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1.
Drug Des Devel Ther ; 18: 2693-2712, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974121

RESUMO

Background: Chronic kidney disease (CKD) is a significant worldwide health concern that leads to high mortality rates. The bioactive substance costunolide (CTD) has demonstrated several pharmacological effects and holds promise as a CKD treatment. This study aims to investigate the impact of CTD on CKD and delve into its mechanisms of action. Methods: Unilateral ureteral obstruction (UUO) methods and renal fibrosis mice models were created. Various concentrations of CTD were injected into UUO mice models to investigate the therapeutic effects of CTD on renal fibrosis of mice. Then, renal morphology, pathological changes, and the expression of genes related to fibrosis, inflammation and ferroptosis were analysed. RNA sequencing was utilized to identify the main biological processes and pathways involved in renal injury. Finally, both overexpression and inhibition of IKKß were studied to examine their respective effects on fibrosis and inflammation in both in vitro and in vivo models. Results: CTD treatment was found to significantly alleviate fibrosis, inflammation and ferroptosis in UUO-induced renal fibrosis mice models. The results of RNA sequencing suggested that the IKKß acted as key regulatory factor in renal injury and the expression of IKKß was increased in vitro and in vivo renal fibrosis model. Functionally, down-regulated IKKß expression inhibits ferroptosis, inflammatory cytokine production and collagen deposition. Conversely, IKKß overexpression exacerbates progressive renal fibrosis. Mechanistically, CTD alleviated renal fibrosis and inflammation by inhibiting the expression of IKKß and attenuating IKKß/NF-κB pathway. Conclusion: This study demonstrates that CTD could mitigate renal fibrosis, ferroptosis and inflammation in CKD by modulating the IKKß/NF-κB pathway, which indicates targeting IKKß has an enormous potential for treating CKD.


Assuntos
Insuficiência Renal Crônica , Sesquiterpenos , Animais , Humanos , Masculino , Camundongos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fibrose/tratamento farmacológico , Quinase I-kappa B/metabolismo , Quinase I-kappa B/antagonistas & inibidores , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Sesquiterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Obstrução Ureteral/tratamento farmacológico , Obstrução Ureteral/metabolismo
2.
Investig Clin Urol ; 65(3): 286-292, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38714519

RESUMO

PURPOSE: To determine the non-contrast computer tomography imaging features of pyonephrosis and evaluate the predictive value of Hounsfield units (HUs) in different hydronephrotic region slices. MATERIALS AND METHODS: We retrospectively reviewed data from patients with hydronephrosis who had renal-ureteral calculi. All patients were categorized into pyonephrosis and simple hydronephrosis groups. Baseline characteristics, the mean HU values in the maximal hydronephrotic region (uHU) slice, and the range of uHU in different slices (ΔuHU) were compared between the two groups. Univariate and multivariate analyses were performed to identify risk factors for pyonephrosis. RESULTS: Among the 181 patients enrolled in the current study, 71 patients (39.2%) were diagnosed with pyonephrosis. The mean dilated pelvis surface areas were comparable between patients with pyonephrosis and simple hydronephrosis (822.61 mm² vs. 877.23 mm², p=0.722). Collecting system debris (p=0.022), a higher uHU (p=0.038), and a higher ΔuHU (p<0.001) were identified as independent risk factors for pyonephrosis based on multivariate analysis. The ΔuHU sensitivity and specificity were 88.7% and 86.4%, respectively, at a cutoff value of 6.56 (p<0.001), whereas the sensitivity and specificity for detecting pyonephrosis at a uHU cutoff value of 7.96 was 50.7% and 70.9%, respectively (p=0.003). CONCLUSIONS: Non-contrast computer tomography was shown to accurately distinguish simple hydronephrosis from pyonephrosis in patients with obstructive uropathy. Evaluation of the ΔuHU in different slices may be more reliable than the uHU acquired from a single slice in predicting pyonephrosis.


