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OBJECTIVE: This study aimed to explore the Liquid-liquid phase separation (LLPS)-related genes associated with the prognosis of bladder cancer (BCa) and assess the potential application of LLPS-related prognostic signature for predicting prognosis in BCa patients. METHODS: Clinical information and transcriptome data of BCa patients were extracted from the Cancer Genome Atlas-BLCA (TCGA-BLCA) database and the GSE13507 database. Furthermore, 108 BCa patients who received treatment at our institution were subjected to a retrospective analysis. The least absolute shrinkage and selection operator (LASSO) analysis was performed to develop an LLPS-related prognostic signature for BCa. The CCK8, wound healing and Transwell assays were performed. RESULTS: Based on 62 differentially expressed LLPS-related genes (DELRGs), three DELRGs were screened by LASSO analysis including kallikrein-related peptidase 5 (KLK5), monoacylglycerol O-acyltransferase 2 (MOGAT2) and S100 calcium-binding protein A7 (S100A7). Based on three DELRGs, a novel LLPS-related prognostic signature was constructed for individualized prognosis assessment. Kaplan-Meier curve analyses showed that LLPS-related prognostic signature was significantly correlated with overall survival (OS) of BCa. ROC analyses demonstrated the LLPS-related prognostic signature performed well in predicting the prognosis of BCa patients in the training group (the area under the curve (AUC) = 0.733), which was externally verified in the validation cohort 1 (AUC = 0.794) and validation cohort 2 (AUC = 0.766). Further experiments demonstrated that inhibiting KLK5 could affect the proliferation, migration, and invasion of BCa cells. CONCLUSIONS: In this study, a novel LLPS-related prognostic signature was successfully developed and validated, demonstrating strong performance in predicting the prognosis of BCa patients.
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INTRODUCTION: This study investigates the relationship between cellularity and capsular characteristics of pleomorphic adenoma and its influence on operative strategies. MATERIAL AND METHODS: The capsular characteristics and clinical data of patients with pleomorphic adenomas were reviewed according to Seifert's definition: (1) classic type with balanced amount of cells and stroma, (2) myxoid type with abundant ground substance, interspersed spindle cells, and (3) cellular type with predominance of ductal trabecular structures and little stroma. The immunoreactivity of cellular proliferation (Ki-67) was semi-quantitatively measured using immunohistochemistry. Variables were analyzed using Fisher's test and one-way ANOVA, with (p < 0.05) considered statistically significant. RESULTS: The duration of presence was associated with cellularity (p = 0.01). In terms of capsular characteristics, satellite nodules and positive resection margins were not related to cellularity, except for incomplete capsules (p = 0.03). There was no difference in the staining scores of Ki-67 (p = 0.12). CONCLUSION: Lower cellularity reflects higher probability of an incomplete capsule, requiring more consideration for operative strategies to prevent recurrence.
INTRODUCCIÓN: Este estudio investiga la relación entre la celularidad y las características capsulares del adenoma pleomórfico y su influencia en las estrategias operativas. MATERIAL Y MÉTODOS: Se revisaron las características capsulares y los datos clínicos de los pacientes con adenomas pleomórficos según la definición de Seifert: 1) tipo clásico con cantidad equilibrada de células y estroma, 2) tipo mixoide con abundante sustancia fundamental, células fusiformes intercaladas y 3) tipo celular con predominio de estructuras trabeculares ductales y poco estroma. La inmunorreactividad de la proliferación celular (Ki-67) se midió semicuantitativamente usando inmunohistoquímica. Las variables se analizaron mediante la prueba de Fisher y ANOVA de una vía, considerándose significativo un valor de p inferior a 0.05. RESULTADOS: La duración de la presencia se asoció con la celularidad (p = 0.01). En cuanto a las características capsulares, los nódulos satélites y los márgenes de resección positivos no se relacionaron con la celularidad, a excepción de las cápsulas incompletas (p = 0.03). No hubo diferencia en las puntuaciones de tinción de Ki-67 (p = 0.12). CONCLUSIONES: La celularidad más baja refleja una mayor probabilidad de una cápsula incompleta, lo que requiere una mayor consideración de las estrategias quirúrgicas para prevenir la recurrencia.
