/tratamiento farmacológico , Trasplante de Riñón , Enfermedades Vasculares/tratamiento farmacológico , Complejo Vitamínico B/uso terapéutico , Adulto , Pueblo Asiatico , Estudios de Casos y Controles , Endotelio Vascular/diagnóstico por imagen , Endotelio Vascular/efectos de los fármacos , Femenino , Ácido Fólico/uso terapéutico , Humanos , Hiperhomocisteinemia/sangre , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Ultrasonografía Intervencional , Enfermedades Vasculares/sangre , Enfermedades Vasculares/diagnóstico por imagen , Vasodilatación/efectos de los fármacos , Vitamina B 12/uso terapéutico , Vitamina B 6/uso terapéuticoRESUMEN
OBJECTIVE: To investigate the effect of phosphodiesterase type 5 (PDE5) small interfering RNA (siRNA) on the cGMP in the smooth muscle cells of human corpus cavernosum, and to provide an experimental groundwork for the gene therapy of erectile dysfunction (ED). METHODS: Small interfering RNAs targeting PDE5 gene were synthesized by using web design software provided by Ambion, three siRNAs and a control siRNA were synthesized by Ambion. siRNAs were transfected into the smooth muscle cells of human corpus cavernosum by using siPORT Lipid reagent. cGMP was detected by ELISA at different times (24, 48, 72 and 96 h) after transfection. RESULTS: The cGMP levels of the siRNA1, siRNA2 and siRNA3 groups were significantly higher than those of the siRNA control and blank control groups (P < 0.05), and so was it in the siRNA1 group than the siRNA2 and siRNA3 groups (P < 0.05), with significant difference between the siRNA control and the blank control group (P > 0.05). CONCLUSION: The synthesized siRNAs in vitro are capable of increasing the level of cGMP in the smooth muscle cells of human corpus cavernosum, different siRNAs with different capabilities. The siRNA technique could provide not only an extremely powerful tool for the functional analysis of genome but also a new approach to ED gene therapy.
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3',5'-GMP Cíclico Fosfodiesterasas/genética , GMP Cíclico/metabolismo , Miocitos del Músculo Liso/metabolismo , ARN Interferente Pequeño/farmacología , Células Cultivadas , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5 , Silenciador del Gen , Humanos , Masculino , Miocitos del Músculo Liso/efectos de los fármacos , Pene/metabolismo , TransfecciónRESUMEN
BACKGROUND: Bladder cancer is a relatively common tumor in the urinary system, in which mitomycin C (MMC)-based chemotherapy or combination chemotherapy has been mainly used to treat patients with advanced bladder cancer. The prognosis of patients with advanced bladder cancer is still extremely poor in spite of recent therapeutic advances. To improve the prognosis, the sensitivity of tumor cells to mitomycin C by the induction of apoptosis with the abating heat shock protein 70 (HSP70) expression in human bladder cancer cell lines of BIU-87 was investigated. METHODS: HSP70 expression was abated in BIU-87 cells by HSP mRNA antisense oligomers. MTT assay and the clone-forming test were used for evaluating the sensitivity of cells to MMC. Apoptosis was assessed using both fluorescent microscopy after staining the cells with Hoechst 33258 and DNA fragment ladder agarose electrophoresis. Thirty-two male six-week-old BALB/c nude mice, at the beginning of the experiment, were used to evaluate the effect of antisense oligomers (ASO) on the tumor formation in vivo. RESULTS: HSP70 expression in BIU-87 was effectively abated by HSP70 mRNA antisense oligomers. The percentage of apoptotic cells in ASO group was greater than in sense oligomers (SO) [P < 0.05, (18.31 +/- 2.89)% vs (1.89 +/- 0.74)%], nonsense oligomers (NO) [P < 0.05, (18.31 +/- 2.89)% vs (1.78 +/- 0.92)%] and blank groups [P < 0.05, (18.31 +/- 2.89)% vs (1.87 +/- 0.84)%], while the sensitivity of tumor cells to mitomycin C was enhanced. The in vivo tumor inhibition rate of ASO plus MMC (> 50%) was more than that of ASO or MMC group alone (all P < 0.05). CONCLUSIONS: The abating level of HSP70 expression can strengthen the sensitivity of BIU-87 to MMC. One of this effect might be related to the induction of apoptosis by abating HSP70 expression.
