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1.
BMC Urol ; 24(1): 32, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38321455

RESUMEN

BACKGROUND: USP54, a ubiquitin-specific protease in the deubiquitinase (DUB) family, facilitates the malignant progression of several types of cancer. However, the role of USP54 in prostate cancer (PCa), especially castration-resistant prostate cancer (CRPC), remains unknown. METHODS: We established the CRPC LNCaP-AI cell line from the hormone-sensitive prostate cancer (HSPC) LNCaP cell line. RNA-Seq was utilized to explore DUB expression levels in LNCaP and LNCaP-AI. USP54 was knocked down, and its effects on cell growth were evaluated in vitro and in vivo. Bioinformatics analyses were conducted to explore signaling pathways affected by USP54 in PCa. Quantitative polymerase chain reaction was used to confirm key signaling pathways involved. RESULTS: USP54 was the most strongly upregulated DUB in LNCaP-AI cells compared with LNCaP cells. USP54 levels were higher in PCa than in normal tissues. USP54 silencing suppressed the proliferation of PCa cell lines, both in vitro and in vivo. USP54 expression was positively correlated with the androgen receptor (AR) signaling level in PCa samples, and USP54 knockdown inhibited AR signaling in PCa cells. CONCLUSIONS: USP54 was upregulated during HSPC progression to CRPC. USP54 depletion suppressed CRPC cell proliferation both in vitro and in vivo. USP54 may facilitate PCa progression by regulating AR signaling.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Línea Celular Tumoral , Proliferación Celular , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Receptores Androgénicos
2.
Biochem Biophys Res Commun ; 698: 149543, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38266312

RESUMEN

ANP32B is a histone chaperone that interacts with various transcription factors that regulate cancer cell proliferation, immigration, and apoptosis. c-Myc, a well-known oncogenic protein, is a principal player in the initiation and progression of prostate cancer (PC). The means by which ANP32B and c-Myc act remain unknown. We downloaded clinical data from the GEO, TCGA, and other databases to explore ANP32B expression and its effects on the survival of PC and normal tissues. ANP32B-knockdown cell lines were used to evaluate how ANP32B affected cell proliferation in vitro and in vivo. Gene set enrichment analysis and RNAseq were employed to define how ANP32B regulated PC pathways. Immunohistochemical measures were used to detect the expression levels of relevant proteins in xenografts and PC tissues. ANP32B expression increased in PC tissues; ANP32B knockdown inhibited cell growth but this was rescued by c-Myc signaling. ANP32B is thus a PC oncogene and may serve as a valuable therapeutic target when seeking to treat PC.


Asunto(s)
Proteínas Nucleares , Neoplasias de la Próstata , Proteínas Proto-Oncogénicas c-myc , Humanos , Masculino , Línea Celular Tumoral , Proliferación Celular , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Próstata/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Transducción de Señal , Animales
3.
Int J Cancer ; 153(4): 792-802, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-36919366

RESUMEN

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Antígeno Prostático Específico , Tiohidantoínas/efectos adversos , Antagonistas de Receptores Androgénicos , Resultado del Tratamiento
4.
Regen Ther ; 22: 136-147, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36793307

RESUMEN

Since a scarcity of sufficient grafting materials, several complications can arise after urothelial defect reconstruction surgery, including severe hypospadias. Accordingly, developing alternative therapies, such as urethral restoration via tissue engineering are needed. In the present study, we developed a potent adhesive and repairing material using fibrinogen-poly(l-lactide-co-caprolactone) copolymer (Fib-PLCL) nanofiber scaffold to achieve effective urethral tissue regeneration after seeding with epithelial cells on the surface. The in vitro result found the Fib-PLCL scaffold promoted the attachment and viability of epithelial cells on their surface. The increased expression levels of cytokeratin and actin filaments were observed in Fib-PLCL scaffold than PLCL scaffold. The in vivo urethral injury repairing potential of Fib-PLCL scaffold was evaluated using a rabbit urethral replacement model. In this study, a urethral defect was surgically excised and replaced with the Fib-PLCL and PLCL scaffolds or autograft. As expected, the animals healed well after surgery in the Fib-PLCL scaffold group, and no significant strictures were identified. As expected, the cellularized Fib/PLCL grafts have induced the luminal epithelialization, urethral smooth muscle cell remodelling, and capillary development all at the same time. Histological analysis revealed that the urothelial integrity in the Fib-PLCL group had progressed to that of a normal urothelium, with enhanced urethral tissue development. Based on the results, the present study suggests that the prepared fibrinogen-PLCL scaffold is more appropriate for urethral defect reconstruction.

