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1.
BMC Med Genomics ; 17(1): 36, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38279119

RESUMEN

Idiopathic congenital nystagmus (ICN) manifests as involuntary and periodic eye movements. To identify the genetic defect associated with X-linked ICN, Whole Exome Sequencing (WES) was conducted in two affected families. We identified two frameshift mutations in FRMD7, c.1492dupT/p.(Y498Lfs*15) and c.1616delG/p.(R539Kfs*2). Plasmids harboring the mutated genes and qPCR analysis revealed mRNA stability, evading degradation via the NMD pathway, and corroborated truncated protein production via Western-blot analysis. Notably, both truncated proteins were degraded through the proteasomal (ubiquitination) pathway, suggesting potential therapeutic avenues targeting this pathway for similar mutations. Moreover, we conducted a comprehensive analysis, summarizing 140 mutations within the FRMD7 gene. Our findings highlight the FERM and FA structural domains as mutation-prone regions. Interestingly, exons 9 and 12 are the most mutated regions, but 90% (28/31) mutations in exon 9 are missense while 84% (21/25) mutations in exon 12 are frameshift. A predominant occurrence of shift code mutations was observed in exons 11 and 12, possibly associated with the localization of premature termination codons (PTCs), leading to the generation of deleterious truncated proteins. Additionally, our conjecture suggests that the loss of FRMD7 protein function might not solely drive pathology; rather, the emergence of aberrant protein function could be pivotal in nystagmus etiology. We propose a dependence of FRMD7 protein normal function primarily on its anterior domain. Future investigations are warranted to validate this hypothesis.


Asunto(s)
Mutación del Sistema de Lectura , Nistagmo Congénito , Humanos , Nistagmo Congénito/genética , Secuencia de Bases , Proteínas de la Membrana/genética , Proteínas del Citoesqueleto/genética , Linaje , Análisis Mutacional de ADN , Mutación
2.
PeerJ ; 11: e16112, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37927797

RESUMEN

Rationale: Overactive bladder (OAB) is a common, distressing condition that worsens with age and impacts quality of life significantly. As a results of its clinical symptoms, patients suffer from serious physical and mental health issues, have a poor quality of life, and participate in a serious economic burden. The key social-psychological factors include living habits, eating habits, and personality characteristics on this disease, even though the pathogenesis of OAB is complex. However, there is few cognitions and research on OAB in the field of psychology. Methods/Search Strategy: Between 2000 and 2022, two electronic databases were systematically searched in accordance with Cochrane library guidelines (PubMed/Medline, Web of Science). An analysis of the remaining articles with relevant information was conducted using a data extraction sheet. An itemized flow diagram was adopted and used to report systematic reviews and meta-analysis. A systematic review of studies published from 2000 to 2022 in English language were conducted and included in the review. The intended audience: Urological surgeon and psychologists majoring in urinary diseases. Implication: As a result of this information, we are able to develop a better understanding of the role of psychological factors in the development of OAB and suggest potential therapeutic directions for OAB patients. This may benefit the recovery of OAB patients.


Asunto(s)
Vejiga Urinaria Hiperactiva , Humanos , Cognición , Estrés Financiero , Calidad de Vida , Vejiga Urinaria Hiperactiva/terapia
3.
Environ Sci Pollut Res Int ; 30(46): 102313-102322, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37665443

RESUMEN

Soil organic carbon (SOC) stability and dynamics are greatly influenced by long-term elevated atmospheric CO2 [CO2]. The priming effect (PE) is vital in SOC stability and dynamics, but its role in paddy soil under long-term elevated [CO2] remains unclear. To examine how SOC stability changed in paddy soil after long-term elevated atmospheric CO2 enrichment, the PE was quantified through a 13C-glucose-induced experiment with different N levels for topsoil (0-20 cm) from paddy free-air CO2 enrichment (FACE) platform. Compared with the ambient CO2 concentration ([CO2]), 10 years of elevated [CO2] (500 µmol·mol-1) significantly increased SOC and TN content by 18.4% and 19.0%, respectively, while the C/N ratio was not changed. The labile C fractions including dissolved organic carbon (DOC) and readily oxidizable organic carbon (ROC), but excluding microbial biomass C (MBC), accumulated faster than SOC in paddy soil, which implied the reduced SOC stability for long-term elevated [CO2] enrichment. With the decline of SOC stability, the exogenously induced cumulative specific PE (PE per gram of SOC) remarkably increased by 41.1-72.7% for elevated [CO2] fumigation. The cumulative PE, especially the cumulative specific PE, was found significantly linearly correlated with the ROC content or ROC/SOC ratio (labile SOC pool). Furthermore, the application of nitrogen fertilizer slowed down the PE under elevated [CO2] condition. Our results showed that long-term elevated [CO2] enrichment reduced SOC stability and, together with exogenous nitrogen fertilizer, regulated the PE in paddy soil.