Asunto(s)
Proteínas HSP70 de Choque Térmico/antagonistas & inhibidores , Mitomicina/farmacología , Oligodesoxirribonucleótidos Antisentido/farmacología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/fisiología , Humanos , ARN Mensajero/análisis , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVE: To explore the diagnosis and treatment of testicular intratubular seminoma. METHODS: One case of testicular intratubular seminoma was diagnosed with testicular biopsy. Epididymal sperm was aspirated and intracytoplasmic sperm injection ( ICSI) was performed. And local radiotherapy was conducted on the bilateral testes after fertilization. RESULTS: The result of testicular biopsy revealed bilateral testicular intratubular seminoma. Large numbers of sperms were found in the epididymal aspirate. ICSI did not succeed for the first time. The second ICSI succeeded. The local radiotherapy by 60Co had been conducted on the bilateral testes, and testicular tumor didn't develop further. CONCLUSION: Testicular intratubular seminoma is a type of intratubular germ cell neoplasia, with no clinical manifestations, and usually found in testicular biopsy. Earlier management promises better prognosis.
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Seminoma/diagnóstico , Seminoma/terapia , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/terapia , Testículo/patología , Adulto , Biopsia , Humanos , Masculino , Seminoma/patología , Inyecciones de Esperma Intracitoplasmáticas , Neoplasias Testiculares/patologíaRESUMEN
OBJECTIVE: To study the effect of vitamin B on treatment of hyperhomocysteinemia and endothelial dysfunction in renal-transplant recipients. METHODS: Thirty-six stable hyperhomocysteinemic renal-transplant recipients were randomly assigned to vitamin treatment (group A, n = 18, folic acid 5 mg/d, vitamin B(6) 50 mg/d, B(12) 1000 microg/d) or controlled group (group B, n = 18) for 6 months. All subjects underwent assessment of levels for creatinine, creatinine clearance, average pressure, total cholesterol, triglyceride and fasting homocysteine. Endothelial function was evaluated using high-resolution vascular ultrasound. RESULTS: The levels of homocysteine markedly decreased in group A [(13 +/- 4) micromol/L vs (20 +/- 5) micromol/L, t = 5.3, P < 0.01] after treatment, whereas no significant changes were observed in group B. In group A, endothelium dependent [(12 +/- 5)% vs (9 +/- 5)%, t = 2.9, P < 0.01] and independent [(18 +/- 4)% vs (12 +/- 5)%, t = 3.4, P < 0.01] vasodilatation responses significantly increased after treatment, no significant changes were observed in group B. Endothelium dependent [(9 +/- 6)%, t = 2.8, P < 0.01] and independent [(12 +/- 5)%, t = 3.5, P < 0.01] vasodilatation responses of group A were significantly lower than that of group B after treatment. CONCLUSIONS: Vitamin B supplementation can reduce the levels of homocysteine and improve the endothelial function in hyperhomocysteinemic renal-transplant recipients.
