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1.
Int Braz J Urol ; 50(1): 7-19, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38166218

RESUMO

PURPOSE: This study aims to evaluate the safety and efficacy of ultrasound-guided balloon dilation compared to non-balloon dilation for percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: A systematic review and meta-analysis were conducted by searching PubMed, EMBASE, and the Cochrane Library. Results were filtered using predefined inclusion and exclusion criteria as described and meta-analysis was performed using Review Manager 5.4 software. RESULTS: A total of six studies involving 1189 patients who underwent PCNL were included. The meta-analysis results demonstrated that compared to non-balloon dilation, balloon dilation was associated with reduced haemoglobin drop [mean difference (MD) = -0.26, 95% CI = -0.40 ~ -0.12, P = 0.0002], decreased transfusion rate [odds ratio (OR) = 0.47, 95% CI = 0.24 ~ 0.92, P = 0.03], shorter tract establishment time (MD = -1.30, 95% CI = -1.87 ~ -0.72, P < 0.0001) and shorter operation time (MD = -5.23, 95% CI = -10.19 ~ -0.27, P = 0.04). CONCLUSIONS: Overall, ultrasound-guided balloon dilatation offered several advantages in PCNL procedures. It facilitated faster access establishment, as evidenced by shorter access creation time. Additionally, it reduced the risk of kidney injury by minimizing postoperative haemoglobin drop and decreasing the need for transfusions. Moreover, it enhanced the efficiency of surgery by reducing the operation time. However, it is important to note that the quality of some included studies was subpar, as they did not adequately control for confounding factors that may affect the outcomes. Therefore, further research is necessary to validate and strengthen these findings.


Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Nefrostomia Percutânea , Humanos , Nefrolitotomia Percutânea/métodos , Dilatação , Rim , Cálculos Renais/cirurgia , Ultrassonografia de Intervenção , Hemoglobinas , Nefrostomia Percutânea/métodos , Resultado do Tratamento
2.
Lab Invest ; 103(7): 100148, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37059268

RESUMO

In multiple clinical trials, immune checkpoint blockade-based immunotherapy has shown significant therapeutic efficacy in bladder cancer (BCa). Sex is closely related to the incidence rate and prognosis of BCa. As one of the sex hormone receptors, the androgen receptor (AR) is a well-known key regulator that promotes the progression of BCa. However, the regulatory mechanism of AR in the immune response of BCa is still unclear. In this study, the expression of AR and programmed death ligand 1 (PD-L1) was negatively correlated in BCa cells, clinical tissues, and tumor data extracted from The Cancer Genome Atlas Bladder Urothelial Carcinoma cohort. A human BCa cell line was transfected to alter the expression of AR. The results show that AR negatively regulated PD-L1 expression by directly binding to AR response elements on the PD-L1 promoter region. In addition, AR overexpression in BCa cells significantly enhanced the antitumor activity of cocultured CD8+ T cells. Injection of anti-PD-L1 monoclonal antibodies into C3H/HeN mice significantly suppressed tumor growth, and stable expression of AR dramatically enhanced the antitumor activity in vivo. In conclusion, this study describes a novel role of AR in regulating the immune response to BCa by targeting PD-L1, thus providing potential therapeutic strategies for immunotherapy in BCa.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Animais , Humanos , Camundongos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/tratamento farmacológico , Camundongos Endogâmicos C3H , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Receptores Androgênicos/uso terapêutico , Neoplasias da Bexiga Urinária/patologia
3.
BMC Urol ; 23(1): 130, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37525149