Assuntos
Hidronefrose , Valor Preditivo dos Testes , Pionefrose , Tomografia Computadorizada por Raios X , Humanos , Pionefrose/diagnóstico por imagem , Pionefrose/complicações , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Hidronefrose/diagnóstico por imagem , Hidronefrose/etiologia , Adulto , Idoso , Cálculos Ureterais/complicações , Cálculos Ureterais/diagnóstico por imagem , Obstrução Ureteral/diagnóstico por imagem , Obstrução Ureteral/complicações , Obstrução Ureteral/etiologia , Cálculos Renais/complicações , Cálculos Renais/diagnóstico por imagem
3.
Front Med (Lausanne) ; 10: 1163371, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38034526

RESUMO

Purpose: This study aimed to evaluate the efficacy and safety of same-session flexible ureteroscopy (fURS) for the treatment of bilateral upper urinary tract stones and to examine the influence of stone load on the outcome of same-session fURS, stratifying by total diameter of stones (TDS) ≤30 mm vs. >30 mm. Patients and methods: We retrospectively reviewed all cases of same-session fURS performed for bilateral upper urinary tract stones at four institutions between January 2017 and September 2020. All patients were divided into two groups based on TDS, ≤30 mm and >30 mm. Data on patient demographics, stone characteristics, surgical results, and complications were collected and analyzed for differences between the two groups. Stone-free rate (SFR) was defined as patients endoscopically stone-free or with radiological fragments <2 mm of each renal unit. Results: A total of 121 patients with bilateral upper urinary tract stones underwent same-session fURS, consisting of 73 patients in the TDS ≤ 30 mm group and 48 patients in the TDS > 30 mm group. The mean bilateral stone size was 28.2 ± 12.2 mm (range: 9.1-38.4 mm), with a mean operating time of 97.1 ± 39.6 min (range: 19-220 min). The SFR was 54.5% after the first fURS, and SFR increased to 97.5% after re-fURS for residual stones. The operation time for the TDS > 30 mm group was longer than that of the TDS ≤ 30 mm group (85.1 ± 36.5 vs. 115.4 ± 37.4 min, p < 0.001). The SFR after the first fURS was significantly lower in the TDS > 30 mm group than in the TDS ≤ 30 mm group (25.0% vs. 73.9%, p < 0.001). Although there was no statistically significant difference in overall SFR between the two groups (93.7% vs. 100%, p = 0.060), the rate of re-fURS for residual stones was higher in the TDS > 30 mm group than in the TDS ≤ 30 mm group (75% vs. 26%, p < 0.001). There were no significant differences in length of hospital stay (LOS) (2.2 ± 0.7 vs. 2.3 ± 1.0, p = 0.329) or complication rate (10.9% vs. 14.6%, p = 0.582) between the two groups. Conclusion: The results suggested that same-session fURS can be effectively performed with a low complication rate. A higher SFR after the first fURS can be achieved in the case of bilateral upper urinary tract stones with TDS ≤ 30 mm, and priority should be given to same-session fURS.

5.
Front Pharmacol ; 13: 984080, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36313281

RESUMO

Immune checkpoint inhibitors have emerged as a novel therapeutic strategy for many different tumors, including clear cell renal cell carcinoma (ccRCC). However, these drugs are only effective in some ccRCC patients, and can produce a wide range of immune-related adverse reactions. Previous studies have found that ccRCC is different from other tumors, and common biomarkers such as tumor mutational burden, HLA type, and degree of immunological infiltration cannot predict the response of ccRCC to immunotherapy. Therefore, it is necessary to further research and construct corresponding clinical prediction models to predict the efficacy of Immune checkpoint inhibitors. We integrated PBRM1 mutation data, transcriptome data, endogenous retrovirus data, and gene copy number data from 123 patients with advanced ccRCC who participated in prospective clinical trials of PD-1 inhibitors (including CheckMate 009, CheckMate 010, and CheckMate 025 trials). We used AI to optimize mutation data interpretation and established clinical prediction models for survival (for overall survival AUC: 0.931; for progression-free survival AUC: 0.795) and response (ORR AUC: 0.763) to immunotherapy of ccRCC. The models were internally validated by bootstrap. Well-fitted calibration curves were also generated for the nomogram models. Our models showed good performance in predicting survival and response to immunotherapy of ccRCC.