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Endotelio Vascular/efectos de los fármacos , Ácido Fólico/administración & dosificación , Hiperhomocisteinemia/tratamiento farmacológico , Trasplante de Riñón , Vitamina B 12/administración & dosificación , Vitamina B 6/administración & dosificación , Adulto , Quimioterapia Combinada , Endotelio Vascular/fisiopatología , Femenino , Humanos , Hiperhomocisteinemia/fisiopatología , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVE: To analyse retrospectively the diagnosis and treatment of severe pneumonia in kidney transplantation recipients. METHODS: Between January 1999 and December 2003, 172 adult patients underwent kidney transplantation at our department. In all severe pneumonia cases, empirical therapy was initiated with aztreonam, erythromycin and ganciclovir. And the therapy was switched to proper antibiotics according to the results of sensitivity testing. Responsible pathogen was detected by study of BAL (bronco-alveolar-lavage), sputum and blood specimen. Analyses included cell differential count, cytopathologic examination and cultures for bacteria, fungi and viruses. The immunosuppressive therapy was drastically reduced. Hypoxia was relieved by BiPAP (Bi-level Positive Airway Pressure) or mechanical ventilation if necessary. RESULTS: Seventeen cases (9.9%) of pneumonia were observed in the 172 recipients, only 11 (65%) patients experienced severe pneumonia, 1 (9%) of them died. Fever was the most common symptom on presentation (82%). On presentation 46% of the patients presented with classical clinical syndrome of fever accompanied by cough and dyspnea. Positive rate of BAL and blood culture were 100% and 46% respectively. BiPAP and mechanical ventilation were required in 6 and 2 cases respectively. CONCLUSION: BAL is preferred for early detection of responsible pathogen. A combination of drastic reduction of the immunosuppressive regimen, implementation of appropriate empirical antibiotics, proper BiPAP or mechanical ventilation are important.
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Trasplante de Riñón/efectos adversos , Neumonía/diagnóstico , Neumonía/terapia , Adulto , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía/etiología , Respiración Artificial , Estudios Retrospectivos , Trasplante Homólogo/efectos adversosAsunto(s)
Apoptosis , Carcinoma de Células Transicionales/química , Proteínas HSP70 de Choque Térmico/análisis , Neoplasias de la Vejiga Urinaria/química , Adulto , Anciano , Carcinoma de Células Transicionales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVE: To investigate the expression of cyclooxygenase-2 (COX-2) in bladder transitional cell carcinoma tissues, and understand its clinical significance. METHODS: Reversal transcription polymerase chain reaction (RT-PCR) was used to assess the expression of COX-2 mRNA in 52 cases of bladder transitional cell carcinoma tissues and 17 cases of normal bladder tissues far from neoplasm; Western blot was used to assess the expression of COX-2 protein in 49 cases of bladder cancerous tissues and 17 cases of normal tissues. RESULTS: Positive expression of COX-2 mRNA was detected in 83% (43/52) of bladder cancer tissues and in 29% (5/17) of normal tissues by RT-PCR and there was significant difference in expression of COX-2 mRNA between cancer tissues and normal tissues. Western blot analysis showed that expression of COX-2 protein was correlation with the stage and grade of cancer. CONCLUSION: COX-2 is overexpressed in bladder transitional cell carcinoma. COX-2 maybe play a certain role in carcinogenesis and progression of bladder cancer and turn into a useful target of chemoprevention of bladder cancer.
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Carcinoma de Células Transicionales/enzimología , Ciclooxigenasa 2/biosíntesis , Neoplasias de la Vejiga Urinaria/enzimología , Vejiga Urinaria/enzimología , Adulto , Anciano , Anciano de 80 o más Años , Western Blotting , Carcinoma de Células Transicionales/patología , Ciclooxigenasa 2/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVE: To investigate whether the heat shock protein (HSP) 70 antisense oligomers can enhance the sensitivity of bladder cancer cell EJ to mitomycin C. METHODS: The HSP70 mRNA of EJ cells was blocked by the 10 micromol/L HSP70 antisense oligomers, while its effect on cell growth was evaluated by methyl thiazolyl tetrazolium (MTT) and colony forming ability test. RESULTS: The HSP70 expressions in HSP70 antisense treated group were lower than the corresponding sense and nonsense treated groups (P < 0.01). While, the increased sensitivity of EJ to mitomycin C was found in antisense treated group, compared with the corresponding sense and nonsense treated groups (P < 0.01). CONCLUSION: The sensitivity of bladder cancer cell EJ to mitomycin C was enhanced by the blockage of the HSP70 expression.