4.
Sensors (Basel) ; 23(15)2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37571596

RESUMEN

The trends of "fashionalization", "personalization" and "customization" of wool fabrics have prompted the textile industry to change the original processing design based on the experience of engineers and trial production. In order to adapt to the promotion of intelligent production, the microstructure of wool fabrics is introduced into the finishing process. This article presents an automated method to extract the microstructure from the micro-CT data of woven wool fabrics. Firstly, image processing was performed on the 3D micro-CT images of the fabric. The raw grayscale data were converted into eigenvectors of the structure tensor to segment the individual yarns. These data were then used to calculate the three parameters of diameter, spacing and the path of the center points of the yarn for the microstructure. The experimental results showed that the proposed method was quite accurate and robust on woven single-ply tweed fabrics.

5.
Cancer Med ; 12(6): 7283-7293, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36567509

RESUMEN

BACKGROUND: Enrichment of urinary exfoliated tumor cells (UETCs) is a noninvasive way of bladder cancer diagnosis, but the lack of specific capture and identification of tumor cells from the urine remains a limitation that impedes the development of liquid biopsy. METHODS: The CytoBot® 2000, a novel circulating cell isolation and enrichment platform, was used for UETCs isolation after comprehensive optimization. The commercial cell lines of bladder cancer were used in spiking assay for cell recovery test. The flow cytometry and immunofluorescent staining assays were performed for expression validation of capture target and identification markers. The performance of optimized platform was validated by 159 clinical samples and analyzed using receiver operator characteristic curve. RESULTS: The chip that had a pore diameter of 15*20 µm could reduce the background residues while maintaining a higher cell recovery rate. We found that the cell capture ability of chip significantly improved after anti-EpCam antibody encapsulation, but not with T4L6FM1. In identification system optimization, the spiking assay and validation of clinical sample showed that the performance of CK20 and DBC-1 were better that pan-CK in tumor cell identification, in addition, the staining quality is more legible with CK20. CONCLUSION: The optimized capture chip is more specific for UETCs isolation. CK20 and DBC-1 are both sensitive biomarkers of UETCs in bladder cancer diagnosis. The performance of this optimized platform is excellent in clinical test that improves the accuracy of urine cell testing and provides a new alternative for the clinical application of BLCA liquid biopsy assessment.


Asunto(s)
Microfluídica , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/patología , Vejiga Urinaria/patología , Biomarcadores , Línea Celular Tumoral , Biomarcadores de Tumor/orina
6.
Front Oncol ; 12: 969106, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36330483

RESUMEN

Background: Renal pelvic urothelial carcinoma with sarcomatoid carcinoma differentiation is a very dangerous malignant tumor and extremely rare in clinical practice. In general, these tumors with a dismal prognosis, and there is no standard treatment. Case presentation: In this case, an 81-year-old male patient was diagnosed with right renal pelvic carcinoma. After an open right radical nephroureterectomy, postoperative pathological examination showed infiltrating urothelial carcinoma with sarcomatoid differentiation. Overexpression of programmed death ligand-1 by immunohistochemistry. The carcinoma recurred 4.5 months after surgery. After informed, tislelizumab combined with anlotinib were used as first-line treatment. The patients showed a clinical partial response that lasted for 20 months. Conclusion: This case demonstrates the efficacy of tislelizumab combined with anlotinib in patients diagnosed with metastatic renal pelvic urothelial carcinoma with sarcomatoid carcinoma differentiation. Moreover, to our knowledge, this is the first application of this treatment.

