RESUMEN
Breast cancer is the most common carcinoma among Chinese women. Interferon α (IFNα) has been used to treat various types of cancer, including breast cancer, but its antitumor activity is relative low, which significantly hinders its clinical application. In this study, we utilized a Ph.D.-12 peptide library screening system to identify a short peptide that specifically binds to MCF-7 breast cancer cells. By fusing the MCF-7 binding peptide (MBP) to the C-terminus of IFNα, we constructed an engineered IFNα-MBP fusion molecule (IMBP), and applied this novel fusion protein to the treatment of breast cancer. We found that IMBP exhibited significantly higher activity than wild-type IFNα in inhibiting cell growth and inducing cell apoptosis. Additionally, IMBP potentiated the therapeutic efficacy of doxorubicin-based breast cancer chemotherapy via the activation of cell cycle arrest and cell apoptosis pathway genes including p53, p21, CDK2, cyclin A, caspase 9, Bcl-2 and Bax. The enhanced activity of the synthetic IMBP was also associated with the activation of signal transducer and activation of transcription 1 (STAT1) pathway target genes (STAT1, IFIT1, IFITM1 and MX1). This study evaluated the potential value of the synthetic IMBP as a novel anti-breast cancer agent.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/administración & dosificación , Interferón-alfa/administración & dosificación , Proteínas de Neoplasias/genética , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/química , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Doxorrubicina/efectos adversos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Interferón-alfa/química , Interferón-alfa/genética , Células MCF-7 , Proteínas de Fusión Oncogénica/administración & dosificación , Proteínas de Fusión Oncogénica/química , Proteínas de Fusión Oncogénica/genética , Biblioteca de Péptidos , Unión ProteicaRESUMEN
OBJECTIVE: HBV infection may cause damage to the immune system and induce lymphomas as a result. Some scholars have indicated that HBsAg(+) reflecting HBV infection may have a relationship with lymphoma development. This study was designed to find out the specific stage of HBV infection which may be related to lymphoma. METHODS: HBV serum markers, including HBsAg, HBsAb, HBeAg, HBeAb, HBcAb were tested among 100 lymphoma patients and 100 other patients who were diagnosed with non-lymphoma diseases in the First Hospital of Jilin University from 2010.1.1 to 2012.12.31. Three subgroups were established depending on different combinations of HBV serum markers. Subgroup 1 was HBsAg(+) representing the early stage of HBV infection. Subgroup 2 was HbsAb(+) representing convalescence and Subgroup 3 was "HbsAg and HbsAb negative combined with other positive markers" representing the intermediate stage of HBV infection. Chi square tests were used to compare the rates of three subgroups in lymphoma and control groups. RESULTS: The rates of Subgroup were 13% and 5% respectively, an association between HBsAg and lymphoma being found (P<0.05). There was no difference between rate of Subgroup 2 of lymphoma group (15%) and that of control group (16%). In lymphoma group and control group , the rate of Subgroup 3 was different (12% vs 4%). This evidence was not specific to T cell lymphoma, B cell lymphoma or Hodgkin's lymphoma. CONCLUSIONS: Among serum markers of HBV, the combination of serum markers representing the early stage and intermediate stage of HBV infection have a relationship with lymphoma. Convalescence from HBV infection appears to have no relationship with lymphoma.