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Proteínas HSP70 de Choque Térmico/biosíntesis , Mitomicina/farmacología , Oligonucleótidos Antisentido/farmacología , Neoplasias de la Vejiga Urinaria/patología , División Celular/efectos de los fármacos , Línea Celular Tumoral , Proteínas HSP70 de Choque Térmico/antagonistas & inhibidores , Proteínas HSP70 de Choque Térmico/genética , Humanos , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
BACKGROUND: Much research has been focused on ischemia/reperfusion injury (IRI) to the transplanted organs. As a free radical, nitric oxide (NO) plays an important role in IRI. In this study, the production of NO and its functions during IRI were monitored in rat models after allotransplantation of kidney grafts. METHODS: Of 75 male LEW rats, 30 served as donors, and the remaining 45 rats were divided into three groups (15 rats in each group): controls (group 1), kidney allotransplantation followed by bilateral nephrectomy during reperfusion (group 2), 2 hours before operation, donors and recipients were treated with N(G)-nitro L-arginine methyl ester (L-NAME), a NO synthase inhibitor, at a dose of 30 mg/kg (group 3). Bilateral nephrectomies were performed while kidney grafts were reperfused. The kidney grafts were hypothemically stored for 24 hours. The production of NO before and after reperfusion was measured by electron paramagnetic resonance (EPR). The creatinine level, the glomerular filtration rate (GFR) and the protein carbonyl content in tissue samples were recorded on the first and the fifth day after operation. The data were evaluated by one-way analysis of variance. Differences were considered to be statistically significant when a P value was less than 0.05. RESULTS: After reperfusion for 15 minutes, the production of NO increased remarkably and kept increasing till 120 minutes, after which the level returned to normal. In group 3, which was pretreated with L-NAME, creatinine levels were higher than those in group 2 at the 24th hour (4.10 +/- 0.50 mg/dl vs. 3.77 +/- 0.42 mg/dl, P < 0.05) and the 120th hour (3.19 +/- 0.79 mg/dl vs. 2.22 +/- 0.53 mg/dl, P < 0.05). GFR levels in group 3 were lower than those in group 2 at the 24th hour (0.50 +/- 0.12 ml/min vs. 0.71 +/- 0.19 ml/min, P < 0.05) and the 120th hour (0.59 +/- 0.38 ml/min vs. 1.27 +/- 0.23 ml/min, P < 0.01). The content of protein carbonyl in tissue samples of group 3 was lower than that in group 2 at the 24th hour (29.01 +/- 7.02 nmol/mg protein vs. 49.39 +/- 13.13 nmol/mg protein, P < 0.05), but was higher than that at the 120th hour (75.71 +/- 16.74 nmol/mg protein vs. 57.93 +/- 15.32 nmol/mg protein, P < 0.05). CONCLUSIONS: After transplantation of hypothemically stored kidney grafts, the increased NO production in the early stage has protective effects on the transplanted kidney. Application of L-NAME to inhibit NO production is harmful to the recovery of the renal functions of kidney grafts.
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Trasplante de Riñón , Óxido Nítrico/biosíntesis , Animales , Creatinina/sangre , Espectroscopía de Resonancia por Spin del Electrón , Tasa de Filtración Glomerular , Masculino , Oxidación-Reducción , Proteínas/metabolismo , Ratas , Ratas Endogámicas Lew , Daño por Reperfusión/metabolismoRESUMEN
OBJECTIVE: The aim of the present study is to compare the effects of two alpha1-adrenoceptor antagonist terazosin and alfuzosin together with one alpha-adrenoceptor antagonist phenoxybenzamine on androgen-independent prostate cancer cell lines PC-3 and DU145. METHODS: Two androgen- independent cell lines, PC-3 and DU145, were used to determine the cell viability, colony-forming ability as well as cell cycle characteristics after exposure to these three drugs. RESULTS: This study showed that terazosin inhibited not only prostate cancer cell growth but also colony-forming ability, which is the main target of clinical treatment. On the other hand, alfuzosin and phenoxybenzamine have no effect on cell viability and colony forming ability of PC-3 and DU145. In addition, the terazosin inhibits cell growth through G(1) phase cell cycle arrest. CONCLUSION: This study provided the evidence that alpha1-adrenoceptor antagonist terazosin may have a therapeutic potential in the treatment of advanced androgen-independent prostate cancer.