RESUMO

BACKGROUND: Cystinuria and xanthinuria are both rare genetic diseases involving urinary calculi. However, cases combining these two disorders have not yet been reported. CASE PRESENTATION: In this study, we report a case of cystinuria with xanthine stones and hyperuricemia. The 23-year-old male patient was diagnosed with kidney and ureteral stones, solitary functioning kidney and hyperuricemia after admission to the hospital. The stones were removed by surgery and found to be composed of xanthine. CONCLUSION: Genetic testing by next-generation sequencing technology showed that the patient carried the homozygous nonsense mutation c.1113 C> A (p.Tyr371*) in the SLC3A1 gene, which was judged to be a functionally pathogenic variant. Sanger sequencing revealed that the patient's parents carried this heterozygous mutation, which is a pathogenic variant that can cause cystinuria. The 24-h urine metabolism analysis showed that the cystine content was 644 mg (<320 mg/24 h), indicating that the patient had cystinuria, consistent with the genetic test results. This case shows that cystinuria and xanthine stones can occur simultaneously, and provides evidence of a possible connection between the two conditions. Furthermore, our findings demonstrate the potential value of genetic testing using next-generation sequencing to effectively assist in the clinical diagnosis and treatment of patients with urinary calculi.


Assuntos
Sistemas de Transporte de Aminoácidos , Cistinúria , Humanos , Masculino , Adulto Jovem , Cistinúria/genética , Sistemas de Transporte de Aminoácidos/genética , Xantina , Cálculos Renais , Hiperuricemia , Códon sem Sentido , Testes Genéticos , Linhagem , Feminino
4.
Ren Fail ; 45(1): 2158870, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36637005

RESUMO

INTRODUCTION: The aim of this study was to evaluate the association between recurrence-free survival (RFS) and perirenal fat thickness (PFT) in a cohort of Chinese population with unilateral nephrolithiasis. METHODS: We retrospectively reviewed the medical records of 81 patients with unilateral nephrolithiasis in our center from January 2019 to June 2019. PFT measured on computed tomography (CT) scans was evaluated. Kaplan-Meier curves and log-rank tests were used to assess significant differences in RSF between high-PFT and low-PFT groups within sexes. Univariable and multivariable Cox regression analyses were used to evaluate the potential risk factors for renal stone recurrence. RESULTS: High PFT was significantly associated with high BMI and hyperlipidemia (p = .003 and.047, respectively). The PFT of stone-bearing kidney was significantly greater than PFT of non-stone-bearing kidney (0.77 ± 0.60 cm vs. 0.67 ± 0.58 cm, p = .002) . During the follow-up periods (median 31 months), 21 (25.9%) patients experienced ipsilateral renal stone recurrence. In addition, Kaplan-Meier survival curves showed that patients with low PFT had a significant better RFS than those with high PFT (p = .012). In the univariable Cox analyses, male sex and high PFT were significantly associated with a poor RFS (p = .042 and .018, respectively). Moreover, both male sex and high PFT retained significance in the multivariable analyses (p = .045 and .020, respectively). CONCLUSIONS: Our findings suggested that PFT is a noninvasive and feasible parameter, which may help in the risk stratification of renal stone recurrence in the follow-up periods.


Assuntos
Cálculos Renais , Nefrolitíase , Humanos , Masculino , População do Leste Asiático , Rim , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/epidemiologia , Nefrolitíase/diagnóstico por imagem , Nefrolitíase/epidemiologia , Obesidade , Recidiva , Estudos Retrospectivos , Fatores de Risco , China
5.
J Cell Biochem ; 120(2): 1492-1502, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30304555

RESUMO

Exosomal microRNAs (miRNAs) are suggested to reflect molecular changes occurring in their cells of origin and are potential indicators in the early detection of cancers. This study aimed to determine whether certain exosomal miRNAs from tumor tissue can be used as noninvasive biomarkers for clear cell renal cell carcinoma (ccRCC). Based on ccRCC miRNA expression profiles and the literature, we selected six miRNAs (miR-210, miR-224, miR-452, miR-155, miR-21, and miR-34a) and analyzed their expression in tissues, sera, and serum exosomes through quantitative real-time polymerase chain reaction in hypoxia-induced (with CoCl2 ) renal cell lines. miR-210, miR-224, miR-452, miR-155, and miR-21 were upregulated in tumor tissues compared with normal tissues. Serum miR-210 and miR-155 levels were higher in patients with ccRCC than in healthy controls (HCs). Furthermore, only exosomal miR-210 was significantly upregulated in patients with ccRCC than in HCs. Moreover, receiver operating characteristic (ROC) curve analysis revealed an area under the ROC curve of 0.8779 (95% confidence interval, 0.7987-0.9571) and a sensitivity and specificity of 82.5% and 80.0%, respectively. Moreover, exosomal miR-210 was upregulated at an advanced stage, and Fuhrman grade and metastasis decreased significantly one month after surgery. Acute hypoxia exposure activates miR-210 and release of exosomes with upregulated miR-210 in both normal and tumor RCC cell lines and interferes with vacuole membrane protein 1 mRNA expression, especially in the metastatic ccRCC cell line. In conclusion, Serum exosomal miR-210 originating from tumor tissue has potential as a novel noninvasive biomarker for the detection and prognosis of ccRCC.