5.
Cancer ; 129(3): 415-425, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36477612

RESUMEN

BACKGROUND: Cryotherapy is a prevalent percutaneous ablative therapy for solid tumors. Here, we report a novel device using liquid nitrogen for endoscopic cryotherapy of bladder cancer. METHODS: In this multicenter, randomized, parallel controlled, Phase 2 trial, we compared endoscopic balloon cryoablation (EBCA) with a single instillation (SI) of pirarubicin after transurethral resection (TUR). Eligible participants were randomly assigned (1:1) to the TUR-EBCA or TUR-SI group. Repeat TUR or tissue biopsies were performed to evaluate residual tumor at 4 to 6 weeks after primary treatment. The primary end point was the local control rate. The secondary end points included the tumor upgrading/upstaging, catheter indwelling duration, and adverse events. RESULTS: In total, 205 patients received EBCA or SI after TUR between November 2017 and September 2020, of whom 163 completed all the required interventions. In the per-protocol set, the local control rate was 91.5% (75/82) in TUR-EBCA group compared with 76.5% (61/81) in TUR-SI group (risk difference, 15%; 95% CI, 0.03-0.27, p < .001), meeting the criteria for noninferiority. Similar results were found in the modified intention-to-treat analysis. Tumor upgrading/upstaging was found in five patients from the TUR-SI group. There was no significant difference in the catheter indwelling duration (5.1 vs. 5.2 days, p = .76) or serious adverse event rate (3.0% vs. 3.9%, p = .52). The median follow-up time of post hoc analysis was 31 (range, 15-50) months. Patients in the TUR-EBCA group had a better recurrence-free survival and progression-free survival. CONCLUSION: EBCA is a safe and effective adjuvant therapy with TUR for non-muscle-invasive bladder cancer. PLAIN LANGUAGE SUMMARY: This is the first randomized trial that evaluated endoscopic cryotherapy after transurethral resection (TUR) of bladder tumors. The efficacy and safety analysis shows endoscopic balloon cryoablation (EBCA) is a promising alternative. Results report that EBCA is not inferior to a single instillation of intravesical chemotherapy in eliminating residual bladder tumor. Further analysis with ∼3 years' median follow-up suggested a better prognosis in patients who received EBCA after TUR.


Asunto(s)
Carcinoma de Células Transicionales , Criocirugía , Neoplasias de la Vejiga Urinaria , Humanos , Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/patología , Procedimientos Quirúrgicos Urológicos , Pronóstico , Administración Intravesical , Recurrencia Local de Neoplasia/tratamiento farmacológico
6.
Am J Med Sci ; 364(2): 220-228, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35289275

RESUMEN

BACKGROUND: Delta-like canonical notch ligand 4 (DLL4) is considered a potential prognostic gene for renal cell carcinoma (RCC). We assessed the molecular mechanisms and novel biomarkers associated with DLL4 during RCC development. METHODS: Four gene expression profiles were downloaded from the GEO database. Differentially expressed genes (DEGs) were identified between RCC and normal renal samples, including common DEGs (co-DEGs). Thereafter, RCC-associated gene exploration was performed and a PPI network was constructed to identify the core genes. Survival analysis of core genes in the high expression group (H group) and low expression group (L group) was also performed. The key genes related to the core genes were investigated, and the miRNA-target genes and TFs-target genes were analyzed. Finally, the expression levels of VEGFA, FLT1, EGLN3, and DLL4 in RCC and paracancerous tissues were determined. RESULTS: A total of 11,867 DEGs and 622 co-DEGs were identified in this study, and 67 RCC-associated genes that were mainly enriched in signal transduction and angiogenesis function were further explored. VEGFA was identified as the core gene. Further, 30 DEGs and 9 DE-miRNAs were identified between the H and L groups. VEGFA was positively correlated with 19 genes, including EGLN3, FLT1, and DLL4. A total of 18 miRNA-target interactions, including miR-134-5p-DLL4, were obtained. VEGFA, FLT1, EGLN3, and DLL4 were significantly expressed in RCC tissues compared with paracancerous tissues. CONCLUSIONS: DLL4 may contribute to the development of RCC by participating in signal transduction and angiogenesis. VEGFA, FLT1, EGLN3, DLL4, and miR-134-5p may be novel biomarkers for RCC.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , MicroARNs , Proteínas Adaptadoras Transductoras de Señales , Biomarcadores , Proteínas de Unión al Calcio/genética , Carcinoma de Células Renales/metabolismo , Perfilación de la Expresión Génica , Humanos , Neoplasias Renales/metabolismo , MicroARNs/genética , Neovascularización Patológica
8.
Pharm Biol ; 60(1): 46-55, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34904911

