RESUMO
PURPOSE: Cholangiocarcinoma (CHOL) comprises a cluster of highly heterogeneous malignant biliary tumors. Flap endonuclease-1 (FEN1) is a member of the Rad2 structure-specific nuclease family. This study aimed to explore the biological functions and mechanisms of FEN1 in CHOL. METHODS: FEN1 expression was analyzed in tissues of patients with CHOL and FEN1 mutations. We observe the influence of FEN1 on cellular proliferation, migration, and invasion, as well as on DNA damage repair and glycolysis. Western blotting was performed to determine the regulatory mechanism of FEN1 in CHOL progression. RESULTS: FEN1 was highly expressed in the cancer tissues of CHOL patients. The high mutation rate of FEN1 in CHOL tissues was mainly due to the amplified repeats. FEN1 promotes the proliferation, migration, and invasion of HUCCT1 and QBC939 cells. In addition, FEN1 induced DNA damage repair and aerobic glycolysis in CHOL cells. FEN1 also promoted xenograft tumor growth in vivo. Moreover, we showed that FEN1 mediated the epithelial-mesenchymal transition (EMT) of CHOL. FEN1-mediated EMT was found to be transduced by the Wnt/ß-catenin signaling pathway. CONCLUSION: FEN1 was significantly overexpressed in CHOL tissues, and FEN1 regulates the progression of CHOL through the Wnt/ß-catenin signaling pathway.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Via de Sinalização Wnt/genética , Endonucleases Flap/genética , Endonucleases Flap/metabolismo , Linhagem Celular Tumoral , Colangiocarcinoma/genética , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos , Transição Epitelial-Mesenquimal/genética , Proliferação de Células/genética , beta Catenina/genética , beta Catenina/metabolismo , Regulação Neoplásica da Expressão Gênica , Movimento CelularRESUMO
OBJECTIVE: Ghrelin is a gastric acyl-peptide that has been identified as an endogenous ligand for the growth hormone secretagogue receptor. It has been reported to have cardioprotective activities independent of growth hormone release. We investigated the effect of ghrelin on apoptosis induced by high glucose and sodium palmitate and the mechanisms underlying the cardioprotective activities of ghrelin. RESEARCH DESIGN AND METHODS: Cardiomyocytes were isolated from hearts of adult rats and cultured in serum-free MEM. High glucose (30 mM) or sodium palmitate (0.5 mM) were used to induce apoptosis. Apoptosis was detected using an annexin V-FITC/PI binding assay and a caspase 3 activity assay. Reactive oxygen species were detected using a DCFH-DA fluorescent probe. Phospho-Akt, phospho-ERK, and NF kappaB levels were determined using ELISA. The transcription of genes was analyzed using real-time PCR. RESULTS: Ghrelin can inhibit apoptosis induced by oxidative stress in cardiomyocytes from adult rats through the activation of the PI3K-Akt signaling pathway. In addition, ghrelin does not decrease intracellular oxidative stress. Activation of the MEK-ERK1/2 signaling pathway has no influence on the inhibition of apoptosis. Finally, ghrelin activates NF kappaB and subsequently increases the transcription of survival genes such as Bcl-2, Bcl-xL, c-iap, and c-fos. CONCLUSION: Our research provides evidence that ghrelin may act as a survival factor under oxidative stress in cardiomyocytes. This may provide a clue for therapy for myocardial disease in diabetes mellitus.
Assuntos
Apoptose/efeitos dos fármacos , Grelina/farmacologia , Glucose/farmacologia , Ácido Palmítico/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Western Blotting , Caspase 3/metabolismo , Células Cultivadas , Inibidores Enzimáticos/farmacologia , Ensaio de Imunoadsorção Enzimática , Masculino , NF-kappa B/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Edulcorantes/farmacologiaRESUMO
PURPOSE: The purpose of this study was to investigate the clinicopathological features of oral condylomas in children and condylomatous lesions of their mothers. Moreover, the authors sought to determine the mode of transmission of this disease and to find the genotype of human papilloma virus (HPV) in the children's oral condyloma. METHODS: Nine instances of oral condyloma acuminatum in children and lesions in their mothers were reviewed. Their HPV genotypes were evaluated by in situ hybridization (ISH). RESULTS: This study revealed that the lesions appeared during 3 years of age and the most common location was the hard and soft palate. Seven of the 9 mothers had experienced vulva and/or oral cavity condylomata during pregnancy. Social evaluation confirmed sexual abuse in 1 girl, and probable sexual abuse in another girl. The results of ISH demonstrated HPV 16/18 DNA being positive in 5 of the 9 cases, and HPV 6 and HPV 11, HPV 6 and HPV 16/18, HPV 6, and HPV 11 DNA being positive, respectively, in 1 case. HPV DNA types in mother-child pairs were not concordant. CONCLUSIONS: Oral condyloma acuminatum in children is probably induced by HPV 16/18. The mode of transmission by sexual abuse is the most likely route. Prenatal transmission of HPV to children is rare. This study provides further confirmation of possible different genotype and transmission in oral CA of children and adults.