6.
BMC Urol ; 22(1): 150, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104697

RESUMO

OBJECTIVES: To investigate the outcomes of internal ureteral stents in comparison with ureteroscopy (URS) for pregnant women with urolithiasis. DATA SOURCES: Relevant studies published from January 1980 to June 2022 were identified through systematic literature searches of MEDLINE, EMBASE, Web of Science and the Cochrane Library. METHODS OF STUDY SELECTION: A total of 499 studies were initially identified. We included pregnant women in any stages of gestation who underwent double-J (D-J) stent insertion only or ureteroscopy for the treatment of urolithiasis; for a study to be included, the number of participants needed to exceed 10. This systematic review was registered on the PROSPERO website (Reference: CRD42020195607). RESULTS: A total of 25 studies were identified with 131 cases undergoing serial stenting and 789 cases undergoing URS. The pooled operative success rate was 97% for D-J stent insertion and 99% for URS. Only a few patients passed stones spontaneously after serial D-J stenting. The pooled stone free rate (SFR) in URS operations was about 91%. For internal ureteral stent therapy, the rate of normal fertility outcomes was 99%, although the pooled incidence of complications was approximately 45%. For group receiving URS treatment, the rate of normal fertility outcome was 99% and the pooled incidence of complications was approximately 1%. However, the pooled rate of premature birth and abortion were the similar between the two groups (< 1%); the rate of serious complications was also similar between the two groups. CONCLUSIONS: Although internal ureteral stents may cause more minor complications, both ureteroscopy and internal ureteral stents showed had low rates of adverse effects on fertility outcomes when used to treat pregnant women with symptomatic urolithiasis. Evidence suggests that URS may have a greater advantage for pregnant patients with urinary stones when conditions permit. Since, it has been proven to be safe and effective, internal ureteral stents could be considered in emergency or other special situations.


Assuntos
Ureter , Cálculos Ureterais , Urolitíase , Feminino , Humanos , Gravidez , Stents/efeitos adversos , Ureter/cirurgia , Cálculos Ureterais/terapia , Ureteroscopia/métodos , Urolitíase/complicações , Urolitíase/cirurgia
7.
Andrologia ; 54(7): 1581-1591, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35413135

RESUMO

METTL3 was known to run through the whole cycle of RNA. It relied on m6A modification in the mRNAs of cancer-related genes to regulate tumour progression. The development of prostate cancer cells could be promoted by METTL3 via hedgehog pathway. Recent studies had shown that the effect of METTL3 on non-coding RNA was mainly dependent on the modification of m6A. However, it is still unknown whether METTL3 promotes tumour development through this mechanism in prostate cancer. The expression of METTL3 in prostate cancer tissues and cells was analysed by qRT-PCR and Western blot assays. CCK-8 assay, colony formation assay, wound-healing assay and transwell assays were conducted to detect the impact of METTL3 on cell proliferation, migration and invasion. Nude mice tumour models were built to evaluate the role of METTL3 in tumorigenesis. N6-methyladenosine (m6A) RNA immunoprecipitation assay (MeRIP) and co-immunoprecipitations assays were performed to verified that METTL3 upregulated the m6A level, interacted with microprocessor protein DGCR8, recognized the m6A modification of pre-miR-182 to regulate its maturation.METTL3 was highly expressed in prostate cancer, and knockdown of METTL3 significantly inhibited cell proliferation, migration, invasion and tumorigenesis, while overexpression of METTL3 promoted cell proliferation, migration, invasion and tumorigenesis in PCa. In addition, we found that METTL3 upregulating the level of m6A, and interacted with DGCR8 to recognize the m6A modification of pre-miR-182 to regulate its splicing and maturation and promote the high expression of miRNA. Our study suggests that METTL3 could be used in targeted therapies for PCa.