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Adenoma Pleomórfico , Neoplasias de la Parótida , Adenoma Pleomórfico/cirugía , Humanos , Antígeno Ki-67 , Márgenes de Escisión , Neoplasias de la Parótida/cirugíaRESUMEN
BACKGROUND: Neuroblastoma (NB) represents the most common extracranial solid tumor in children. Accumulating evidence shows that microRNAs (miRs) play an important role in the carcinogenesis of NB. Here, we investigated the biological function of miR-1247 in NB in vitro. METHODS/RESULTS: We found miR-1247 was downregulated in NB tissues and cells using quantitative PCR analysis. Gain- and loss-of-function studies demonstrated that miR-1247 significantly suppressed cell proliferation and induced cell cycle G0/G1 phase arrest and cell apoptosis of NB cells in vitro by using MTT, colony formation assay and Flow cytometry analysis. Luciferase assay suggested ZNF346 was the target of miR-1247 and its expression could be downregulated by miR-1247 overexpression using Western blotting. Furthermore, downregulation of ZNF346 by siRNA performed similar effects with overexpression of miR-1247 in NB cells. CONCLUSIONS: Our findings suggested miR-1247 directly targeted to repress ZNF346 expression, thus suppressing the progression of NB, which might be a novel therapeutic target against NB.
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Proteínas de Unión al ADN/metabolismo , MicroARNs/metabolismo , Neuroblastoma/metabolismo , Proteínas de Unión al ARN/metabolismo , Proliferación Celular/genética , Preescolar , Ensayo de Unidades Formadoras de Colonias , Proteínas de Unión al ADN/genética , Regulación hacia Abajo , Femenino , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , MicroARNs/genética , Neuroblastoma/genética , Neuroblastoma/patología , Fenotipo , Proteínas de Unión al ARN/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Tiempo , Células Tumorales CultivadasRESUMEN
BACKGROUND: Neuroblastoma (NB) represents the most common extracranial solid tumor in children. Accumulating evidence shows that microRNAs (miRs) play an important role in the carcinogenesis of NB. Here, we investigated the biological function of miR-1247 in NB in vitro. METHODS/RESULTS: We found miR-1247 was downregulated in NB tissues and cells using quantitative PCR analysis. Gain- and loss-of-function studies demonstrated that miR-1247 significantly suppressed cell proliferation and induced cell cycle G0/G1 phase arrest and cell apoptosis of NB cells in vitro by using MTT, colony formation assay and Flow cytometry analysis. Luciferase assay suggested ZNF346 was the target of miR-1247 and its expression could be down-regulated by miR-1247 overexpression using Western blotting. Furthermore, downregulation of ZNF346 by siRNA performed similar effects with overexpression of miR-1247 in NB cells. CONCLUSIONS: Our findings suggested miR-1247 directly targeted to repress ZNF346 expression, thus suppressing the progression of NB, which might be a novel therapeutic target against NB.
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Humanos , Masculino , Femenino , Proteínas de Unión al ARN/metabolismo , MicroARNs/metabolismo , Proteínas de Unión al ADN/metabolismo , Neuroblastoma/metabolismo , Fenotipo , Factores de Tiempo , Células Tumorales Cultivadas , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Preescolar , Proteínas de Unión al ARN/genética , Ensayo de Unidades Formadoras de Colonias , MicroARNs/genética , Proliferación Celular/genética , Proteínas de Unión al ADN/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Citometría de Flujo , Neuroblastoma/genética , Neuroblastoma/patologíaRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of bipolar transurethral enucleation and resection of the prostate (B-TUERP) versus bipolar transurethral resection of the prostate (B-TURP) in the treatment of prostates larger than 60g. MATERIAL AND METHODS: Clinical data for 270 BPH patients who underwent B-TUERP and 204 patients who underwent B-TURP for BPH from May 2007 to May 2013 at our center were retrospectively analyzed. Outcome measures included operative time, decreased hemoglobin level, total prostate specific antigen (TPSA), International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), quality of life (QoL) score, post void residual urine volume (RUV), bladder irrigation duration, hospital stay, and the weight of resected prostatic tissue. Other measures included perioperative complications including transurethral resection syndrome (TURS), hyponatremia, blood transfusion, bleeding requiring surgery, postoperative acute urinary retention, urine incontinence and urinary sepsis. Patients in both groups were followed for two years. RESULTS: Compared with the B-TURP group, the B-TUERP group had shorter operative time, postoperative bladder irrigation duration and hospital stay, a greater amount of resected prostatic tissue, less postoperative hemoglobin decrease, better postoperative IPSS and Qmax, as well as lower incidences of hyponatremia, urinary sepsis, blood transfusion requirement, urine incontinence and reoperation (P<0.05 for all). CONCLUSIONS: B-TUERP is superior to B-TURP in the management of large volume BPH in terms of efficacy and safety, but this finding needs to be validated in further prospective, randomized, controlled studies.
