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1.
Exp Anim ; 2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-38030240

RESUMEN

Transmembrane protein (TMEM230) is located in secretory/recycling vesicles, including synaptic vesicles in neurons. However, the functional relationship between TMEM230 and epilepsy is still a mystery. The aims of this study were to investigate the expression of TMEM230 in patients with temporal lobe epilepsy (TLE) and two different mice models of chronic epilepsy, and to determine the probable roles of TMEM230 in epilepsy. Our results showed that TMEM230 expression was increased in the temporal neocortex of epileptic patients and the hippocampus and cortex of epileptic mice compared with that in the control tissues. Moreover, TMEM230 was mainly expressed in the neurons in both humans and mice epileptic brain. TMEM230 co-localized with glutamate vesicular transporter 1 (VGLUT-1), but not with vesicular GABA transporter (VGAT). Mechanistically, coimmunoprecipitation confirmed that TMEM230 interacted with VGLUT-1, but not with VGAT in the hippocampus of epileptic mice. Lentivirus mediated overexpression of TMEM230 increased mice susceptibility to epilepsy and behavioural phenotypes of epileptic seizures during the kainite (KA)-induced chronic phase of epileptic seizures and the pentylenetetrazole (PTZ) kindling process, whereas lentivirus-mediated TMEM230 downregulation had the opposite effect. These results shed light on the functions of TMEM230 in neurons, suggesting that TMEM230 may play a critical role in the regulation of epileptic activity via influencing excitatory neurotransmission.

2.
Clin Cancer Res ; 26(21): 5646-5654, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-33037018

RESUMEN

PURPOSE: Urothelial carcinoma is a malignant cancer with frequent chromosomal aberrations. Here, we investigated the application of a cost-effective, low-coverage whole-genome sequencing technology in detecting all chromosomal aberrations. EXPERIMENTAL DESIGN: Patients with urothelial carcinomas and nontumor controls were prospectively recruited in clinical trial NCT03998371. Urine-exfoliated cell DNA was analyzed by Illumina HiSeq XTen, followed by genotyping with a customized bioinformatics workflow named Urine Exfoliated Cells Copy Number Aberration Detector (UroCAD). RESULTS: In the discovery phase, urine samples from 126 patients with urothelial carcinomas and 64 nontumor disease samples were analyzed. Frequent chromosome copy-number changes were found in patients with tumor as compared with nontumor controls. A novel diagnosis model, UroCAD, was built by incorporating all the autosomal chromosomal changes. The model reached performance of AUC = 0.92 (95% confidence interval, 89.4%-97.3%). At the optimal cutoff, |Z| ≥ 3.21, the sensitivity, specificity, and accuracy were 82.5%, 96.9%, and 89.0%, respectively. The prediction positivity was found correlated with tumor grade (P = 0.01). In the external validation cohort of 95 participants, the UroCAD assay identified urothelial carcinomas with an overall sensitivity of 80.4%, specificity of 94.9%, and AUC of 0.91. Meanwhile, UroCAD assay outperformed cytology tests with significantly improved sensitivity (80.4% vs. 33.9%; P < 0.001) and comparable specificity (94.9% vs. 100%; P = 0.49). CONCLUSIONS: UroCAD could be a robust urothelial carcinoma diagnostic method with improved sensitivity and similar specificity as compared with cytology tests. It may be used as a noninvasive approach for diagnosis and recurrence surveillance in urothelial carcinoma prior to the use of cystoscopy, which would largely reduce the burden on patients.


Asunto(s)
Carcinoma de Células Transicionales/orina , Citodiagnóstico , Neoplasias de la Vejiga Urinaria/orina , Urotelio/metabolismo , Anciano , Aneuploidia , Biomarcadores de Tumor/genética , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/patología , Aberraciones Cromosómicas , ADN Tumoral Circulante/genética , Análisis Costo-Beneficio , Variaciones en el Número de Copia de ADN/genética , Supervivencia sin Enfermedad , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/orina , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/patología , Urotelio/patología , Secuenciación Completa del Genoma
3.
Aging (Albany NY) ; 12(10): 9205-9223, 2020 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-32420905