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Antagonistas Adrenérgicos alfa/farmacología , Antineoplásicos/farmacología , Prazosina/análogos & derivados , Neoplasias de la Próstata/patología , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Fenoxibenzamina/farmacología , Prazosina/administración & dosificación , Prazosina/farmacología , Quinazolinas/farmacologíaRESUMEN
OBJECTIVE: To study the prostate specific antigen (PSA), prostate-specific membrane antigen (PSMA) and human glandular kallikrein (hK2) mRNA in peripheral blood samples of prostate cancer (PC) patients with bone metastasis by nested reverse transcriptase polymerase chain reaction (RT-PCR) based assay, and to discuss their clinical implications. METHODS: Samples of peripheral blood were analyzed by nested RT-PCR to identify PSA, PSMA and hK2 mRNA expression. RESULTS: RT-PCR assay was applied to identify the PSA, PSMA and hK2 mRNA expressing LNCaP cells, which were diluted by lymphocytes to 10(-6), 10(-6) and 10(-7) separately. Positive rates of the three markers in newly diagnosed PC patients with bone metastasis were 59.45%, 51.35% and 59.46% respectively, and 32.43% cases showed three positives. In PC patients who had developed bone metastasis after endocrine therapy, the positive rates were 57.14%, 85.71% and 83.33% respectively, and 52.48% cases showed three positives. All samples were negative in regional PC patients and healthy individuals, and all samples were positive for beta actin mRNA, the internal control. CONCLUSION: Nested RT-PCR based assay for PSA, PSMA or hK2 mRNA helps to detect prostate cancer cells in the circulation system, thus providing evidence for occult metastasis. PSMA and hK2 were advisable markers to monitor disease progression after androgen blockage. Combined assays of PSMA and hK2 are suitable for patients who underwent endocrine therapy, and combined assays of the three markers have enhanced sensitivity.
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Antígenos de Superficie/genética , Glutamato Carboxipeptidasa II/genética , Antígeno Prostático Específico/genética , Neoplasias de la Próstata/sangre , ARN Mensajero/sangre , Calicreínas de Tejido/genética , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y EspecificidadRESUMEN
PURPOSE: We investigated whether recombinant human endostatin can inhibit the growth of bladder cancer in an experimental model and its possible mechanism of action. MATERIALS AND METHODS: The recombinant human endostatin protein was induced and confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot assays. Its biological activities and the possible mechanisms of action were studied in vitro and in vivo. RESULTS: Recombinant human endostatin inhibited the proliferation of endothelial cells (ECV304) but not bladder tumor cells (EJ). Endostatin induced the expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in bladder cancer cells. Endostatin slowed the growth of xenograft bladder tumors. Immunohistochemistry revealed that endostatin blocked angiogenesis by decreasing vascular endothelial growth factor expression and inducing apoptosis in bladder cancer cells. CONCLUSIONS: These findings demonstrate that endostatin can inhibit xenograft bladder cancer growth and this effect is likely to be mediated by regulating matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases and vascular endothelial growth factor expression, and by inducing apoptosis.
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División Celular/efectos de los fármacos , Endostatinas/farmacología , Neovascularización Patológica/patología , Células Tumorales Cultivadas/efectos de los fármacos , Neoplasias de la Vejiga Urinaria/irrigación sanguínea , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Relación Dosis-Respuesta a Droga , Electroforesis en Gel de Poliacrilamida , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/patología , Inducción Enzimática/efectos de los fármacos , Humanos , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Microscopía Electrónica , Trasplante de Neoplasias/patología , Proteínas Recombinantes/farmacología , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Células Tumorales Cultivadas/patología , Neoplasias de la Vejiga Urinaria/patología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: To detect serum levels of MMP-9 and VEGF in patients with bladder cancer. METHODS: Serum levels of MMP-9 and VEGF in 58 patients with bladder cancer and 45 healthy controls were measured by sandwich-ELISA. RESULTS: Serum levels of MMP-9 and VEGF (737.12 micro g/L and 1148.88 ng/L) were significantly higher in the cancer patients than those of controls (423.51 micro g/L and 846.96 ng/L, P < 0.01). The serum levels were associated with tumor stage and grade. In patients with invasive cancer, the levels were significantly higher than those of superficial cancer (P < 0.01). Patients with distant metastasis had significantly higher levels of MMP-9 and VEGF than those with localized invasion (P < 0.01). But there was no significant difference between patients with superficial cancer and controls. Patients with G(3) tumors had significantly higher levels of MMP-9 and VEGF than those of patients with G(1) and G(2) tumors (P < 0.01). CONCLUSIONS: Elevated MMP-9 and VEGF levels are associated with a high stage and grade of bladder cancer and they may serve as markers of tumor progression in the future.
