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1.
World J Urol ; 42(1): 273, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38689135

RESUMEN

PURPOSE: The purpose of this study is to evaluate the incidence, risk factors, and salvage management of retrievable covered expandable metallic stent (RCEMS) migration in patients with persistent benign ureter strictures. MATERIALS AND METHODS: A retrospective study was performed on 117 consecutive patients who underwent implantation of RCEMS. Univariate and multivariate analyses were used to identify prognostic factors for stent migration, including stricture location and length, hydronephrosis-cortex ratio, ureteral dilation, and the diameter of the narrowest portion of the stricture. RESULTS: Stent migration occurred in 22 (19.5%) of 113 patients who met inclusion criteria. Of the 22 patients, 16 (72.7%) had ordinary ureteral stricture, 3 (13.6%) had stricture in transplanted kidneys, and 3 patients (13.6%) had ureter stricture in orthotopic neobladders. The mean creatinine for the entire cohorts showed significant improvement (p = 0.038). Multivariate analysis identified the following prognostic factors for migration: distal ureteral stricture (p = 0.006), patients who underwent balloon dilation (p = 0.003), hydronephrosis-cortex ratio ≧10 (p = 0.017), larger diameter of wasting of RCEMS (p < 0.001), and patients with a shorter stricture length (p = 0.006). Salvage management was required in 4 of the 22 patients. The strictures in the remaining 18 patients improved with observation. CONCLUSIONS: Stent migration is more likely to occur in patients with the five prognostic factors mentioned above. Our study developed a nomogram to predict stent migration in patients with ureteral strictures treated using RCEMS.


Asunto(s)
Migración de Cuerpo Extraño , Obstrucción Ureteral , Humanos , Masculino , Estudios Retrospectivos , Obstrucción Ureteral/etiología , Obstrucción Ureteral/terapia , Obstrucción Ureteral/cirugía , Femenino , Persona de Mediana Edad , Migración de Cuerpo Extraño/epidemiología , Factores de Riesgo , Adulto , Anciano , Remoción de Dispositivos , Stents Metálicos Autoexpandibles , Falla de Prótesis , Constricción Patológica , Stents/efectos adversos , Diseño de Prótesis , Adulto Joven
2.
Cancer Sci ; 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38480904

RESUMEN

Dissolving the lipid droplets in tissue section with alcohol during a hematoxylin and eosin (H&E) stain causes the tumor cells to appear like clear soap bubbles under a microscope, which is a key pathological feature of clear cell renal cell carcinoma (ccRCC). Mitochondrial dynamics have been reported to be closely associated with lipid metabolism and tumor development. However, the relationship between mitochondrial dynamics and lipid metabolism reprogramming in ccRCC remains to be further explored. We conducted bioinformatics analysis to identify key genes regulating mitochondrial dynamics differentially expressed between tumor and normal tissues and immunohistochemistry and Western blot to confirm. After the target was identified, we created stable ccRCC cell lines to test the impact of the target gene on mitochondrial morphology, tumorigenesis in culture cells and xenograft models, and profiles of lipid metabolism. It was found that mitofusin 2 (MFN2) was downregulated in ccRCC tissues and associated with poor prognosis in patients with ccRCC. MFN2 suppressed mitochondrial fragmentation, proliferation, migration, and invasion of ccRCC cells and growth of xenograft tumors. Furthermore, MFN2 impacted lipid metabolism and reduced the accumulation of lipid droplets in ccRCC cells. MFN2 suppressed disease progression and improved prognosis for patients with ccRCC possibly by interrupting cellular lipid metabolism and reducing accumulation of lipid droplets.

3.
Mitochondrion ; 75: 101847, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38246334

RESUMEN

Mitochondrial dynamics and autophagy play essential roles in normal cellular physiological activities, while abnormal mitochondrial dynamics and mitochondrial autophagy can cause cancer and related disorders. Abnormal mitochondrial dynamics usually occur in parallel with mitochondrial autophagy. Both have been reported to have a synergistic effect and can therefore complement or inhibit each other. Progress has been made in understanding the classical mitochondrial PINK1/Parkin pathway and mitochondrial dynamical abnormalities. Still, the mechanisms and regulatory pathways underlying the interaction between mitophagy and mitochondrial dynamics remain unexplored. Like other existing reviews, we review the molecular structure of proteins involved in mitochondrial dynamics and mitochondrial autophagy, and how their abnormalities can lead to the development of related diseases. We will also review the individual or synergistic effects of abnormal mitochondrial dynamics and mitophagy leading to cellular proliferation, differentiation and invasion. In addition, we explore the mechanisms underlying mitochondrial dynamics and mitochondrial autophagy to contribute to targeted and precise regulation of mitochondrial function. Through the study of abnormal mitochondrial dynamics and mitochondrial autophagy regulation mechanisms, as well as the role of early disease development, effective targets for mitochondrial function regulation can be proposed to enable accurate diagnosis and treatment of the associated disorders.