7.
J Fungi (Basel) ; 8(11)2022 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-36354926

RESUMEN

In recent years, many publications have established histone lysine methylation as a central epigenetic modification in the regulation of chromatin and transcription. The histone lysine methyltransferases contain a conserved SET domain and are widely distributed in various organisms. However, a comprehensive study on the origin and diversification of the SET-domain-containing genes in fungi has not been conducted. In this study, a total of 3816 SET-domain-containing genes, which were identified and characterized using HmmSearch from 229 whole genomes sequenced fungal species, were used to ascertain their evolution and diversification in fungi. Using the CLANS program, all the SET-domain-containing genes were grouped into three main clusters, and each cluster contains several groups. Domain organization analysis showed that genes belonging to the same group have similar sequence structures. In contrast, different groups process domain organizations or locations differently, suggesting the SET-domain-containing genes belonging to different groups may have obtained distinctive regulatory mechanisms during their evolution. These genes that conduct the histone methylations (such as H3K4me, H3K9me, H3K27me, H4K20me, H3K36me) are mainly grouped into Cluster 1 while the other genes grouped into Clusters 2 and 3 are still functionally undetermined. Our results also showed that numerous gene duplication and loss events have happened during the evolution of those fungal SET-domain-containing proteins. Our results provide novel insights into the roles of SET-domain genes in fungal evolution and pave a fundamental path to further understanding the epigenetic basis of gene regulation in fungi.

8.
Opt Express ; 30(20): 36134-36143, 2022 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-36258549

RESUMEN

The lateral distortion of a surface measuring Fizeau interferometer may cause distorted image features in the lateral direction, as well as the surface form error in the axial direction (which is a source of the retrace error). Traditional method for lateral distortion measurement requires a high-accuracy calibration plate featuring a grid pattern. Such a calibration plate is not always available, especially when the required accuracy of the grid pattern comes to the order of sub-micrometer or even nanometer level. To remove the dependence on the plate accuracy, we propose a self-calibration method for the measurement and correction of lateral distortion in Fizeau interferometer. The self-calibration technique may separate the lateral distortion and the geometric error of the calibration plate. This method is verified using a 108-mm-aperture Fizeau interferometer. The experiments show that the form measurement error of a surface tilted at approximately 5° and 16° can be reduced from 92 nm to 43 nm and from 251 nm to 144 nm (peak-to-valley value), respectively, after the distortion correction.

9.
Int J Comput Assist Radiol Surg ; 17(10): 1787-1799, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35843963

RESUMEN

PURPOSE: Flexible ureteroscopy (FURS) plays an important role in the diagnosis and treatment of urological diseases. However, manipulating a flexible ureteroscope to the target quickly and safely may be challenging because of the tortuous lumen or poor visibility. Thus, information on the shape of the anterior part of a flexible ureteroscope in addition to the real-time pose is needed to perform accurate maneuvering in the lumen with minimal impingement on the inner renal wall and resulting tissue damage in FURS. METHODS: An adaptive mixed-order Bézier curve fitting algorithm and electromagnetic tracking (EMT) technique were developed for shape estimation utilizing the length of the anterior part, kinematic constraints and the pose information provided by two electromagnetic (EM) sensors mounted at the tip and base of the anterior part. A series of experiments were performed to qualitatively and quantitatively verify the validity of our method. Moreover, algorithm threshold conditions with reference significance under various shape cases were studied. RESULTS: The performance of our method was evaluated based on 19 representative planar bending shapes that often appear in FURS and eight non-planar shapes, yielding an average error (AE) of 1.0 mm. Moreover, the experiments proved the feasibility of applying our method in cases in which large bending angles (near 270 degrees) occur. CONCLUSION: Based on data from two EM sensors mounted at the tip and base of the anterior part of a flexible ureteroscope, the proposed algorithm adaptively selects a cubic or quartic Bézier curve to fit the shape of the anterior part. Experimental results prove the feasibility of our shape estimation method over a broad bending range. The proposed method demonstrates significant potential for use in ureteroscopic navigation systems and robot-assisted surgery.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Ureteroscopios , Fenómenos Electromagnéticos , Diseño de Equipo , Humanos , Ureteroscopía/métodos
10.
Front Cell Dev Biol ; 9: 704683, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34595165

RESUMEN

Circular RNA (circRNA) is a newly discovered endogenous non-coding RNA (ncRNA), which is characterized with a closed circular structure. A growing body of evidence has verified the vital roles of circRNAs in human cancer. In this research, we selected circPPP1CB as a study object by circRNA sequencing and quantitative real-time PCR (qRT-PCR) validation in human bladder cancer (BC). CircPPP1CB is downregulated in BC and is negatively correlated with clinical stages and histological grades. Functionally, circPPP1CB modulated cell growth, metastasis, and epithelial-to-mesenchymal transition (EMT) process in vitro and in vivo. Mechanically, we performed various experiments to verify the circPPP1CB/miR-1307-3p/SMG1 regulatory axis. Taken together, our results demonstrated that circPPP1CB participates in tumor growth, metastasis, and EMT process by interacting with the miR-1307-3p/SMG1 axis, and that circPPP1CB might be a novel therapeutic target and diagnostic biomarker in human BC.

