RESUMEN
OBJECTIVE: To evaluate the effectiveness and safety of low-concentration hydrogen peroxide solution (HPS) for continuous bladder irrigation after transurethral resection of the prostate (TURP). METHODS: We retrospectively analyzed the clinical data about 148 cases of benign prostatic hyperplasia (BPH) treated by TURP from January 2013 to January 2016. Seventy-six of the patients received postoperative continuous bladder irrigation with 0.15% HPS (group A) and the other 72 with normal saline (group B). We compared the two groups of patients in their postoperative hemoglobin (Hb) levels, duration of bladder irrigation, frequency of catheter blockage, time of catheterization, and length of hospital stay. RESULTS: There were no statistically significant differences between the two groups of patients preoperatively in the prostate volume, International Prostate Symptoms Score, maximum urinary flow rate, postvoid residual urine, or levels of serum PSA and Hb (P > 0.05). At 48 hours after operation, a significantly less reduction was observed in the Hb level in group A than in group B (ï¼»3.38 ± 2.56ï¼½ vs ï¼»7.29 ± 6.58ï¼½ g/L, P < 0.01). The patients of group A, in comparison with those of group B, also showed remarkably shorter duration of postoperative bladder irrigation (ï¼»32.57 ± 5.99ï¼½ vs ï¼»46.10 ± 8.79ï¼½ h, P < 0.01), lower rate of catheter blockage (3.3% vs 11.8%, P < 0.01), shorter time of catheterization (ï¼»3.74 ± 0.79ï¼½ vs ï¼»4.79 ± 0.93ï¼½ d, P < 0.01), and fewer days of postoperative hospital stay (ï¼»4.22 ± 0.81ï¼½ vs ï¼»4.67 ± 0.88ï¼½ d, P < 0.01). CONCLUSIONS: Low-concentration HPS for continuous bladder irrigation after TURP can reduce blood loss, catheter blockage, bladder irrigation duration, catheterization time, and hospital stay, and therefore deserves a wide clinical application.
Asunto(s)
Antiinfecciosos Locales/administración & dosificación , Peróxido de Hidrógeno/administración & dosificación , Hiperplasia Prostática/cirugía , Resección Transuretral de la Próstata , Vejiga Urinaria , Obstrucción del Catéter , Humanos , Tiempo de Internación , Masculino , Hemorragia Posoperatoria/prevención & control , Periodo Posoperatorio , Hiperplasia Prostática/sangre , Calidad de Vida , Estudios Retrospectivos , Irrigación Terapéutica/métodos , Irrigación Terapéutica/estadística & datos numéricos , Resultado del Tratamiento , Obstrucción del Cuello de la Vejiga Urinaria/prevención & control , Retención UrinariaRESUMEN
Castrationresistant prostate cancer (CRPC) is difficult to treat in current clinical practice. Hypoxia is an important feature of the CRPC microenvironment and is closely associated with the progress of CRPC invasion. However, no research has been performed on the immune escape of CRPC from NK cells. The present study focused on this subject. Firstly, when the CRPC cell lines C42 and CWR22Rv1 were induced by hypoxia, the expression of the UL16 binding protein (ULBP) ligand family of natural killer (NK) group 2D (NKG2D; ULBP1, ULBP2 and ULBP3) and MHC class I chainrelated proteins A and B (MICA/MICB) decreased. NKG2D is the main activating receptor of NK cells. Tumor cells were then cocultured with NK cells to conduct NK cellmediated cytotoxicity experiments, which revealed the decreased immune cytolytic activity of NK cells on hypoxiainduced CRPC cells. In exploring the mechanism behind this observation, an increase in programmed deathligand 1 (PDL1) expression in CRPC cells induced by hypoxia was observed, while the addition of PDL1 antibody effectively reversed the expression of NKG2D ligand and enhanced the cytotoxic effect of NK cells on CRPC cells. In the process of exploring the upstream regulatory factors of PDL1, inhibition of the Janus kinase (JAK)1,2/signal transducer and activator of transcription 3 (Stat3) signaling pathway decreased the expression of PDL1 in CRPC cells. Finally, it was observed that combined inhibition of JAK1,2/PDL1 or Stat3/PDL1 was more effective than inhibition of a single pathway in enhancing the immune cytolytic activity of NK cells. Taking these results together, it is thought that combined inhibition of the JAK1,2/PDL1 and Stat3/PDL1 signaling pathways may enhance the immune cytolytic activity of NK cells toward hypoxiainduced CRPC cells, which is expected to provide novel ideas and targets for the immunotherapy of CRPC.