RESUMEN

CONTEXT: Yougui pill combined with Buzhong Yiqi decoction (YPBYD) is used to relieve sexual dysfunction in clinical practice. OBJECTIVE: To investigate changes in microbial composition caused by sexual dysfunction and identify dominant bacteria related to YPBYD treatment. MATERIALS AND METHODS: Female Sprague-Dawley rats were randomly divided into four groups (n = 6): one group underwent Sham operation (Sham group), while three groups underwent ovariectomy (one model and two treatment groups). The ovariectomized (OVX) rats received oestradiol benzoate (250 µg/kg/week) or YPBYD (3.6 mL/d) via oral gavage for 4 weeks. Vaginal smear assay was performed; the serum levels of cyclic adenosine monophosphate (cAMP) and oestradiol (E2) were measured, followed by collection of stool samples for 16S rRNA sequencing. RESULTS: After YPBYD treatment, the levels of E2 and cAMP in OVX rats significantly increased (E2: from 20.45 ± 1.60 ng/L to 24.38 ± 1.70 ng/L; cAMP: from 261.41 ± 9.21 pg/mL to 373.75 ± 17.37 pg/mL). OVX treatment decreased diversity of gut microbiota and YPBYD treatment restored gut microbiota composition. Compared with Sham group, the abundance of Romboutsia significantly increased, while those of Proteobacteria and Staphylococcus markedly decreased in OVX group (all p < 0.05); meanwhile, the abundance of these microbes showed an opposite trend after YPBYD treatment. These microbiotas were involved in tyrosine and tryptophan biosynthesis and fatty acid metabolism. DISCUSSION AND CONCLUSIONS: These findings are the first to indicate YPBYD can alleviate female sexual dysfunction by modulating gut microbiota in OVX rats, which will help enhance the understanding on potential mechanism of YPBYD against sexual dysfunction.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Disfunciones Sexuales Fisiológicas/tratamiento farmacológico , Animales , AMP Cíclico/metabolismo , Medicamentos Herbarios Chinos/administración & dosificación , Estradiol/análogos & derivados , Estradiol/farmacología , Femenino , Ovariectomía , ARN Ribosómico 16S , Ratas , Ratas Sprague-Dawley , Disfunciones Sexuales Fisiológicas/microbiología
9.
Front Genet ; 13: 1110723, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36704352

RESUMEN

The clinical and molecular phenotypes of prostate cancer (PCa) exhibit substantial heterogeneity, ranging from indolent to metastatic disease. In this study, we aimed to identify PCa subtypes and construct a gene signature that can predict the recurrence-free survival (RFS) of PCa patients based on chromatin regulators genes (CRGs). Strikingly, we identified two heterogeneous subtypes with distinct clinical and molecular characteristics. Furthermore, by performing differential analysis between the two CRGs subtypes, we successfully constructed a gene signature to predict PCa prognosis. The signature, comprising four genes (MXD3, SSTR1, AMH and PPFIA2), was utilized to classify PCa patients into two risk groups; the high-risk group was characterized by poor prognosis and more aggressive clinical features. Moreover, we investigated the immune profile, mutation landscape and molecular pathways in each of the groups. Additionally, drug-susceptibility testing was performed to explore sensitive drugs for high-risk patients. Furthermore, we found that MXD3 downregulation suppressed the proliferation of PCa cell lines in vitro. Overall, our results highlight the signature based on CRGs as a powerful tool for predicting RFS of PCa patients, as well as an indicator for personalized treatment of those patients.