11.
J Proteome Res ; 20(8): 4022-4030, 2021 08 06.
Artículo en Inglés | MEDLINE | ID: mdl-34279957

RESUMEN

More and more evidence has proved that urinary metabolites can instantly reflect disease state. Therefore, ultra-sensitive and reproducible detection of urinary metabolites in a high-throughput way is urgently desirable for clinical diagnosis. Matrix-free laser desorption/ionization mass spectrometry (LDI-MS) is a high-throughput platform for metabolites detection, but it is encountered by severe interference from numerous salts in urine samples, because the crystallized urine salt on dried samples could result in poor reproducibility in LDI-MS detection. The present work proposed a tip-contact extraction (TCE) technique to eliminate interference from the urine salt. Vertical silicon nanowire arrays decorated with the fluorinated ethylene propylene film (FEP@VSiNWs) could effectively extract metabolites from the urine sample dropping on its surface. High salt tolerance was observed in the subsequent LDI-MS detection of the metabolites extracted on the tip of FEP@VSiNWs even in the presence of 1 M urea. Stable and reproducible mass spectra for non-target metabolic analysis were obtained in real urine samples with different dilution folds. Urinary metabolites collected from bladder cancer (BC) patients were reliably profiled by the TCE method coupled with negative LDI-MS. Based on this platform, potential metabolic biomarkers that can distinguish BC patients and normal controls were uncovered.


Asunto(s)
Rayos Láser , Silicio , Humanos , Espectrometría de Masas , Reproducibilidad de los Resultados , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
12.
Int J Med Robot ; 17(4): e2274, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33960604

RESUMEN

BACKGROUND: During flexible ureteroscopy (FURS), surgeons may lose orientation due to intrarenal structural similarities and complex shape of the pyelocaliceal cavity. Decision-making required after initially misjudging stone size will also increase the operative time and risk of severe complications. METHODS: A intraoperative navigation system based on electromagnetic tracking (EMT) and simultaneous localization and mapping (SLAM) was proposed to track the tip of the ureteroscope and reconstruct a dense intrarenal three-dimensional (3D) map. Furthermore, the contour lines of stones were segmented to measure the size. RESULTS: Our system was evaluated on a kidney phantom, achieving an absolute trajectory accuracy root mean square error (RMSE) of 0.6 mm. The median error of the longitudinal and transversal measurements was 0.061 and 0.074 mm, respectively. The in vivo experiment also demonstrated the effectiveness. CONCLUSION: The proposed system worked effectively in tracking and measurement. Further, this system can be extended to other surgical applications involving cavities, branches and intelligent robotic surgery.


Asunto(s)
Cálculos Renales , Ureteroscopios , Fenómenos Electromagnéticos , Humanos , Cálculos Renales/cirugía , Tempo Operativo , Ureteroscopía
13.
J Exp Clin Cancer Res ; 40(1): 44, 2021 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-33499877