Asunto(s)
Antígeno B7-H1/metabolismo , Janus Quinasa 1/metabolismo , Janus Quinasa 2/metabolismo , Células Asesinas Naturales/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Escape del Tumor , Línea Celular Tumoral , Expresión Génica , Humanos , Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Células Asesinas Naturales/inmunología , Masculino , Neoplasias de la Próstata Resistentes a la Castración/etiología , Neoplasias de la Próstata Resistentes a la Castración/patología , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal/efectos de los fármacosRESUMEN
Castration-resistant prostate cancer (CRPC), also known as androgen-independent prostate cancer, frequently develops local and distant metastases, the underlying mechanisms of which remain undetermined. In the present study, surgical specimens obtained from patients with clinical prostate cancer were investigated, and it was revealed that the expression levels of ataxia telangiectasia mutated kinase (ATM) were significantly enhanced in prostate cancer tissues isolated from patients with CRPC compared with from patients with hormonedependent prostate cancer. CRPC C42 and CWR22Rv1 cells lines were subsequently selected to establish prostate cancer models, and ATM knockout cells were established via lentivirus infection. The results of the present study demonstrated that the migration and epithelialmesenchymal transition (EMT) of ATM knockout cells were significantly decreased, which suggested that ATM is closely associated with CRPC cell migration and EMT. To further investigate the mechanisms underlying this process, programmed cell death 1 ligand 1 (PDL1) expression was investigated in ATM knockout cells. In addition, inhibitors of Janus kinase (JAK) and signal transducer and activator of transcription 3 (STAT3; Stattic) were added to C42Sc and CWR22Rv1Sc cells, and the results demonstrated that PDL1 expression was significantly decreased following the addition of JAK inhibitor 1; however, no significant change was observed following the addition of Stattic. Furthermore, a PDL1 antibody and JAK inhibitor 1 were added to C42Sc and CWR22Rv1Sc cells, and it was revealed that cell migration ability was significantly decreased and the expression of EMTassociated markers was effectively reversed. The results of the present study suggested that via inhibition of the ATMJAKPDL1 signaling pathway, EMT, metastasis and progression of CRPC may be effectively suppressed, which may represent a novel therapeutic approach for targeted therapy for patients with CRPC.
Asunto(s)
Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Antígeno B7-H1/metabolismo , Transición Epitelial-Mesenquimal , Quinasas Janus/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/patología , Transducción de Señal , Anciano , Anciano de 80 o más Años , Proteínas de la Ataxia Telangiectasia Mutada/genética , Antígeno B7-H1/genética , Línea Celular Tumoral , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Quinasas Janus/genética , Masculino , Metástasis de la Neoplasia/genética , Metástasis de la Neoplasia/patología , Neoplasias de la Próstata Resistentes a la Castración/genéticaRESUMEN
The focus of the present study was to evaluate transrectal real-time tissue elastography (RTE)-targeted two-core biopsy coupled with peak strain index for the detection of prostate cancer (PCa) and to compare this method with 10-core systematic biopsy. A total of 141 patients were enrolled for evaluation. The diagnostic value of peak strain index was assessed using a receiver operating characteristic curve. The cancer detection rates of the two approaches and corresponding positive cores and Gleason score were compared. The cancer detection rate per core in the RTE-targeted biopsy (44%) was higher compared with that in systematic biopsy (30%). The peak strain index value of PCa was higher compared with that of the benign lesion. PCa was detected with the highest sensitivity (87.5%) and specificity (85.5%) using the threshold value of a peak strain index of ≥5.97 with an area under the curve value of 0.95. When the Gleason score was ≥7, RTE-targeted biopsy coupled with peak strain index detected 95.6% of PCa cases, but 84.4% were detected using systematic biopsy. Peak strain index as a quantitative parameter may improve the differentiation of PCa from benign lesions in the prostate peripheral zone. Transrectal RTE-targeted biopsy coupled with peak strain index may enhance the detection of clinically significant PCa, particularly when combined with systematic biopsy.
RESUMEN
Naturally occurring compounds are reported as effective candidates for prevention and treatment of various cancers. Breviscapine (BVP) is a mixture of flavonoid glycosides, derived from the Chinese herbs. Previous researches have indicated that BVP has comprehensive pharmacological functions. However, little is known about whether BVP has preventive effects on human prostate cancer. Here, we attempted to explore if BVP inhibits human prostate cancer in vitro and in vivo in a comprehensive manner. We found that BVP triggered cytotoxicity in prostate cancer cell lines dose-dependently. BVP-induced DNA damage caused the cell cycle arrest and apoptosis and further induced cell death. High expression of MCM-7 was reduced in BVP-treated cancer cells and tumor tissues, and also the DNA damage response marker of γH2AX is down-regulated by BVP, associated with MCM-7 expression through regulating retinoblastoma protein (Rb) and checkpoint control proteins expression. Additionally, BVP induced apoptotic response in prostate cancer cells and tumors via activating Caspase-3 and PARP. In vivo studies indicated that BVP impeded tumor growth in xenograft animal models. In conclusion, our data indicates that breviscapine (BVP) can be further explored for its potential, which might be used in human prostate cancer therapeutics.