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Metaloproteinasa 9 de la Matriz/sangre , Neoplasias de la Vejiga Urinaria/sangre , Factor A de Crecimiento Endotelial Vascular/sangre , Anciano , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVES: To analyze the preoperative serum levels of endostatin and matrix metalloproteinase-9 (MMP-9) in patients with primary transitional cell carcinoma of the bladder according to tumor stage and grade and to evaluate their clinical diagnostic application. METHODS: Preoperative serum levels of endostatin and MMP-9 were determined in 52 patients with transitional cell carcinoma of the bladder (13 with superficial carcinoma and 39 with advanced carcinoma) and 32 healthy controls by enzyme-linked immunosorbent assay. RESULTS: The serum levels of endostatin and MMP-9 were significantly greater in the 52 patients with bladder cancer than in the healthy controls (endostatin 46.8 ng/mL versus 30.6 ng/mL, P <0.001; MMP-9 786 ng/mL versus 417 ng/mL, P <0.001). The endostatin level correlated positively with the MMP-9 level (R = 0.55, P <0.01). Furthermore, the levels of endostatin and MMP-9 were associated with the tumor stage and grade. Patients with distant metastasis (n = 7) had significantly greater levels of endostatin and MMP-9 than patients without metastasis (n = 45) (endostatin 69.8 ng/mL versus 43.3 ng/mL, P <0.001; MMP-9 1529 ng/mL versus 674 ng/mL, P <0.001). CONCLUSIONS: Elevated endostatin and MMP-9 levels are associated with a greater stage and grade of primary transitional cell carcinoma of the bladder.
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Carcinoma de Células Transicionales/sangre , Colágeno/sangre , Metaloproteinasa 9 de la Matriz/sangre , Fragmentos de Péptidos/sangre , Neoplasias de la Vejiga Urinaria/sangre , Carcinoma de Células Transicionales/enzimología , Carcinoma de Células Transicionales/patología , Endostatinas , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/enzimología , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVE: To investigate if downregulation of two mitotic checkpoint proteins, MAD2 and p55CDC, is a frequent event in human prostate cancer and whether decreased expression of these two proteins are associated with progression of prostate cancer. METHODS: Using immunohistochemistry technique, the expressions of MAD2 and p55CDC proteins are examined in 46 benign prostate hyperplasia (BPH) and 65 prostate cancer tissues. Differential expressions were compared first between BPH and prostate cancer specimens, and then among prostate cancer samples with different Gleason grades. RESULTS: We found that down-regulation of MAD2 and p55CDC expressions was significant in prostate cancer (96% and 83%, respectively) compared to BPH (19.5% and 4.3%, respectively) (P<0.001). In addition, decreased expression levels of these two proteins were associated with increased Gleason grade. CONCLUSION: Our results indicate that loss of MAD2 and p55CDC protein expression is a frequent event in prostate carcinoma and the decreased expressions of these two proteins are associated with increased Gleason grade. Our results provide first in vivo evidence to support the hypothesis that down regulation of certain mitotic checkpoint proteins plays an important part in human tumourigenesis.