RESUMEN

BACKGROUND: Transcriptional coactivator with PDZ-binding motif (TAZ) has been reported to be involved in tumor progression, angiogenesis, epithelial-mesenchymal transition (EMT), glycometabolic modulation and reactive oxygen species (ROS) buildup. Herein, the underlying molecular mechanisms of the TAZ-induced biological effects in bladder cancer were discovered. METHODS: qRT-PCR, western blotting and immunohistochemistry were performed to determine the levels of TAZ in bladder cancer cells and tissues. CCK-8, colony formation, tube formation, wound healing and Transwell assays and flow cytometry were used to evaluate the biological functions of TAZ, miR-942-3p and growth arrest-specific 1 (GAS1). QRT-PCR and western blotting were used to determine the expression levels of related genes. Chromatin immunoprecipitation and a dual-luciferase reporter assay were performed to confirm the interaction between TAZ and miR-942. In vivo tumorigenesis and colorimetric glycolytic assays were also conducted. RESULTS: We confirmed the upregulation and vital roles of TAZ in bladder cancer. TAZ-induced upregulation of miR-942-3p expression amplified upstream signaling by inhibiting the expression of large tumor suppressor 2 (LATS2, a TAZ inhibitor). MiR-942-3p attenuated the impacts on cell proliferation, angiogenesis, EMT, glycolysis and ROS levels induced by TAZ knockdown. Furthermore, miR-942-3p restrained the expression of GAS1 to modulate biological behaviors. CONCLUSION: Our study identified a novel positive feedback loop between TAZ and miR-942-3p that regulates biological functions in bladder cancer cells via GAS1 expression and illustrated that TAZ, miR-942-3p and GAS1 might be potential therapeutic targets for bladder cancer treatment.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Péptidos y Proteínas de Señalización Intracelular/metabolismo , MicroARNs/genética , Transducción de Señal , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo , Animales , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Modelos Animales de Enfermedad , Técnicas de Silenciamiento del Gen , Glucólisis , Humanos , Inmunohistoquímica , Ratones , Modelos Biológicos , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Interferencia de ARN , Especies Reactivas de Oxígeno/metabolismo , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ , Neoplasias de la Vejiga Urinaria/patología , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Transl Cancer Res ; 10(7): 3429-3435, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35116647

RESUMEN

BACKGROUND: Ligating clip migration (LCM) after robot-assisted laparoscopic radical prostatectomy (RARP) is a rare but troublesome complication, that may result in calculus formation, bladder neck contracture, and anastomotic stricture. Herein, we describe our experiences with LCM after RARP and explore its risk factors, potential pathogenesis, and preventive measures. METHODS: We retrospectively reviewed patients who underwent RARP at our medical center between December 2015 and June 2019, identifying individuals with LCM. Clinical and surgical data were collected from these patients. RESULTS: Of the 682 patients who underwent RARP at our institution, 26 (3.8%) had LCM. The duration from RARP to the identification of LCM ranged from 1 to 37 (13±10) months. Clips migrated into the urethrovesical anastomosis in 22 patients (84%), prompting cytoscopic extraction to remove the migrated clips. The length of stay after RARP was longer in LCM-positive patients than in LCM-negative patients (13.5 vs. 9.4 days, P=0.034). Additionally, the rates of urine leakage (15% vs. 6%, P=0.046) and anastomotic stenosis (54% vs. 5%, P=0.000) were higher among LCM-positive patients. More positive urethra/apex margins were found in LCM-positive patients (38% vs. 21%, P=0.039). CONCLUSIONS: The incidence of clip migration after RARP may not be as low as previously thought. Cystoscopy is recommended in post-RARP patients with recurrent lower urinary tract symptoms (LUTS) and/or urinary retention. Prolonged length of stay after the first RARP, urine leakage, anastomotic stenosis, and positive urethra/apex margin might be predictors of LCM. We recommend reduced ligating clip usage and electrotome near the urethrovesical anastomosis to reduce clip migration incidence. Meanwhile, more researches are needed to determine the practicality of reducing the risk of clip migration after RARP.

15.
Carcinogenesis ; 42(1): 31-37, 2021 02 11.
Artículo en Inglés | MEDLINE | ID: mdl-32772072

RESUMEN

Epidemiological cohort studies investigating the association between vasectomy and prostate cancer risk have yielded inconsistent results. The aim of the present meta-analysis is to update the evidence on the association between vasectomy and prostate cancer. A comprehensively literature search of relevant studies was performed in December 2019 using PubMed. A DerSimonian and Laird random-effects model was used to calculate the summary relative risk (RR) and its 95% confidence interval (CI). A total of 15 eligible cohort studies (16 data sets) with more than four million of participants were eventually included in this meta-analysis. There was a statistically significant higher risk of prostate cancer among men who underwent vasectomy (RR: 1.09, 95% CI: 1.04-1.13) with obvious heterogeneity among included studies (P < 0.001, I2 = 64.2%). Vasectomy was also associated with the risk of advanced prostate cancer (RR: 1.07, 95% CI: 1.02-1.13), which is less likely to be affected from detection bias. In conclusion, findings from this meta-analysis of prospective studies indicate that vasectomy may be positively associated with the risk of prostate cancer. Further large prospective studies with long follow-up are warranted to verify the findings from this meta-analysis. In addition, the potential underlying molecular mechanism needed further exploration with in vitro and animal studies.