Assuntos
Metiltransferases , MicroRNAs , Neoplasias da Próstata , Animais , Carcinogênese , Linhagem Celular Tumoral , Proteínas Hedgehog/metabolismo , Humanos , Masculino , Metiltransferases/genética , Metiltransferases/metabolismo , Camundongos , Camundongos Nus , MicroRNAs/genética , Neoplasias da Próstata/genética , Proteínas de Ligação a RNA/genética
8.
Biomed Res Int ; 2022: 8218053, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35321070

RESUMO

Background: The association between arterial stiffness and cardiovascular risk in CKD and ESRD patients is well established. However, the relationship between renal function estimation and properties of large arteries is unclear due to the four different methods used to quantify glomerular filtration. This study investigated the relationship between carotid-femoral pulse wave velocity (c-fPWV), as a measure of arterial stiffness, and accepted metrics of renal function. Methods: This cross-sectional study was conducted in 431 health examination individuals in China, enrolled from January 2017 to June 2019. c-fPWV and blood pressure were measured, and blood samples were obtained for all participants. Four different methods were used to determine the estimated glomerular filtration rate (eGFR) as described by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations: (i) CKD-EPISCr formula based on SCr, (ii) CKD-EPICysC formula based on CysC, (iii) CKD-EPISCr/CysC formula based on Cr and CysC, and (iv) MDRD. Results: Of all of the study participants (average age 53.1 ± 13.0 years, 68.1% male), 23.7% had diabetes mellitus and 66.6% had hypertension. The average eGFR values determined by the CKD-EPISCr, CKD-EPICysC, CKD-EPISCr/CysC, and MDRD equations were 91.9 ± 15.6, 86.8 ± 21.4, 89.6 ± 18.3, and 90.7 ± 16.6 ml/min/1.73m2, respectively. c-fPWV was significantly and negatively correlated with eGFR determined by CKD-EPISCr (r = -0.336, P < 0.001), CKD-EPICysC (r = -0.385, P < 0.001), CKD-EPISCr/CysC (r = -0.378, P < 0.001), and MDRD (r = -0.219, P < .001) equations. After adjusting for confounding factors, c-fPWV remained significantly and negatively correlated with eGFR determined by the CKD-EPICysC equation (ß = -0.105, P = 0.042) and significantly and positively correlated with age (ß = 0.349, P ≤ 0.01), systolic pressure (ß = 0.276, P ≤ 0.01), and hypoglycemic drugs (ß = 0.101, P = 0.019). Conclusion: In a health examination population in China, c-fPWV is negatively correlated with eGFR determined by four different equations; however, only the metric of eGFR determined by the equation for CKD-EPICysC showed an independent relation with c-fPWV.


Assuntos
Insuficiência Renal Crônica , Rigidez Vascular , Adulto , Idoso , Creatinina , Estudos Transversais , Dieta , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso
9.
Transl Androl Urol ; 10(6): 2447-2453, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34295731

RESUMO

BACKGROUND: Increasing evidence has demonstrated aquaporins (AQPs) to be critical players in carcinogenesis. Here, we aimed to explore the role of hydropenia in the progression of bladder cancer (BCa), as well as to assess the expression of AQP1, AQP3, and AQP4 in bladder tissues from hydropenic and N-methyl-N-nitrosourea (MNU)-treated rats. METHODS: An orthotopic BCa model was induced by administering Sprague Dawley rats with MNU. A hydropenic rat model was established by administrating rats with 2/3 of the amount of water given to the control group. At week 8, the rats were sacrificed and their bladder tissues were collected. Then, pathological alterations in the rat bladders were assessed by hematoxylin and eosin staining. The RNA and protein expression levels of AQP1, AQP3, and AQP4 were determined by using qRT-PCR and western blot assays. RESULTS: All of the rats (100%) administrated with MNU developed tumors, of which 5 were large (diameter, 0.5-1.0 cm), 10 were medium (diameter, 0.2-0.5 cm), and 5 were small (diameter, <0.2 cm) in size. The tumors were nodular and cauliflower shaped, with multiple satellite focus, and were accompanied by bleeding, ulcers, stones, and residual urine. Hematoxylin and eosin staining revealed that the bladder mucosa was incomplete, with a large amount of necrotic tissue and obvious leukocytic infiltration. The tumor volume in the MNU + hydropenia group was significantly larger than that in the MNU group. Noticeably, hydropenia exacerbated pathological changes induced by MNU administration. QRT-PCR and western blot analysis revealed that the MNU group, hydropenia group, and MNU + hydropenia group had significantly increased levels of AQP1, AQP3, and AQP4 compared to the control group, with the most dramatic increase seen in the MNU + hydropenia group. CONCLUSIONS: Hydropenia exacerbates pathological alterations induced by MNU in rats with orthotopic BCa by increasing the expression levels of AQP1, AQP3, and AQP4. This study reveals a possible mechanism of the occurrence of BCa.