RESUMEN

Clear cell renal cell carcinoma (ccRCC) remains one of the most common cancer types globally, and while it has been extensively studied, the molecular basis for its pathology remains incompletely understood. Herein, we profiled three previously published datasets (GSE66272, GSE100666, and GSE105261) in a single integrated analysis aimed at identifying disease-associated patterns of gene expression that may offer mechanistic insight into the drivers of this disease. We pooled expression data from 39 normal kidney samples and 39 kidney tumors, leading us to identify 310 differentially expressed genes (DEGs) that were linked to kidney cancer in all three analyzed datasets. Of these genes, 133 and 177 were up- and down-regulated, respectively, in cancer samples. We then incorporated these DEGs into a protein-protein interaction network with the STRING and Cytoscape tools, and we were able to identify signaling pathways significantly enriched for these DEGs. The relationship between DEG expression and ccRCC patient survival was further evaluated using a Kaplan-Meier approach, leading us to identify TIMP1 as an independent prognostic factor in ccRCC patients. When TIMP1 expression was disrupted in ccRCC cell lines, this impaired their migratory and invasive capabilities. In summary, we employed an integrative bioinformatics approach to identify ccRCC-related DEGs and associated signaling pathways. Together these findings offer novel insight into the mechanistic basis for ccRCC, potentially helping to identify novel therapeutic targets for the treatment of this deadly disease.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Transcriptoma/genética , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/genética , Células HEK293 , Humanos , Riñón/patología , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Neoplasias Renales/mortalidad , Neoplasias Renales/patología
4.
J BUON ; 24(2): 791-796, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31128037

RESUMEN

PURPOSE: To explore the expression of mir-143 in the serum of bladder cancer patients and its correlation with clinical pathological features and prognosis. METHODS: A retrospective study was performed on 68 patients (observation group) diagnosed with bladder cancer and treated in the Qilu Hospital of Shandong University from June 2013 to January 2014 and another 40 healthy individuals (control group) in the physical examination center at the same period. Real-time PCR (RT-PCR) was used to detect the expression levels of mir-143 in the serum of bladder cancer patients and healthy subjects. The expression of mir-143 in the serum of bladder cancer patients and its correlation with clinical pathological indicators and prognosis were explored. RESULTS: The expression level of mir-143 in the serum of bladder cancer patients was significantly lower than that of healthy people (p<0.05). There was no statistically significant difference in age and sex (p>0.05). There was a correlation between the expression level of mir-143 and differentiation grade, lymph node metastasis, distant metastasis and clinical stage (p<0.05). The median expression level of mir-143 in the serum of bladder cancer patients was 0.652. Thirty four patients with lower expression than the median of mir-143 were in the low expression group, and 34 patients with higher expression than the median of mir-143 were in the high expression group. The mean survival time of bladder cancer patients with the low expression of mir-143 was 37.32±1.26 months, significantly lower than that with the high expression of mir-143 (46.17±1.54;p<0.05). CONCLUSION: mir-143 is lowly expressed in the serum of bladder cancer patients. Its expression level is correlated with clinical stage, lymph node metastasis, distant metastasis and prognosis.


Asunto(s)
Biomarcadores de Tumor/sangre , MicroARNs/sangre , Pronóstico , Neoplasias de la Vejiga Urinaria/sangre , Adulto , Factores de Edad , Anciano , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Caracteres Sexuales , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología
6.
J Pediatr Urol ; 14(1): 14.e1-14.e7, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29133168

RESUMEN

INTRODUCTION: Tubularized urethroplasty is commonly performed in clinical practice using genital skin flaps, bladder mucosa, and buccal mucosa. However, the long-term effects are not satisfying, and donor site morbidities remain a problem. Besides, those grafts are unavailable with malignant conditions of the urinary tract, a history of lichen sclerosis, or oral disease. OBJECTIVE: An autologous granulation tissue tube of any required length and diameter can be produced by implanting foreign objects subcutaneously (Summary Fig.). The current study aimed to investigate to what extent of length this fully autologous tissue could be used for tubularized urethroplasty, satisfying urethral patency and tissue regeneration, in male rabbits. STUDY DESIGN: Twenty-seven New Zealand male rabbits were randomly divided into three groups. Silastic tubes were implanted subcutaneously in Group 1 and Group 2. By 2 weeks the granulation tissue encapsulating the tubes was harvested. In Group 1, pendulous urethral segments of 1 cm were excised, and urethroplasty was performed with the granulation tissue tube in an end-to-end fashion. In Group 2, a pendulous urethral segment of 1.5 cm was replaced with the tissue tube. In Group 3, a pendulous urethral defect of 1 cm was repaired by re-anastomosis as control. Serial urethrograms were performed at 1, 2 and 6 months postoperatively. Meanwhile, the neo-urethra were harvested and analyzed grossly and histologically. RESULTS: The urethrograms showed that all animals in Group 1 maintained a wide urethral caliber. In contrast, animals in Group 2 and Group 3 developed progressive strictures. Histologically, an intact urothelium with one to two cell layers lined the graft by 1 month, which was surrounded by increasing organized smooth muscle in Group 1. By 6 months, the grafts were completely integrated into native urethra. Nevertheless, extensive fibrosis occurred in Group 2 and Group 3. DISCUSSION: The tissue successfully maintained patency and guided urethral regeneration across a distance of 1 cm. As an epithelium-free graft, the tissue showed better results than acellular matrix for tubularized urethroplasty compared with previous studies. Nevertheless, several limitations existed: (1) the urethral defect was created in healthy urethra, which could not fully simulate the clinical situation; (2) as a small animal model, rabbit was less informative for clinical problems; (3) the tissue was inadequate for long segmental urethral replacement. Further study is needed before the procedure is used clinically. CONCLUSION: An autologous granulation tissue tube grown subcutaneously could be successfully used to repair urethral defects of 1 cm in male rabbits.