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Proteínas de Unión al Calcio/análisis , Proteínas de Ciclo Celular/análisis , Neoplasias de la Próstata/química , Proteínas Cdc20 , Humanos , Inmunohistoquímica , Proteínas Mad2 , Masculino , Estadificación de Neoplasias , Neoplasias de la Próstata/patología , Proteínas RepresorasRESUMEN
OBJECTIVES: To investigate the effects of antisense oligodeoxynucleotide(ASON) on the cyclic nucleotide monophosphates (cNMP) in smooth muscle cells of human corpus cavernosum, and provide experimental groundwork for the gene therapy of erectile dysfunction. METHODS: PDE5 gene ASON(containing exon 1) was transfected into the corpus cavernosum smooth muscle cells with the presence of liposome DOTAP. Another sense oligodeoxynucleotide(SON) and 1% of bovine serum were also transducted into the cells as controls. Two of cNMP, cAMP and cGMP, were probed and measured by ELISA at 1, 2, 4, 6, 10, 24 and 48 h after transfection. RESULTS: After transfection, the level of cGMP(1-6 h) in human corpus cavernosum smooth muscle cells was significantly higher than that in controls(P < 0.01). CONCLUSIONS: The PDE5 gene ASON had been showed to manifest stimulative effect on the cGMP in smooth muscle cells of human corpus cavernosum in vitro, and it provides experimental groundwork for the gene therapy of erectile dysfunction.
Asunto(s)
3',5'-GMP Cíclico Fosfodiesterasas/antagonistas & inhibidores , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Músculo Liso/efectos de los fármacos , Oligodesoxirribonucleótidos Antisentido/farmacología , Pene/citología , 3',5'-GMP Cíclico Fosfodiesterasas/genética , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5 , Humanos , Masculino , Músculo Liso/metabolismoRESUMEN
OBJECTIVE: To analyze the effect of castration on risk factors for arteriosclerosis of patients with prostate cancer. METHODS: Thirty patients with primary regional prostate adenocarcinoma limited to the prostate theca were selected in this study. Serum levels of testosterone (T), free testosterone (FT), dehydroepiandrosterone (DHEA), sex hormone-binding globulin (SHBG), prostatic specific antigen (PSA), triglyceride (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), apoprotein alpha(1) (APOalpha(1)) and apoprotein beta (APObeta), insulin, plasma fibrinopeptide A (FPA), plasminogen activator inhibitor-1 (PAI-1) and fibrinogen were determined just prior to, 1 week and 1, 4 and 8 months after castration. RESULTS: T, FT and PSA decreased significantly 1 week after castration (21.12 +/- 15.11 ng/ml vs 383.9 +/- 62.6 ng/ml, P < 0.001; 4.08 +/- 3.29 pmol/L vs 34.11 +/- 11.59 pmol/L, P < 0.001; 14.34 +/- 7.77 ng/ml vs 23.51 +/- 6.57 ng/ml, P = 0.001, respectively) and continued to decrease until reaching their lowest levels 8 months after castration. DHEA and SHBG did not undergo any changes. TG, fasting insulin and glucose, 2-hour insulin and glucose levels were significantly elevated 1 month after castration (1.84 +/- 0.61 mmol/L vs 1.30 +/- 0.40 mmol/L, P < 0.05; 18.16 +/- 5.57 mU/L vs 9.47 +/- 3.81 mU/L, P < 0.05; 4.77 +/- 0.66 mmol/L vs 3.92 +/- 0.34 mmol/L, P < 0.05; 65.52 +/- 14.78 mU/L vs 36.94 +/- 17.12 mU/L, P < 0.01; 6.98 +/- 0.79 mmol/L vs 6.01 +/- 0.23 mmol/L, P = 0.001, respectively). TC, LDL-C, FPA and PAI-1 levels were elevated 4 months after castration (6.56 +/- 0.99 mmol/L vs 5.29 +/- 0.75 mmol/L, P < 0.01; 4.09 +/- 0.86 mmol/L vs 3.04 +/- 0.15 mmol/L, P < 0.01; 3.39 +/- 1.67 nmol/L vs 1.48 +/- 0.50 nmol/L, P < 0.01; 27.02 +/- 5.98 ng/ml vs 21.78 +/- 3.16 ng/ml, P < 0.05, respectively), continuing to increase after that point. Insulin sensitive index (ISI) decreased significantly 1 month after surgery (-4.42 +/- 0.36 vs -3.50 +/- 0.39, P < 0.001), and continued to decrease from that point forward. HDL-C, APOalpha(1), APObeta and fibrinogen remained at pre-operative levels. There was a negative linear correlation between FT and TG, TC, LDL-C, PAI-1, FPA, fasting insulin and glucose, 2-hour insulin and glucose (r = -0.311, -0.384, -0.385, -0.339, -0.353, -0.381, -0.303, -0.460 and -0.395, respectively; P < 0.05). A similar phenomenon occurred with T (r = -0.308, -0.309, -0.356, -0.320, -0.430, -0.453, -0.435, -0.483 and -0.512, respectively; P < 0.05). T and FT were positively associated with ISI (r = 0.555 and 0.501; P < 0.001). CONCLUSIONS: At 8 months follow-up of the study subjects, we found that lower androgen levels have adverse effects on lipid metabolism, coagulative function and insulin sensitivity, related to arteriosclerosis in men.