Asunto(s)
Autofagia , Dinámicas Mitocondriales , Estructura Molecular , Mitofagia , Ubiquitina-Proteína Ligasas/metabolismo , Mitocondrias/metabolismo
4.
J Endourol ; 37(12): 1241-1247, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37756365

RESUMEN

Introduction: Percutaneous nephrolithotomy (PCNL) is the recommended treatment for 2-4-cm renal stones. Minimally invasive PCNL (MPCNL) with ≤22F sheath was frequently used instead of standard PCNL. MPCNL uses pressurized irrigation to flush out stone fragments through a conventional nephrostomy sheath (cNS), which may result in higher intrarenal pressure (IRP) and longer operating time. The novel vacuum-assisted nephrostomy sheath (vaNS) was developed to mitigate higher IRP and to facilitate stone removal. It might improve the performance of MPCNL. This prospective and randomized trial compares these two sheaths. Materials and Methods: In total, 120 patients with 2-4-cm renal stones were accrued in six tertiary medical centers with equal numbers in 2021. In total, 120 patients underwent mPCNL, 60 using 18F cNS and 60 using 18F vaNS, in a prospective and randomized assignment. The primary outcome measurement is decrease in IRP. The secondary outcome is efficacy in stone retrieval. Results: The IRP was lower with vaNS than with cNS: mean IRP during lithotripsy was 12.0 ± 2.7 mm Hg with vaNS vs 20.4 ± 6.0 mm Hg with cNS, p = 0.000. IRP duration ≥30 mm Hg was shorter with vaNS than with cNS (6.7 ± 7.4 seconds vs 113.4 ± 222.7 seconds, p = 0.001). vaNS has shorter stone removal time (26.9 ± 14.3 minutes vs 35.7 ± 11.8 minutes, p = 0.000). Stone extraction rate was higher (166.4 ± 88.1 mm3/min vs 90.4 ± 31.7 mm3/min, p = 0.000). Stone grasper usage was less (1.4 ± 2.6 vs 11.9 ± 9.7, p = 0.000). vaNS maintained the safety profile. Blood loss, creatinine changes, perioperative complications, and hospital stays were the same in both groups, all p > 0.05. Conclusion: MPCNL for stones 2-4 cm using vaNS has shorter stone removal time, higher stone extraction rate, and less use of stone extractor. vaNS is superior to cNS at reducing IRP and is associated with improved stone free rates at 3 days but not at 30 days postoperatively. The trial was registered with Chinese Clinical Trial Registry (ClinicalTrials.gov, NCT ChiCTR2000039681).


Asunto(s)
Cálculos Renales , Nefrolitotomía Percutánea , Nefrostomía Percutánea , Humanos , Estudios Prospectivos , Resultado del Tratamiento , Cálculos Renales/cirugía
5.
Sci Rep ; 13(1): 12846, 2023 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-37553480

RESUMEN

This work proposed KidneyRegNet, a novel deep registration pipeline for 3D CT and 2D U/S kidney scans of free breathing, which comprises a feature network, and a 3D-2D CNN-based registration network. The feature network has handcrafted texture feature layers to reduce the semantic gap. The registration network is an encoder-decoder structure with loss of feature-image-motion (FIM), which enables hierarchical regression at decoder layers and avoids multiple network concatenation. It was first pretrained with a retrospective dataset cum training data generation strategy and then adapted to specific patient data under unsupervised one-cycle transfer learning in onsite applications. The experiment was performed on 132 U/S sequences, 39 multiple-phase CT and 210 public single-phase CT images, and 25 pairs of CT and U/S sequences. This resulted in a mean contour distance (MCD) of 0.94 mm between kidneys on CT and U/S images and MCD of 1.15 mm on CT and reference CT images. Datasets with small transformations resulted in MCDs of 0.82 and 1.02 mm, respectively. Large transformations resulted in MCDs of 1.10 and 1.28 mm, respectively. This work addressed difficulties in 3DCT-2DUS kidney registration during free breathing via novel network structures and training strategies.


