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1.
Urol Oncol ; 41(7): 327.e9-327.e18, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37208228

RESUMO

PURPOSE: To explore the role of circadian clock gene NR1D1 (REV-erbα) in bladder cancer (BC). METHODS: Firstly, the association of NR1D1 level with clinical characteristics and prognosis was investigated among patients diagnosed with BC. Secondly, CCK-8, transwell, and colony formation experiments were performed among BC cells treated with Rev-erbα agonist (SR9009), as well as lentivirus and siRNA, for which NR1D1 were overexpressed (OE) and knocked down (KD), respectively. Thirdly, cell cycle and apoptosis were tested by flowcytometry. PI3K/AKT/mTOR pathway proteins were determined in OE-NR1D1 cells. Finally, OE-NR1D1 and OE-Control BC cells were subcutaneously implanted in BALB/c nude mice. The tumor size and protein levels were compared between groups. A P < 0.05 was considered as statistically significant. RESULTS: Patients with NR1D1 positive status had a longer disease-free survival than those with negative expression. The cell viability, migration, and colony formation of BC cells after treated with SR9009 were significantly suppressed. OE-NR1D1 cells had obviously inhibited cell viability, migration, and colony formation, while those were found strengthened in KD-NR1D1 cells. Besides, KD-NR1D1 cells were observed with a lower proportion of dead cells and G0/G1 cells, but a higher ratio of G2/M. The changes of p-AKT, p-S6, p-4EBP1, and FASN involved in PI3K/AKT/mTOR pathway were detected in OE- and KD-NR1D1 BC cells. Finally, in vivo data demonstrated that overexpression of NR1D1 suppressed the tumorigenicity of BC cells. CONCLUSION: NR1D1 played a role of tumor suppressor and it might become a novel target for the treatment of BC.


Assuntos
Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares , Neoplasias da Bexiga Urinária , Animais , Camundongos , Camundongos Nus , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismo , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TOR , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Humanos
3.
Urol J ; 17(5): 480-485, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32715451

RESUMO

PURPOSE: Several studies have compared the short-term outcomes of extraperitoneal robot-assisted laparoscopic radical prostatectomy (EP-RALP) and transperitoneal RALP (TP-RALP). The study was designed to evaluate the long-term outcomes of the two methods. MATERIALS AND METHODS: A prospective, non-randomized study was conceived. The demographics and operative outcomes of patients with prostate cancer undergoing RALP from September 2016 to January 2017 at our center were included. RESULTS: A total of eighty-six patients were enrolled. Thirty-seven patients underwent EP-RALP, and forty-nine patients received TP-RALP. No significant difference was observed in age, body mass index, pathological T stage, pathological N stage, M stage, 2014 International Society of Urological Pathology group, comorbidities or American Society of Anesthesiologists score. A lower preoperative prostate-specific antigen (PSA) was detected in the EP-RALP group. No significant differences were observed in overall operation time, robotic console time, surgical margin status, postoperative hospitalization time, drop of hemoglobin and complications, except that patients with EP-RALP had a shorter time to first exsufflation after surgery than those with TP-RALP (41.35 vs. 51.80 h, P < .001). Postoperative PSA until 12 months was deemed comparable in both groups. Complete continence until 12 months after surgery was desirable but not significantly different between two groups (75.0% in EP- RALP vs. 86.7%. in TP-RALP, P = .179). CONCLUSION: The long-term outcomes of EP-RALP were analogous to those of TP-RALP. Therefore, EP-RALP is an alternative approach for patients with localized prostate cancer.


Assuntos
Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Peritônio , Estudos Prospectivos , Prostatectomia/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
4.
Onco Targets Ther ; 12: 7157-7164, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564900

RESUMO

PURPOSE: To evaluate the association between tertiary Gleason pattern 5 (TGP5) and biochemical recurrence (BCR) in patients with prostate cancer (PCa) with a Gleason score (GS) of 7 after radical prostatectomy (RP). PATIENTS AND METHODS: This retrospective study identified 350 patients who received RP and were graded as GS 7 (3+4 or 4+3) at the West China Hospital from January 2009 to December 2017. Initially, the patients were divided into two groups, TGP5 absence and TGP5 presence, independent of Gleason score. We further stratified the patients by adding the Gleason score into four groups: GS 3+4, GS 3+4/TGP5, GS 4+3, and GS 4+3/TGP5. Cox proportional-hazards models were used to evaluate the association between the status of TGP5 and BCR after adjusting for the confounding factors. RESULTS: The risk of BCR was significantly higher in patients with TGP5 when compared to patients without TGP5 (P=0.04, HR=2.17 95%, Cl: 1.03-4.59). For patients with primary Gleason pattern 4, the risk of BCR for patients with Gleason 4+3/TGP5 was statistically significantly higher than Gleason 4+3 (P=0.04, HR=2.45, 95% Cl: 1.04-5.76). CONCLUSION: The TGP5 in patients with GS 7 had strong association with the risk of BCR and was an independent predictor for BCR. Further research on larger data sets is needed to confirm these findings.

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