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Excision repair cross-complementation group 2 (ERCC2) encodes the DNA helicase xeroderma pigmentosum group D, which functions in transcription and nucleotide excision repair. Point mutations in ERCC2 are putative drivers in around 10% of bladder cancers (BLCAs) and a potential positive biomarker for cisplatin therapy response. Nevertheless, the prognostic significance directly attributed to ERCC2 mutations and its pathogenic role in genome instability remain poorly understood. We first demonstrated that mutant ERCC2 is an independent predictor of prognosis in BLCA. We then examined its impact on the somatic mutational landscape using a cohort of ERCC2 wild-type (n = 343) and mutant (n = 39) BLCA whole genomes. The genome-wide distribution of somatic mutations is significantly altered in ERCC2 mutants, including T[C>T]N enrichment, altered replication time correlations, and CTCF-cohesin binding site mutation hotspots. We leverage these alterations to develop a machine learning model for predicting pathogenic ERCC2 mutations, which may be useful to inform treatment of patients with BLCA.
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Laparoscopic total adrenalectomy has become the standard treatment for adrenal mass. Meanwhile, there has been a growing trend toward laparoscopic adrenal-sparing surgery worldwide to avoid the risk and potential complications of adrenal insufficiency. The objectives of this study were to describe a retroperitoneoscopic adrenal tumor enucleation technique, to assess the clinical outcomes of this technique in the treatment of 20-40 mm nonsecreting adrenal tumor (NAT) with low potential of malignancy, and to provide a feasible choice for patients who have preference on resection. This study was a retrospective analysis of 61 patients with low potential of malignancy in 20-40 mm NAT identified at the first imaging examination or during follow-up. All patients were scheduled for planned enucleation adrenalectomy by a single surgeon between July 2016 and December 2020 in Xuanwu Hospital, Beijing, China. In all patients, retroperitoneoscopic surgery was performed via a retroperitoneoscopic process for all the patients. The crucial techniques of enucleation are presented in the video. Safety and feasibility factors of enucleation technique were measured for this study. No blood transfusion or organ injury was registered during the operation. The median operation time was 75 min, and the median blood loss was 35 mL. All operations were successfully performed without open conversion. A total of 58 patients received successful enucleation surgery. Three cases were converted to retroperitoneoscopic total adrenalectomy. In this study, surgical outcomes of retroperitoneoscopic enucleation adrenalectomy as a method to remove adrenal tumors were assessed. This procedure is a feasible and safe technique with the added benefit of preserving the remaining functional adrenal tissue.
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BACKGROUND: Recent studies have raised concerns about genotoxic effects associated with titanium dioxide nanoparticles (TiO2 NPs), which are commonly used. This meta-analysis aims to investigate the potential genotoxicity of TiO2 NPs and explore influencing factors. METHODS: This study systematically searched Chinese and English literature. The literature underwent quality evaluation, including reliability evaluation using the toxicological data reliability assessment method and relevance evaluation using routine evaluation forms. Meta-analysis and subgroup analyses were performed using R software, with the standardized mean difference (SMD) as the combined effect value. RESULTS: A total of 26 studies met the inclusion criteria and passed the quality assessment. Meta-analysis results indicated that the SMD for each genotoxic endpoint was greater than 0. This finding implies a significant association between TiO2 NP treatment and DNA damage and chromosome damage both in vivo and in vitro and gene mutation in vitro. Subgroup analysis revealed that short-term exposure to TiO2 NPs increased DNA damage. Rats and cancer cells exhibited heightened susceptibility to DNA damage triggered by TiO2 NPs (p < 0.05). CONCLUSIONS: TiO2 NPs could induce genotoxicity, including DNA damage, chromosomal damage, and in vitro gene mutations. The mechanism of DNA damage response plays a key role in the genotoxicity induced by TiO2 NPs.