Asunto(s)
Aprendizaje Profundo , Humanos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Respiración , Riñón/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos
6.
Urolithiasis ; 51(1): 89, 2023 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-37347309

RESUMEN

Steinstrasse is an iatrogenic condition resulting from upper urinary tract lithotripsy. Uncomplicated steinstrasse can be managed expectantly. Complex steinstrasse can pose a therapeutic challenge. The vacuum-assisted ureteral access sheath (vaUAS) is similar to a conventional ureteral access sheath but has a side branch that can be connected to vacuum apparatus. This device seemed to be useful in the management of complex steinstrasse. 35 patients with complex steinstrasse, defined as steinstrasse containing ≥ 4 stones or with an aggregate length of ≥ 1.5 cm, were treated in four tertiary medical centers using the vaUAS in this prospective and non-randomized study. The vaUAS was inserted into the ureter over a guidewire until the tip of the vaUAS was in contact with the lowermost stone fragment. A 7 Fr./8.4 Fr. semirigid ureteroscope and a holmium laser were used to pulverize the obstructing stone. All the stone fragments were aspirated either in the space between the scope and the sheath, or through the channel of the sheath by withdrawing the scope to the proximal of the aspiration port. All patients were steinstrasse-free at end of the procedure, as assessed visually and by KUB. At the 3-month follow-up, 94.3% of patients were stone-free with or without a supplementary procedure. There were no perioperative complications. Five patients experienced postoperative fever and/or significant hematuria, and one patient had transient sepsis, a grade I and IV Clavien complication, respectively. vaUAS can be an effective adjunctive device in the management of complex steinstrasse.


Asunto(s)
Litotripsia por Láser , Litotricia , Uréter , Cálculos Ureterales , Humanos , Uréter/cirugía , Cálculos Ureterales/cirugía , Estudios Prospectivos , Litotricia/métodos , Ureteroscopios , Ureteroscopía/efectos adversos , Ureteroscopía/métodos , Resultado del Tratamiento , Litotripsia por Láser/métodos
7.
Liver Int ; 43(6): 1307-1319, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36892418

RESUMEN

BACKGROUND AND AIMS: Liver diseases present a wide range of fibrosis, from fatty liver with no inflammation to steatohepatitis with varying degrees of fibrosis, to established cirrhosis leading to HCC. In a multivariate analysis, serum levels of spermidine were chosen as the top metabolite from 237 metabolites and its levels were drastically reduced along with progression to advanced steatohepatitis. Our previous studies that showed spermidine supplementation helps mice prevent liver fibrosis through MAP1S have prompted us to explore the possibility that spermidine can alleviate or cure already developed liver fibrosis. METHODS: We collected tissue samples from patients with liver fibrosis to measure the levels of MAP1S. We treated wild-type and MAP1S knockout mice with CCl4 -induced liver fibrosis with spermidine and isolated HSCs in culture to test the effects of spermidine on HSC activation and liver fibrosis. RESULTS: Patients with increasing degrees of liver fibrosis had reduced levels of MAP1S. Supplementing spermidine in mice that had already developed liver fibrosis after 1 month of CCl4 induction for an additional 3 months resulted in significant reductions in levels of ECM proteins and a remarkable improvement in liver fibrosis through MAP1S. Spermidine also suppressed HSC activation by reducing ECM proteins at both the mRNA and protein levels, and increasing the number of lipid droplets in stellate cells. CONCLUSIONS: Spermidine supplementation is a potentially clinically meaningful approach to treating and curing liver fibrosis, preventing cirrhosis and HCC in patients.


Asunto(s)
Carcinoma Hepatocelular , Hígado Graso , Cirrosis Hepática , Neoplasias Hepáticas , Animales , Ratones , Autofagia/fisiología , Carcinoma Hepatocelular/patología , Hígado Graso/patología , Fibrosis , Células Estrelladas Hepáticas/metabolismo , Hígado/patología , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/genética , Neoplasias Hepáticas/patología , Proteínas Asociadas a Microtúbulos/metabolismo , Espermidina/farmacología , Espermidina/uso terapéutico , Espermidina/metabolismo , Humanos
8.
Mol Clin Oncol ; 18(1): 4, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36591597

RESUMEN

Long non-coding RNAs (lncRNAs) are involved in the gene expression regulation and usually play important roles in various human cancers, including the renal cell carcinoma (RCC). Dysregulation of certain lncRNAs are associated with the prognosis of patients with RCC. In the present review, several recently studied lncRNAs were discussed and their critical roles in proliferation, migration, invasion, apoptosis and drug resistance of renal cancer cells were revealed. The research on lncRNAs further increases our understanding on the development and progression of RCC. It is suggested that lncRNAs can be used as biomarkers or therapeutic targets for diagnosis or treatment of renal cancer.

