RESUMEN
Recent studies have shown that long non-coding RNAs (lncRNAs) play a pivotal role in the pathogenesis and progression of hepatocellular carcinoma (HCC). However, the biological action and potential mechanism of liver cancer cell drug resistance have not been clearly clarified. In this study, lncRNAs were screened and differentially expressed in parental and cisplatin-resistant cell lines (HepG2 and HepG2/CDDP). A novel lncRNA, termed NRAL (Nrf2 regulation-associated lncRNA), was identified, and the initial results indicated that it was highly expressed in HepG2 cisplatin resistant cell lines compared to their parental counterparts. Functionally, NRAL depletion significantly enhanced CDDP-mediated cytotoxicity and apoptosis in two cisplatin-resistant HCC cell lines. Mechanistically, the results indicated that NRAL regulates Nrf2 expression through miR-340-5p serving as a competing endogenous RNA (ceRNA), thus influencing the CDDP-induced phenotype in HCC. Collectively, the present investigation suggest that the NRAL/miR-340-5p/Nrf2 axis mediates cisplatin resistance in HCC, which may provide novel targets for overcoming cisplatin resistance in hepatocellular carcinoma cells.
RESUMEN
Objective To observe the clinical application of all seeing needle system system in diagnosis and treatment of patients with hematospermia. Methods From May 2015 to September 2016, 22 patients with hemospermia were treated with seminal vesiculoscopy and seminal vesicle lithotripsy by using a all seeing needle system instead of traditional seminal vesicle. Results All the patients were successfully found the seminal vesicle gland and successfully entered the seminal vesicle gland, 16 cases had chronic inflammation of the seminal vesicle, dilute iodine rinse, 6 cases of seminal vesicle, holmium laser lithotripsy, stone basket to remove. The average operation time was (15.7 ± 6.2) min. The catheterization was performed the next day after operation. The average hospital stay was 2 d. After follow-up for 3 to 6 months, 20 patients had disappeared (90.9％). No complication was found Disease and long-term complications. Conclusion The all seeing needle system can replace the traditional seminal vesicle for the operation of seminal vesicle. The puncture system is short, directional and maneuverable. It has advantages of short operation time, simple operation, easy to master and no complications.
Asunto(s)
Ginecomastia/genética , Infertilidad Masculina/genética , Mutación/genética , Receptores Androgénicos/genética , Adulto , Secuencia de Aminoácidos , Exones/genética , Ginecomastia/sangre , Ginecomastia/diagnóstico , Humanos , Infertilidad Masculina/sangre , Infertilidad Masculina/diagnóstico , Masculino , Datos de Secuencia Molecular , Receptores Androgénicos/análisis , Testosterona/sangreAsunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Genes erbB-1/genética , Neoplasias Pulmonares/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , MutaciónRESUMEN
BACKGROUND: Recently, peroxiredoxin3 (PRDX3) was identified as a novel molecular marker for the progression of hepatocellular carcinoma (HCC). However, its potential clinical application as a serum marker for the early diagnosis and prognosis of HCC has not been investigated. METHODS: PRDX3, alpha-fetaprotein (AFP), and other biochemical parameters were measured in serum samples from 297 Chinese patients, including 96 with HCC, 98 with liver cirrhosis (LC), and 103 healthy controls (HCs). Correlations between serum PRDX3 expression and clinicopathological variables and the relationship between serum PRDX3 expression and prognosis were analyzed. RESULTS: Serum PRDX3 was significantly higher in HCC patients than in the LC and HC groups. The sensitivity and specificity of serum PRDX3 for the diagnosis of HCC were 85.9% and 75.3%, respectively, at a cutoff of 153.26 ng/mL, and the area under the curve was 0.865. Moreover, serum PRDX3 expression was strongly associated with AFP level, tumor diameter, TNM stage, and portal vein invasion. Kaplan-Meier curve analysis revealed that HCC patients with high serum PRDX3 expression had a shorter median survival time than those with low PRDX3 expression. Moreover, serum PRDX3 expression was an independent risk factor for overall survival. The inverse correlation between serum PRDX3 and patient survival remained significant in patients with early-stage HCC and in those with normal serum AFP levels. CONCLUSIONS: Serum PRDX3 can be used as a noninvasive biomarker for the diagnosis and/or prognosis of HCC.