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BACKGROUND: In bladder cancer, recurrent ADGRG6 enhancer hotspot mutations (chr. 6: 142,706,206 G>A, chr. 6:142,706,209 C>T) were reported at a high mutation rate of approximately 50%. Thus, ADGRG6 enhancer mutation status might be a candidate for diagnostic biomarker. METHODS: To improve test efficacy, an amplification refractory mutation system combined with quantitative real-time PCR (ARMS-qPCR) assay was developed to detect the ADGRG6 mutations in a patient as a clinical diagnostic test. To validate the performance of the ARMS-qPCR assay, artificial plasmids, cell DNA reference standard were used as templates, respectively. To test the clinical diagnostic ability, we detected the cell free DNA (cfDNA) and sediment DNA (sDNA) of 30 bladder cancer patients' urine by ARMS-qPCR comparing with Sanger sequencing, followed by the droplet digital PCR to confirm the results. We also tested the urine of 100 healthy individuals and 90 patients whose diagnoses urinary tract infections or urinary stones but not bladder cancer. RESULTS: Sensitivity of 100% and specificity of 96.7% were achieved when the mutation rate of the artificial plasmid was 1%, and sensitivity of 96.7% and specificity of 100% were achieved when the mutation frequency of the reference standard was 0.5%. Sanger sequencing and ARMS-qPCR both detected 30 cases of bladder cancer with 93.3% agreement. For the remaining unmatched sites, ARMS-qPCR results were consistent with droplet digital PCR. Among 100 healthy individuals, three of them carried hotspot mutations by way of ARMS-qPCR. Of 90 patients with urinary tract infections or urinary stones, no mutations were found by ARMS-qPCR. Based on clinical detection, the ARMS-qPCR assay's sensitivity is 83.3%, specificity is 98.4%. CONCLUSION: We here present a novel urine test for ADGRG6 hotspot mutations with high accuracy and sensitivity, which may potentially serve as a rapid and non-invasive tool for bladder cancer early screening and follow-up relapse monitoring.
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Neoplasias de la Vejiga Urinaria , Cálculos Urinarios , Humanos , Detección Precoz del Cáncer , Recurrencia Local de Neoplasia , Mutación , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/genética , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
N6-Methyladenosine (m6A) is the most prevalent internal modification of mammalian mRNAs. Recent studies have shown that m6A methyltransferases METTL3 and METTL14 play important roles in urothelial bladder carcinoma (BLCA). To provide a more comprehensive understanding of the m6A regulatory landscape in bladder cancer, we investigated the role of YTHDF2, a crucial m6A reader, in BLCA. YTHDF2 was frequently upregulated at both the RNA and protein level in BLCA. Functionally, YTHDF2 promoted the proliferation and tumor growth of BLCA cells in vitro and in vivo, respectively. Integrative RNA sequencing and m6A sequencing analyses identified RIG-I as a downstream target of YTHDF2. Mechanistically, YTHDF2 bound to the coding sequence of DDX58 mRNA, which encodes RIG-I, and mediated its degradation in an m6A-dependent manner. Knockdown of RIG-I inhibited apoptosis and promoted the proliferation of BLCA cells. Depleting RIG-I was also able to reverse the effects of YTHDF2 deficiency. YTHDF2-deficient BLCA cells implanted orthotopically in recipient mice activated an innate immune response and promoted recruitment of CD8+ T lymphocytes into the tumor bed and the urothelium. Moreover, YTHDF2 deficiency enhanced the efficacy of Bacillus Calmette-Guérin immunotherapy treatment. This study reveals that YTHDF2 acts as an oncogene in BLCA. YTHDF2 inhibits RIG-I to facilitate immune evasion, supporting testing YTHDF2 inhibition in combination with immunotherapy. SIGNIFICANCE: YTHDF2 regulates RIG-I-mediated innate immune signaling to support bladder cancer progression, highlighting the functional importance of m6A modifications in bladder cancer and uncovering therapeutic opportunities to improve patient outcomes.
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Neoplasias de la Vejiga Urinaria , Vejiga Urinaria , Animales , Ratones , Proteína 58 DEAD Box/genética , Proteína 58 DEAD Box/metabolismo , Inmunidad , Metiltransferasas/metabolismo , Transducción de Señal , Neoplasias de la Vejiga Urinaria/genética , HumanosRESUMEN
Current cancer treatment regimens such as chemotherapy and traditional chemical drugs have adverse side effects including the appearance of drug-resistant tumor cells. For these reasons, it is imperative to find novel therapeutic agents that overcome these factors. To this end, we explored a cationic antimicrobial peptide derived from Litopenaeus vannamei hemocyanin (designated LvHemB1) that induces cancer cell death, but sparing normal cells. LvHemB1 inhibits the proliferation of human cervical (HeLa), esophageal (EC109), hepatocellular (HepG2), and bladder (EJ) cancer cell lines, but had no significant effect on normal liver cell lines (T-antigen-immortalized human liver epithelial (THLE-3) cells). In addition to its antiproliferative effects, LvHemB1 induced apoptosis, by permeating cells and targeting mitochondrial voltage-dependent anion channel 1 (VDAC1). Colocalization studies revealed the localization of LvHemB1 in mitochondria, while molecular docking and pull-down analyses confirmed LvHemB1-VDAC1 interaction. Moreover, LvHemB1 causes loss in mitochondrial membrane potential and increases levels of reactive oxygen species (ROS) and apoptotic proteins (caspase-9, caspase-3, and Bax (Bcl-2-associated X)), which results in mitochondrial-mediated apoptosis. Thus, peptide LvHemB1 has the potential of being used as an anticancer agent due to its antiproliferation effect and targeting to VDAC1 to cause mitochondrial dysfunction in cancer cells, as well as its ability to induce apoptosis by increasing ROS levels, and the expression of proapoptotic proteins.