9.
World J Urol ; 40(12): 3055-3060, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36208313

RESUMEN

OBJECTIVE: This study aimed to prove the vacuum-assisted ureteral access sheath (vaUAS) is more effective in maintaining a lower IRP than conventional ureteral access sheath (cUAS). MATERIALS: The model consisted of 12 freshly harvested adult porcine kidneys. METHODS: Either a 12/14F cUAS or vaUAS was alternately inserted into the ureter to one cm below the renal pelvis. Upper, middle, and lower calyces were punctured, and 6F pressure monitor catheters were introduced. IRP with cUAS was monitored using various irrigation rates. IRP with vaUAS was monitored with the same irrigation rates; various aspiration pressures; and vent fully closed, 50% closed, and fully open. RESULTS: cUAS with irrigation rate of 50 cc/min resulted in IRP < 30 mmHg. 50 to 100 cc/min should be used with caution. When irrigation rate exceeded 100 cc/min, IRP rose to ≥ 30 mmHg in most instances. With vent closed, vaUAS with vacuum pressure ≥ 150 mmHg and irrigation rate of 50 cc, 100 cc, and 150 cc/min generally resulted in IRPs < 5 mmHg. With vent half closed, vaUAS with vacuum pressure ≥ 300 mmHg and irrigation rate of ≤ 100 cc/min avoided IRP > 30 mmHg. vaUAS with vent open showed limited advantages over cUAS. CONCLUSION: vaUAS maintains lower IRP than cUAS under same parameters. Both vaUAS and cUAS can be used when irrigation is ≤ 50 cc/min vaUAS showed clear advantages over cUAS in maintaining lower pressure when irrigation rate is ≥ 100 cc/min.


Asunto(s)
Uréter , Porcinos , Animales , Ureteroscopios , Ureteroscopía/métodos , Irrigación Terapéutica/métodos , Presión , Riñón
10.
FEBS Open Bio ; 12(11): 2083-2095, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36106411

RESUMEN

Myosin phosphatase target subunit 1 (MYPT1) is a subunit of myosin phosphatase that is capable of regulating smooth muscle contraction. MYPT1 has been reported to be involved in a wide variety of tumours, but its expression and biological functions in renal clear cell carcinoma (ccRCC) remain obscure. Herein, we analysed the relationship between patient clinicopathological characteristics and MYPT1 expression levels in ccRCC patients using a tissue microarray (TMA) and data retrieved from the TCGA-KIRC dataset. MYPT1 was overexpressed or depleted using siRNA in ccRCC cells to assess the effects on migration and invasion in vitro and in vivo. Additionally, RNA-sequencing and bioinformatics analysis were performed to investigate the precise mechanism. MYPT1 expression in ccRCC tissues was observed to be lower than that in nonmalignant tissues (P < 0.05). In addition, MYPT1 downregulation was closely linked to advanced pathological stage (P < 0.05), and poor OS (overall survival; P < 0.05). Functionally, increased expression of MYPT1 suppressed ccRCC migration and invasion in vitro, and inhibited tumour metastasis in vivo. In addition, MYPT1 overexpression exerted its suppressive effects via the MAPK8/N-cadherin pathway in ccRCC.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Cadherinas/genética , Carcinoma de Células Renales/metabolismo , Movimiento Celular/genética , Neoplasias Renales/metabolismo , Fosfatasa de Miosina de Cadena Ligera/genética , Fosfatasa de Miosina de Cadena Ligera/metabolismo , Proteína Quinasa 8 Activada por Mitógenos/metabolismo
11.
Bioact Mater ; 16: 162-172, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35415283