Asunto(s)
Tejido de Granulación/trasplante , Ingeniería de Tejidos , Uretra/cirugía , Procedimientos Quirúrgicos Urológicos/métodos , Animales , Biopsia con Aguja , Modelos Animales de Enfermedad , Rechazo de Injerto , Supervivencia de Injerto , Inmunohistoquímica , Masculino , Conejos , Distribución Aleatoria , Recuperación de la Función , Medición de Riesgo , Recolección de Tejidos y Órganos , Trasplante Autólogo/métodos , Resultado del Tratamiento , Uretra/anomalías
7.
Biomed Res Int ; 2017: 7450459, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28812020

RESUMEN

To evaluate the role of Cystatin C (Cys-C) in tumorigenesis and progression of prostate cancer (PCa), we retrospectively collected the clinical information from the records of 492 benign prostatic hyperplasia (BPH), 48 prostatic intraepithelial neoplasia (PIN), and 173 PCa patients, whose disease was newly diagnosed and histologically confirmed. Pretreatment serum Cys-C levels were compared across the various groups and then analyzed to identify relationships, if any, with clinical and pathological characteristics of the PCa patient group. There were no significant differences in serum Cys-C levels among the three groups (P > 0.05). In PCa patients with normal SCr levels, patient age was correlated with serum Cys-C level (P ≤ 0.001) but did not correlate with alkaline phosphatase (AKP), lactate dehydrogenase (LDH), prostate specific antigen (PSA), Gleason score, or bone metastasis status (P > 0.05). Age and SCr contributed in part to the variations in serum Cys-C levels of PCa patients (r = 0.356, P ≤ 0.001; r = 0.520, P ≤ 0.001). In conclusion, serum Cys-C levels predict renal function in patients with prostate neoplasia, but were not a biomarker for the development of prostate neoplasia, and were not correlated with the clinicopathological characteristics of PCa.


Asunto(s)
Cistatina C/sangre , Hiperplasia Prostática/sangre , Neoplasia Intraepitelial Prostática/sangre , Neoplasias de la Próstata/sangre , Anciano , Anciano de 80 o más Años , Fosfatasa Alcalina , Biomarcadores de Tumor/sangre , Neoplasias Óseas/sangre , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Humanos , L-Lactato Deshidrogenasa/sangre , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Próstata/patología , Antígeno Prostático Específico/sangre , Hiperplasia Prostática/patología , Neoplasia Intraepitelial Prostática/patología , Neoplasias de la Próstata/patología
8.
Biomed Res Int ; 2017: 1850256, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28337443

RESUMEN

Objective. This study was to evaluate the utility of the compound graft for tubularized urethroplasty by seeding mesothelial cells onto autogenous granulation tissue. Methods. Silastic tubes were implanted subcutaneously in 18 male rabbits, of which nine underwent omentum biopsies simultaneously for in vitro expansion of mesothelial cells. The granulation tissue covering the tubes was harvested 2 weeks after operation. Mesothelial cells were seeded onto and cocultured with the tissue for 7 days. A pendulous urethral segment of 1.5 cm was totally excised. Urethroplasty was performed with mesothelial cell-seeded tissue tubes in an end-to-end fashion in nine rabbits and with unseeded grafts in others as controls. Serial urethrograms were performed at 1, 2, and 6 months postoperatively. Meanwhile, the neourethra was harvested and analyzed grossly and histologically. Results. Urethrograms showed cell-seeded grafts maintained wide at each time point, while strictures formation was found in unseeded grafts. Histologically, layers of urothelium surrounded by increasingly organized smooth muscles were observed in seeded grafts. In contrast, myofibroblasts accumulation and extensive scarring occurred in unseeded grafts. Conclusions. Mesothelial cell-seeded granulation tissue tube can be successfully used for tubularized urethroplasty in male rabbits.