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Neoplasias , Canal Aniónico 1 Dependiente del Voltaje , Péptidos Catiónicos Antimicrobianos/metabolismo , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Antimicrobianos , Apoptosis , Proteínas Reguladoras de la Apoptosis/metabolismo , Hemocianinas/metabolismo , Hemocianinas/farmacología , Humanos , Potencial de la Membrana Mitocondrial , Mitocondrias/metabolismo , Simulación del Acoplamiento Molecular , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Canal Aniónico 1 Dependiente del Voltaje/química , Canal Aniónico 1 Dependiente del Voltaje/metabolismoRESUMEN
BACKGROUND: Accumulating evidence indicates that dysregulation of miR-182-5p can serve as diagnostic and prognostic biomarkers for some cancers, whereas the role of miR-182-5p has not been explored in nasopharyngeal carcinoma (NPC). Our study aims to elucidate the biological function of miR-182-5p in NPC and the potential molecular mechanism involved. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine miR-182-5p expression in NPC primary tissues and cell lines. Immunohistochemistry (IHC) for ZFP36L1 was conducted in NPC samples. Western blot was used to evaluate protein expression in cell lines. A series of functional assays were carried out to evaluate the roles of miR-182-5p and ZFP36L1 in tumor development and progression of NPC. Bioinformatics tools and luciferase reporter assays were utilized to identify the potential mechanisms of action. Moreover, rescue experiments were applied to explore whether ZFP36L1 mediated the effects of miR-182-5p in NPC. RESULTS: Up-regulation of miR-182-5p was significantly associated with tumor development and poor prognosis in patients with NPC. Functional study demonstrated that miR-182-5p overexpression enhanced, whereas suppression of miR-182-5p impeded NPC cell proliferation, migration, tumorigenesis and metastasis. Mechanistically, miR-182-5p interacted with ZFP36L1 at two sites in its 3' un-translated region (UTR) and repressed ZFP36L1 expression in NPC. Consistently, an inverse correlation was observed between the expression levels of miR-182-5p and ZFP36L1 using clinical NPC tissues, and down-regulation of ZFP36L1 in NPC predicts poor survival. Furthermore, overexpression of miR-182-5p in NPC was partly attributable to the transcriptional activation effect induced by hypoxia-inducible factor 1α (HIF-1α). CONCLUSIONS: Our data suggests that miR-182-5p facilitates cell proliferation and migration in NPC through its ability to down-regulate ZFP36L1 expression, and that the HIF-1α/miR-182-5p/ZFP36L1 axis may serve as a novel therapeutic target in the management of NPC.
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Polo-like kinase 4 (PLK4) has been reported to contribute to tumor growth, invasion, and metastasis. However, the role of PLK4 in human bladder cancer (BC) remains unclear. Here, we demonstrate the regulatory function of PLK4 in human BC progression. PLK4 is overexpressed in BC cell lines and tissues, and its overexpression correlated with poor prognosis. Our transcriptome analysis combined with subsequent functional assays indicated that PLK4 inhibition can suppress BC cell growth and induce cell cycle arrest at G1 phase via activation of the p38/p53/p21 pathway in vitro and in vivo. Overall, our data suggest that PLK4 is a critical regulator of BC cell proliferation, and thus, it may have potential as a novel molecular target for BC treatment.