RESUMEN

Moderately regulating vascularization and immune microenvironment of wound site is necessary to achieve scarless wound healing of the skin. Herein, we have prepared an angiogenesis-promoting and scar-preventing band-aid with a core-shell structure, that consists of MXene-loaded nanofibers (MNFs) as the core and dopamine-hyaluronic acid hydrogel (H) as the shell (MNFs@V-H@DA) to encapsulate a growth factor (vascular endothelial growth factor, VEGF, abbreviated as V) and H2S donor (diallyl trisulfide, DATS, abbreviated as DA). The continuous release of DA from this system produced H2S, which would successfully induce macrophages to polarize into M2-lile phenotype, regulating the immune microenvironment and inhibiting an excessive inflammatory response at the wound sites. It is conducive to the proliferation of skin cells, facilitating the wound healing. In addition, an appropriate amount of VEGF can be released from the MXene nanofibrous skeleton by adjusting the time of near-infrared (NIR) light exposure, preventing excessive neovascularization and extracellular matrix deposition at the wound sites. Collectively, this NIR photothermal-responsive band-aid achieved scarless wound healing through gradient-controlled vascularization and a related immune sequential reaction of damaged skin tissue.

12.
Zhonghua Nan Ke Xue ; 27(6): 489-498, 2021 Jun.
Artículo en Chino | MEDLINE | ID: mdl-34914287

RESUMEN

OBJECTIVE: To identify the key genes associated with the pathogenesis of PCa using the bioinformatics approach for a deeper insight into the molecular mechanisms underlying the development and progression of PCa. METHODS: The microarray datasets GSE70770, GSE32571 and GSE46602 were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEG) in the normal prostate tissue and PCa were identified with the GEO2R tool, followed by functional enrichment analysis. A protein-protein interaction (PPI) network of DEGs was constructed by STRING and visualized with the Cytoscape software. RESULTS: A total of 235 DEGs were identified, including 61 up-regulated and 174 down-regulated genes, which were mainly enriched in focal adhesion kinase (FAK), ECM-receptor interaction, and other signaling pathways. From the PPI network were screened out 12 highly connected hub genes, including MYH11, TPM1, TPM2, SMTN, MYL9, VCL, ACTG1, CNN1, CALD1, ACTC1, MYLK and SORBS1, which were shown by hierarchical cluster analysis to be capable of distinguishing prostate cancer from non-cancer tissue. CONCLUSIONS: A total of 235 DEGs and 12 hub genes were identified in this study, which may contribute to a further understanding of the molecular mechanisms of the development and progression of PCa, and provide new candidate targets for the diagnosis and treatment of the malignancy.


Asunto(s)
Biología Computacional , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/genética
13.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 4064-4067, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34892122

RESUMEN

In this paper, we focus on the issue of rigid medical image registration using deep learning. Under ultrasound, the moving of some organs, e.g., liver and kidney, can be modeled as rigid motion. Therefore, when the ultrasound probe keeps stationary, the registration between frames can be modeled as rigid registration. We propose an unsupervised method with Convolutional Neural Networks. The network estimates from the input image pair the transform parameters first then the moving image is wrapped using the parameters. The loss is calculated between the registered image and the fixed image. Experiments on ultrasound data of kidney and liver verified that the method is capable of achieve higher accuracy compared with traditional methods and is much faster.


Asunto(s)
Hígado , Redes Neurales de la Computación , Hígado/diagnóstico por imagen , Ultrasonografía
14.
Front Oncol ; 11: 726671, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34760693

RESUMEN

Clear cell renal cell carcinoma (ccRCC) carrying wild-type Von Hippel-Lindau (VHL) tumor suppressor are more invasive and of high morbidity. Concurrently, competing endogenous RNA (ceRNA) network has been suggested to play an important role in ccRCC malignancy. In order to understand why the patients carrying wild-type VHL gene have high degrees of invasion and morbidity, we applied bioinformatics approaches to identify 861 differentially expressed RNAs (DE-RNAs) between patients carrying wild-type and patients carrying mutant VHL from The Cancer Genome Atlas (TCGA) database, established a ceRNA network including 122 RNAs, and elected six survival-related DE-RNAs including Linc00942, Linc00858, RP13_392I16.1, hsa-miR-182-5p, hsa-miR-183-5p, and PAX3. Examining clinical samples from our hospital revealed that patients carrying wild-type VHL had significantly higher levels of all six RNAs than those carrying mutant VHL. Patients carrying wild-type VHL had significantly higher risk scores, which were calculated based on expression levels of all six RNAs, than those carrying mutant VHL. Patients with higher risk scores had significantly shorter survival times than those with lower risk scores. Therefore, the risk scores serve well to predict malignancy and prognosis.