6.
Cancer Cell Int ; 19: 328, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827402

RESUMO

BACKGROUND: Circular RNA Itchy E3 ubiquitin protein ligase (Circ-ITCH) is significantly down-regulated in various kinds of tumors, however, the mechanisms of action and functions of circITCH gene in prostate cancer (PC) are still under investigation. The mail goal of this research was to study the functional role of Circ-ITCH gene in prostate cancer and to illuminate the function role of circ-ITCH gene in prostate cancer by targeting miR-17-5p/HOXB13. METHODS: RT-qPCR was applied to measure the expression level of circ-ITCH and miR-17-5p in PC cell lines and tissues. CCK-8, colony formation, Brdu incorporation labeling and flow cytometry assays were applied to detect the effects of circ-ITCH and miR-17-5p on proliferation and cell apoptosis. Target gene prediction and screening, luciferase reporter gene assays were utilized to assess downstream target genes of miR-17-5p and Circ-ITCH. The protein and expression of HOXB13 gene were measured by Western blotting and RT-qPCR. RESULTS: CircITCH was significantly reduced in PC cell lines and tissues. Low circITCH expression level was highly related with preoperative PSA, tumor stage and Gleason score. Overexpression of circITCH can inhibit the malignant phenotype of prostate cancer. There was a high negative relationship between the expression level of microRNA-17-5p and circITCH in PC tissues, however, there existed a positive relationship between the expression of HOXB13 and circITCH. CircITCH acted as a sponge of miR-17-5p to increase HOXB13 gene expression. In addition, miR-17-5p overexpression or HOXB13 silencing can reduce the carcinogenic effects of circICCH in prostate cancer. CONCLUSION: CircITCH promoted prostate cancer progression by regulating the HOXB13/miR-17-5p axis, and circITCH have a potential usage as therapeutic target for PC tumors.

8.
Int Braz J Urol ; 45(5): 901-909, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31626518

RESUMO

PURPOSE: It has been reported that calcitonin receptor (CALCR) gene polymorphisms might be associated with calcium stone urolithiasis. Owing to mixed and inconclusive results, we conducted a meta-analysis to summarize and clarify this association. MATERIALS AND METHODS: A systematic search of studies on the association between CALCR gene polymorphisms and calcium stone urolithiasis susceptibility was conducted in databases. RESULTS: Odds ratios and 95% confi dence intervals were used to pool the effect size. Five articles were included in our meta-analysis. CONCLUSIONS: CALCR rs1801197 might be associated with increased risk of calcium stone urolithiasis. There is insufficient data to fully confirm the association between CALCR rs1042138 and calcium stone urolithiasis susceptibility. Well-designed studies with larger sample size and more subgroups are required to validate the risk identified in the current meta-analysis.


Assuntos
Polimorfismo de Nucleotídeo Único , Receptores da Calcitonina/genética , Urolitíase/genética , Cálcio/metabolismo , Feminino , Estudos de Associação Genética , Humanos , Masculino , Medição de Risco , Fatores de Risco
9.
Mol Med ; 24(1): 40, 2018 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-30134837