10.
Chin Med J (Engl) ; 134(10): 1209-1214, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33813518

RESUMO

BACKGROUND: The optimal treatment for large impacted proximal ureteral stones remains controversial. The aim of this study was to evaluate the efficacy, safety, and potential complications of mini-percutaneous nephrolithotomy (MPCNL) and retroperitoneal laparoscopic ureterolithotomy (RPLU) in the treatment of impacted proximal ureteral stones with size greater than 15 mm. METHODS: A total of 268 patients with impacted proximal ureteral stones greater than 15 mm who received MPCNL or RPLU procedures were enrolled consecutively between January 2014 and January 2019. Data on surgical outcomes and complications were collected and analyzed. RESULTS: Demographic and ureteral stone characteristics found between these two groups were not significantly different. The surgical success rate (139/142, 97.9% vs. 121/126, 96.0%, P = 0.595) and stone-free rate after 1 month (139/142, 97.9% vs. 119/126, 94.4%, P = 0.245) of RPLU group were marginally higher than that of the MPCNL group, but there was no significant difference. There was no significant difference in the drop of hemoglobin between the two groups (0.8 ±â€Š0.6 vs. 0.4 ±â€Š0. 2 g/dL, P = 0.621). The mean operative time (68.2 ±â€Š12.5 vs. 87.2 ±â€Š16.8 min, P = 0.041), post-operative analgesics usage (2/121, 1.7% vs. 13/139, 9.4%, P = 0.017), length of hospital stay after surgery (2.2 ±â€Š0.6 vs. 4.8 ±â€Š0.9 days, P < 0.001), double J stent time (3.2 ±â€Š0.5 vs. 3.9 ±â€Š0.8 days, P = 0.027), time of catheterization (1.1 ±â€Š0.3 vs. 3.5 ±â€Š0.5 days, P < 0.001), and time of drainage tube (2.3 ±â€Š0.3 vs. 4.6 ±â€Š0.6 days, P < 0.001) of MPCNL group were significantly shorter than that of the RPLU group. The complication rate was similar between the two groups (20/121, 16.5% vs. 31/139, 22.3%, P = 0.242). CONCLUSIONS: MPCNL and RPLU have similar surgical success and stone clearance in treating impacted proximal ureteral stones greater than 15 mm, while patients undergoing MPCNL had a lower post-operative pain rate and a faster recovery.


Assuntos
Laparoscopia , Nefrolitotomia Percutânea , Cálculos Ureterais , Humanos , Tempo de Internação , Nefrolitotomia Percutânea/efeitos adversos , Espaço Retroperitoneal/cirurgia , Resultado do Tratamento , Cálculos Ureterais/cirurgia
11.
BMC Surg ; 21(1): 118, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676481