Asunto(s)
Daño del ADN/efectos de los fármacos , Flavonoides/farmacología , Componente 7 del Complejo de Mantenimiento de Minicromosoma/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , ADN/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias de la Próstata/metabolismo , Proteína de Retinoblastoma/metabolismoRESUMEN
The decoction of Pteris multifida had been applied to attenuate symptoms of benign prostatic hyperplasia in Chinese folk medicine. In this study, the total flavonoid extract of Pteris multifida was processed at first. High performance liquor chromatography and tandem mass spectrometer assay revealed 10 flavonoids as key constituents of this extract. After 60-day administration, the total flavonoid extract (180 mg/kg, i. g.) decreased the prostate index in mice of benign prostatic hyperplasia apparently. Immunohistochemical assay revealed inhibition of vascular endothelial growth factor expression, together with activation of transforming growth factor-beta 1 expression in the prostatic samples after administration of the extract. A 90-day subchronic toxicity test was further undertaken in male Sprague-Dawley rats, and the no-observed-adverse-effect level for the extract was 200 mg/kg body weight/day. These results revealed that the total flavonoid extract of Pteris multifida exhibited positive effect with safety, which might be applied in treatment of benign prostatic hyperplasia.
Asunto(s)
Flavonoides/farmacología , Flavonoides/toxicidad , Extractos Vegetales/farmacología , Extractos Vegetales/toxicidad , Hiperplasia Prostática/tratamiento farmacológico , Pteris/química , Animales , Peso Corporal/efectos de los fármacos , Esquema de Medicación , Flavonoides/química , Masculino , Estructura Molecular , Extractos Vegetales/química , Ratas , Ratas Sprague-DawleyRESUMEN
Special AT-rich sequence binding protein 1 (SATB1) plays important role in the regulation of chromatin structure and gene expression. Recent studies have indicated oncogenic role of SATB1. However, the function of SATB1 in prostate cancer progression and metastasis remains unclear. In this study SATB1 expression vector or siRNA was employed to modulate the expression level of SATB1 in prostate cancer cells and xenograft tumor in nude mouse model. Immunohistochemical analysis was performed on clinical prostate cancer samples. Silencing SATB1 inhibited the growth of DU-145 cells subcutaneous tumor in nude mice, while SATB1 overexpression promoted the growth of LNCaP cells subcutaneous tumor in nude mice. Immunohistochemical and Western blot analysis of the xenografts showed that silencing SATB1 led to decreased expression of vimentin and MMP2 and increased expression of E-cadherin, while SATB1 overexpression led to increased expression of vimentin and MMP2 and decreased expression of E-cadherin. Furthermore, SATB1, vimentin and MMP2 expression was increased significantly while E-cadherin expression was reduced significantly in clinical samples of prostate carcinoma with metastasis compared to prostate carcinoma without metastasis and benign prostate hyperplasia. Taken together, these findings suggest that the modulation of epithelial-mesenchymal transition by SATB1 may contribute to prostate cancer metastasis.
Asunto(s)
Transición Epitelial-Mesenquimal , Proteínas de Unión a la Región de Fijación a la Matriz/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Animales , Antígenos CD , Biomarcadores de Tumor/metabolismo , Cadherinas/metabolismo , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Masculino , Proteínas de Unión a la Región de Fijación a la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones Endogámicos BALB C , Ratones Desnudos , Metástasis de la Neoplasia , Neoplasias de la Próstata/genética , Tejido Subcutáneo/patología , Vimentina/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The aim of this study is to assess the overall efficacy and safety of photoselective vaporization of the prostate (PVP) with GreenLight 120-W laser versus transurethral resection of the prostate (TURP) for treating patients of benign prostate hyperplasia (BPH) with lower urinary tract symptoms (LUTS). We performed a literature search of The Cochrane Library and the electronic databases, including Embase, Medline, and Web of Science. Manual searches were conducted of the conference proceedings, including European Association of Urology and American Urological Association (2007 to 2012). Outcomes reviewed included clinical baseline characteristics, perioperative data, complications, and postoperative functional results, such as postvoid residual (PVR), international prostate symptom score (IPSS), quality of life (QoL), and maximum flow rate (Qmax). Six randomized controlled trials (RCTs) were enrolled. Three hundred and forty-seven patients undergone 120-W PVP, and 350 patients were treated with TURP in the RCTs. There were no significant differences for clinical characteristics in these trials. In perioperative data, catheterization time and length of hospital stay were shorter in the PVP group. However, the operation time was shorter in the TURP group. Capsular perforation, blood transfusion, clot retention, and macroscopic hematuria were markedly less likely in PVP-treated subjects. The other complications between PVP and TURP did not demonstrate a statistic difference. There were no significant differences in QoL, PVR, IPSS, and Qmax in the 1, 3, 6, 12, and 24 months of postoperative follow-up. There was no significant difference at postoperation follow-up of functional outcomes including IPSS, PVR, Qmax, and QoL between the TURP-treated subjects and PVP-treated subjects. Owing to a shorter catheterization time, reduced hospital duration and less complication, PVP could be used as an alternative and a promising minimal invasive surgical procedure for the treatment of BPH.
