RESUMO
PURPOSE: Previous studies have indicated that transient receptor potential (TRP) channels can influence cancer development. The TRPC subfamily consists of seven subtypes, TRPC1 - TRPC7. Interestingly, the expression levels of TRPC1 have been shown to be totally different in different breast cancer cell lines. Nevertheless, the underlying mechanism remains unknown. In this study, we explore the significance of TRPC1 expression in breast cancer. METHODS: Immunohistochemical TRPC1 staining was performed in 278 samples. TRPC1 expression in different breast tissues were examined. Then, the influence of TRPC1 on migration, invasion and proliferation was explored. We analyzed the protein of TRPC1 by Western blot to prove which pathway may be involved in. Finally, we use online database to predict the prognosis of TRPC1 in breast cancer. RESULTS: Through immunohistochemistry and in vitro experiments, we found that the expression level of TRPC1 was higher in breast cancer cells as compared with that in normal breast epithelial cells. Moreover, the expression level of TRPC1 was different between estrogen receptor-positive (ER +) and -negative (ER -) breast cancer. It was shown that TRPC1 inhibited MCF7 cell proliferation, migration, and invasion in vitro. Western blotting revealed that TRPC1 inhibited the PI3K/AKT pathway and epithelium-mesenchymal transformation, leading to subsequent inhibition of cell proliferation and metastasis. In luminal A and luminal B patients, those with high TRPC1 expression had a better prognosis. On the contrary, in basal-like and triple-negative breast cancer (TNBC) subtypes, patients with high-TRPC1 expression had a worse prognosis. CONCLUSIONS: We confirmed that TRPC1 was high expression in breast cancer. Overexpression of TRPC1 inhibits proliferation and migration of ER + breast cancer and gives a better prognosis by inhibiting PI3K/AKT pathway activation. TRPC1 may be an independent prognostic predictor in breast cancer patients.
Assuntos
Biomarcadores Tumorais/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Estrogênio/metabolismo , Canais de Cátion TRPC/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/genética , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Canais de Cátion TRPC/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
Estrogen receptor α (ERα) serves as an essential therapeutic predictor for breast cancer (BC) patients and is regulated by epigenetic modification. Abnormal methylation of cytosine phosphoric acid guanine islands in the estrogen receptor 1 (ESR1) gene promoter could silence or decrease ERα expression. In ERα-negative BC, we previously found snail family transcriptional repressor 2 (SNAI2), a zinc-finger transcriptional factor, recruited lysine-specific demethylase 1 to the promoter to transcriptionally suppress ERα expression by demethylating histone H3 lysine 4 dimethylation (H3K4me2). However, the role of SNAI2 in ERα-positive BC remains elusive. In this study, we observed a positive correlation between SNAI2 and ESR1 methylation, and SNAI2 promoted ESR1 methylation by recruiting DNA methyltransferase 3 beta (DNMT3B) rather than DNA methyltransferase 1 (DNMT1) in ERα-positive BC cells. Subsequent enrichment analysis illustrated that ESR1 methylation is strongly correlated with cell adhesion and junction. Knocking down DNMT3B could partially reverse SNAI2 overexpression-induced cell proliferation, migration, and invasion. Moreover, high DNMT3B expression predicted poor relapse-free survival and overall survival in ERα-positive BC patients. In conclusion, this study demonstrated the novel mechanisms of the ESR1 methylation mediated with the SNAI2/DNMT3B complex and enhanced awareness of ESR1 methylation's role in promoting epithelial-mesenchymal transition in BC.