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Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Puntos de Control de la Fase G1 del Ciclo Celular/genética , Proteínas Serina-Treonina Quinasas/genética , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Transducción de Señal , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone and is involved in tumor progression by promoting angiogenesis. However, the regulatory network of HSP47 in angiogenesis remains elusive. In this study, we report a novel mechanism of HSP47-induced angiogenesis in bladder cancer (BC). We find that HSP47 is abnormally overexpressed in BC and is correlated with poor prognosis. HSP47 down-regulation suppresses angiogenesis in BC cells. Mechanistically, activation of the ERK pathway and induction of C-C Motif Chemokine Ligand 2 (CCL2) are responsible for HSP47-induced angiogenesis. The correlation between HSP47 with CCL2 and angiogenesis is further confirmed in BC clinical samples. Taken together, our findings suggest that HSP47 contributes to BC angiogenesis by induction of CCL2 and provide a potential anti-angiogenesis target for BC therapy.
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Proteínas del Choque Térmico HSP47 , Neoplasias de la Vejiga Urinaria , Quimiocina CCL2 , Quimiocinas , Proteínas del Choque Térmico HSP47/metabolismo , Humanos , Ligandos , Neovascularización PatológicaRESUMEN
Bladder cancer is one of the most common malignancy in the urinary tract with high recurrence and drug resistance in clinics. Alternative treatments from existing drugs might be a promising strategy. Nitazoxanide (NTZ), an FDA-approved antiprotozoal drug, has got increasingly noticed because of its favorable safety profile and antitumor potential, yet the effects in bladder cancer and underlying mechanisms remain poorly understood. Herein, we find that NTZ induces mitochondrial damage and mitophagy initiation through PINK1-generated phospho-ubiquitin(pS65-Ub) and autophagy receptor-mediated pathway even in the absence of Atg5/Beclin1. Meanwhile, NTZ inhibits lysosomal degradation activity, leading to mitophagy flux impairment at late stage. Mitochondrial reactive oxygen species (ROS) production is critical in this process, as eliminating ROS with N-acetylcysteine (NAC) efficiently inhibits PINK1 signaling-mediated mitophagy initiation and alleviates lysosomal dysfunction. Co-treatment with NTZ and autophagy inhibitor Chloroquine (CQ) to aggravate mitophagy flux impairment promotes NTZ-induced apoptosis, while alleviation of mitophagy flux impairment with ROS scavenger reduces cell death. Moreover, we also discover a similar signaling response in the 3D bladder tumor spheroid after NTZ exposure. In vivo study reveals a significant inhibition of orthotopic bladder tumors with no obvious systemic toxicity. Together, our results uncover the anti-tumor activities of NTZ with the involvement of ROS-mediated mitophagy modulation at different stages and demonstrate it as a potential drug candidate for fighting against bladder tumors.
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Antineoplásicos/farmacología , Lisosomas/metabolismo , Mitofagia/efectos de los fármacos , Nitrocompuestos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Tiazoles/farmacología , Neoplasias de la Vejiga Urinaria/metabolismo , Animales , Antineoplásicos/uso terapéutico , Antiparasitarios/farmacología , Antiparasitarios/uso terapéutico , Relación Dosis-Respuesta a Droga , Femenino , Células HEK293 , Humanos , Lisosomas/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Mitofagia/fisiología , Nitrocompuestos/uso terapéutico , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Tiazoles/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
BACKGROUND: Bladder cancer is one of the most common malignancies. So far, no effective biomarker for bladder cancer prognosis has been identified. Aberrant DNA methylation is frequently observed in the bladder cancer and holds considerable promise as a biomarker for predicting the overall survival (OS) of patients. MATERIALS AND METHODS: We downloaded the DNA methylation and transcriptome data for bladder cancer from The Cancer Genome Atlas (TCGA), a public database, screened hypo-methylated and up-regulated genes, similarly, hyper-methylation with low expression genes, then retrieved the relevant methylation sites. Cox regression analysis was used to identify a nine-methylation site signature of a training group. Predictive ability was validated in a test group by receiver operating characteristic (ROC) analysis. RESULTS: We identified nine bladder cancer-specific methylation sites as potential prognostic biomarkers and established a risk score system based on the methylation site signature to evaluate the OS. The performance of the signature was accurate, with area under curve was 0.73 in the training group and 0.71 in the test group. Taking clinical features into consideration, we constructed a nomogram consisting of the nine-methylation site signature and patients' clinical variables, and found that the signature was an independent risk factor. CONCLUSIONS: Overall, the significant nine methylation sites could be novel prediction biomarkers, which could aid in treatment and also predict the overall survival likelihoods of bladder cancer patients.