Asunto(s)
Terapia por Láser/métodos , Próstata/cirugía , Hiperplasia Prostática/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Resección Transuretral de la Próstata/métodos , Humanos , Terapia por Láser/efectos adversos , Masculino , Próstata/efectos de la radiación , Resección Transuretral de la Próstata/efectos adversos , VolatilizaciónRESUMEN
OBJECTIVE: To investigate the effect and safety of extracorporeal shock wave (ESW) in the treatment of pain symptom of type III B prostatitis. METHODS: We treated 50 cases of type III B prostatitis by ESW once a week for 4 weeks. Then we evaluated the clinical effect and safety of the therapy based on the NIH-CPSI scores, visual analogue scale (VAS) scores, IIEF-5 scores, prostate volume and morphous, state of urination, color of urine, results of routine semen analysis, and changes of cytokines (IL-6, TNF-α and IL-1ß) in expressed prostatic secretion (EPS). RESULTS: All the patients successfully accomplished the treatment. Compared with the baseline, decreases were observed after 4 weeks of cytokine treatment in the pain scores (14. 61 ± 1. 82 vs 9. 36 ± 1. 47, P <0. 01), urination symptom scores (4. 59 ± 1. 01 vs.4. 66 ± 0. 89, P >0. 05) , quality of life scores (6. 51 ± 1. 03 vs 4. 56 ± 1. 02, P <0. 01), NIH-CPSI (25. 43 ± 1. 72 vs 18. 28 ± 2. 32, P <0. 01 ), and VAS (6. 59 ± 1. 10 vs 3. 02 ± 1. 07, P < 0. 01). The concentration of IL-6 in the EPS was significantly increased ([55.82 ± 6. 28] vs [86.59 ± 4. 55] ng/ml, P <0. 01) , while the level of TNF-α ([3.89 ± 0. 12] vs [3. 19 ± 0.22] ng/ml, P<0.01) and that of IL-1ß ([3.21 ± 1.01] vs [1.48 ± 0.95] ng/ml, P< 0. 01) remarkably reduced after treatment. However, there were no statistically significant differences in IIEF-5 scores (18. 58 ± 2. 03 vs 18. 51 1. 89, P >0. 05) or various sperm parameters before and after treatment (P >0. 05). And no significant changes were observed in the prostate volume, morphous or internal echoes. CONCLUSION: The ESW therapy is effective and safe for the pain symptom of type III B prostatitis.
Asunto(s)
Manejo del Dolor/métodos , Prostatitis/terapia , Terapia por Ultrasonido/métodos , Adulto , Líquidos Corporales , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Persona de Mediana Edad , Dolor/etiología , Dolor/metabolismo , Prostatitis/complicaciones , Prostatitis/metabolismo , Calidad de Vida , Espermatozoides/fisiología , Factor de Necrosis Tumoral alfa/metabolismo , OrinaRESUMEN
Recent studies suggest that SATB1 is a promising therapeutic target for prostate cancer. To develop novel SATB1-based therapeutic agents for prostate cancer, in this study, we aimed to construct ZD55-SATB1, an oncolytic adenovirus ZD55 carrying shRNA targeting SATB1, and investigate its effects on the inhibition of prostate cancer growth and metastasis. ZD55-SATB1 was constructed and used to infect human prostate cancer cell lines DU145 and LNCaP. The inhibitory effect of ZD55-SATB1 on SATB1 expression was evaluated by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The cytotoxicity of ZD55-SATB1 was detected by MTT assay. Cell invasion was detected by Matrigel invasion assay. The in vivo antitumor activities of ZD55-SATB1 were evaluated in xenograft mouse model. We found that ZD55-SATB1 selectively replicated and significantly reduced SATB1 expression in DU145 and LNCaP cells. ZD55-SATB1 effectively inhibited the viability and invasion of DU145 and LNCaP cells in vitro and inhibited prostate cancer growth and metastasis in xenograft nude mice. In conclusion, replicative oncolytic adenovirus armed with SATB1 shRNA exhibits effective antitumor effect in human prostate cancer. Our study provides the basis for the development of ZD55-SATB1 for the treatment of prostate cancer.
