RESUMEN
Glioma is the most common malignant tumor of the adult central nervous system. In this study, we aimed to identify a novel model for predicting glioma prognosis and a potential therapeutic target. Here, lncRNAs related to prognosis and ferroptosis were analyzed and screened through R software and online websites. A nomogram model was established and evaluated with calibration curve, receiver operating characteristic curve and decision curve analysis. Further, an enrichment analysis and immune infiltration analysis were performed. In addition, the expression level and biological function of ITGA6-AS1 were verified in vitro. We obtained a ferroptosis-related 7-lncRNA signature, and constructed a nomogram prognostic model with good predictability for 1-, 3- and 5-year overall survival of glioma patients. The enrichment analysis indicated potential involvement of certain pathways and suggested a correlation between the high-risk group and infiltration of M2 macrophages and MDSCs. Furthermore, the expression level of ITGA6-AS1 in the U118, U87, and LN229 cells was upregulated compared to the H1800 cell. Interestingly, knockdown of ITGA6-AS1 may inhibit U118 cells' proliferation, migration and invasion in vitro. while overexpression of ITGA6-AS1 in LN229 cells plays a promoting role. This study implies that the 7-lncRNA signature may contribute to the stratification of glioma prognosis, and the immune suppressive microenvironment may be associated with macrophage-ferroptosis crosstalk. Furthermore, ITGA6-AS1 may be a potential therapeutic target for patients with glioma.
Asunto(s)
Neoplasias Encefálicas , Movimiento Celular , Proliferación Celular , Ferroptosis , Regulación Neoplásica de la Expresión Génica , Glioma , Integrina alfa6 , ARN Largo no Codificante , Humanos , Glioma/genética , Glioma/patología , Glioma/metabolismo , Glioma/mortalidad , Glioma/inmunología , Ferroptosis/genética , Movimiento Celular/genética , Pronóstico , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Línea Celular Tumoral , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/mortalidad , Integrina alfa6/metabolismo , Integrina alfa6/genética , Invasividad Neoplásica/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , NomogramasRESUMEN
Colletotrichum siamense is a hemibiotrophic ascomycetous fungus responsible for mango anthracnose. The key genes involved in C. siamense infection remained largely unknown. In this study, we conducted weighted gene co-expression network analysis (WGCNA) of RNA-seq data to mine key genes involved in Colletotrichum siamense-mango interactions. Gene modules of Turquoise and Salmon, containing 1039 and 139 respectively, were associated with C. siamense infection, which were conducted for further analysis. GO enrichment analysis revealed that protein synthesis, organonitrogen compound biosynthetic and metabolic process, and endoplasmic reticulum-related genes were associated with C. siamense infection. A total of 568 proteins had homologs in the PHI database, 370 of which were related to virulence. The hub genes in each module were identified, which were annotated as O-methyltransferase (Salmon) and Clock-controlled protein 6 (Turquoise). A total of 24 proteins exhibited characteristics of SCRPs. By using transient expression in Nicotiana benthamiana, the SCRPs of XM_036637681.1 could inhibit programmed cell death (PCD) that induced by BAX (BCL-2-associated X protein), suggesting that it may play important roles in C. siamense infection. A mango-C. siamense co-expression network was constructed, and the mango gene of XM_044632979.1 (auxin-induced protein 15A-like) was positively associated with 5 SCRPs. These findings help to deepen the current understanding of necrotrophic stage in C. siamense infection.
Asunto(s)
Colletotrichum , Mangifera , Mangifera/genética , Mangifera/microbiología , Redes Reguladoras de Genes , Perfilación de la Expresión Génica , Colletotrichum/genéticaRESUMEN
PURPOSE: To investigate the safety and efficacy of locoregional therapy plus adoptive transfer of allogeneic gamma delta (γδ) T cells for patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). METHODS: Thirty patients with HCC and 29 patients with ICC were randomly assigned to receive locoregional therapy (HCC, Group A, n = 15; ICC, Group C, n = 15) or locoregional therapy plus γδ T cell therapy (HCC, Group B, n = 15; ICC, Group D, n = 14). Groups A and C only received locoregional ablation (cryoablation or irreversible electroporation), whereas Groups B and D received locoregional therapy followed by adoptive transfer of allogeneic γδ T cells. The primary endpoints were safety, distant progression-free survival (PFS), local PFS, and overall survival (OS). RESULTS: The median distant PFS was significantly longer in the combined treatment groups than the locoregional treatment groups (HCC: 8 vs 4 months, P = .04; ICC: 8 vs 4 months, P = .021). There was no significant difference in local PFS between the 2 treatment modalities. Patients with HCC in the combined treatment group had a longer OS (median OS: 13 vs 8 months, P = .029). However, there was no significant difference in OS in patients with ICC between the 2 treatment modalities (median OS: 9.5 vs 8 months, P = .546). All adverse events were manageable with no significant difference in incidence between groups. CONCLUSIONS: The novel combination of locoregional ablation with adoptive transfer of allogeneic γδ cells was safe, with encouraging clinical efficacy against HCC and ICC.
Asunto(s)
Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Trasplante de Células Madre Hematopoyéticas , Neoplasias Hepáticas , Traslado Adoptivo , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos , Carcinoma Hepatocelular/patología , Colangiocarcinoma/patología , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Linfocitos T/patologíaRESUMEN
A synthetic strategy for the modeling construction of the highly bridged azatetracyclic ABEF ring system of numerous lycoctonine-type C19-diterpenoid alkaloids bearing a characteristic oxygenated quaternary center at C-7 has been successfully developed. The tetracyclic core was constructed rapidly from a readily prepared 6,7-bicyclic AB ring precursor through a 13-step sequence via an advanced tetracyclic N,O-acetal intermediate, which belong to another core structure of natural 7,17-seco-type alkaloids. The key step involves an SmI2-promoted intramolecular radical coupling reaction of an N,O-acetal with a carbonyl group, mimicking a plausible biogenetic transformation.