10.
Zhonghua Nan Ke Xue ; 27(1): 45-49, 2021 Jan.
Artículo en Chino | MEDLINE | ID: mdl-34914280

RESUMEN

OBJECTIVE: To study the effects of 1470 nm semiconductor laser enucleation of the prostate (SCLEP) and transurethral plasma electrotomy (TUPE) on erectile function and pelvic floor muscle strength in BPH patients. METHODS: We retrospectively analyzed the clinical data on 72 cases of BPH treated in our hospital from July 2017 to July 2019 by TUPE (group A, n = 36) or 1470 nm SCLEP (group B, n = 36). We observed and compared the postoperative penile erectile function, retrograde ejaculation and pelvic floor muscle strength between the two groups of patients. RESULTS: Compared with group A, group B showed a significantly higher IIEF-5 score (19.43 ± 1.61 vs 21.15 ± 1.32, P < 0.05) and pelvic floor muscle strength (electromyographic ï¼»EMGï¼½ value) during rapid contraction (36.36 ± 1.38 vs 43.53 ± 2.04, P < 0.05), continuous contraction (34.27 ± 1.63 vs 39.46 ± 1.48, P < 0.05) and endurance test (35.24 ± 1.57 vs 38.19 ± 1.67, P < 0.05), but lower incidence rates of ED and retrograde ejaculation. CONCLUSIONS: Compared with TUPE, 1470 nm SCLEP affects less the erectile function and pelvic floor muscle strength of BPH patients.


Asunto(s)
Disfunción Eréctil , Hiperplasia Prostática , Disfunción Eréctil/etiología , Humanos , Láseres de Semiconductores , Masculino , Fuerza Muscular , Diafragma Pélvico/cirugía , Próstata , Hiperplasia Prostática/cirugía , Estudios Retrospectivos , Volatilización
11.
Biochem Biophys Rep ; 28: 101151, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34703906

RESUMEN

Kruppel-like factors (KLFs) play an important role in many biological processes including cell proliferation, differentiation and development. Our study showed that the level of KLF9 is lower in PCa cell lines compared to a benign prostate cell line; the androgen-independent cell line PC3 expresses significantly lower KLF9 than the androgen-dependent cell line, LNCaP. Forced overexpression of KLF9 suppressed cell growth, colony formation, and induced cell apoptosis in LNCaP cells. We also found that KLF9 expression was induced in response to apoptosis caused by flutamide, and further addition of dihydrotestosterone antagonized the action of flutamide and significantly decreased KLF9 expression. Furthermore, activation of the androgen receptor (AR) was inhibited by the overexpression of KLF9. Our research shows that KLF9 is lower in androgen-independent cell lines than in androgen-dependent cell lines; Overexpression of KLF9 dramatically suppresses the proliferation, anchorage-independent growth, and induces apoptosis in androgen-dependent cells; KLF9 inhibition on prostate cancer cell growth may be acting through the AR pathway. Our results therefore suggest that KLF9 may play a significant role in the transition from androgen-dependent to androgen-independent prostate cancer and is a potential target of prevention and therapy.

12.
Front Surg ; 8: 670123, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34336915

RESUMEN

Background: This study aimed to evaluate the clinical efficacy of Yun-type optimized pelvic floor training therapy for middle-aged women with severe overactive bladder (OAB). Methods: This randomized, observer-blinded, parallel-group controlled clinical trial included 108 middle-age women with severe OAB and assigned them to the intervention group (treated with combination of Yun-type optimized pelvic floor training with solifenacin for 12 weeks) and control group (treated with solifenacin for 6 weeks and, after 2 weeks of elution, received the combination of Yun-type optimized pelvic floor training and solifenacin for 6 weeks). The outcomes associated with OAB, pelvic floor muscle (PFM) function, and sexual function were compared after 6 and 12/14 weeks of treatment. Results: The primary variables were OAB-associated outcomes, including overactive bladder symptom score (OABSS), urgent urination, urine, nocturia, urge urinary incontinence, patient's perception of bladder condition, urogenital distress inventory-6, incontinence impact questionnaire-7, voiding volume, average flow rate, and maximum flow rate. The secondary variables were indicators related to PFM function and sexual function. These indicators were significantly improved in both groups after interventions. Notably, the improvements in most of these indicators were superior in the intervention group than in the control group after 6 weeks and 12/14 weeks of treatment. Conclusions: The use of Yun-type optimized pelvic floor training adds to the benefits of solifenacin regarding severe OAB-associated outcomes, PMF function, and sexual function in middle-aged women with severe OAB. Combining Yun-type optimized pelvic floor training with traditional drug therapies may improve clinical outcomes in patients with severe OAB. Trial Registration: ChiCTR-INR-17012189.