Asunto(s)
Proliferación Celular/genética , Proteínas de Unión a la Región de Fijación a la Matriz/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/terapia , Animales , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Proteínas de Unión a la Región de Fijación a la Matriz/antagonistas & inhibidores , Proteínas de Unión a la Región de Fijación a la Matriz/biosíntesis , Ratones , Virus Oncolíticos/genética , Neoplasias de la Próstata/patología , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Subcapsular renal hematoma (SRH) after ureteroscopic lithotripsy (URSL) using holmium:yttrium-aluminum-garnet (Ho:YAG) laser to treat ureteric stones is a rare complication. We aimed to review our unit's experience of post-URSL subcapsular renal hematoma. From 2006 to 2012, 2059 URSLs using F9.5 rigid ureteroscope were performed in our unit. Patients with post-URSL symptomatic renal hematoma were reviewed. Perioperative information on patients' renal function, stone characteristics, and degree of renal hydronephrosis were reviewed. Operative data, postoperative information such as clinical manifestation, changes in blood parameters, CT findings, and subsequent treatment were documented. Of the 2059 patients treated with URSL and Ho:YAG laser, three patients were diagnosed as subcapsular renal hematoma after surgery; the age is 57, 61, and 63 years old, respectively. Preoperative imaging examination showed that two patients and one patient had obstructing middle and proximal ureteral stones ranging in size from 0.8 to 1.6 cm, and three patients had thin renal cortices. The double-J ureteral stents were inserted in all cases regularly. All three subcapsular renal hematoma patients had the loin pain of the operation side and fever, and one patient had significant hemoglobin drop (from 111 to 61 g/L) who need to transfusion. Two patients presented within 24 h of URSL, and one patient presented on day 10. One patient was treated conservatively for 3 weeks and recovered with bed rest, antibiotics, hemostasis, and analgesia with no intervention or drain. The other two patients underwent ultrasonography-guided drainage of the hematoma. Two-month follow-up CT scans or ultrasonography confirmed the resolution of the hematoma in all three cases. Renal subcapsular hematoma after URSL is a rare and one of serious complications. Subcapsular renal hematoma should be considered when patients have the symptoms of significant loin pain after URSL for obstructing ureteral stones with thin renal cortices. The treatment of post-URSL renal subcapsular hematomas needs to be customized for each patient.
Asunto(s)
Hematoma/etiología , Enfermedades Renales/etiología , Láseres de Estado Sólido/uso terapéutico , Litotripsia por Láser/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cálculos Ureterales/terapia , Ureteroscopía/efectos adversosRESUMEN
OBJECTIVE: To determine whether there have been any changes in the causes and management of urethral strictures in China. PATIENTS AND METHODS: The data from 4,764 men with urethral stricture disease who underwent treatment at 13 medical centres in China between 2005 and 2010 were retrospectively collected. The databases were analysed for the possible causes, site and treatment techniques for the urethral stricture, as well as for changes in the causes and management of urethral strictures. RESULTS: The most common cause of urethral strictures was trauma, which occurred in 2,466 patients (51.76%). The second most common cause was iatrogenic injures, which occurred in 1,643 patients (34.49%). The most common techniques to treat urethral strictures were endourological surgery (1,740, 36.52%), anastomotic urethroplasty (1,498, 31.44%) and substitution urethroplasty (1,039, 21.81%). A comparison between the first 3 years and the last 3 years showed that the constituent ratio of endourological surgery decreased from 54% to 32.75%, whereas the constituent ratios of anastomotic urethroplasty and substitution urethroplasty increased from 26.73% and 19.18% to 39.93% and 27.32%, respectively (P < 0.05). CONCLUSIONS: During recent years, there has been an increase in the incidence of urethral strictures caused by trauma and iatrogenic injury. Endourological urethral surgery rates decreased significantly, and open urethroplasty rates increased significantly during the last 3 years.