RESUMO

BACKGROUND: It is proposed a new running suture technique called Needle Adjustment Free (NAF) technique, or PAN suture. The efficiency and the safety were evaluated in laparoscopic partial nephrectomy. METHODS: This new running suture technique avoids the Needle Adjustment method used in traditional techniques. The new continuous suture technique (11 patients) was compared with the traditional continuous suture method (33 patients) used in both transperitoneal and retroperitoneal laparoscopic partial nephrectomy (LPN) in terms of suture time (ST), warm ischemia time (WIT), blood loss (BL), open conversion rate and post-op discharge time, post-op bleeding, post-op DVT, ΔGFR (affected side, 3 months post-op). Differences were considered significant when P < 0.05. RESULTS: ST in the PAN suture group was 30.37 ± 16.39 min, which was significant shorter (P = 0.0011) than in the traditional technique group which was 13.68 ± 3.33 min. WIT in the traditional technique group was 28.73 ± 7.89 min, while in the PAN suture group was 20.64 ± 5.04 min, P = 0.0028. The BL in entirety in the traditional technique group was 141.56 ± 155.23 mL, and in the PAN suture group was 43.18 ± 31.17 mL (P = 0.0017). BL in patients without massive bleeding in the traditional technique group was significantly greater than in the PAN suture group at 101.03 ± 68.73 mL versus 43.18 ± 31.17 mL (P = 0.0008). The open conversion rate was 0 % in both groups. There was no significant difference between the two groups in postoperative discharge time, post-op bleeding, post-op DVT, ΔGFR (affected side, 3 months post-op). CONCLUSIONS: The NAF running suture technique, or PAN suture, leading to less ST, WIT and BL, which was shown to be more effective and safer than the traditional technique used for LPN. A further expanded research with larger sample size is needed.


Assuntos
Laparoscopia , Nefrectomia , Técnicas de Sutura , Humanos , Nefrectomia/métodos , Resultado do Tratamento
12.
J Endourol ; 35(4): 466-472, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33050738

RESUMO

Objective: To investigate the outcomes of retrograde flexible ureteroscopy in managing parapelvic renal cysts and speculate the factors affecting therapeutic efficacy. Methods: Thirty-eight patients with parapelvic renal cysts were recruited and underwent retrograde flexible ureteroscopy using holmium laser. Parapelvic cysts were divided into peripheral type and central type based on the position of cyst convex to the perirenal tissue. Feasibility and safety were retrospectively evaluated, and cases were analyzed to detect their distinctive characteristics. Independent-sample t-test and chi-square test were undertaken for continuous variables and categorical variables, respectively. Results: Radiologic evidence of success was achieved in 31 (81.58%) cases after a mean follow-up of 14.4 months (range 6-26 months). No significant perioperative complications were identified. There were seven cases with features of peripherally located parapelvic cyst. Four cysts shown as irregular protrusion were unable reduce to less half of previous size. Reductions were recorded in the other three patients with spherically peripheral protrusion. There was significant difference between these two types (p = 0.029). Among the 31 patients with centrally located parapelvic cyst, 28 of these have simple cysts that achieved radiologic success and 3 of the 31 patients were identified as failed cases indicated by renal pelvis enveloped by cyst on radiologic investigation. The success rate of simple cysts was significantly higher than that of the later type (p < 0.001). Conclusion: The location and shape of parapelvic cyst may play a critical role in the radiologic outcome of internal incision and patients with simple central or spherical peripheral cyst may benefit more from retrograde flexible ureteroscopy combined with laser incision.


Assuntos
Doenças Renais Císticas , Ureteroscopia , Humanos , Doenças Renais Císticas/diagnóstico por imagem , Doenças Renais Císticas/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Ureteroscópios
13.
J Exp Clin Cancer Res ; 39(1): 190, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938489