RESUMO

BACKGROUND: This study aimed to investigate the effect of over-expressing circular RNA CEP128 (circCEP128) on cell functions and explore the molecular mechanism of which in bladder carcinoma. METHODS: The differentially expressed circRNAs and mRNAs in bladder carcinoma cells and cells in adjacent tissues were screened out using microarray analysis. Expression levels of circRNAs and mRNAs in tissues and cells were determined by qRT-PCR. Expression of SOX11 was detected by western blot. Luciferase reporter assay and RNA pull-down assay were used to investigate the interactions between the specific circRNA, miRNA and mRNA. Cell cycle and apoptosis were measured using flow cytometry after transfection. MTT assay was also performed to detect the cell proliferation. RESULTS: In present study, circCEP128 and SOX11 were observed significantly up-regulated in bladder cancer tissues, while the expression of miR-145-5p was decreased in cancer samples compared to normal samples. Cytoscape was used to visualize circCEP128-miRNA-target gene interactions based on the TargetScan and circular RNA interactome, which revealed that circCEP128 served as a sponge of miR-145-5p and indirectly regulated SOX11. Knockdown of circCEP128 induced the inhibition of cell proliferation and the increased bladder cancer cell apoptosis rate. CONCLUSIONS: CircCEP128 functions as a ceRNA for miR-145-5p, which could up regulates SOX11 and further promotes cell proliferation and inhibits cell apoptosis of bladder cancer.


Assuntos
MicroRNAs , RNA , Fatores de Transcrição SOXC , Neoplasias da Bexiga Urinária , Apoptose , Linhagem Celular , Proliferação de Células , Humanos , RNA Circular , Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXC/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo
10.
Amino Acids ; 49(7): 1247-1254, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28474127

RESUMO

The forkhead box (FOX) transcription factor is a family of tumor suppressors that negatively regulates the tumorigenesis activity of prostate cancer; stabilization of FOX-DNA complex architecture has been recognized as a new and promising strategy for sensitizing cancer chemotherapy. Here, we described a systematic method that combined in silico analysis and in vitro assay to investigate the intermolecular interaction between FOX DNA-binding domain (DBD) and its cognate DNA partner. The structural and energetic information harvested from the molecular investigation were used to guide high-throughput virtual screening against a structurally diverse, nonredundant library of natural product compounds, aiming at discovery of novel small-molecule medicines that can conformationally stabilize and promote FOX-DNA recognition and interaction. The screening identified a number of theoretically promising hits, which were then examined by using fluorescence anisotropy assay to determine their binding potency for FOX DBD domain. The antitumor activity of identified high-affinity compounds was also tested at cellular level. Structural dynamics analysis found that the small-molecule stabilizers can shift the conformational equilibrium of FOX DBD to DNA-bound state, thus promoting the protein domain to bind tightly with its DNA partner.


Assuntos
Antineoplásicos/farmacologia , DNA de Neoplasias , Fatores de Transcrição Forkhead , Simulação de Dinâmica Molecular , Proteínas de Neoplasias , Neoplasias da Próstata , Antineoplásicos/química , Linhagem Celular Tumoral , DNA de Neoplasias/química , DNA de Neoplasias/farmacologia , Fatores de Transcrição Forkhead/química , Fatores de Transcrição Forkhead/metabolismo , Humanos , Masculino , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Neoplasias da Próstata/química , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Domínios Proteicos
11.
World J Surg Oncol ; 13: 311, 2015 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-26542246

RESUMO

BACKGROUND: The aim of the study is to investigate whether body mass index (BMI) affected pathological characteristics and biochemical recurrence (BCR) of prostate cancer after radical prostatectomy in Chinese men. METHODS: Medical records of 211 Chinese patients who underwent radical prostatectomy between 2006 and 2014 were retrospectively reviewed, with follow-up time of 24.5 ± 27.0 months. Multivariate logistic and Cox regression analyses were applied to address the impact of BMI on adverse pathological outcomes and BCR following prostatectomy. A meta-analysis of published studies from MEDLINE or EMBASE was conducted to determine the relationship between BMI and BCR following prostatectomy among Asian populations. RESULTS: Higher BMI was positively correlated with higher biopsy Gleason score (odds ratios (OR) 1.163, 95 % confidence interval (CI) 1.023-1.322, P = 0.021) and pathological Gleason score (OR 1.220, 95 % CI 1.056-1.410, P = 0.007) in multivariate analysis. BCR was detected in 48 patients (22.7 %). Multivariate Cox proportional hazards analysis revealed that higher BMI (hazard ratio (HR) 1.145, 95 % CI 1.029-1.273, P = 0.013) and prostate-specific antigen (HR 1.659, 95 % CI 1.102-2.497, P = 0.015) levels were independent predictors of BCR. The meta-analysis enrolled eight Asian studies of 4145 patients treated by radical prostatectomy. Based on random-effects approach, a 5 kg/m(2) increase in BMI was correlated with 28 % higher risk of BCR (HR 1.22, 95 % CI 0.86-1.72) without statistical significance. CONCLUSIONS: The present study suggested that higher BMI was an independent risk factor for a higher Gleason score, as well as an independent predictor of BCR after radical prostatectomy in Chinese patients. Meta-analysis of Asian studies also indicated that obese patients, although without statistical significance, might be more likely to suffer from BCR.