15.
Int Med Case Rep J ; 14: 765-771, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34803407

RESUMEN

BACKGROUND: Bladder paraganglioma (BPG) is one of the rare neuroendocrine neoplasms that develops from neural crest cells. It categorizes into functional and non-functional types based on the catecholamines secretion. Currently, functional BPG is predicted in advance based on signs and symptoms of catecholamine excess, such as hypertension and "micturition attacks". However, it is often overlooked because of its rareness. Misdiagnosis of a functional tumor may increase the risk of surgical intervention. CASE PRESENTATION: We reported 3 cases of BPG that they were admitted to the hospital due to abdominal pain or gross hematuria. Computed tomography (CT) scans showed space-occupying lesions in the bladders with diameters less than 3cm. There were no typical catecholamine excess symptoms before surgical intervention. Postoperative pathology confirmed BPG after removal of the tumor. We also analyze 69 cases of BPG that has been reported and found that 78.0% cases were functional among the tumors larger than 3cm. CONCLUSION: Bladder tumors larger than 3cm in diameter can serve as an additional predictor of functional BPG. Patients who are suspected should undergo magnetic resonance imaging (MRI) scans, 123/131 metaiodobenzylguanidine (MIBG) scan, and have their catecholamine levels tested. Once the diagnosis is confirmed, patients should be started on fluid replacement therapy and adrenergic blockade to abate the disorders associated with catecholamine excess.

16.
Oncol Lett ; 22(5): 764, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34589143

RESUMEN

Double-stranded RNA-specific adenosine deaminase (ADAR1) is a member of the adenosine deaminases acting on RNA family that catalyze the adenosine-to-inosine editing of double-stranded RNA substrates. Several studies have reported that ADAR1 is closely associated with numerous malignancies. However, the functional roles of ADAR1 in prostate cancer (PCa) have not been fully elucidated. Thus, the present study aimed to investigate the effects of ADAR1 on PCa. The results demonstrated that ADAR1 was highly expressed in PCa tissues compared with normal tissues. Furthermore, the protein expression level of ADAR1 was significantly increased in castration-resistant PCa (CRPCa) tissues and CRPCa cell lines. Thus, these findings indicated that ADAR1 may act as a tumor promoter for PCa development. Next, the potential effects of ADAR1-knockdown on the proliferation of DU145 and PC3 cells were investigated. ADAR1 was knocked down via small interfering RNA transfection, which was found to exert antitumor effects on DU145 and PC3 cells at 24 and 48 h post transfection. Furthermore, a significant positive association was observed between ADAR1-knockdown and the apoptosis of DU145 and PC3 cells, which increased the phosphorylation of H2A.X variant histone. The results of the present study indicated a positive association between ADAR1 expression and PCa, which may promote the development of CRPCa. Moreover, ADAR1-knockdown may serve as a tumor suppressor and represent a potential target for the treatment of PCa.

18.
Oncogene ; 39(19): 3879-3892, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32203162

RESUMEN

Mutants in the gene encoding mitochondrion-associated protein LRPPRC were found to be associated with French Canadian Type Leigh syndrome, a human disorder characterized with neurodegeneration and cytochrome c oxidase deficiency. LRPPRC interacts with one of microtubule-associated protein family MAP1S that promotes autophagy initiation and maturation to suppress genomic instability and tumorigenesis. Previously, although various studies have attributed LRPPRC nuclear acid-associated functions, we characterized that LRPPRC acted as an inhibitor of autophagy in human cancer cells. Here we show that liver-specific deletion of LRPPRC causes liver-specific increases of YAP and P27 and decreases of P62, leading to an increase of cell polyploidy and an impairment of autophagy maturation. The blockade of autophagy maturation and promotion of polyploidy caused by LRPPRC depletion synergistically enhances diethylnitrosamine-induced DNA damage, genome instability, and further tumorigenesis so that LRPPRC knockout mice develop more and larger hepatocellular carcinomas and survive a shorter lifespan. Therefore, LRPPRC suppresses genome instability and hepatocellular carcinomas and promotes survivals in mice by sustaining Yap-P27-mediated cell ploidy and P62-HDAC6-controlled autophagy maturation.