Asunto(s)
Arteriosclerosis/etiología , Orquiectomía/efectos adversos , Neoplasias de la Próstata/cirugía , Anciano , Humanos , Hiperinsulinismo/complicaciones , Resistencia a la Insulina , Lípidos/sangre , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/sangre , Factores de RiesgoRESUMEN
OBJECTIVES: To detect the level of matrix metalloproteinase-2 (MMP-2) mRNA and the tissue inhibitor of metalloproteinase-2 (TIMP-2) mRNA in bladder transitional cell carcinoma (BTCC), and to estimate the prognosis for bladder tumor based on the quality and quantity of MMP-2 and TIMP-2 mRNA. METHODS: Thirty-five samples of human BTCC and 15 normal fresh bladder tissues were studied by RT-PCR analysis followed by computer-assisted image analysis. RESULTS: The level of the MMP-2 mRNA in BTCC was significantly increased compared with that in normal bladder epithelium. The positive rates of MMP-2 and TIMP-2 mRNA were 71.4% and 65.7% in BTCC, and 66.7% and 60.0% in the normal bladder wall. The expression intensity of the MMP-2 mRNA by image analysis tended to increase with tumor grading and staging, which showed statistical significance. Similarly, the MMP-2 to TIMP-2 ratio also showed statistically significant difference between normal bladder tissue and bladder carcinoma (P < 0.01). CONCLUSIONS: A high level of the MMP-2 mRNA exists in BTCC, which may function to damage collagen IV inside the basement membrane and the extracellular basement of the bladder. The level of the MMP-2 mRNA is proportional to BTCC grading and staging, which may have prognostic value. The MMP-2 to TIMP-2 ratio may play a more significant role in the determination of the aggressiveness and prognosis of bladder tumor.
Asunto(s)
Metaloproteinasa 2 de la Matriz/genética , ARN Mensajero/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/genética , Neoplasias de la Vejiga Urinaria/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , ARN Mensajero/genética , Vejiga Urinaria/metabolismo , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVE: To investigate a non-invasive, effective and rapid mode of detecting the recurrence of bladder cancer during follow-up. METHODS: Ninety patients following transurethral resection of bladder tumor (TURBt) surgery were recruited from January 1998 to March 2000. Standard ELISA was used to determine the quantity of nuclear matrix protein (NMP-22) in urine of all bladder cancer patients during their follow-up periods. Urine bladder tumor antigen (BTA) stat test was simultaneously performed and followed by cystoscopy. RESULTS: The total positive rates of urinary NMP-22 and BTA stat test were 76.7% (33/43) and 67.4% (29/43), respectively. Comparatively, this positive rate would increase to 93.0% (40/43) when the combination of both urine NMP-22 and BTA test were adopted. CONCLUSION: Examination of NMP-22 in urine is a rapid and effective way to detect the recurrence of bladder cancer. If combined with BTA test, NMP-22 may be used as a non-invasive method in surveillance of recurring of bladder cancer, which may reduce the frequency of patients needing to undergo conventional invasive cystoscopy.