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Biomarcadores de Tumor/genética , Metilación de ADN , Técnicas de Apoyo para la Decisión , Perfilación de la Expresión Génica , Nomogramas , Proteoma , Neoplasias de la Vejiga Urinaria/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
BACKGROUND: Transurethral seminal vesiculoscopy (TSV) is a safe and effective method for intractable hemospermia. It uses a natural cavity, is fast, involves little trauma, and boasts a low incidence of complications. Because uncontrollable penile erection during general anesthesia will severely influence the surgical operation or even damage the endoscope, spinal anesthesia was applied more on TSV. But spinal anesthesia extends the length of stay in the hospital and brings patients unnecessary discomfort. As the TSV is a quick recovery operation, we should think about a more suitable mode for these patients. METHODS: A total of 141 patients received TSV between January 2015 and July 2019: 81 patients received day surgery under caudal block (group A), and 60 received inpatient surgery under spinal anesthesia (group B). Operative time, postoperative hospital stay, hemospermia remission rate, magnetic resonance imaging (MRI) remission rate are compared. Visual analog scale (VAS) scores of groups were taken and compared at 2 time points: when there was pain during surgery (T1) and at the end of surgery (T2). Surgical methods of two groups are the same. RESULTS: The mean operative time of two groups are 34 min (group A) and 32 min (group B), and there was no statistical difference. Postoperative hemospermia remission rates are both 100% at 3 months, which at 6 months are 60% and 48%, and there was no statistical difference. MRI remission at 3 months are 72% and 57%, which has no statistical difference. Postoperative complications were mild in two groups like hematuria and dysuria which can relieve within one day, and there were no severe complications. Intraoperative pain was present in 18.5% (15/81) of group A. Their highest VAS score was 3 points, indicating mild pain, which did not influence the surgical process or postoperative recovery. The postoperative VAS scores were similar between the 2 groups. Group A did not require postoperative hospitalization, whereas the average postoperative hospitalization in group B was 2 days. CONCLUSIONS: Seminal vesiculoscopy can be performed as a day surgery under caudal block, which has obvious advantages in accelerating postoperative recovery and shortening the hospital stay.
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Bladder cancer is one of the most common and highly vascularized cancers. To better understand its genomic structure and underlying etiology, we conduct whole-genome and targeted sequencing in urothelial bladder carcinomas (UBCs, the most common type of bladder cancer). Recurrent mutations in noncoding regions affecting gene regulatory elements and structural variations (SVs) leading to gene disruptions are prevalent. Notably, we find recurrent ADGRG6 enhancer mutations and FRS2 duplications which are associated with higher protein expression in the tumor and poor prognosis. Functional assays demonstrate that depletion of ADGRG6 or FRS2 expression in UBC cells compromise their abilities to recruit endothelial cells and induce tube formation. Moreover, pathway assessment reveals recurrent alterations in multiple angiogenesis-related genes. These results illustrate a multidimensional genomic landscape that highlights noncoding mutations and SVs in UBC tumorigenesis, and suggest ADGRG6 and FRS2 as novel pathological angiogenesis regulators that would facilitate vascular-targeted therapies for UBC.
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Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas de la Membrana/genética , Mutación , Receptores Acoplados a Proteínas G/genética , Neoplasias de la Vejiga Urinaria/irrigación sanguínea , Neoplasias de la Vejiga Urinaria/genética , Línea Celular Tumoral , Análisis Mutacional de ADN , Exoma , Dosificación de Gen , Predisposición Genética a la Enfermedad , Humanos , Neovascularización Patológica , Secuencias Reguladoras de Ácidos Nucleicos , Neoplasias de la Vejiga Urinaria/patología , Secuenciación Completa del GenomaRESUMEN
Primary carcinoma of the renal calyx is extremely rare. The present study reported nephron sparing endoscopic treatment for primary carcinoma of the renal calyx. An 81-year-old female presented with a 1-year history of intermittent painless gross hematuria. Computed tomography and X-ray of the urinary tract were unable to definitively identify any lesion. Flexible ureteroscopic examination revealed a tumor with epicenter in the lower calyx of the right kidney, with additional involvement around the calyx. Biopsies were obtained and pathology revealed low-grade urothelial carcinoma. Considering additional co-morbidities, the patient elected to undergo endoscopic management with thulium laser. The present report described the feasibility of flexible ureteroscopic thulium laser resection for the treatment of renal calyx carcinoma.