Asunto(s)
Carcinoma Hepatocelular/sangre , Neoplasias Hepáticas/sangre , Peroxiredoxina III/sangre , Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidad , China , Comorbilidad , Progresión de la Enfermedad , Detección Precoz del Cáncer , Femenino , Humanos , Estimación de Kaplan-Meier , Cirrosis Hepática/sangre , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , alfa-Fetoproteínas/metabolismoRESUMEN
Molecular epidemiological studies have shown that gene polymorphisms of estrogen receptor alpha gene (ESR-α) are associated with breast cancer risk. However, previous results from many molecular studies have been inconsistent. In this study, we examined two polymorphisms (PvuII and XbaI RFLPs) of the ESR-α gene in 542 breast cancer cases and 1,016 controls from China. Associations between the polymorphisms and breast cancer risk were calculated with an unconditional logistic regression model. Linkage disequilibrium and haplotypes were analyzed with the SHEsis software. In addition, we also performed a systematic meta-analysis of 24 published studies evaluating the association. No significant associations were found between the PvuII polymorphism and breast cancer risk. However, a significantly decreased risk of breast cancer was observed among carriers of the XbaI 'G' allele (age-adjusted OR = 0.80; 95% CI = 0.66- 0.97) compared with carriers of the 'A' allele. Haplotype analysis showed significantly decreased cancer risk for carriers of the 'CG' haplotype (OR = 0.79; 95% CI = 0.66- 0.96). In the systematic meta-analysis, the XbaI 'G' allele was associated with an overall significantly decreased risk of breast cancer (OR = 0.90, 95% CI = 0.82- 1.00). In addition, the PvuII 'C' allele showed a 0.96- fold decreased disease risk (95% CI = 0.92- 0.99). In subgroup analysis, an association between the PvuII 'C' and XbaI 'G' alleles and breast cancer risk was significant in Asians ('C' vs. 'T': OR = 0.93, 95% CI = 0.85- 1.00; 'G' vs. 'A': OR = 0.82, 95% CI = 0.68- 0.98), but not in Euro-Americans. Thus, our results provide evidence that ESR-α polymorphisms are associated with susceptibility to breast cancer. These associations may largely depend on population characteristics and geographic location.
Asunto(s)
Neoplasias de la Mama/etiología , Carcinoma Ductal de Mama/etiología , Receptor alfa de Estrógeno/genética , Neoplasias de las Paratiroides/etiología , Polimorfismo Genético/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Estudios de Casos y Controles , China , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Desequilibrio de Ligamiento , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias de las Paratiroides/patología , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Pronóstico , Factores de Riesgo , Adulto JovenRESUMEN
Many chemotherapeutic agents have been successfully used to treat hepatocellular carcinoma (HCC); however, the development of chemoresistance in liver cancer cells usually results in a relapse and worsening of prognosis. It has been demonstrated that DNA methylation and histone modification play crucial roles in chemotherapy resistance. Currently, extensive research has shown that there is another potential mechanism of gene expression control, which is mediated through the function of short noncoding RNAs, especially for microRNAs (miRNAs), but little is known about their roles in cancer cell drug resistance. In present study, by taking advantage of miRNA effects on the resistance of human hepatocellular carcinoma cells line to cisplatin, it has been demonstrated that miR-340 were significantly downregulated whereas Nrf2 was upregulated in HepG2/ CDDP (cisplatin) cells, compared with parental HepG2 cells. Bioinformatics analysis and luciferase assays of Nrf2-3'-untranslated region-based reporter constructor indicated that Nrf2 was the direct target gene of miR- 340, miR-340 mimics suppressing Nrf2-dependent antioxidant pathway and enhancing the sensitivity of HepG2/ CDDP cells to cisplatin. Interestingly, transfection with miR-340 mimics combined with miR-340 inhibitors reactivated the Nrf2 related pathway and restored the resistance of HepG2/CDDP cells to CDDP. Collectively, the results first suggested that lower expression of miR-340 is involved in the development of CDDP resistance in hepatocellular carcinoma cell line, at least partly due to regulating Nrf2-dependent antioxidant pathway.