Asunto(s)
Tratamiento Basado en Trasplante de Células y Tejidos , Tejido de Granulación/crecimiento & desarrollo , Ingeniería de Tejidos , Uretra/crecimiento & desarrollo , Animales , Técnicas de Cocultivo , Dimetilpolisiloxanos/uso terapéutico , Células Epiteliales/patología , Células Epiteliales/trasplante , Tejido de Granulación/trasplante , Masculino , Miofibroblastos/patología , Miofibroblastos/trasplante , Cavidad Peritoneal , Conejos , Procedimientos de Cirugía Plástica , Uretra/patología , Uretra/trasplante , Urotelio/patología , Urotelio/trasplante
9.
Mol Cell Biochem ; 406(1-2): 111-9, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25957503

RESUMEN

Prostate cancer (PCa) is lethal type of genitourinary cancer due to its high morbidity and gradual resistance to androgen deprivation therapy. Accumulating evidence has recently suggested that the daily intake of flavonoids is negatively correlated with the risk of cancer. In this study, we aimed to investigate the potential effects of baicalein on androgen-independent PCa cells and the underlying mechanisms through which baicalein exerts its actions. Cell viability and flow cytometric apoptosis assays indicated that baicalein potently suppressed the growth and induced the apoptosis of DU145 and PC-3 cells in a time- and dose-dependent manner. Consistently, the inhibitory effects of baicalein on migration and invasion were also observed in vitro. Mechanistically, we found that baicalein can suppress caveolin-1 and the phosphorylation of AKT and mTOR in a time- and dose-dependent manner. Moreover, the inhibition of the activation of AKT with LY294002 significantly promoted the apoptosis and metastasis induced by baicalein. In conclusion, these findings suggested that baicalein can induce apoptosis and inhibit metastasis of androgen-independent PCa cells through inhibition of the caveolin-1/AKT/mTOR pathway, which implies that baicalein may be a potential therapeutic agent for the treatment of androgen-independent prostate cancer patients.


Asunto(s)
Antineoplásicos/farmacología , Flavanonas/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Caveolina 1/metabolismo , Movimiento Celular , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Masculino , Metástasis de la Neoplasia , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo
10.
PLoS One ; 10(5): e0124292, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26010447

RESUMEN

Tumor development and progression are influenced by macrophages of the surrounding microenvironment. To investigate the influences of an inflammatory tumor microenvironment on the growth and metastasis of prostate cancer, the present study used a co-culture model of prostate cancer (PCa) cells with tumor-associated macrophage (TAM)-conditioned medium (MCM). MCM promoted PCa cell (LNCaP, DU145 and PC-3) growth, and a xenograft model in nude mice consistently demonstrated that MCM could promote tumor growth. MCM also stimulated migration and invasion in vitro. Somatostatin derivate (smsDX) significantly attenuated the TAM-stimulated proliferation, migration and invasion of prostate cancer. Immunohistochemistry revealed that NF-κB was over-expressed in PCa and BPH with chronic inflammatory tissue specimens and was positively correlated with macrophage infiltration. Further investigation into the underlying mechanism revealed that NF-κB played an important role in macrophage infiltration. SmsDX inhibited the paracrine loop between TAM and PCa cells and may represent a potential therapeutic agent for PCa.


Asunto(s)
Movimiento Celular/efectos de los fármacos , Macrófagos/metabolismo , Neoplasias de la Próstata/patología , Somatostatina/análogos & derivados , Somatostatina/farmacología , Anciano , Animales , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Línea Celular Tumoral , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Humanos , Inmunohistoquímica , Macrófagos/efectos de los fármacos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , FN-kappa B , Invasividad Neoplásica , Fosforilación/efectos de los fármacos , Próstata/metabolismo , Próstata/patología , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Prostatitis/metabolismo , Prostatitis/patología , Transporte de Proteínas/efectos de los fármacos , Factor de Transcripción ReIA/metabolismo , Ensayo de Tumor de Célula Madre , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Mol Med Rep ; 9(6): 2251-6, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24691570

RESUMEN

Previous studies have demonstrated that metformin (Met) may reduce the risk of cancer development. In the present study, the anti-cancer effects of Met in A498 cells were investigated. It was found that Met inhibited A498 cell proliferation in a time- and dose-dependent manner, as well as induced the activation of AMP-activated protein kinase. It was also demonstrated that Met promoted A498 cell apoptosis and mechanistic studies suggested that this was mediated by the downregulation of B-cell lymphoma 2 and concurrent upregulation of Bcl-2-associated X protein. In addition, it was observed that Met induced G1 cell cycle arrest by decreasing cyclin D1 expression. Furthermore, the results demonstrated that Met reduced A498 cell migration and invasion in vitro by decreasing matrix metalloproteinase-2, which indicated its potential to inhibit renal cancer metastasis. In combination, these results provide evidence that Met is important in anti-renal cancer therapy, and thus may serve as a novel and efficient agent for renal cancer treatment.