Assuntos
Povo Asiático , Índice de Massa Corporal , Recidiva Local de Neoplasia/sangue , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/cirurgia , Idoso , Idoso de 80 Anos ou mais , China , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Obesidade/sangue , Obesidade/complicações , Obesidade/patologia , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Fatores de Risco
12.
Front Surg ; 8: 707022, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646858

RESUMO

Background: ShuoTong ureteroscopy (Sotn-ureteroscopy, ST-URS), a new lithotripsy operation method developed on the basis of ureteroscopy, is widely used to treat ureteral stones in China. Its composition includes rigid ureteral access sheath, standard mirror, lithotripsy mirror, and ShuoTong perfusion aspirator (ST-APM). Here, we compared the efficacy and safety of the ST-URS and the flexible ureteroscope (F-URS) holmium laser lithotripsy in the treatment of unilateral upper ureteral calculi. Methods: Retrospective analysis was conducted on the clinical data of 280 patients who met the inclusion 1) urinary tract CT was diagnosed with unilateral single upper ureteral calculi above the L4 lumbar spine; 2) patient age was from 18 to 80 years old; 3) patients were informed and consented to this study; and 4) patients were approved by the hospital ethics committee (proof number: KY-2019-020) and the exclusion criteria for unilateral upper ureteral calculi in the First Affiliated Hospital of Xiamen University from January 2018 to November 2020, and they were divided into the ST-URS group and the flexible ureteroscopy (F-URS) group. Results: The stone-free rate of 1 day after operation of the ST-URS group was significantly higher than the F-URS group (63.71 vs. 34.62%, P < 0.0001). The operative time (38.45 vs. 46.18 min, P = 0.005) and hospitalization cost (27,203 vs. 33,220 Yuan, P < 0.0001) of the ST-URS group were significantly lower than the F-URS group. There were no significant differences in the success rate of ureteral access sheath placement, operative blood loss, stone-free rate of 1 month after operation, postoperative complications, postoperative hospital stay, and postoperative visual analog scale (VAS) pain score between the two groups (P > 0.05). In subgroups of a diameter of calculi ≥ 1.5 cm, calculi CT numerical value ≥ 1,000 Hounsfield unit and the preoperative hydronephrosis range ≥ 3.0 cm, ST-URS shows more advantages in the operative time, stone-free rate of 1 day after the operation, the hospitalization cost, and the incidence of postoperative complications. Conclusion: In unilateral upper ureteral stones treated with a holmium laser, compared with the simple F-URS, the ST-URS has a shorter operative time, lower hospitalization cost, and a higher stone-free rate of 1 day after the operation, suggesting that the ST-URS could be more widely applied in clinics.