RESUMO
BACKGROUND: Lymphatic metastasis is one of the main factors affecting prognosis in esophageal squamous cell carcinoma (ESCC). Vascular endothelial growth factor-C (VEGF-C) is an important factor that promotes lymphangiogenesis. Survivin also plays a significant role in lymphatic invasion. However, the role and mechanism of their co-expression are still unclear in ESCC. The purpose of this study was to investigate whether the co-expression of VEGF-C and survivin could be a potential marker to predict patient prognosis and survival in ESCC. METHODS: The levels of VEGF-C, vascular endothelial growth factor receptor 3 (VEGFR-3), survivin, and Ki-67 were determined by immunohistochemistry (IHC) in 97 ESCC patient tumors. The correlations of co-expression of VEGF-C and survivin with pathological features and survival results were also assessed. RESULTS: High VEGF-C expression was observed in 64.9% of the patients and significantly correlated with T stage (P=0.024), node status (P=0.038), and lymph node metastasis (P=0.015). High survivin expression was significantly associated with T stage (P=0.013), N stage (P=0.016), lymph node metastasis (P=0.005), and differentiation (P=0.044) in 67.0% of the patients. Co-expression of VEGF-C and survivin (V+S+) was significantly associated with T stage (P<0.001), N stage (P=0.015), lymph node metastasis (P=0.003), differentiation (P=0.0045), and Ki-67 levels (P=0.024). High expression of VEGF-C or survivin was associated significantly with worse disease-free survival (DFS) and overall survival (OS) (P<0.05). Moreover, the V+S+ group had a worse DFS (P<0.001) and OS (P=0.001) than any other group (i.e., V-S-, V+S-, V-S+). Furthermore, multivariate DFS analyses (95% CI: 1.147-2.220, P=0.006) and multivariate OS analyses (95% CI: 1.080-2.193, P=0.017) revealed that co-expression of VEGF-C and survivin was an independent prognostic factor in ESCC patients. CONCLUSIONS: Co-expression of VEGF-C and survivin was predictive of poor prognosis in ESCC. Combined detection of VEGF-C and survivin could represent a feasible and effective marker to predict the prognosis and survival of ESCC patients.
RESUMO
OBJECTIVE: To explore the effect of proteins extraceed from mycelia of Omphalia lapidescens on inhibiting H22 liver cancer in vivo. METHODS: 50 hepatoma 22 tumor bearing mice models were divided into five groups randomly:control group( CG), cyclophosphamide group, and 3 groups of incremental Hepatoma 22 dosages (5, 3, 1 mg/kg). All groups were i.v. with drugs once a day. After 8 consecutive days, the concentrations of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) in serum were detected by enzyme-linked immunoabsorbent assay (ELISA). The weight changes of tumor, thymus, liver, heart, spleen, lung and kidney were observed. RESULTS: It showed the tumors' weight were significant heavier in CG than in EGs. The tumor-inhibition rate (IR) was 36.4% in high dosage group,which was lower than 43.2% in cyclophosphamide group. The spleen mass of proteins groups increased significantly. The concentration of IFN-gamma in serum of proteins groups increased as CG, but IL-4 in inverse direction. The observations of thymus, liver, heart, lung and kidney in EGs were the same as CG. CONCLUSION: The proteins extracted from mycelium of Omphalia lapidescens can inhibit the growth of tumour and enhance the immune function of H22 tumor-bearing mice.
Assuntos
Antineoplásicos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Polyporaceae , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Ciclofosfamida/farmacologia , Ciclofosfamida/uso terapêutico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Interferon gama/sangue , Interleucina-2/sangue , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas Experimentais/sangue , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fitoterapia , Polyporaceae/química , Distribuição Aleatória , Baço/efeitos dos fármacos , Baço/imunologia , Timo/efeitos dos fármacos , Timo/imunologiaRESUMO
OBJECTIVE: To observe the influence of modeling sodium on the dialysis disequilibrium syndrome in hemodialysis. METHODS: Sixteen patients received hemodialysis for the first time. Eight of them received the hemodialysis in the order of common sodium, modeling sodium, common sodium, and modeling sodium, whereas the other 8 patients were treated in the order of modeling sodium, common sodium, modeling sodium, and common sodium. The symptoms of the dialysis disequilibrium syndrome were observed and blood sodium concentration was examined before and after the dialysis. RESULTS: The main symptoms of the dialysis disequilibrium syndrome were headache, nausea, vomiting, hypertension, and dyspnea. Modeling sodium hemodialysis could significantly decrease the occurrence of these symptoms (P < 0.05). The blood sodium concentration after the hemodialysis was not significantly changed compared with that before the hemodialysis (P > 0.05). CONCLUSION: Modeling sodium hemodialysis can effectively prevent the occurrence of the dialysis disequilibrium syndrome without increasing the natrium load of the patients.