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OBJECTIVE: To compare extracorporeal shock wave lithotripsy (ESWL) and ureteroscopic lithotripsy (URSL) in terms of efficacy, complications, and overall efficiency in the management of proximal ureteral calculi. ESWL and URSL are the 2 most common modalities for treating ureteral stones. Previous studies and meta-analyses suggest that for stones <10 mm, ESWL is safer and of comparable efficacy compared with URSL. However, the choice between one modality over the other for the treatment of stones >10 mm is not as clear. METHODS: The literature was reviewed in the databases, and resulting reports were screened for relevance. This process yielded 10 articles, which were analyzed in terms of the initial stone-free rate (primary outcome measure) compared between the 2 treatment modalities. Pretreatment rate, operation time, auxiliary procedure rate, and complication rate constituted secondary measures in the analysis. RESULTS: A statistically higher initial stone-free rate was demonstrated for URSL compared with ESWL (odds ratio [OR] = 0.349; 95% confidence interval [CI] = 0.183-0.666; P = .001). ESWL showed a statistically higher retreatment rate compared with URSL (OR = 7.192; 95% CI = 4.934-10.482; P <.001). The 2 treatment modalities did not show statistically significant differences in mean operating time (OR = 10.35; 95% CI = -0.29 to 20.99; P = .056), auxiliary procedure rate (OR = 1.043; 95% CI = 0.415-2.616; P = .929), or in the complication rate (OR = 0.78; 95% CI = 0.304-1.984; P = .598). CONCLUSION: For treating large (>10 mm) proximate ureteral stones, URSL tends to be more effective than ESWL, yet without adding significant risk.
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Litotricia/métodos , Cálculos Ureterales/terapia , Humanos , Litotricia/efectos adversos , Tempo Operativo , Resultado del Tratamiento , Cálculos Ureterales/patología , UreteroscopíaRESUMEN
Prostate cancer is a common cancer in men. Genetic variations in inflammatory response genes can potentially influence the risk of prostate cancer. We aimed to examine the association between PPARG Pro12Ala, NFKB1 -94 ins/del, NFKBIA -826C/T, COX-1 (50C>T), and COX-2 (-1195G>A) polymorphisms on prostate cancer risk. The genotypes of the polymorphisms were ascertained in 543 prostate cancer patients and 753 controls through PCR-RFLP and the risk association was evaluated statistically using logistic regression analysis. The NFKB1 -94 polymorphism was shown to decrease prostate cancer risk in both heterozygous and homozygous comparison models (odds ratios of 0.74 (95% CI = 0.58-0.96) (P = 0.02) and 0.57 (95% CI = 0.42-0.78) (P < 0.01), resp.). An opposite finding was observed for COX-2 (-1195) polymorphism (odds ratios of 1.58 (95% CI = 1.15-2.18) (P < 0.01) for heterozygous comparison model and 2.08 (95% CI = 1.48-2.92) (P < 0.01) for homozygous comparison model). No association was observed for other polymorphisms. In conclusion, NFKB1 -94 ins/del and COX-2 (-1195G>A) polymorphisms may be, respectively, associated with decreased and increased prostate cancer risk in the Chinese population.
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Ciclooxigenasa 2/genética , Estudios de Asociación Genética , Subunidad p50 de NF-kappa B/genética , Neoplasias de la Próstata/genética , Ciclooxigenasa 1/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Proteínas I-kappa B/genética , Masculino , Inhibidor NF-kappaB alfa , PPAR gamma/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Neoplasias de la Próstata/patología , Factores de RiesgoRESUMEN
An Ussuri catfish Pseudobagrus ussuriensis skin (UCS) cell line was developed and subcultured for more than 60 passages. UCS cells consisted of mostly epithelial-like cells and multiplied well in TC199 medium supplemented with 10% fetal bovine serum at 25°C. Chromosome analysis revealed that most UCS cells had a normal diploid karyotype with 2n=52. UCS cells showed differential cytopathic effects (CPEs) after inoculation of spring viremia of carp virus (SVCV, a negative-strand RNA virus), grass carp reovirus (GCRV, a multi-segmented double-stranded RNA virus) and Rana grylio virus (RGV, a large double-stranded DNA virus), and were indicative of high sensitivities to these three aquatic animal viruses by a virus titration study. The CPE caused by SVCV appeared as rounded and granular cells, grape-like clusters and small lytic plaques. Characteristic CPE containing plaque-like syncytia was induced by GCRV. RGV-infected cells produced typical CPE characterized by cells shrinkage and aggregation, formation of clear plaques and cell sheet detachment. Furthermore, significant fluorescent signals were observed after UCS cells were transfected with green fluorescent protein reporter plasmids, and the development of CPE induced by a recombinant RGV, ΔTK-RGV, in UCS cells was illustrated using a combination of light and fluorescence microscopy. The data from this study suggested that UCS cell line can potentially serve as a useful tool for the comparison study of different aquatic animal viruses and the isolation of some newly emerging viruses in Ussuri catfish farming.