Asunto(s)
Neoplasias de la Próstata/epidemiología , Vasectomía/efectos adversos , Humanos , Masculino , Estadificación de Neoplasias , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Vasectomía/estadística & datos numéricos
16.
Mol Ther Nucleic Acids ; 19: 751-758, 2020 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-31954329

RESUMEN

UCA1 (urothelial carcinoma associated 1) is a long non-coding RNA (lncRNA) that was found overexpressed in various human cancers including prostate cancer (PCa). However, the aspect of UCA1-miRNA-mRNA interaction in PCa remains unclear. In this study, we confirmed the role of UCA1 in PCa and found that UCA1 downregulation inhibited cell proliferation of PCa cells. Then we demonstrated that repressed UCA1 promoted the microRNA-143 (miR-143) expression and miR-143 could bind to the predicted binding site of UCA1. We then proved the anti-tumor role of miR-143 in PCa. Furthermore, we found that miR-143 displays its role in PCa via modulating the MYO6 expression. In summary, our study demonstrated that UCA1 exerts oncogenes activity in PCa, acting mechanistically by upregulating MYO6 expression through "sponging" miR-143.

17.
Oncol Rep ; 42(5): 1924-1934, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31545458

RESUMEN

The present study aimed to investigate the potential mechanisms of human miR­942 in the sunitinib­resistance of renal cell carcinoma (RCC). A sunitinib­resistant OS­RC­2 cell line was established by continuous exposure to increasing concentrations of sunitinib for ~12 weeks. The expression levels of four miRNAs were determined by reverse transcription­quantitative (RT­q)PCR. miR­942 mimics were transfected into OS­RC­2 cells and RNA sequencing was performed on the miR­942­ and negative control­transfected cells. Downregulated genes, including those of long non­coding RNAs (lncRNAs) and mRNAs, were identified. The target genes of miR­942 were predicted, followed by protein­protein interaction network construction and functional enrichment analyses of miR­942 target genes. In addition, RCC RNA­seq and miRNA­seq data were downloaded from The Cancer Genome Atlas (TCGA) database. The contributions of lncRNA and/or mRNAs to survival prediction were assessed and a competing endogenous RNA (ceRNA) network consisting of miR­942, lncRNA and mRNAs was constructed. The expression levels of LINC00461, miR­942, spalt­like transcription factor 1 (SALL1), methionyl aminopeptidase 1 (METAP1) and DDB1 and CUL4 associated factor 1 (DCAF11) were verified using RT­qPCR. The role of LINC00461 in cell viability was detected by MTT assay. The expression level of miR­942 was significantly increased in sunitinib­resistant cells. A total of seven lncRNAs and 155 mRNAs were predicted as target genes of miR­942 in the miR­942 mimic­treated samples, compared with the mimic control­treated group. These potential target genes were significantly associated with 'protein binding', 'TNF­ß signaling pathway', 'negative transcriptional regulation' and 'RNA binding'. Through the integrated analysis of RNA­sequencing and TCGA data, an miR­942­related ceRNA network, which was predicted to significantly affect the survival of patients with RCC, was constructed. The expression levels of lncRNA LINC00461 and the genes SALL1, METAP1, and DCAF11 were further verified. The viability of OS­RC­2 cells was decreased following co­transfection with miR­942 mimics and LINC00641 siRNA, and was comparable to that of wild type OS­RC­2 cells (P>0.05). Therefore, lncRNA LINC00461 may act as an miR­942 ceRNA, and affect the survival of patients with RCC by regulating the expression of SALL1, METAP1 and DCAF11.


Asunto(s)
Carcinoma de Células Renales/mortalidad , Resistencia a Antineoplásicos , Neoplasias Renales/mortalidad , MicroARNs/genética , ARN Largo no Codificante/genética , Aminopeptidasas/genética , Carcinoma de Células Renales/genética , Línea Celular Tumoral , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/genética , Pronóstico , Mapas de Interacción de Proteínas , Análisis de Secuencia de ARN , Sunitinib/farmacología , Análisis de Supervivencia , Factores de Transcripción/genética , Complejos de Ubiquitina-Proteína Ligasa/genética
18.
Oncol Rep ; 42(5): 2039-2048, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31485624