13.
Cancer Cell Int ; 21(1): 430, 2021 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-34399732

RESUMEN

BACKGROUND: DDX52 is a type of DEAD/H box RNA helicase that was identified as a novel prostate cancer (PCa) genetic locus and possible causal gene in a European large-scale transcriptome-wide association study. However, the functions of DDX52 in PCa remain undetermined. The c-Myc oncogene plays a crucial role in the development of PCa, but the factors that regulate the activity of c-Myc in PCa are still unknown. METHODS: We determined DDX52 protein levels in PCa tissues using immunohistochemistry (IHC). DDX52 expression and survival outcomes in other PCa cohorts were examined using bioinformatics analysis. The inhibition of DDX52 via RNA interference with shRNA was used to clarify the effects of DDX52 on PCa cell growth in vitro and in vivo. Gene set enrichment analysis and RNA sequencing were used to explore the signaling regulated by DDX52 in PCa. Western blotting and IHC were used to determine the possible DDX52 signaling mechanism in PCa. RESULTS: DDX52 expression was upregulated in PCa tissues. Bioinformatics analysis showed that the level of DDX52 further increased in advanced PCa, with a high DDX52 level indicating a poor outcome. In vitro and in vivo experiments showed that downregulating DDX52 impeded the growth of PCa cells. High DDX52 levels contributed to activating c-Myc signaling in PCa patients and PCa cells. Furthermore, DDX52 expression was regulated by c-Myc and positively correlated with c-Myc expression in PCa. CONCLUSION: DDX52 was overexpressed in PCa tissues in contrast to normal prostate tissues. DDX52 knockdown repressed the growth of PCa cells in vitro and in vivo. Deleting c-Myc inhibited DDX52 expression, which affected the activation of c-Myc signaling.

14.
Clin Transl Med ; 11(7): e495, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34323404

RESUMEN

Castration-resistant prostate cancer (CRPC) is the latest stage of PCa, and there is almost no effective treatment available for the patients with CRPC when next-generation androgen deprivation therapy drugs, such as enzalutamide (ENZ), fail. The androgen receptor (AR) plays key roles in PCa and CRPC progression and drug resistance. Histone acetyltransferase 1 (HAT1) has recently been reported to be highly expressed in some tumors, such as lung carcinoma. However, what relationship between the AR and HAT1, and whether or how HAT1 plays roles in CRPC progression and drug resistance remain elusive. In the present study, we found that HAT1 is highly expressed in PCa cells, and the overexpression of HAT1 is linked with CRPC cell proliferation. Moreover, the HAT1 expression is positively correlated with the expression of AR, including both AR-FL (full-length) and AR-V7 (variant 7), which is mainly mediated by a bromodomain containing protein 4 (BRD4) -mediated pathway. Furthermore, knockdown of HAT1 can re-sensitize the response of CRPC cells to ENZ treatment in cells and mouse models. In addition, ascorbate was observed to decrease AR expression through downregulation of HAT1 expression. Collectively, our findings reveal a novel AR signaling regulation pathway in PCa and CRPC and suggest that HAT1 serves as a critical oncoprotein and an ideal target for the treatment of ENZ resistance in CRPC patients.