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Bagres , Línea Celular , Efecto Citopatogénico Viral , Ranavirus/crecimiento & desarrollo , Reoviridae/crecimiento & desarrollo , Rhabdoviridae/crecimiento & desarrollo , Piel , Animales , Medios de Cultivo/química , Células Epiteliales/fisiología , Células Epiteliales/virología , Ranavirus/patogenicidad , Reoviridae/patogenicidad , Rhabdoviridae/patogenicidad , Temperatura , Ensayo de Placa ViralRESUMEN
The MaMV-DC cyanophage, which infects the bloom-forming cyanobacterium Microcystis aeruginosa, was isolated from Lake Dianchi, Kunming, China. Twenty-one cyanobacterial strains were used to detect the host range of MaMV-DC. Microcystic aeruginosa FACHB-524 and plaque purification were used to isolate individual cyanophages, and culturing MaMV-DC with cyanobacteria allowed us to prepare purified cyanophages for further analysis. Electron microscopy demonstrated that the negatively stained viral particles are tadpole-shaped with an icosahedral head approximately 70 nm in diameter and a contractile tail approximately 160 nm in length. Using one-step growth experiments, the latent period and burst size of MaMV-DC were estimated to be 24-48 hours and approximately 80 infectious units per cell, respectively. Restriction endonuclease digestion and agarose gel electrophoresis were performed using purified MaMV-DC genomic DNA, and the genome size was estimated to be approximately 160 kb. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed four major structural proteins. These results support the growing interest in using freshwater cyanophages to control bloom-forming cyanobacterium.
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Cianobacterias/crecimiento & desarrollo , Cianobacterias/aislamiento & purificación , Lagos/virología , Microcystis/virología , China , Cianobacterias/fisiología , Cianobacterias/ultraestructura , ADN Viral/genética , ADN Viral/aislamiento & purificación , Electroforesis en Gel de Agar , Electroforesis en Gel de Poliacrilamida , Especificidad del Huésped , Microscopía Electrónica de Transmisión , Mapeo Restrictivo , Ensayo de Placa Viral , Proteínas Estructurales Virales/análisis , Virión/ultraestructuraRESUMEN
OBJECTIVES: To characterize the hemodynamics comparing thulium laser vaporesection of the prostate with traditional transurethral resection of the prostate. METHODS: A total of 80 consecutive patients with benign prostatic hyperplasia were randomly assigned into the thulium laser vaporesection of the prostate group or transurethral resection of the prostate group. Transpulmonary thermodilution hemodynamic monitoring was used before and 1 h after surgery to assess patient hemodynamics. Acute complications and treatment efficiency were evaluated after surgery. RESULTS: There were no statistical differences in age, prostate volume, anticoagulants and International Prostate Symptom Score between the two groups. The postoperative Stroke Volume Index was significantly higher in the thulium laser vaporesection of the prostate group (P = 0.007). The extravascular lung water and intrathoracic blood volume indices differed significantly pre- and postoperatively, and were similar in both groups. Decreases in serum sodium and hemoglobin concentrations after surgery were lower in the thulium laser vaporesection of the prostate group (P < 0.01). Acute complications, and improvements in International Prostate Symptom Score and maximum urinary flow rates, were similar in both groups. CONCLUSIONS: Transpulmonary thermodilution hemodynamic monitoring provides additional safety measures during surgical procedures. Thulium laser vaporesection of the prostate is associated with fewer hemodynamic changes and provides similar efficacy to transurethral resection of the prostate. Thus, it can be considered a safe and effective procedure.