Asunto(s)
Carcinoma Hepatocelular/genética , Deficiencia de Citocromo-c Oxidasa/genética , Histona Desacetilasa 6/genética , Enfermedad de Leigh/genética , Neoplasias Hepáticas/genética , Proteínas de Neoplasias/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Autofagia/genética , Canadá , Carcinogénesis/genética , Carcinoma Hepatocelular/patología , Deficiencia de Citocromo-c Oxidasa/patología , Inestabilidad Genómica/genética , Células HeLa , Humanos , Enfermedad de Leigh/patología , Hígado/metabolismo , Hígado/patología , Neoplasias Hepáticas/patología , Ratones , Ratones Noqueados , Ploidias , Antígeno Nuclear de Célula en Proliferación/genética , Proteínas de Unión al ARN/genética , Factores de Transcripción/genética , Proteínas Señalizadoras YAP
19.
BJU Int ; 125(6): 898-904, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32077229

RESUMEN

OBJECTIVE: To compare the safety and effectiveness of using a conventional nephrostomy sheath (NS) vs using a new NS with suction and evacuation functions in minimally invasive percutaneous nephrolithotomy (MPCNL) for the treatment of staghorn stones. PATIENTS AND METHODS: A prospective and randomised study of 60 patients with staghorn stones randomly assigned into two groups of 30 patients. One group underwent MPCNL using conventional NS, whereas the other group underwent MPCNL with suction-evacuation NS (SENS). Patient demographics, stone characteristics, intraoperative data, perioperative data, and surgical results were collected and analysed. RESULTS: The patient demographics and stone characteristics were similar amongst the two groups. The SENS group had a significantly lower peak and a significantly lower average renal pelvic pressure (RPP) throughout the procedure. The SENS group was more efficient for stone removal and had a much shorter stone treatment time, a lesser use of the stone extractor, and ultimately a higher stone-free rate (SFR). The effects of a lower RPP and shorter stone treatment time translated into less severe postoperative complications as measured per modified Clavien grade. CONCLUSION: Using SENS in MPCNL for the treatment of staghorn stones has the advantages of lower RPP, increased effectiveness in stone retrieval, decreased surgery related complications, and an improved SFR.


Asunto(s)
Nefrostomía Percutánea , Cálculos Coraliformes/cirugía , Adulto , Diseño de Equipo , Femenino , Humanos , Pelvis Renal/cirugía , Masculino , Persona de Mediana Edad , Nefrostomía Percutánea/efectos adversos , Nefrostomía Percutánea/instrumentación , Nefrostomía Percutánea/métodos , Complicaciones Posoperatorias , Estudios Prospectivos , Succión/instrumentación
20.
J Endourol ; 34(3): 339-344, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31950860

RESUMEN

Objective: To assess the safety and efficacy of a novel vacuum-assisted access sheath (VAAS) in minimally invasive percutaneous nephrolithotomy (MPCNL). Materials and Methods: Seventy-five consecutive patients with single renal pelvic stone were treated with MPCNL combined with a novel VAAS. Patients' demographics and surgical outcomes, as well as perioperative and postoperative data, were recorded. Matched-pair analysis in a 1:1 scenario was done in patients who underwent MPCNL by peel-away access sheath (PAAS). All MPCNL was done with a rigid 12F mini-nephroscope and an 18F access sheath. MINDRAY-PM9000 monitor was used to record the renal pelvic pressure (RPP) data. Results: Patients' demographics, stone size, burden, and density (HU) were comparable between the two groups. Operative time was significantly shorter in the study group, at a mean of 32.4 ± 9.6 vs 46.2 ± 11.8 minutes (p < 0.001). The immediate stone-free rate was 89.3% for the VAAS group and 77.3% for the PAAS group (p = 0.049). Patients in the VAAS group had a lower visual analogue pain scale score at postoperative 6 and 24 hours. Mean perioperative RPP was lower in the VAAS group (10.3 ± 4.3 vs 17.8 ± 5.1 mmHg, p < 0.001). More than 50 seconds of accumulative time of high RPP (>30 mmHg) was shown in 13 patients of the VAAS group vs 30 of the PAAS group (p = 0.002). Conclusion: Combining VAAS with high-power holmium laser in MPCNL significantly improves the efficiency of stone retrieval with low RPP. This novel approach also reduces operative time, postoperative fever, and pain due to its simultaneous suction property.


Asunto(s)
Cálculos Renales , Nefrolitotomía Percutánea , Nefrostomía Percutánea , Estudios de Factibilidad , Humanos , Cálculos Renales/cirugía , Pelvis Renal , Procedimientos Quirúrgicos Mínimamente Invasivos , Tempo Operativo , Resultado del Tratamiento
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