RESUMEN

The clinical treatment of renal cell carcinoma (RCC) remains a major challenge. A number of novel agents and therapeutic strategies are currently undergoing active investigation. In the present study, we investigated the potential of GNF­5837, a Trk inhibitor, in the treatment of RCC. Tropomyosin­related kinases (Trk), a family of neurotrophin receptors, are vital for neural development and have also been identified as prognostic markers in malignancies of diverse origins. In the present study, we demonstrated that GNF­5837, an inhibitor of TrkA and TrkB, suppressed the cell viability of renal carcinoma 786O and Caki­2 cells in a concentration­dependent manner. GNF­5837 treatment led to decreased activities of TrkA and TrkB signaling, accompanied by reduced phosphorylation levels of AKT and extracellular signal­regulated kinase (ERK) kinases, which was detected by western blot assay. GNF­5837 induced G0/G1­phase arrest and apoptosis. Consistently, GNF­5837 affected the expression of p21, c­Myc, and survivin proteins. Meanwhile, a wound healing assay showed that GNF­5837 inhibited the migration ability of RCC cells by impairing Rac1 activity. GNF­5837 also enhanced the cytotoxic effects of sunitinib via inhibition of ERK kinase. Taken together, these results identify the pharmacological potential of targeting Trk signaling as a therapeutic strategy for RCC.


Asunto(s)
Carcinoma de Células Renales/genética , Neoplasias Renales/genética , Inhibidores de Proteínas Quinasas/farmacología , Receptor trkA/antagonistas & inhibidores , Carcinoma de Células Renales/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Renales/tratamiento farmacológico , Fosforilación/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proteína de Unión al GTP rac1/genética
19.
Cancer Manag Res ; 11: 6651-6661, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31410058

RESUMEN

PURPOSE: The clinical impacts of serum lipid levels on prostate cancer recurrence after radical prostatectomy have been evaluated by several observational studies with conflicting results. We performed the present meta-analysis to summarize the evidence evaluating the role of serum lipid profile in prostate cancer patients. METHODS: We comprehensively searched the PubMed database for potentially relevant studies through January 2019. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) for the highest versus the lowest level of serum lipid levels were calculated with the DerSimonian and Laird random-effects model. RESULTS: A total of 12 eligible studies with 10,978 prostate cancer cases were included in this study. The pooled HRs of prostate cancer recurrence after racial prostatectomy were 0.92 (95% CI 0.73-1.16, P=0.462), 0.87 (95% CI 0.56-1.35, P=0.535), 1.09 (95% CI 0.92-1.30, P=0.320), and 1.01 (95% CI 0.78-1.31, P=0.938) for serum total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride, respectively. Sensitivity analysis was conducted by excluding each study sequentially and the results showed that all the summary risk estimates were stable and not influenced by any single study. CONCLUSION: The present meta-analysis indicated that serum lipid levels in patients undergoing radical prostatectomy were not associated with prostate cancer recurrence.

20.
Medicine (Baltimore) ; 98(27): e16341, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31277188

RESUMEN

BACKGROUND: Mediterranean dietary pattern has attracted great attention in terms of its effect on human health. However, whether Mediterranean dietary pattern is an independent protective factor for prostate cancer remains controversial. Our goal was to evaluate this association by conducting a meta-analysis of observational studies. METHODS: We searched the PubMed and EMBASE database through February 2019 for relevant studies that examined the association between Mediterranean Diet and prostate cancer risk. The combined risk estimates were computed using a DerSimonian random-effects model. RESULTS: A total of 10 eligible studies were included in this meta-analysis. The pooled risk estimates and 95% confidence interval (CI) in relation to Mediterranean diet pattern were 0.95 (95% CI: 0.90 to 1.01) for total prostate cancer, 0.93 (95% CI: 0.75 to 1.14) for advanced prostate cancer, 0.96 (95% CI: 0.81 to 1.14) for localized prostate cancer, and 0.92 (95% CI: 0.76 to 1.11) for fatal prostate cancer. There was no evidence of heterogeneity for total (P = .326, I = 12.7%), localized (P = .706, I = 0.0%) and fatal prostate cancer (P = .282, I = 13.0%), but not for advanced prostate cancer (P = .018, I = 63.4%). CONCLUSION: This large meta-analysis of observational studies suggests that Mediterranean dietary pattern has no relationship with prostate cancer risk.


Asunto(s)
Dieta Mediterránea , Neoplasias de la Próstata/epidemiología , Humanos , Masculino , Neoplasias de la Próstata/patología , Riesgo
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