Asunto(s)
Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Metformina/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos
12.
PLoS One ; 8(5): e62823, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23690956

RESUMEN

Renal cell carcinoma (RCC) is the most lethal type of genitourinary cancer due to its occult onset and resistance to chemotherapy and radiation. Recently, accumulating evidence has suggested stains, inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, were associated with the risk reduction of cancer. In the present study, we aimed to investigate the potential effects of simvastatin on RCC cells and the underlying mechanisms by which simvastatin exerted its actions. With cell viability, colony formation, and flow cytometric apoptosis assays, we found that simvastatin potently suppressed cell growth of A498 and 786-O cells in a time- and dose- dependent manner. Consistently, the xenograft model performed in nude mice exhibited reduced tumor growth with simvastatin treatment. In addition, the inhibitory effects of simvastatin on migration and invasion were also observed in vitro. Mechanically, we presented that simvastatin could suppress the proliferation and motility of RCC cells via inhibiting the phosphorylation of AKT, mTOR, and ERK in a time- and dose- dependent manner. Further investigation of the underlying mechanism revealed simvastatin could exert the anti-tumor effects by suppressing IL-6-induced phosphorylation of JAK2 and STAT3. In conclusion, these findings suggested that simvastatin-induced apoptosis and its anti-metastasis activity in RCC cells were accompanied by inhibition of AKT/mTOR, ERK, and JAK2/STAT3 pathways, which imply that simvastatin may be a potential therapeutic agent for the treatment of RCC patients.


Asunto(s)
Carcinoma de Células Renales/fisiopatología , Proliferación Celular/efectos de los fármacos , Metástasis de la Neoplasia/prevención & control , Simvastatina/farmacología , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Carcinoma de Células Renales/tratamiento farmacológico , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Humanos , Etiquetado Corte-Fin in Situ , Janus Quinasa 2/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Ratones Desnudos , Fosforilación/efectos de los fármacos , Interferencia de ARN , Factor de Transcripción STAT3/metabolismo , Serina-Treonina Quinasas TOR/metabolismo
13.
Eur J Pharmacol ; 661(1-3): 1-7, 2011 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-21545798

RESUMEN

Bladder cancer is the ninth most common type of cancer, and its surgery is always followed by chemotherapy to prevent recurrence. Berberine is non-toxic to normal cells but has anti-cancer effects in many cancer cell lines. This study was aimed to determine whether berberine inhibits the cell proliferation and induces cell cycle arrest and apoptosis in BIU-87 and T24 bladder cancer cell line. The superficial bladder cancer cell line BIU-87 and invasive T24 bladder cancer cells were treated with different concentrations of berberine. MTT assay was used to determine the effects of berberine on the viability of these cells. The cell cycle arrest was detected through propidium iodide (PI) staining. The induction of apoptosis was determined through Annexin V-conjugated Alexa Fluor 488 (Alexa488) staining. Berberine inhibited the viability of BIU-87 and T24 cells in a dose- and time-dependent manner. It also promoted cell cycle arrest at G0/G1 in a dose-dependent manner and induced apoptosis. We observed that H-Ras and c-fos mRNA and protein expressionswere dose-dependently and time-dependently decreased by berberine treatment. Also, we investigated the cleaved caspase-3 and caspase-9 protein expressions increased in a dose-dependent manner. Berberine inhibits the cell proliferation and induces cell cycle arrest and apoptosis in BIU-87, bladder cancer cell line and T24, invasive bladder cancer cell line. Berberine can inhibit the oncogentic H-Ras and c-fos in T24 cells, and can induce the activation of the caspase-3 and caspase-9 apoptosis. Therefore, berberine has the potential to be a novel chemotherapy drug to treat the bladder cancer by suppressing tumor growth.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Berberina/farmacología , Fase G1/efectos de los fármacos , Neoplasias de la Vejiga Urinaria/patología , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Genes fos/genética , Genes ras/genética , Humanos , Invasividad Neoplásica , Factores de Tiempo , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo
14.
J Exp Clin Cancer Res ; 29: 162, 2010 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-21143993

RESUMEN

BACKGROUND: Somatostatin prevents cell proliferation by inducing apoptosis. Downregulation of the XAF1 transcript may occur during the development of prostate cancer. It is interesting to evaluate the potential regulatory effects of somatostatin on XAF1 expression during the development of prostate cancer cells. METHODS: XAF1 mRNA and protein expression in human prostate epithelial cells RWPE-1, androgen dependent prostate cancer LNCaP, and androgen independent DU145 and PC3 cells were evaluated using RT-PCR and Western blot. The regulation of XAF1 mRNA and protein expression by somatostatin and its analogue Octreotide was evaluated. RESULTS: Substantial levels of XAF1 mRNA and proteins were detected in RWPE-1 cells, whereas prostate cancer cells LNCaP, DU145 and PC3 exhibited lower XAF1 expression. Somatostatin and Octreotide up-regulated XAF1 mRNA and protein expression in all prostate cancer cell lines. CONCLUSIONS: XAF1 down-regulation may contribute to the prostate cancer development. The enhanced XAF1 expression by somatostatin indicates a promising strategy for prostate cancer therapy.


