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1.
Exp Cell Res ; 405(2): 112685, 2021 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-34090863

RESUMEN

Tumor progression and metastasis, especially in invasive cancers (such as triple-negative breast cancer [TNBC]), depend on angiogenesis, in which vascular epithelial growth factor (VEGF)/vascular epithelial growth factor receptor [1] has a decisive role, followed by the metastatic spread of cancer cells. Although some studies have shown that anti-VEGFR2/VEGF monoclonal antibodies demonstrated favorable results in the clinic, this approach is not efficient, and further investigations are needed to improve the quality of cancer treatment. Besides, the increased expression of epithelial cell adhesion molecule (EpCAM) in various cancers, for instance, invasive breast cancer, contributes to angiogenesis, facilitating the migration of tumor cells to other parts of the body. Thus, the main goal of our study was to target either VEGFR2 or EpCAM as pivotal players in the progression of angiogenesis in breast cancer. Regarding cancer therapy, the production of bispecific antibodies is easier and more cost-effective compared to monoclonal antibodies, targeting more than one antigen or receptor; for this reason, we produced a recombinant antibody to target cells expressing EpCAM and VEGFR2 via a bispecific antibody to decrease the proliferation and metastasis of tumor cells. Following the cloning and expression of our desired anti-VEGFR2/EPCAM sequence in E. coli, the accuracy of the expression was confirmed by Western blot analysis, and its binding activities to VEGFR2 and EPCAM on MDA-MB-231 and MCF-7 cell lines were respectively indicated by flow cytometry. Then, its anti-proliferative potential was indicated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and apoptosis assay to evaluate inhibitory effects of the antibody on tumor cells. Subsequently, the data indicated that migration, invasion, and angiogenesis were inhibited in breast cancer cell lines via the bispecific antibody. Furthermore, cytokine analysis indicated that the bispecific antibody could moderate interleukin 8 (IL-8) and IL-6 as key mediators in angiogenesis progression in breast cancer. Thus, our bispecific antibody could be considered as a promising candidate tool to decrease angiogenesis in TNBC.


Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Anticuerpos Biespecíficos/farmacología , Molécula de Adhesión Celular Epitelial/inmunología , Neovascularización Patológica/tratamiento farmacológico , Anticuerpos Biespecíficos/inmunología , Anticuerpos Monoclonales/farmacología , Antineoplásicos Inmunológicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Molécula de Adhesión Celular Epitelial/efectos de los fármacos , Humanos , Morfogénesis/inmunología
2.
Arch Oral Biol ; 79: 87-94, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28347886

RESUMEN

OBJECTIVES: Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor which displays biological, histological and clinical diversity thus representing a challenge for its diagnosis and management. Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein identified as a tumor specific antigen due to its frequent overexpression in the majority of epithelial carcinomas and its correlation with prognosis. It is considered to be a promising biomarker used as a therapeutic target already in ongoing clinical trials. The purpose of this study was to investigate the pattern, cellular characterization and level of EpCAM expression in MEC and demonstrate its correlation with histologic grading which may benefit future clinical trials using EpCAM targeted therapy. MATERIALS AND METHODS: 48 specimens (12 normal salivary gland tissue and 36 MEC) were collected and EpCAM membranous expression was evaluated by immunohistochemistry. Total immunoscore (TIS) was evaluated, the term 'EpCAM overexpression' was given for tissues showing a total immunoscore >4. RESULTS: A highly significant difference was observed between TIS percent values in control and different grades of MEC (p<0.001). High grade MEC (HG-MEC) was the highest EpCAM expressor. In addition, EpCAM expression pattern differed among the different grades. CONCLUSION: EpCAM expression was detected in MEC, and its overexpression correlated with increasing the histological grade. The diffuse membranous expression in HG-MEC could be of diagnostic value in relation to the patchy expression observed in both low grade and intermediate grade MEC.


Asunto(s)
Carcinoma Mucoepidermoide/metabolismo , Carcinoma Mucoepidermoide/patología , Molécula de Adhesión Celular Epitelial/metabolismo , Neoplasias de las Glándulas Salivales/metabolismo , Neoplasias de las Glándulas Salivales/patología , Glándulas Salivales/metabolismo , Glándulas Salivales/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Carcinoma Mucoepidermoide/diagnóstico por imagen , Niño , Molécula de Adhesión Celular Epitelial/efectos de los fármacos , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Pronóstico , Neoplasias de las Glándulas Salivales/diagnóstico por imagen , Glándulas Salivales/diagnóstico por imagen , Adulto Joven
3.
Am J Chin Med ; 45(1): 85-104, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28081630

RESUMEN

Notch signaling has been demonstrated to be involved in ductular reactions and fibrosis. Previous studies have shown that Huang Qi Decoction (HQD) can prevent the progression of cholestatic liver fibrosis (CLF). However, whether HQD affects the Notch signaling pathway is unclear. In this study, CLF was established by common bile duct ligation (BDL) in rats. At the end of the first week, the rats were randomly divided into a model group (i.e., BDL), an HQD group, and a sorafenib positive control group (SORA) and were treated for 3 weeks. Bile duct proliferation and liver fibrosis were determined by tissue staining. Activation of the Notch signaling pathway was evaluated by analyzing expressions of Notch-1, -2, -3, and -4, Jagged (JAG) 1, and Delta like (DLL)-1, -3, and -4. The results showed that HQD significantly reduced the deposition of collagen and the Hyp content of liver tissue and inhibited the activation of HSCs compared with the BDL group. In addition, HQD significantly decreased the protein and mRNA expressions of TGF-[Formula: see text]1 and [Formula: see text]-SMA. In contrast, HQD significantly enhanced expression of the Smad 7 protein. HQD also reduced biliary epithelial cell proliferation, and reduced the mRNA levels of CK7, CK8, CK18, SRY-related high mobility group-box gene (SOX) 9, epithelial cell adhesion molecule (EpCAM) and the positive areas of CK19 and OV6. In addition, the mRNA and protein expressions of Notch-3, -4, JAG1, and DLL-1, -3 were significantly reduced in the HQD compared to the BDL group. These results demonstrated that HQD may prevent biliary liver fibrosis through inhibition of the Notch signaling pathway, and it may be a potential treatment for cholestatic liver disease.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Hígado/efectos de los fármacos , ARN Mensajero/efectos de los fármacos , Receptores Notch/efectos de los fármacos , Actinas/efectos de los fármacos , Actinas/genética , Actinas/metabolismo , Animales , Astragalus propinquus , Sistema Biliar/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Colestasis/etiología , Colestasis/prevención & control , Colágeno/efectos de los fármacos , Colágeno/metabolismo , Conducto Colédoco/cirugía , Modelos Animales de Enfermedad , Molécula de Adhesión Celular Epitelial/efectos de los fármacos , Molécula de Adhesión Celular Epitelial/genética , Células Epiteliales/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteína Jagged-1/efectos de los fármacos , Proteína Jagged-1/genética , Proteína Jagged-1/metabolismo , Queratinas/efectos de los fármacos , Queratinas/genética , Ligadura , Hígado/metabolismo , Cirrosis Hepática/etiología , Cirrosis Hepática/prevención & control , Proteínas de la Membrana/efectos de los fármacos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratas , Receptores Notch/genética , Receptores Notch/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína smad7/efectos de los fármacos , Factor de Crecimiento Transformador beta1/efectos de los fármacos , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo
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