Asunto(s)
Antineoplásicos/farmacología , Benzamidas/farmacología , Proliferación Celular/efectos de los fármacos , Histona Acetiltransferasas/metabolismo , Nitrilos/farmacología , Feniltiohidantoína/farmacología , Neoplasias de la Próstata Resistentes a la Castración/patología , Receptores Androgénicos/metabolismo , Animales , Antineoplásicos/uso terapéutico , Benzamidas/uso terapéutico , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Histona Acetiltransferasas/antagonistas & inhibidores , Histona Acetiltransferasas/genética , Humanos , Masculino , Ratones , Ratones Endogámicos NOD , Nitrilos/uso terapéutico , Feniltiohidantoína/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , ARN Interferente Pequeño/uso terapéutico , Receptores Androgénicos/genética , Transducción de Señal , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Trasplante Heterólogo
15.
J Exp Clin Cancer Res ; 40(1): 59, 2021 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-33546726

RESUMEN

BACKGROUND: c-Myc, a well-established oncogene, plays an important role in the initiation and progression of various cancers, including prostate cancer. However, its mechanism in cancer cell remains largely unknown and whether there exist a deubiquitinase targeting c-Myc also remains elusive. METHODS: Bioinformatic analysis and shRNA screening methods were used to identify potential deubiquitinases that correlate with c-Myc gene signature. Cell proliferation and viability were measured by Cell-Counting-Kit 8 and colony formation assays. A mouse xenograft model of PC3 cells was established to confirm the function of USP16 in vivo. The interaction between USP16 and c-Myc protein was assessed by co-immunoprecipitation and protein co-localization assays. Immunohistochemistry staining was performed to detect the expression of USP16, Ki67, and c-Myc in xenograft tissues and clinical tumour tissues. Furthermore, the correlation between USP16 and c-Myc was confirmed by RNA sequencing. RESULTS: Functional analyses identified USP16, known as a deubiquitinase, was strongly correlated with the c-Myc gene signature. Depletion of USP16 was shown to significantly suppress the growth of PCa cells both in vitro and in vivo. Co-immunoprecipitation and ubiquitination assays confirmed that USP16 served as a novel deubiquitinase of c-Myc and overexpression of c-Myc significantly rescued the effects of USP16 disruption. Immunohistochemistry staining and RNA-seq tactics were further used to confirm the positive correlation between USP16 and c-Myc expression. Expression of USP16 in human PCa tissues was higher than that seen in normal prostate tissues and its high expression was found associated with poor prognosis. CONCLUSIONS: USP16 serves as a novel deubiquitinase of c-Myc. Downregulation of USP16 markedly suppressed PCa cell growth both in vitro and in vivo. USP16 regulates PCa cell proliferation by deubiquitinating and stabilizing c-Myc, making it a potential therapeutic candidate for the treatment of PCa.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Ubiquitina Tiolesterasa/metabolismo , Ubiquitinación/genética , Animales , Proliferación Celular , Humanos , Masculino , Ratones , Ratones Desnudos , Transfección
16.
Urol Int ; 105(1-2): 124-130, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33176322

RESUMEN

PURPOSE: Sexual dysfunction in women with overactive bladder (OAB) syndrome has been an important topic, while the sexual satisfaction of partners has not been fully investigated. Our aim was to explore the association between the severity of OAB with female sexual dysfunction and sexual satisfaction of partners. METHODS: A total of 323 patients with OAB recruited in our hospital were included in our study from September 2017 to March 2019. Data were collected by Overactive Bladder Symptom Score (OABSS) questionnaire, self-designed questionnaire for basic characteristics; Female Sexual Function Index (FSFI); and sexual satisfaction survey for sex partners of patients. χ2 test or 1-way ANOVA was used to compare the variables among groups. Logistic regression analysis was performed to analyze the severity of OAB with female sexual dysfunction and sexual satisfaction of partners. The correlations between different OABSS domains with female sexual dysfunction and sexual satisfaction of partners were assessed. RESULTS: All the patients were classified into mild (n = 107), moderate (n = 98), severe (n = 118) OAB group based on OABSS. Most of the basic information were similar among groups, except for BMI, highest education, occupation, fertility, and history of pelvic floor surgery. After multiple factors correction, the severity of OAB, exercise frequency, and the history of pelvic floor surgery were statistically associated with the female sexual dysfunction and sexual satisfaction of partners. Urgency score was significantly correlated with female sexual dysfunction, and the urge incontinence was most significantly associated with the sexual satisfaction of partners. CONCLUSION: Severe OAB was closely associated with female sexual dysfunction and sexual satisfaction of partners. The urgency and urge incontinence should be focused for OAB management.