13.
Curr Med Sci ; 41(1): 140-144, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33582918

RESUMO

The effect of preoperative Double-J (DJ) ureteral stenting before flexible ureterorenoscopy (FURS) in the treatment for urinary stones was evaluated. We retrospectively enrolled 306 consecutive patients who underwent FURS from Jan. 2014 to Dec. 2017. All the patients were classified into two groups according to whether they had DJ ureteral stenting before FURS. Baseline characteristics (age, sex, stone location, stone size, surgical success rate, operation time, stone-free rate of the first day after surgery, stone-free rate of the first month after surgery, total complication rate) were compared using Chi-square test for categorical variables and Kruskal-Wallis test for continuous variables. In total, 306 patients were included in this study. The group of DJ stenting before FURS included 203 (66.3%) patients, and non-DJ stenting before FURS was observed in 103 (33.7%) patients. The group of DJ stenting before FURS was significantly associated with a shorter operation time (53.8 vs. 59.3 min, P<0.001), a higher stone-free rate of the first day after surgery (69.0% vs. 51.5%, P=0.003). However, statistical significant differences were not found in the age, sex, stone location, stone size, surgical success rate, stone-free rate of the first month after surgery (89.2% vs. 81.6%, P=0.065) and total complication rate (5.4% vs. 9.7%, P=0.161) between the two groups. Preoperative DJ ureteral stenting before FURS could reduce the operation time and increase stone-free rate of the first day after surgery. However, it might not benefit the stone-free rate of the first month after surgery and reduce the complication rate. Preoperative DJ stenting should be not routinely performed.


Assuntos
Complicações Pós-Operatórias/epidemiologia , Ureteroscopia/métodos , Cálculos Urinários/cirurgia , Cateterismo Urinário/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Ureteroscopia/efeitos adversos , Cateterismo Urinário/efeitos adversos , Cateterismo Urinário/instrumentação , Cateteres Urinários/efeitos adversos , Cateteres Urinários/normas
14.
J Cancer ; 11(5): 1115-1124, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31956358

RESUMO

Emerging evidences have shown that Dihydroartemisinin (DHA), used in malaria treatment, possess anti-cancer activity. However, the study of its potential functional roles and the anti-cancer mechanisms in bladder cancer is limited. We performed this study to elucidate the influence of DHA in the biological behavior of bladder cancer cells and tried to explore the molecular mechanism. The results of CCK-8 assay showed that DHA significantly inhibited bladder cancer cell 5637, UMUC3 and T24 proliferation and the inhibitory effect is dose- and time- dependent. Further mechanism study showed that DHA performed its function via down-regulating the expression of histone demethylase KDM3A and inducing p21 expression. Moreover, wound healing and transwell migration/invasion assays revealed that DHA inhibited the ability of migration and metastasis in bladder cancer cell line T24. Finally, flow cytometry and colony formation assays demonstrated that DHA significantly promoted apoptosis of T24 cells and suppressed tumorigenesis as expected. Taken together, our study identifies the anti-cancer capacity of DHA in bladder cancer and explores the underlying mechanism.

15.
Cancer Manag Res ; 12: 2719-2729, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368149

RESUMO

PURPOSE: Prostate cancer (PCa) is the third most common cancer in men and the second leading cause of cancer-related death in men. DLX1 belongs to the DLX homeobox family and exhibits antitumor activity in many kinds of tumors. MicroRNAs (miRNAs) play important roles in the progression of cancer. However, whether miRNAs affect the development of PCa by targeting DLX1 has not been determined. In this study, we aimed to investigate the role of miR-489-3p in the regulation of DLX1 expression and PCa progression and to provide a potential therapeutic target for PCa treatment. METHODS AND MATERIALS: The Cancer Genome Atlas database was used to analyze the divergent expression of DLX1 in carcinomas and adjacent normal tissues. The expression level of DLX1 in malignant and normal prostate cells was also measured using RT-qPCR and Western blotting. A dual-luciferase reporter assay was performed to determine whether miR-489-3p directly targets DLX1. We transfected 22Rv1 and DU145 cells with miR-489-3p mimics to overexpress miR-489-3p and then evaluated its effect on cellular function. MTT, EdU, colony formation and cell cycle assays were used to evaluate cell growth. JC-1 and ROS assays with flow cytometry were performed to indirectly analyze apoptosis. Transwell assays were conducted to investigate metastasis. RESULTS: The expression level of DLX1 was upregulated in both PCa tissues and cell lines. MiR-489-3p directly targeted DLX1 and downregulated its expression. Overexpression of miR-489-3p significantly suppressed cell growth. MiR-489-3p induced apoptosis through mitochondrial function impairment. Overexpression of miR-489-3p also inhibited cell migration and invasion. DLX1 overexpression reversed the above effects induced by miR-489-3p. CONCLUSION: We identified the involvement of the miR-489-3p/DLX1 pathway in PCa for the first time. In this pathway, miR-489-3p acts as a tumor suppressor by negatively regulating the expression of DLX1. MiR-489-3p may be a potential therapeutic target for PCa treatment.