Asunto(s)
Estrechez Uretral/epidemiología , Estrechez Uretral/etiología , Estrechez Uretral/cirugía , China/epidemiología , Humanos , Masculino , Estudios RetrospectivosRESUMEN
OBJECTIVE: To explore the effects of stromal interaction molecule 1 (STIM1) on the expression of apoptosis-related proteins in prostate cancer PC-3 cells. METHODS: We transfected the lentivirus vector STIM1-pGCSIL-GFP carrying STIM shRNA into human hormone-independent prostate cancer PC-3 cells, and 3 days later observed the transfection efficiency by fluorescence microscopy. At 7 days after transfection, we determined the expression of STIM1 in the PC-3 cells by RT-PCR and Western blot and those of apoptosis-related proteins Bcl-2, Bax, survivin and activated Caspase-3 by Western blot. RESULTS: At 3 days, inverted microscopy revealed a transfection efficiency of > 80%. At 7 days, the STIM1 expression was significantly inhibited at both mRNA and protein levels. The Bcl-2/Bax rate was remarkably decreased as compared with that of the control group (0. 31 vs 1.24 ) , and the survivin expression was markedly reduced, 0. 14 times that of the relative expression in the control. However, the Caspase-3 cleavage was significantly activated, 1.52 times that of the control (P <0.05). CONCLUSION: STIM1 can be regarded as an oncogene in prostate cancer PC-3 cells. Inhibition of its expression can induce PC-3 cell apoptosis by reducing the Bcl-2/Bax rate, decreasing the survivin expression, and activating the Caspase-3 pathway.
Asunto(s)
Proteínas de la Membrana/genética , Proteínas de Neoplasias/genética , Neoplasias de la Próstata/metabolismo , ARN Interferente Pequeño , Apoptosis , Caspasa 3/metabolismo , Línea Celular Tumoral , Humanos , Proteínas Inhibidoras de la Apoptosis/metabolismo , Masculino , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , ARN Interferente Pequeño/genética , Molécula de Interacción Estromal 1 , Survivin , Transfección , Proteína X Asociada a bcl-2/metabolismoRESUMEN
PURPOSE: The objective of this study was to evaluate the safety and feasibility of single channel laparoscopy in the treatment of patients with varicocele. PATIENTS AND METHODS: Ninety patients with clinically palpable varicoceles were randomly assigned to receive laparoendoscopic single-site with a single channel varicocele ligation (LESS[sc]-VL) (n=45) or conventional transperitoneal laparoscopic varicocele ligation (CTL-VL) (n=45). Patient characteristics, perioperative details, total procedural cost, time to return to work, visual analogue scale (VAS) pain score, semen parameters, and cosmetic results were recorded. RESULTS: There were no differences in operative time (P=0.102), postoperative hospitalization time (P=0.130), total cost (P=0.112), or postoperative complications (P>0.05) between the two groups. Time to return to normal activities was shorter in the LESS(sc)-VL group than that in the CTL-VL group (P=0.018). The mean of all semen parameters were improved statistically 3 months after ligation (P<0.001). The VAS incision pain score was significantly lower 6 and 24 hours after surgery in patients who underwent LESS(sc)-VL(P<0.05). Patients who underwent LESS(sc)-VL had a better cosmetic result, reflected by both the verbal response scale and the numeric scale (P=0.008 and P=0.005, respectively). CONCLUSIONS: LESS(sc)-VL is a safe and effective minimally invasive surgical alternative for varicocelectomy. Compared with CTL-VL, LESS(sc)-VL may decrease postoperative pain and hide the surgical incision better within the umbilicus.
Asunto(s)
Laparoscopía/métodos , Dolor Postoperatorio/etiología , Complicaciones Posoperatorias , Varicocele/cirugía , Procedimientos Quirúrgicos Vasculares/métodos , Adulto , Estudios de Factibilidad , Estudios de Seguimiento , Humanos , Laparoscopía/efectos adversos , Ligadura , Masculino , Tempo Operativo , Pronóstico , Estudios Prospectivos , Varicocele/complicaciones , Procedimientos Quirúrgicos Vasculares/efectos adversos , Adulto JovenRESUMEN
This study treated the isolation and passage of muscle-derived stem cells (MDSCs) from rat penile corpora cavernosa, detection of stem cell marker expression, observation of their self-renewal and continuous proliferation, and demonstration of their potential to differentiate into smooth muscle cells in co-culture. Muscle-derived stem cells from the rat penile corpora cavernosa were isolated and purified. The expression of stem cell markers Sca-1 and desmin was detected in PP6 cells, thus confirming that the main components of PP6 cells are MDSCs. The expression of Sca-1 and desmin occurred both in PP6 cells and cells at passages 3, 6, and 8, and there was no significant decrease in the expression level with increasing passage number. The growth curves indicated that the cell doubling time was approximately 48 h. The cells entered the stationary phase after approximately 7 days of culture. The proliferative activity of the cells at passage 8 remained unchanged. After 2 days of co-culture with smooth muscle cells, the DAPI-labeled MDSCs tended to exhibit smooth muscle cell morphology and expression of α-SMA was detected. MDSCs exist in the rat penile corpora cavernosa and possess the potential to differentiate into smooth muscle cells. This discovery serves as the basis in view of the potential use of endogenous stem cells for the treatment of erectile dysfunction (ED).