Asunto(s)
Orgasmo , Disfunciones Sexuales Fisiológicas/complicaciones , Parejas Sexuales , Vejiga Urinaria Hiperactiva/complicaciones , Adulto , Correlación de Datos , Femenino , Humanos , Masculino , Autoinforme , Índice de Severidad de la Enfermedad
17.
Zhonghua Nan Ke Xue ; 26(4): 321-325, 2020 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33351298

RESUMEN

OBJECTIVE: To investigate the application of a metamorphic mechanism-based special dressing system (MMDS) in improving the prognosis and comfort of the patient after scrotal surgery. METHODS: We included 48 cases of scrotal surgery using the traditional method for postoperative dressing from June 2017 to June 2018 (the control group) and another 48 cases employing MMDS postoperatively from July 2018 to June 2019 (the MMDS group). We observed the differences between the two groups of patients in the incidence of scrotal edema, pain score, hospitalization days, patients' satisfaction, and dressing time. RESULTS: The scrotal edema score showed no statistically significant difference between the MMDS and control groups at 24 hours after operation (P > 0.05) but remarkably lower in the former than in the latter group at 48 hours (1.42 ± 0.5 vs 2.27 ± 0.7, P < 0.05) and 72 hours postoperatively (1.35 ± 0.2 vs 2.25 ± 0.7, P < 0.05). The MMDS group, compared with the controls, also exhibited a lower pain score (2.2 ± 1.0 vs 3.4 ± 1.5, P < 0.05), shorter hospitalization time (ï¼»5.96 ± 1.2ï¼½ vs ï¼»9.13 ± 2.3ï¼½ d, P < 0.05) and higher satisfaction score (98.1 ± 1.6 vs 92.8 ± 2.8, P < 0.05), as well as shorter dressing time at 24, 48 and 72 hours after operation (P < 0.05). CONCLUSIONS: The metamorphic mechanism-based special dressing system is a safe, efficient, simple and feasible method for dressing after scrotal surgery, which can effectively promote recovery and improve the quality of life of the patients.


Asunto(s)
Vendajes , Edema/prevención & control , Calidad de Vida , Escroto/cirugía , Estudios de Casos y Controles , Humanos , Masculino , Pronóstico , Resultado del Tratamiento
18.
Onco Targets Ther ; 13: 3739-3750, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32440143

RESUMEN

BACKGROUND: Eukaryotic initiation factor 3 (eIF3) is the largest translation initiation factor, and oncogenic roles have been discovered for its subunits, including the f subunit (ie, eIF3f), in various human cancers. However, the roles of eIF3f in the development and progression of prostate cancer (PCa) have not been reported. MATERIALS AND METHODS: We performed in silico analysis to screen the expression of eIF3 subunits. Relevant shRNAs were used to knock down eIF3 subunits in 22Rv1 cells and cell proliferation was analyzed. eIF3f expression in PCa specimens was confirmed by immunohistochemistry. eIF3f knockdown was established to evaluate the effects of eIF3f on cell proliferation in vitro and in vivo. RNA-seq, bioinformatics analysis and Western blotting were applied to explore the molecular details underlying the biological function of eIF3f in PCa cells. shRNA-resistant eIF3f and myristoylated-Akt were used to rescue the effects of eIF3f disturbance on PCa cells. RESULTS: Functional analyses confirmed that eIF3f is essential for PCa proliferation. Notably, the expression of eIF3f was found to be elevated in human PCa tissues as well as in PCa cell lines. eIF3f silencing significantly suppressed the growth of PCa cells, both in vitro and in vivo. eIF3f expression was positively correlated with Akt signaling activity in RNA-seq profiles and published prostate cohorts. Knockdown of eIF3f markedly reduced the levels of phosphorylated Akt in PCa cells. Exogenous expression of shRNA-resistant eIF3f in eIF3f knockdown cells restored Akt phosphorylation levels and cell growth. Importantly, rescue experiments revealed that ectopic expression of myristoylated-Akt partially alleviated the suppressive effects of eIF3f disturbance with respect to the growth of PCa cells. CONCLUSION: These results suggested that eIF3f has an oncogenic role in PCa, mediated at least partially through the regulation of Akt signaling, and that eIF3f represents a potential target for the inhibition of PCa growth and progression.