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Próstata/cirugía , Hiperplasia Prostática/cirugía , Resección Transuretral de la Próstata/métodos , Anciano , Estudios de Seguimiento , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Tempo Operativo , Periodo Posoperatorio , Antígeno Prostático Específico/sangre , Calidad de Vida , Estudios Retrospectivos , Centros de Atención Terciaria , Irrigación Terapéutica , Resección Transuretral de la Próstata/efectos adversos , Resultado del Tratamiento , Retención Urinaria/etiología , MicciónRESUMEN
ABSTRACT Objective: To evaluate the efficacy and safety of bipolar transurethral enucleation and resection of the prostate (B-TUERP) versus bipolar transurethral resection of the prostate (B-TURP) in the treatment of prostates larger than 60g. Material and Methods: Clinical data for 270 BPH patients who underwent B-TUERP and 204 patients who underwent B-TURP for BPH from May 2007 to May 2013 at our center were retrospectively analyzed. Outcome measures included operative time, decreased hemoglobin level, total prostate specific antigen (TPSA), International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), quality of life (QoL) score, post void residual urine volume (RUV), bladder irrigation duration, hospital stay, and the weight of resected prostatic tissue. Other measures included perioperative complications including transurethral resection syndrome (TURS), hyponatremia, blood transfusion, bleeding requiring surgery, postoperative acute urinary retention, urine incontinence and urinary sepsis. Patients in both groups were followed for two years. Results: Compared with the B-TURP group, the B-TUERP group had shorter operative time, postoperative bladder irrigation duration and hospital stay, a greater amount of resected prostatic tissue, less postoperative hemoglobin decrease, better postoperative IPSS and Qmax, as well as lower incidences of hyponatremia, urinary sepsis, blood transfusion requirement, urine incontinence and reoperation (P<0.05 for all). Conclusions: B-TUERP is superior to B-TURP in the management of large volume BPH in terms of efficacy and safety, but this finding needs to be validated in further prospective, randomized, controlled studies.
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Humanos , Masculino , Anciano , Próstata/cirugía , Hiperplasia Prostática/cirugía , Resección Transuretral de la Próstata/métodos , Periodo Posoperatorio , Calidad de Vida , Micción , Estudios Retrospectivos , Estudios de Seguimiento , Retención Urinaria/etiología , Resultado del Tratamiento , Antígeno Prostático Específico/sangre , Resección Transuretral de la Próstata/efectos adversos , Tempo Operativo , Centros de Atención Terciaria , Irrigación Terapéutica , Tiempo de Internación , Persona de Mediana EdadRESUMEN
BACKGROUND: The use of trastuzumab has proven to be a successful strategy in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer; however, it is associated with an increased risk of cardiac dysfunction. We performed an up-to-date, comprehensive meta-analysis to clarify the risk of congestive heart failure (CHF) in patients with early breast cancer receiving different durations of adjuvant trastuzumab with the longest-term follow-up. METHODS: Eligible studies included randomized control trials of HER2-positive early breast cancer patients with or without trastuzumab in adjuvant chemotherapy. Adequate reporting of CHF data were required for inclusion. Statistical analyses were conducted to calculate the overall incidence, relative risk (RR), and 95% confidence interval (CI) by use of a fixed-effects model. RESULTS: Six randomized control trials including 18,111 patients were identified. The overall incidence of high-grade CHF in patients treated with trastuzumab versus placebo was 1.44% (95% CI, 0.79%-2.64%) and the RR was 3.19 (95% CI, 2.03-5.02; p < .00001). In subgroup analysis, the difference in CHF incidence failed to achieve significance. The RR for 8 mg/kg trastuzumab (high dose) was greater than that for 4 mg/kg (low dose) (RR, 6.79, 95% CI, 2.03-22.72, p = .0001; versus RR, 2.64; 95% CI, 1.61-4.32; p = .002). Additionally, higher RRs were observed for patients receiving trastuzumab for 1 year (RR, 3.29; 95% CI, 2.07-5.25) and 2 years (RR, 9.54; 95%CI, 2.19-41.43), but not 9 weeks (RR, 0.50; 95% CI, 0.05-5.49) compared with control groups. No evidence of publication bias was observed. CONCLUSION: Adjuvant trastuzumab therapy was strongly associated with an increased risk of significant CHF in patients with early breast cancer, particularly in 2-year use. IMPLICATIONS FOR PRACTICE: This comprehensive meta-analysis evaluated the risk of congestive heart failure with a usage profile of adjuvant trastuzumab in patients with early breast cancer. Before initiating treatment with trastuzumab, a risk-benefit analysis for individual patients should be critically evaluated, considering that the prognosis is closely related to drug dose and duration of use. Cardiac function should be monitored throughout the treatment period and also during follow-up. Thus, early identification of trastuzumab-related cardiac dysfunction can allow effective medical intervention, elimination of symptoms, recovery of function, and continuation of trastuzumab therapy.