16.
Cancer Biol Ther ; 21(8): 709-716, 2020 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-32449441

RESUMO

Patients with urothelial carcinoma (UC) of the bladder have a high risk of death in China. However, a lack of comprehensive molecular profiling in Chinese Han population hinders the development of targeted therapies for bladder cancer. In our present study, we collected fresh bladder tumors from low-grade (T1, N0, M0, G1) non-muscle invasive bladder cancer (NMIBC) patients (n = 16) and high-grade (T2-4, N0, M0, Gx) muscle-invasive bladder cancer (MIBC) patients (n = 16) with their paired normal bladder tissues, and subjected the total genomic DNAs to targeted next-generation sequencing (NGS) for 94 cancer-associated genes. NGS results showed that 30.9% of detected genes (29/94) was mutated in 32 urothelial carcinoma bladder tissues. Furthermore, our results and ICGC database showed that FGFR3, KMT2D, TP53, KDM6A, and ARID1A were the most frequently mutated genes in UC patients. Of note, NMIBC and MIBC displayed distinguishable genomic alterations. FGFR3, KMT2D, AKT1, ARID1A, and STAG2 were the most frequently mutated genes in NMIBC patients, whereas mutations of TP53, CREBBP, FGFR3, KDM6A, KMT2D, and ARID1A were frequently detected in MIBC. Intriguingly, gene ontology and clustering analysis revealed that these frequently mutated genes were highly enriched in signaling pathways responsible for cancer development. Taken together, the mutation frequency of genes associated with UC development in NMIBC and MIBC was screened out in Chinese Han population and elucidation of the related mechanisms provides theoretical basis and technical support for the development of early diagnosis and therapeutic strategies in UC.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Mutação , Neoplasias da Bexiga Urinária/patologia
17.
Cancer Biol Ther ; 21(1): 4-11, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31597506

RESUMO

People who suffers renal angiomyolipoma (AML) has a low quality of life. It is widely known that genetic factors including TSC2 mutation contribute to certain populations of renal AML-bearing patients. In this study, we are the first to identify novel TSC2 mutations in one Chinese renal epithelioid AML patient: c.2652C>A; c.2688G>A based on sequencing result from biopsy tissue. These two somatic mutations cause a translational stop of TSC2, which leads to mTORC1 activation. Given the fact that activation of mTORC1 ensures cell growth and survival, we applied its inhibitor, FDA-approved everolimus, to this woman. After months of treatment with everolimus, Computer-Tomography (CT) scan results showed that everolimus successfully reduced tumor growth and distal metastasis and achieved partial response (PR) to everolimu according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). Further Blood Routine Examination results showed the concentration of red cell mass, hemoglobin, white blood cell (WBC), platelets and hematocrit (HCT) significantly returned to normal levels indicating patients with these two TSC2 mutations could be effectively treated by everolimus.


Assuntos
Angiomiolipoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Células Epitelioides/efeitos dos fármacos , Everolimo/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Angiomiolipoma/genética , Angiomiolipoma/patologia , Células Epitelioides/metabolismo , Células Epitelioides/patologia , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteína 2 do Complexo Esclerose Tuberosa
18.
Clin Genitourin Cancer ; 17(5): e1036-e1047, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31281063