RESUMO

BACKGROUND: Insulin-like growth factor 2 (IGF2) messenger RNA binding protein 3 (IMP3) has been testified to be overexpressed in prostate cancer and strongly related to patients' poor prognosis. However, the functions of IMP3 and the underlying mechanisms in prostate cancer still remain unknown. Therefore, the current study was carried out to reveal the role and molecular mechanism of IMP3 in prostate cancer progression. METHODS: The expression levels of IMP3 in prostate cancer tissues and cells were detected by immunohistochemistry (IHC), western blotting and RT-PCR. CCK-8, clone formation, flow cytometry and in vivo tumor formation assays were used to determine cell growth, clone formation apoptosis and tumorigenesis, respectively. The effect of IMP3 on the expression levels of the key proteins in PI3K/AKT/mTOR signaling pathway, including PIP2, PIP3, p-AKT, AKT, p-mTOR, mTOR, PTEN and BAD activation of was determined by western blotting. IP (Immunoprecipitation) assay was used to evaluate the effects of IMP3 and SMURF1 (SMAD specific E3 ubiquitin protein ligase 1) on the ubiquitination of PTEN protein. RESULTS: IMP3 expression level was significantly increased in prostate cancer tissues and cell lines (LNCap, PC3 and DU145) as compared with the paracancerous normal tissues and cells (RWPE-1), respectively. High expression of IMP3 apparently promoted cell viability, tumorigenesis and inhibited cell apoptosis in prostate cancer LNCap, DU145 and PC3 cell lines. In mechanism, IMP3 upregulation significantly increased the phosphorylation levels of AKT and mTOR, and elevated PIP3 expression level, while induced significant reductions in the expression levels of BAD, PTEN and PIP2. And, IMP3 overexpression increased SMURF1 expression, which facilitated PTEN ubiquitination. In addition, SMURF1 overexpression enhanced prostate cancer cell viability and inhibited cell apoptosis. Silence of SMURF1 rescued the enhancements in cell proliferation and tumorigenesis and the inhibition in cell apoptosis rates induced by IMP3 in prostate cancer DU145 and LNCap cells. CONCLUSION: This study reveals that IMP3 is overdressed in prostate cancer, which accelerates the progression of prostate cancer through activating PI3K/AKT/mTOR signaling pathway via increasing SMURF1-mediated PTEN ubiquitination.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , PTEN Fosfo-Hidrolase/antagonistas & inibidores , Neoplasias da Próstata/patologia , Proteínas de Ligação a RNA/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Ciclo Celular , Movimento Celular , Proliferação de Células , Progressão da Doença , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosforilação , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteínas de Ligação a RNA/genética , Transdução de Sinais , Taxa de Sobrevida , Células Tumorais Cultivadas , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Gland Surg ; 9(6): 2116-2124, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33447562

RESUMO

BACKGROUND: Beforehand transection and suturing (BTS) of the dorsal vascular complex (DVC), a novel technique in non-neurovascular bundle sparing (NVB-sparing) extraperitoneal laparoscopic radical prostatectomy (eLRP), had been proposed; this study aimed to evaluate this technique in clinical laparoscopic procedures. METHODS: Using this new technique, the DVC was transected and sutured after dissection of the pelvic fascia and before dissection of the prostate, especially before ligation of the bilateral prostatic pedicles. This study retrospectively analyzed the data of 90 non NVB-sparing eLRP patients [traditional technique (n=60) and BTS technique (n=30)]. RESULTS: The surgical time in the BTS technique group was 121.73±24.53 min, which was significantly shorter (P=0.0015) than the traditional technique group (144.12±39.68 min). The calculated blood loss in the traditional technique group was 388.45±232.78 mL, and 264.16±130.70 mL in the BTS technique group (P=0.0016). The estimated blood loss in the traditional technique group was 350.34±311.80 mL, which was significantly greater than the BTS technique group (250.33±145.31 mL, P=0.0422). The transfusion rate in the traditional technique group was significantly greater than the BTS technique group (15.00% vs. 0.00%; P=0.0266). The biochemical recurrence rate in traditional technique group was 48.33%, which was higher than in the BTS group (30.00%) (P=0.0465). There was no significant difference between the 2 groups with respect to the pre-operative hemoglobin (Hb) concentration, pre-operative hematocrit (HCT), post-operative Hb concentration, post-operative HCT, ΔHCT, pre-operative blood volume, rectal perforation, open conversion, apical capsule residue, false suture, post-operative bleeding, urinary leakage, re-operation, surgical site infection, post-operative stay, and emission time of urinary incontinence. CONCLUSIONS: In managing the relationship between the DVC and prostate in patients undergoing non NVB-sparing eLRP, the BTS technique was shown to be more effective and safer than the traditional technique.

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