Asunto(s)
Antineoplásicos Hormonales/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proteínas de Neoplasias/biosíntesis , Octreótido/farmacología , Neoplasias de la Próstata/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Proteínas Reguladoras de la Apoptosis , Western Blotting , Línea Celular Tumoral , Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Masculino , Proteínas de Neoplasias/genética , Neoplasias de la Próstata/genética , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Somatostatina/farmacología
15.
Zhonghua Nan Ke Xue ; 14(6): 542-4, 2008 Jun.
Artículo en Chino | MEDLINE | ID: mdl-18649756

RESUMEN

OBJECTIVE: To explore the clinical presentation, pathologic characteristics, diagnosis and treatment of cutaneous T-cell lymphoma of the penis. METHODS: A 49-year-old man presented with painful swelling and inflammation of the foreskin, failed to respond to antibiotic treatment and dorsal incision, and was instead complicated by Fournier gangrene. Then he underwent debridement and pathological examination. RESULTS: Pathological results indicated cutaneous T-cell lymphoma of the penis. Immunohistochemistry showed CD3 and CD45 RO to be positive, but CD30, CD79a, CD20 and HMB negative. The patient was treated by interferon alpha and ultraviolet B for 2 weeks, followed by total removal of the external genitalia because of necrosis of the corpus spongiosum, which involved the scrotum and right testis on pathological examination. CONCLUSION: Cutaneous T-cell lymphoma of the penis is a rare condition and easily mis diagnosed in the early phase. Definitive diagnosis depends on pathological study.


Asunto(s)
Gangrena de Fournier/patología , Linfoma Cutáneo de Células T/patología , Neoplasias del Pene/patología , Complejo CD3/análisis , Diagnóstico Diferencial , Gangrena de Fournier/etiología , Humanos , Inmunohistoquímica , Antígenos Comunes de Leucocito/análisis , Linfoma Cutáneo de Células T/complicaciones , Linfoma Cutáneo de Células T/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias del Pene/complicaciones , Neoplasias del Pene/metabolismo
16.
Zhonghua Yi Xue Za Zhi ; 88(10): 697-700, 2008 Mar 11.
Artículo en Chino | MEDLINE | ID: mdl-18642773

RESUMEN

OBJECTIVE: To investigate the relationship of transforming growth factor beta1 (TGFbeta1) and basic fibroblast growth factor (bFGF) to detrusor underactivity following bladder outlet obstruction (BOO). METHODS: Female Wistar rats underwent ligation of the urethra to establish BOO models and were divided into BOO model 2-week group (11 rats) and BOO model 6-week group (10 rats). 8 rats underwent sham operation as control group. The detrusor urine was taken out and stimulated by carbachol to measure the detrusor contraction force (DCF). RT-PCR method was employed to measure the mRNA expression of TGFbeta1 and bFGF in the detrusor urine. Urine TGFbeta1 and bFGF were determined by ELISA. RESULTS: The maximum DCF levels of the BOO 2-week group under the 1 x 10(-4) mmol/L and 1 x 10(-3) mmol/L carbachol concentrations were 0.96 g +/- 0.11 g and 1.98 g +/- 0.21 g respectively, both significantly higher than those of the sham operation group (0.85 g +/- 0.18 g and 1.82 g +/- 0.19 g respectively, both P < 0.05). The maximum DCF levels of the BOO 6-week group under the 1 x 10(-5), 1 x 10(-4), 1 x 10(-3) and 1 x 10 (-2) mmol/L carbachol concentrations were 0.19 g +/- 0.02 g, 0.65 g +/- 0.06 g, 1.12 g +/- 0.08 g, and 1.40 g +/- 0.19 g respectively, all significantly lower than those of the BOO 2-week group (0.24 g +/- 0.03 g, 0.96 g +/- 0.11 g, 1.98 g +/- 0.21 g, and 2.16 g +/- 0.21 g respectively, all P < 0.05) and those of the sham operation group (0.23 g +/- 0.04 g, 0.85 g +/- 0.18 g, 1.82 g +/- 0.19 g, and 2.12 g +/- 0.26 g respectively, all P < 0.05). The mRNA expression of TGFbeta1 of the BOO 6-week group, BOO 2-week group, and sham operation group was 0.72 +/- 0.21, 0.34 +/- 0.10, and 0.32 +/- 0.01 respectively, there was a significant difference between the BOO 6-week group and the BOO 2-week group (P < 0.01). The mRNA expression level of bFGF of the BOO 6-week group was 0.38 +/- 0.13, significantly higher than those of the BOO 2-week group and sham operation group (0.21 +/- 0.07 and 0.10 +/- 0.05 respectively, both P <0.05). DCF was negatively correlated with the mNRA expression of TGFbeta1 and the mNRA expression bFGF in detrusor (both P < 0.05). The urine TGFbeta1 of the BOO 6-week group was (606 +/- 216) microg/mol Cr, significantly higher than that of the BOO 2-week group [(131 +/- 49) microg/mol Cr] and that of the sham operation group [(107 +/- 22) microg/mol Cr, both P <0.05]. CONCLUSION: With the progression of BOO, there is a sustained rise of bFGF mRNA expression in detrusor; however, the TGFbeta1 mRNA expression only increases during the decompensation stage. Urine TGFbeta1 level is very high 6 weeks after BOO, which may help predict the contraction function of bladder after BOO.


