RESUMEN
Molecular-targeted therapies for lung squamous cell carcinoma (LSCC) are limited mainly because targetable oncogenic aberrations are absent in LSCC. Recent genomic analyses have revealed that the fibroblast growth factor (FGF) signaling pathway plays a fundamental role in LSCC progression via cancer cell proliferation and angiogenesis. In the present study, we designed, expressed, and purified a fibroblast growth factor receptor fragment (FGFR1-Fc) fusion protein using NS/0 cells. In FGF2-FGFR1 overexpressed NCI-H1703 cells, the FGFR1-Fc fusion protein effectively inhibited proliferation and invasion and arrested the cell cycle at the G0-G1 phase. In NCI-H1703 cells treated with the FGFR1-Fc fusion protein, the phosphorylation levels of FGFR1, FRS2, ERK, and AKT were significantly reduced. Using an siRNA assay, we demonstrated that FGF2-FGFR1 is the major anti-tumor target of FGFR1-Fc fusion the FGFR1-Fc fusion protein, which also significantly inhibited proliferation and invasion by NCI-H1703 cells via the FGF2-FGFR1 signaling pathway. In addition, the FGFR1-Fc fusion protein significantly inhibited angiogenesis in an embryonic chorioallantoic membrane model. The FGFR1-Fc fusion protein may be an effective therapeutic candidate for LSCC.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Inmunoglobulina G , Neoplasias Pulmonares , Proteínas Recombinantes de Fusión , Humanos , Factor 2 de Crecimiento de Fibroblastos , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Proliferación Celular , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Pulmón/metabolismo , Línea Celular TumoralRESUMEN
BACKGROUND: To evaluate through meta-analysis whether long-term use of proton pump inhibitor (PPI) increases the risk of precancerous lesions in the stomach. METHODS: Randomized controlled trials that compared the occurrence and progression of precancerous lesions in patients receiving PPI treatment versus non-PPI treatment were retrieved from CNKI, VIP, Wanfang, CBM, Pubmed, Embase, Web of Science, and Cochrane Library databases (from database inception to May 1, 2023). The Revman 5.3 and STATA 17.0 software were used for analysis, and subgroup analysis was conducted based on follow-up time (≤12 months and > 12 months) and lesion type (atrophic gastritis, intestinal metaplasia, and epithelial dysplasia). RESULTS: Six randomized controlled trials with a total of 1623 cases were included, including 1015 cases in the experimental group and 608 cases in the control group. The meta-analysis results showed that the overall abnormal lesion rate combined with statistical relative risk (RR) = 1.31 (0.85-2.02), P = .23. Subgroup analysis showed that the follow-up time > 12 months combined result was RR = 2.21 (1.47-3.33), P = .0001, the intestinal metaplasia group combined result was RR = 1.96 (0.91-2.47), P = .04. CONCLUSION SUBSECTIONS: During long-term follow-up, patients using PPI exhibited a significantly higher incidence of overall abnormal lesions compared to the control group, particularly with a higher risk observed for intestinal metaplasia. However, there were no statistically significant differences between the 2 groups in terms of short-term follow-up and other types of lesions. It is important to exercise caution when interpreting these findings due to the limited number of nominated investigations included in the meta-analysis.
Asunto(s)
Carcinoma in Situ , Lesiones Precancerosas , Humanos , Inhibidores de la Bomba de Protones/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estómago , Lesiones Precancerosas/inducido químicamente , Lesiones Precancerosas/epidemiologíaRESUMEN
Diabetic keratopathy, commonly associated with a hyperactive inflammatory response, is one of the most common eye complications of diabetes. The peptide hormone fibroblast growth factor-21 (FGF-21) has been demonstrated to have anti-inflammatory and antioxidant properties. However, whether administration of recombinant human (rh) FGF-21 can potentially regulate diabetic keratopathy is still unknown. Therefore, in this work, we investigated the role of rhFGF-21 in the modulation of corneal epithelial wound healing, the inflammation response, and oxidative stress using type 1 diabetic mice and high glucose-treated human corneal epithelial cells. Our experimental results indicated that the application of rhFGF-21 contributed to the enhancement of epithelial wound healing. This treatment also led to advancements in tear production and reduction in corneal edema. Moreover, there was a notable reduction in the levels of proinflammatory cytokines such as TNF-α, IL-6, IL-1ß, MCP-1, IFN-γ, MMP-2, and MMP-9 in both diabetic mouse corneal epithelium and human corneal epithelial cells treated with high glucose. Furthermore, we found rhFGF-21 treatment inhibited reactive oxygen species production and increased levels of anti-inflammatory molecules IL-10 and SOD-1, which suggests that FGF-21 has a protective role in diabetic corneal epithelial healing by increasing the antioxidant capacity and reducing the release of inflammatory mediators and matrix metalloproteinases. Therefore, we propose that administration of FGF-21 may represent a potential treatment for diabetic keratopathy.