RESUMEN
Bladder urothelial carcinoma (BUC) accounts for â¼90% of all cases of bladder cancer. Reduced expression of TGFBR3 has been frequently observed in several types of human cancers. However, little is known about whether expression of TGFBR3 reduced in BUC and the underlying mechanisms. In the present study, we performed quantitative real-time PCR to examine the mRNA expression of TGFBR3 and GATA3, and bisulfite genomic sequencing to evaluate the methylation status in TGFBR3 and GATA3 promoter regions in fresh tumor and the corresponding paracarcinoma tissues from 29 patients with BUC. As a result, the expression of TGFBR3 and GATA3, a transcriptional factor of the TGFBR3 gene, were found to be co-downregulated in BUC. Moreover, our findings indicated that GATA3 promoter methylation was one of the reasons for silencing of GATA3 and TGFBR3 in BUC, albeit TGFBR3 methylation and mutation were not associated with reduced expression of TGFBR3 mRNA in BUC. In summary, our findings suggest that methylation in the GATA3 promoter region may inhibit the expression of GATA3 mRNA, which leads to the reduced expression of TGFBR3 mRNA in BUC.
Asunto(s)
Carcinoma de Células Transicionales/metabolismo , Metilación de ADN/fisiología , ADN de Neoplasias/metabolismo , Regulación hacia Abajo/fisiología , Factor de Transcripción GATA3/metabolismo , Proteoglicanos/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Carcinoma de Células Transicionales/genética , Femenino , Factor de Transcripción GATA3/genética , Regulación Neoplásica de la Expresión Génica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Regiones Promotoras Genéticas/genética , Proteoglicanos/genética , ARN Mensajero/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/genética , Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
Prostate cancer (PCa) stem/progenitor cells are known to have higher chemoresistance than non-stem/progenitor cells, but the underlying molecular mechanism remains unclear. We found the expression of testicular nuclear receptor 4 (TR4) is significantly higher in PCa CD133(+) stem/progenitor cells compared with CD133(-) non-stem/progenitor cells. Knockdown of TR4 levels in the established PCa stem/progenitor cells and the CD133(+) population of the C4-2 PCa cell line with lentiviral TR4 siRNA led to increased drug sensitivity to the two commonly used chemotherapeutic drugs, docetaxel and etoposide, judging from significantly reduced IC50 values and increased apoptosis in the TR4 knockdown cells. Mechanism dissection studies found that suppression of TR4 in these stem/progenitor cells led to down-regulation of Oct4 expression, which, in turn, down-regulated the IL-1 receptor antagonist (IL1Ra) expression. Neutralization experiments via adding these molecules into the TR4 knockdown PCa stem/progenitor cells reversed the chemoresistance, suggesting that the TR4-Oct4-IL1Ra axis may play a critical role in the development of chemoresistance in the PCa stem/progenitor cells. Together, these studies suggest that targeting TR4 may alter chemoresistance of PCa stem/progenitor cells, and this finding provides the possibility of targeting TR4 as a new and better approach to overcome the chemoresistance problem in PCa therapeutics.