Asunto(s)
Factor 2 de Crecimiento de Fibroblastos/genética , Factor de Crecimiento Transformador beta1/genética , Obstrucción del Cuello de la Vejiga Urinaria/fisiopatología , Vejiga Urinaria/metabolismo , Animales , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Factor 2 de Crecimiento de Fibroblastos/orina , Expresión Génica , Contracción Muscular , Músculo Liso/metabolismo , Músculo Liso/patología , Músculo Liso/fisiopatología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Crecimiento Transformador beta1/orina , Vejiga Urinaria/patología , Vejiga Urinaria/fisiopatología , Obstrucción del Cuello de la Vejiga Urinaria/orina
17.
Zhonghua Yi Xue Za Zhi ; 87(24): 1723-5, 2007 Jun 26.
Artículo en Chino | MEDLINE | ID: mdl-17825161

RESUMEN

OBJECTIVE: To establish a new rat model of neurogenic bladder dysfunction caused by lumbar intervertebral disk hernia, and to confirm the model by urodynamic examination. METHODS: Twenty male Wistar rats were divided into two groups at random:experimental group (n = 15) and pseudo-operation group (n = 5). The rats underwent laparotomy to disclose the intervertebral disk of L(6)-S(1), and a 1.50 mm x 4.50 mm blunt screw with flat end was inserted into the intervertebral disk of L(6)-S(1) of the rats in the experimental group so as to establish the model of lumbar intervertebral disk hernia. Computed radiography (CR) was performed 3 days after the operation to conform the successful insertion of the screw. Combined behavioral score (CBS) was used 1 d, 3 d, 1 week, 2 weeks, and 4 weeks after the operation. Four weeks after the laparotomy a vesical fistula above the pubis was made in all of the rats, and then urodynamic examination was performed three days after this operation. RESULTS: CR after operation confirmed that the blunt screw had been inserted into the lumbar disk of L(6). The CBS scores of the 2 groups at different time points all decreased along with time, and basically remained unchanged 1 week after. The CBS scores of the experiment group were significantly higher than those of the pseudo-operation group (all P < 0.05). The spontaneous vesical contraction rate in the filling period of the experimental group was (4.37 +/- 2.13) times/min, significantly higher than that of the pseudo-operation group [(0.06 +/- 0.13) times/min, t = 4.425, P = 0.000], the maximum bladder capacity of the experimental group was (1.20 +/- 0.34) ml, significantly greater than that of the pseudo-operation group [(0.60 +/- 0.14) ml, t = 5.141, P = 0.002], and bladder compliance of the experimental group was (0.024 +/- 0.012) ml/cm H(2)O, significantly lower than that of the pseudo-operation group [(0.096 +/- 0.088) ml/cm H(2)O, t = 2.891, P = 0.011], and the leak point pressure of the experimental group was (75 +/- 27) cm H(2)O, not significantly different from that of the pseudo-operation group [(62 +/- 23) cm H(2)O]. The urodynamic examination on the conscious rats confirmed the successful establishment of the neurogenic bladder dysfunction caused by lumbar intervertebral disk hernia. CONCLUSION: A new model of neurogenic bladder dysfunction caused by lumbar intervertebral disk hernia has been established by insertion of a blunt screw into the lumbar intervertebral disk of L(6). The model is confirmed by urodynamic examination.


