RESUMEN
BACKGROUND/AIMS: Berberine (BBR) is an isoquinoline alkaloid and is beneficial for the anticancer effect on a variety of human tumor cells. However, BBR's anti-angiogenesis property and its clinical potential as an inhibitor of tumor angiogenesis in breast cancer cells have not been fully elucidated. Here, we investigated the effect of BBR on TPA-induced VEGF and fibronectin (FN) as well as VEGF-induced FN in breast cancer cells. METHODS: The secretion of VEGF protein was detected by ELISA. Fibronectin mRNA and protein expression was analyzed by Real-Time PCR and western blotting, respectively. The overexpressions of CA-MEK, and CA-Akt were examined by adenovirus system. RESULTS: Our results showed that TPA, a tumor promoter, significantly increased the level of VEGF and FN expression in both MCF7 and T47D breast cancer cells. On the other hand, TPA-induced VEGF and FN expression was suppressed by LY294002, a PI-3K inhibitor. In contrast, the level of FN expression also significantly increased by constitutively active (CA)-AKT overexpression. We also found that TPA-induced VEGF and FN expression was decreased by BBR treatment. Finally, our results showed that VEGF augmented the expression of FN whereas VEGF-induced FN expression was decreased by BBR treatment. CONCLUSION: Taken together, we suggest that BBR may suppress TPA-induced VEGF and FN as well as VEGF-induced FN through the inhibition of the PI-3K/AKT pathway in breast cancer cells. Therefore, we suggest that BBR may be used as a candidate drug for the inhibition of angiogenesis of human breast cancer.
Asunto(s)
Berberina/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Fibronectinas/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Humanos , Células MCF-7/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Factor A de Crecimiento Endotelial Vascular/farmacologíaRESUMEN
Endoscopic thyroidectomy is gaining greater acceptance because of its excellent cosmetic result. As the surgical skill and understanding of the endoscopic cervical anatomy has improved, the surgical indications for endoscopic thyroidectomy have recently expanded to small size thyroid cancer. Despite the many advantages of laparoscopic surgery, there have been incidental reports about recurrences at the site of insertion of the laparoscope or other instruments in other cancers. Herein, we present a case of 25-year-old woman who had recurrent cancers around the operative bed and subcutaneous tunnel after endoscopic thyroidectomy.
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Endoscopía/efectos adversos , Siembra Neoplásica , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/cirugía , Tiroidectomía/métodos , Adulto , Biopsia con Aguja Fina , Femenino , Humanos , Punciones , Tiroidectomía/efectos adversosRESUMEN
PURPOSE: The aim of the current study is to assess the spectrum of genetic variation in the BRIP1 gene among Korean high-risk breast cancer patients who tested negative for the BRCA1/2 mutation. MATERIALS AND METHODS: Overall, 235 Korean patientswith BRCA1/2 mutation-negative high-risk breast cancerwere screened for BRIP1 mutations. The entire BRIP1 gene was analyzed using fluorescent-conformation sensitive gel electrophoresis. In silico analysis of BRIP1 variants was performed using PolyPhen-2 and SIFT. RESULTS: A total of 20 sequence alterations including 12 exonic and eight intronic variantswere found. Among the 12 exonic variants, 10 were missense and two were silent mutations. No protein-truncating mutation was found among the tested patients. Among the 10 missense variants, four (p.L263F, p.L340F, p.L474P, and p.R848H) were predicted to be pathogenic by both PolyPhen-2 and SIFT, and these variants were found in five patients. Of the four missense variants, p.L263F, p.L474P, and p.R848H localize to regions between the helicase motifs, while p.L340F resides in an iron-sulfur domain of BRIP1. CONCLUSION: No protein-truncating mutation in BRIP1 was found among the tested patients. The contribution of BRIP1 variants is thought to be minor in Korean non-BRCA1/2 high-risk breast cancer.
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Pueblo Asiatico/genética , Neoplasias de la Mama/genética , Proteínas del Grupo de Complementación de la Anemia de Fanconi/genética , Predisposición Genética a la Enfermedad/genética , ARN Helicasas/genética , Adulto , Anciano , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/epidemiología , Análisis Mutacional de ADN/métodos , Exones/genética , Femenino , Humanos , Intrones/genética , Persona de Mediana Edad , Mutación Missense , Dominios Proteicos/genética , República de Corea/epidemiología , Mutación Silenciosa , Adulto JovenRESUMEN
The purpose of the present study was to analyze genetic variations in the NBS1 gene and to evaluate the contribution of heterozygous NBS1 mutation to the risk of breast cancer among Korean patients with high-risk breast cancer negative for BRCA1/2 mutation. We screened 235 non-BRCA1/2 Korean patients with high-risk breast cancer for NBS1 mutations. The entire NBS1 gene was sequenced using fluorescent conformation-sensitive capillary electrophoresis. In silico analysis of the NBS1 variants was performed using PolyPhen-2 and SIFT. The frequency of variants predicted to be deleterious by in silico analysis was compared between breast cancer patients and controls. Twenty-eight sequence variants in the NBS1 gene were identified: 9 exonic variants, including 5 missense mutations (p.R169C, p.I171V, p.E185Q, p.E564K, and p.F603L) and 4 silent mutations, and 19 variants within introns. Among the five missense variants, p.I171V (c.511A > G) was the only variant predicted to be deleterious by in silico analysis. Heterozygosity for p.I171V was found in 4/235 patients with breast cancer and 3/281 individuals in the control group. The frequency of p.I171V was not significantly different between the patient and control groups (1.7 vs. 1.06%, p = 0.7). Heterozygosity of p.I171V in the NBS1 gene was found in a small proportion of Korean patients with high-risk breast cancer. The contribution of the p.I171V variant to the development of breast cancer among Korean patients was not significant.
Asunto(s)
Neoplasias de la Mama/genética , Proteínas de Ciclo Celular/genética , Mutación de Línea Germinal , Proteínas Nucleares/genética , Adulto , Pueblo Asiatico/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama Masculina/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Heterocigoto , Humanos , Masculino , Mutación MissenseRESUMEN
PURPOSE: The purpose of this study is to evaluate the role of regular postoperative surveillance to improve the prognosis of patients with breast cancer after curative surgery. MATERIALS AND METHODS: We retrospectively analyzed the medical records of 4,119 patients who received curative surgery for breast cancer at Samsung Medical Center between January 2000 and September 2008. Patients were divided into two groups (group I, regular postoperative surveillance; group II, control group) according to their post-therapy follow-up status for the first 5 years after surgery. RESULTS: Among the 3,770 patients selected for inclusion, groups I and II contained 3,300 (87%) and 470 (13%) patients, respectively. The recurrence rates at 5 years for groups I and II were 10.6% and 16.4%, respectively (hazard ratio, 0.85; 95% confidence interval [CI], 0.67 to 1.09; p=0.197). The 10-year mortality cumulative rates were 8.8% for group I and 25.4% for group II (hazard ratio, 0.28; 95% CI, 0.22 to 0.35; p < 0.001). In multivariate analysis for recurrence-free survival (RFS), age over 40 years (p < 0.001), histologic grade 1 (p < 0.001), and pathologic stage I (p < 0.001) were associated with longer RFS but not with follow-up status. Multivariate analysis for overall survival (OS) revealed that patients in group I showed significantly improved OS (hazard ratio, 0.29; 95% CI, 0.23 to 0.37; p < 0.001). Additionally, age over 40 years, histologic grade I, and pathologic stage I were independent prognostic factors for OS. CONCLUSION: Regular follow-up for patients with breast cancer after primary surgery resulted in clinically significant improvements in patient OS.