RESUMEN
Aim: We evaluated the incidence, clinicopathological features, prognostic factors and survival of gastric cancer (GC) with bone metastasis in a single large cancer center in China. Patients & methods: Patients with bone metastasis of GC were retrospectively analyzed. Overall survival was estimated using the Kaplan-Meier method. Clinicopathological factors, which were associated with prognostic factors for survival, were evaluated. Results: The incidence of bone metastasis was 11.3% for metastatic GC patients. Median overall survival time was 6.5 months. Multivariate analysis revealed two independent poor prognostic factors: Eastern Cooperative Oncology Group ≥2 (p = 0.023) and lack of palliative chemotherapy (p = 0.018). Conclusion: The incidence of bone metastasis from metastatic GC was underestimated. The prognosis of GC with bone metastasis was poor.
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Biomarcadores de Tumor/genética , Neoplasias Óseas/epidemiología , Pronóstico , Neoplasias Gástricas/epidemiología , Adulto , Anciano , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , China/epidemiología , Supervivencia sin Enfermedad , Femenino , Gastrectomía , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Factores de Riesgo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologíaRESUMEN
Recent lentiviral-based microRNA (miRNA) library screening has identified miRNA-7 (miR-7) as an antiangiogenic miRNA in human umbilical vein endothelial cells (HUVECs). However, the underlying mechanism of miR-7 in the suppression of angiogenesis remains largely unknown. In the present study, we report that miR-7 inhibition promoted angiogenesis by upregulating vascular endothelial growth factor (VEGF) and directly targeting Krüppel-like factor 4 (KLF4). Downregulation of miR-7 promoted tube formation of HUVECs, accompanied by upregulation of mRNA and protein levels of both VEGF and KLF4. miR-7 directly targeted KLF4 as demonstrated by luciferase reporter assay and miR-7 mimics decreased KLF4. Furthermore, bioinformatic analysis revealed the presence of multiple DNA-binding elements of KLF4 in the VEGF promoter. Chromatin immunoprecipitation (ChIP) demonstrated that the KLF4 antibody specifically pulled down the VEGF promoter in the HUVECs. Furthermore, ectopic overexpression of KLF4 induced VEGF mRNA and protein levels. In addition, KLF4 silencing inhibited the angiogenesis induced by the miR-7 inhibitor in the HUVECs. Our results demonstrated that KLF4 is a direct target of miR-7 and a transcription activator of VEGF. These findings indicate that the miR-7-KLF4-VEGF signaling axis plays an important role in the regulation of angiogenesis in HUVECs, suggesting that miR-7 is a potential agent for the development of anti-angiogenic therapeutics in vascular diseases and solid tumors.
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Regulación de la Expresión Génica/fisiología , Células Endoteliales de la Vena Umbilical Humana/patología , Factores de Transcripción de Tipo Kruppel/biosíntesis , MicroARNs/metabolismo , Neovascularización Patológica/metabolismo , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Western Blotting , Inmunoprecipitación de Cromatina , Ensayo de Inmunoadsorción Enzimática , Técnicas de Silenciamiento del Gen , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Factor 4 Similar a Kruppel , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación hacia ArribaRESUMEN
OBJECTIVES: Xiaochaihutang (XCHT) has antidepressant effects in multiple animal models of depression in our previous studies. But the antidepressant effects and exact mechanisms of XCHT in a rat model of chronic social isolation stress (CSIS) have never been studied. We therefore aimed to investigate the effects of XCHT on depressive/anxiety-related behaviours of CSIS-exposed rats and understand the neurological mechanism involving neurogenesis. METHODS: We established the CSIS model and then investigated the effects of XCHT on behavioural change. HPLC-MS/MS was adopted to quantify neurotransmitter levels in the cerebrospinal fluid (CSF). Immunofluorescence technology was used to study the effects of XCHT on neurogenesis; while expressions of 5-HT1A receptor signalling pathway in the hippocampus were measured using Western blotting. KEY FINDINGS: Xiaochaihutang significantly alleviated depressive/anxiety-like behaviours of CSIS-exposed rats. XCHT significantly regulated levels of monoamine neurotransmitters in the CSF without affecting Glu, GABA and ACh. XCHT also significantly increased neurogenesis in CSIS-exposed rats. Additionally, XCHT reversed CSIS-induced decrease of 5-HT1A receptor expression and promoted the expression of BDNF in the hippocampus. CONCLUSION: Our results suggest that XCHT could significantly regulate the depressive/anxiety-like behaviours induced by CSIS, which are likely attributed to the promotion of hippocampal neurogenesis and neurotrophin expressions through the activation of serotonergic system.