Asunto(s)
Desplazamiento del Disco Intervertebral/complicaciones , Vértebras Lumbares , Vejiga Urinaria Neurogénica/fisiopatología , Animales , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Wistar , Vejiga Urinaria Neurogénica/etiología , Urodinámica
18.
Zhonghua Wai Ke Za Zhi ; 42(14): 874-6, 2004 Jul 22.
Artículo en Chino | MEDLINE | ID: mdl-15363280

RESUMEN

OBJECTIVE: To investigate the change of nerve growth factor (NGF) mRNA in human detrusor in bladder outlet obstruction (BOO) with benign prostatic hyperplasia (BPH) and their implication. METHODS: Eight cases of bladder cancer and 40 patients with BPH were included in this study. All patients were divided into three groups, a control group, an obstructive detrusor stability group and an obstructive detrusor instability group. NGF mRNA in detrusor from all patients was measured using a RT-PCR. RESULTS: The RT-PCR study indicated that NGF mRNA was expressed in detrusor of three groups of patients. There were significant differences among the three groups (P < 0.01). The expression of NGF mRNA in the obstructive instability group was higher than that in the obstructive stability group and in the control group. The NGF mRNA level in the obstructive stability group was higher than that in the control group. CONCLUSION: The expression of NGF mRNA in detrusor was elevated in BOO with BPH. The elevated expression of NGF mRNA might be correlated with detrusor instability (DI) due to BOO.


Asunto(s)
Factor de Crecimiento Nervioso/metabolismo , Hiperplasia Prostática/metabolismo , Obstrucción del Cuello de la Vejiga Urinaria/metabolismo , Vejiga Urinaria/metabolismo , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Factor de Crecimiento Nervioso/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Urodinámica/fisiología
19.
Ai Zheng ; 23(6): 704-6, 2004 Jun.
Artículo en Chino | MEDLINE | ID: mdl-15191676

RESUMEN

BACKGROUND & OBJECTIVE: Urokinase-type plasminogen activator (uPA)/its receptor (uPAR), serine protease system, plays a key role in the degradation of extracellular matrix and basement membranes, and intensifying the tumor invasion. The study was designed to investigate the expression of uPA and uPAR in urinary transitional cell carcinoma. The correlation between their expression and tumor invasion was evaluated. METHODS: The expression and localization of uPA and uPAR were examined among 50 cases of renal pelvic and ureter carcinoma and 40 cases of bladder cancer using the PicTure(TM) current type of immunohistochemical two-step method. RESULTS: The normal pelvic, ureter, and bladder did not express uPA and uPAR. The positive expression of uPA and uPAR were concentrated in tumor tissues compared with that in the adjacent tissues. The positive rates of uPA and uPAR expressed the tissues were 33.33% and 50.00% in G1 grade; 88.47% and 96.15% in G3 grade; 37.50% and 50.00% in Ta-T1 tissues; 100.0% and 100.0% in T4 tissues, respectively. The positive rates of uPA and uPAR expression in tumor tissues with higher grade and stage were obviously increased (P< 0.05); meanwhile, there were close correlation between uPA and uPAR (rs=0.979). CONCLUSION: The co-expression of uPA and uPAR was one of the characteristics of urinary transitional cell carcinoma and significantly correlated with tumor stage and grade.


Asunto(s)
Carcinoma de Células Transicionales/metabolismo , Receptores de Superficie Celular/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Neoplasias Urológicas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/patología , Femenino , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Pelvis Renal , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Receptores del Activador de Plasminógeno Tipo Uroquinasa , Neoplasias Ureterales/metabolismo , Neoplasias Ureterales/patología , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Neoplasias Urológicas/patología
20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 35(1): 57-9, 2004 Jan.
Artículo en Chino | MEDLINE | ID: mdl-14981816

RESUMEN

OBJECTIVE: To probe into the expression and clinical significance of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in urinary transitional cell carcinoma. METHODS: Expression of uPA and uPAR were detected in 50 cases of renal pelvis and ureter carcinoma and 40 cases of bladder cancer immunohistochemically. RESULTS: The positive rates of uPA and uPAR were closely correlated to the grade and the stage of urinary transitional cell carcinoma (r = 0.979, P < 0.01), whereas uPA and uPAR were not detected in normal kidney, ureter and bladder tissue. CONCLUSION: uPA and uPAR are highly expressed in urinary transitional cell carcinoma and they may be responsible for the tumor invasion and metastasis.


Asunto(s)
Carcinoma de Células Transicionales/metabolismo , Receptores de Superficie Celular/biosíntesis , Neoplasias de la Vejiga Urinaria/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Carcinoma de Células Transicionales/patología , Femenino , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Receptores de Superficie Celular/genética , Receptores del Activador de Plasminógeno Tipo Uroquinasa , Neoplasias de la Vejiga Urinaria/patología , Activador de Plasminógeno de Tipo Uroquinasa/genética
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