Asunto(s)
Antígenos CD , Antineoplásicos Fitogénicos/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Etopósido/farmacología , Glicoproteínas , Proteína Antagonista del Receptor de Interleucina 1/metabolismo , Células Madre Neoplásicas/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Péptidos , Neoplasias de la Próstata , Receptores de Esteroides/metabolismo , Receptores de Hormona Tiroidea/metabolismo , Taxoides/farmacología , Antígeno AC133 , Línea Celular Tumoral , Docetaxel , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/genética , Técnicas de Silenciamiento del Gen , Humanos , Proteína Antagonista del Receptor de Interleucina 1/genética , Masculino , Células Madre Neoplásicas/patología , Factor 3 de Transcripción de Unión a Octámeros/genética , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Receptores de Esteroides/genética , Receptores de Hormona Tiroidea/genéticaRESUMEN
OBJECTIVE: To investigate and compare the effectiveness and safety of 80-W GreenLight laser vaporization and GreenLight high-performance system (HPS) 120-W laser vaporization for the treatment of benign prostatic hyperplasia (BPH) in high-risk patients. METHODS: We allocated 290 high-risk patients with BPH to two groups to receive 80-W (n = 220) and HPS 120-W GreenLight laser vaporization (n = 70). We recorded and compared the pre-, intra- and post-operative clinical data of the two groups. RESULTS: The operations were successful in both of the groups. There were statistically significant differences in the prostate volume, IPSS, Qmax and PVR before and after surgery (P < 0.01), but not between the two groups (P > 0.05). The operation time, lasing time and energy consumption were (56.5 +/- 22.6) min, (31.2 +/- 10.3) min and (159.8 +/- 29.0) kJ in the 80-W group, as compared with (45.1 +/- 20.4) min, (24.6 +/- 8.3) min and (134.2 +/- 23.3) kJ in the 120 W group, with significant differences between the two (P < 0.01). CONCLUSION: GreenLight laser vaporization of the prostate is a safe and effective procedure for the treatment of BPH, and the new HPS 120-W laser therapy, with its advantages of easier operation and shorter surgical time, is an even better minimally invasive option for elderly high-risk patients.
Asunto(s)
Terapia por Láser/efectos adversos , Terapia por Láser/métodos , Hiperplasia Prostática/cirugía , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Resultado del TratamientoRESUMEN
OBJECTIVE: To report the initial urological applications of single trocar laparoscopic surgery. METHODS: From April to December 2010, a total of 45 urologic patients underwent single trocar laparoscopic surgery. The procedures included high ligations of spermatics vessels (n = 17), unroofing of renal cysts (n = 24) and ureterolithotomy (n = 4). Transperitoneal approach: A 15 mm incision was made in umbilicus and CO(2) pneumoperitoneum created. A 10-mm trocar was inserted into enterocoelia. After the installation of single punch laparoscope (STROZ), the operating instruments were guided through integrated working channel to complete operative procedures. Retroperitoneal approach: A 15 mm incision was made above the diseased-side crista iliaca for around 4 cm. Retroperitoneal cavity was prepared for retroperitoneoscopy with the IUPU (Institute of Urology, Peking University) technique. In the same way, a 10-mm trocar was inserted. And the single punch laparoscope was installed to complete operative procedures. RESULTS: The procedures were successful in 41 cases. But the others (renal cysts, n = 2; ureteral calculus, n = 2) were successfully managed by adding a 5 mm trocar. Operation time: transperitoneal approach, 23 - 70 min; retroperitoneal approach, 45 - 175 min. The intra-operative volume of blood loss was minimal. And the hospital stay was 1 - 5 days. No significant postoperative complication occurred. CONCLUSION: For some relatively simple procedures, a new and more minimally invasive approach of single trocar laparoscopic surgery may be attempted.
Asunto(s)
Laparoscopios , Laparoscopía , Humanos , Espacio Retroperitoneal , Instrumentos Quirúrgicos , OmbligoRESUMEN
OBJECTIVE: To detect the expressions of transforming growth factor-beta1 (TGF-beta1), Desmin and CD34 in the penile corpus cavernosum of SD rats in different age groups. METHODS: We randomly selected 10 SD rats in each of the 2-, 5- and 20-month age groups, harvested their penile corpus cavernosum tissues under ether anesthesia, and detected the mRNA and protein expressions of TGF-beta1, Desmin and CD34 by RT-PCR and immunohistochemistry. RESULTS: The results of RT-PCR showed the mRNA expressions of TGF-beta1, Desmin and CD34 in the corpus cavernosum tissues, with significant differences between every two groups (P < 0.01). The TGF-beta1 protein was mainly expressed in the trabeculae and around the arteries of the corpus cavernosum for membrane and cytoplasm staining, the Desmin protein mainly in the membrane and cytoplasm for muscle tissue staining; and the CD34 protein mainly in the vascular and sinusoidal endothelia. The mRNA expression of TGF-beta1 was correlated positively (r = 0.944, P < 0.01) while those of Desmin and CD34 negatively with the age of the rats (r = -0.947, P < 0.01; r = -0.934, P < 0.01). And the mRNA expressions of both Desmin and CD34 had a significant correlation with that of TGF-beta1 (r = -0.888, P < 0.01; r = -0.887, P < 0.01). CONCLUSION: With the increase of age, the expression of TGF-beta1 is significantly up-regulated, while those of Desmin and CD34 significantly down-regulated in the corpus cavernosum tissues, and it is negatively correlated with the latter two. TGF-beta1 is an important influencing factor on ED.