RESUMO

BACKGROUND: The aim of this study was to evaluate the association between periprostatic fat thickness (PPFT) and time to castration-resistant prostate cancer (CRPC) in newly diagnosed patients with prostate cancer (PCa) treated with androgen deprivation therapy (ADT). PATIENTS AND METHODS: We retrospectively reviewed the medical records of 150 patients with PCa treated with ADT at our hospital between June 2011 and June 2017. PPFT measured on magnetic resonance imaging (MRI) and PPFT/periprostatic fat volume (PPFV) measured on computed tomography (CT) were evaluated. Kaplan-Meier curves and log-rank tests were used to assess significant differences in time to CRPC between the 2 groups (high PPFT vs. low PPFT, determined by PPFT > or < the median value, respectively). Univariable and multivariable Cox regression analyses were employed to identify the potential prognostic factors for survival. RESULTS: The median value of PPFT measured on MRI was 0.555 cm. PPFT was significantly associated with PPFV measured on CT images (with a correlation coefficient of 0.825; P < .001). A total of 66 patients (44%) progressed to CRPC during the follow-up period. Patients with high PPFT (measured on MRI) showed a significantly shorter PFS than patients with low PPFT. Multivariable Cox analysis demonstrated that T stage, presence of distant metastasis, shorter time to prostate-specific antigen nadir, higher prostate-specific antigen nadir, Gleason score (greater than 4 + 4), and high PPFT were significantly associated with shorter PFS. CONCLUSIONS: PPFT is significantly associated with PPFV measured on CT images. PPFT measured on MRI is a readily available and significant predictor of time to CRPC in patients with PCa receiving ADT as the primary treatment.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Antagonistas de Androgênios/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Humanos , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Estudos Retrospectivos
19.
Cancer Biomark ; 25(2): 161-168, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31104008

RESUMO

LINC01638 lncRNA is known as an oncogenic lncRNA in triple negative breast cancer. However, the role of LINC01638 lncRNA in other diseases is unknown. In the present study we observed that plasma levels of LINC01638 lncRNA and Notch1 were upregulated in prostate carcinoma patients comparing with healthy controls. LINC01638 lncRNA and Notch1 were positively correlated in prostate carcinoma patients but not in healthy controls. Upregulation of LINC01638 lncRNA distinguished prostate carcinoma patients from healthy controls. LINC01638 lncRNA overexpression in prostate carcinoma cells led to upregulated Notch1 expression. Notch1 overexpression also led to increased expression level of LINC01638 lncRNA. Both LINC01638 lncRNA and Notch1 overexpression promoted the proliferation, migration and invasion of prostate carcinoma cells. We concluded that LINC01638 lncRNA might promote the proliferation, migration and invasion of prostate carcinoma cells by interacting with Notch1.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata/genética , RNA Longo não Codificante/genética , Receptor Notch1/genética , Adulto , Idoso , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Transição Epitelial-Mesenquimal/genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Interferência de RNA , Curva ROC , Receptor Notch1/metabolismo
20.
Int. braz. j. urol ; 50(1): 7-19, Jan.-Feb. 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1558042

RESUMO

ABSTRACT Purpose: This study aims to evaluate the safety and efficacy of ultrasound-guided balloon dilation compared to non-balloon dilation for percutaneous nephrolithotomy (PCNL). Materials and methods: A systematic review and meta-analysis were conducted by searching PubMed, EMBASE, and the Cochrane Library. Results were filtered using predefined inclusion and exclusion criteria as described and meta-analysis was performed using Review Manager 5.4 software. Results: A total of six studies involving 1189 patients who underwent PCNL were included. The meta-analysis results demonstrated that compared to non-balloon dilation, balloon dilation was associated with reduced haemoglobin drop [mean difference (MD) = -0.26, 95% CI = -0.40 ~ -0.12, P = 0.0002], decreased transfusion rate [odds ratio (OR) = 0.47, 95% CI = 0.24 ~ 0.92, P = 0.03], shorter tract establishment time (MD = -1.30, 95% CI = -1.87 ~ -0.72, P < 0.0001) and shorter operation time (MD = -5.23, 95% CI = -10.19 ~ -0.27, P = 0.04). Conclusions: Overall, ultrasound-guided balloon dilatation offered several advantages in PCNL procedures. It facilitated faster access establishment, as evidenced by shorter access creation time. Additionally, it reduced the risk of kidney injury by minimizing postoperative haemoglobin drop and decreasing the need for transfusions. Moreover, it enhanced the efficiency of surgery by reducing the operation time. However, it is important to note that the quality of some included studies was subpar, as they did not adequately control for confounding factors that may affect the outcomes. Therefore, further research is necessary to validate and strengthen these findings.

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