19.
Onco Targets Ther ; 13: 1303-1310, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32103997

RESUMEN

BACKGROUND: KLF16, a member of the Kruppel-like factor (KLF) family, functions in the regulation of dopaminergic transmission, metabolism, and endocrinology. However, the role of KLF16 in prostate cancer (PCa) remains unknown. METHODS: We screened the expression of KLFs in PCa based on bioinformatics analysis. The protein levels of KLF16 in PCa specimens were confirmed by immunohistochemistry. Inhibiting KLF16 by RNA interference with shRNA was used to determine the effects of KLF16 on PCa cell growth in vitro and in vivo. RNA sequencing was used to investigate the signaling regulated by KLF16 in PCa. Bioinformatics analysis was also used to determine the possible correlations of KLF16 and signaling in PCa cohorts. RESULTS: Bioinformatics analysis showed that KLF16 may be required for PCa development. Notably, the expression of KLF16 was elevated in human PCa tissues. In vitro and in vivo experiments both demonstrated that depleting KLF16 significantly inhibited the growth of PCa cells. Downregulation of KLF16 significantly decreased the expression of MYC signaling in PCa cells. Furthermore, KLF16 expression was correlated with MYC signaling activity. CONCLUSION: KLF16 was overexpressed in PCa tissues compared to normal tissues. KLF16 knockdown suppressed PCa cell growth in vitro and in vivo, and a deficiency of KLF16 inhibited activation of MYC signaling.

20.
Urology ; 138: 129-133, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31972178

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of 1470-nm Diode Laser Enucleation of the Prostate (DiLEP) in patients with benign prostatic hyperplasia continuously receiving oral anticoagulants or antiplatelet drugs. METHODS: From January 2016 to June 2017, 144 patients were submitted to 1470-nm DiLEP, including 49 (34.0%) continuously administered anticoagulants or antiplatelet drugs per os due to cardiac and/or cerebrovascular diseases (group A), while 95 (66.0%) were not (group B). Evaluation was performed preoperatively, and at postoperative 3, 6, and 12 months, respectively. Patient baseline features, operative data, perioperative complications, and postsurgical outcomes were assessed. RESULTS: Both groups had comparable preoperative parameters, except age (77.3 ± 7.5 vs 73.2 ± 8.8 years, P = .007). Meanwhile, surgical time, sodium decrease, catheterization duration, and hospital stay markedly differed between the 2 groups. In comparison with group B, group A patients had statistically higher blood loss (14.9 ± 7.3 g/L vs 10.2 ± 7.0 g/L, P < .001) and increased bladder irrigation time (21.1 ± 10.9 hours vs 16.1 ± 9.0 hours, P = .004). One case required blood transfusion in group A, because of moderate anemia preoperatively. Both groups showed similar blood transfusion and complication rates. International Prostate Symptom Score, quality of life score, maximum flow rate, and postvoid residual were markedly improved in both groups at 3-, 6-, and 12-month follow-up postoperatively compared with baseline values. However, no statistically significant differences were observed between the 2 groups in various assessment parameters at follow-up (P > .05). CONCLUSION: These findings demonstrated that 1470-nm DiLEP is efficient and safe in benign prostatic hyperplasia cases receiving continuous oral anticoagulant or antiplatelet drugs. Anticoagulation therapy did not significantly influence the results and complication rates.


Asunto(s)
Anticoagulantes/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Hemorragia Posoperatoria/epidemiología , Prostatectomía/efectos adversos , Hiperplasia Prostática/cirugía , Administración Oral , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Trastornos Cerebrovasculares/complicaciones , Trastornos Cerebrovasculares/tratamiento farmacológico , Cardiopatías/complicaciones , Cardiopatías/tratamiento farmacológico , Humanos , Láseres de Semiconductores/efectos adversos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Tempo Operativo , Inhibidores de Agregación Plaquetaria/administración & dosificación , Hemorragia Posoperatoria/etiología , Próstata/patología , Próstata/cirugía , Prostatectomía/instrumentación , Prostatectomía/métodos , Hiperplasia Prostática/complicaciones , Estudios Retrospectivos , Resultado del Tratamiento
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