Whether baseline metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) measured by FDG-PET/CT affected prognosis of patients with lymphoma was controversial. We searched PubMed, EMBASE and ...Cochrane to identify studies assessing the effect of baseline TMTV and TLG on the survival of lymphoma patients. Pooled hazard ratios (HR) for overall survival (OS) and progression-free survival (PFS) were calculated, along with 95% confidence intervals (CI). Twenty-seven eligible studies including 2,729 patients were analysed. Patients with high baseline TMTV showed a worse prognosis with an HR of 3.05 (95% CI 2.55-3.64, p<0.00001) for PFS and an HR of 3.07 (95% CI 2.47-3.82, p<0.00001) for OS. Patients with high baseline TLG also showed a worse prognosis with an HR of 3.44 (95% CI 2.37-5.01, p<0.00001) for PFS and an HR of 3.08 (95% CI 1.84-5.16, p<0.00001) for OS. A high baseline TMTV was significantly associated with worse survival in DLBCL patients treated with R-CHOP (OS, pooled HR = 3.52; PFS, pooled HR = 2.93). A high baseline TLG was significantly associated with worse survival in DLBCL patients treated with R-CHOP (OS, pooled HR = 3.06; PFS, pooled HR = 2.93). The negative effect of high baseline TMTV on PFS was demonstrated in HL (pooled HR = 3.89). A high baseline TMTV was significantly associated with worse survival in ENKL patients (OS, pooled HR = 2.24; PFS, pooled HR = 3.25). A high baseline TLG was significantly associated with worse survival in ENKL patients (OS, pooled HR = 2.58; PFS, pooled HR = 2.99). High baseline TMTV or TLG predict significantly worse PFS and OS in patients with lymphoma. Future studies are warranted to explore whether TMTV or TLG could be integrated into various prognostic models for clinical decision making.
The enhancer of zeste homolog 2 (EZH2) plays a critical role in different components of anti-tumor immunity. However, the specific role of EZH2 in modulating MHC Class I antigen presentation and T ...cell infiltration have not been investigated in HCC. This study analyzed the expression and clinical significance of EZH2 in HCC. The EZH2 genetic alterations were identified using cBioPortal. The EZH2 mRNA and protein levels were found to be significantly higher in HCC than in adjacent normal liver tissues in multiple datasets from the GEO and TCGA databases. High expression of EZH2 was significantly correlated with poor overall survival, disease-specific survival, progression-free survival, and relapse-free survival in almost all patients with HCC. The gene set variance analysis (GSVA) showed that the expression of EZH2 is positively correlated with an immunosuppressive microenvironment and negatively correlated with major MHC class I antigen presentation molecules. Gene set enrichment analysis (GSEA) showed that high EZH2 expression is positively associated with the MYC and glycolysis signaling pathway and negatively associated with the interferon-gamma signaling pathway in HCC tissues. These findings demonstrate that EZH2 is a potential prognostic biomarker and therapeutic target in HCC.
As a significant cause of malignancy mortality, gastric carcinoma (GC) has been well documented to be an often-fatal diagnosis. Despite the limitations of effective therapy, immunotherapy has emerged ...as a promising therapeutic approach capable of killing cancer cells via the immune system. The current study was conducted to investigate the effect of cytokine C-C motif chemokine ligand 21 (CCL21) on GC progression through the metastasis-associated lung adenocarcinoma transcript 1/serine arginine-rich splicing factor 1/mammalian target of rapamycin (MALAT1/SRSF1/mTOR) axis.
Bioinformatics analysis was conducted to identify the key genes associated with GC and to subsequently predict their downstream genes. The effect of CCL21, MALAT1, and SRSF1 on the malignant phenotypes and epithelial-mesenchymal transition (EMT) of SGC-7901 and MGC-803 cells in-vitro and the tumorigenesis of SGC-7901 and MGC-803 cells in-vivo were assessed by expression determination and plasmid transfection. Additionally, RNA pull-down and RNA binding protein immunoprecipitation experiments were performed to determine the MALAT1-microRNA-202-3p (miR-203-3p) interaction and miR-202-3p-SRSF1 interaction followed by the analysis of their effect on the mTOR pathway.
CCL21 was identified as a key GC immune gene. Overexpressed CCL21, MALAT1, and SRSF1 along with poorly expressed miR-202-3p were identified in the GC cells. CCL21 induced the MALAT1 expression in a time- and dose-dependent manner. Functionally, MALAT1 targeted miR-202-3p but upregulated SRSF1 and activated mTOR. Crucially, evidence was obtained indicating that CCL21 promoted both the malignant phenotypes and EMT of SGC-7901 and MGC-803 cells in-vitro and the tumorigenesis of SGC-7901 and MGC-803 cells in-vivo by increasing the MALAT1-induced upregulation of SRSF1.
Taken together, the key observations of our study provide evidence that CCL21 enhances the progression of GC via the MALAT1/SRSF1/mTOR axis, providing a novel therapeutic target for the treatment of GC.
•Dietary 1.00 g/kg dandelion extract (DE) supplementation significantly increased weight gain rate of golden pompano.•Dietary DE improved intestinal morphology of golden pompano.•Dietary DE improved ...intestinal microbiota of golden pompano.
The gut microbiota plays an important role in growth performance, intestinal mucosal barrier, digestion and absorption of nutrients and immune responses. In this study, we investigated the effect of dietary dandelion extract (DE) on growth performance, expression of immune related genes in the spleen, intestinal morphology and microbiota of golden pompano (Trachinotus ovatus). Golden pompanos were fed three diets adding 0 (DE0), 0.50 (DE1), 1.00 (DE2) g/kg DE for 8 weeks. At the end of this trial, dietary 1.00 g/kg DE supplementation significantly increased weight gain rate and feed intake compared to those of the control group (P < 0.05). Meanwhile, dietary 1.00 g/kg DE supplementation significantly up-regulated transcription levels of glutathione peroxidase and interleukin 10 in the spleen of fish. However, dietary DE supplementation had no significant effect on transforming growth factor β1, glutathione reductase and catalase in the spleen of fish. Moreover, dietary 0.50–1.00 g/kg DE supplementation improved the richness and diversity of gut microbiota, increase the relative abundance of Actinobacteria and Firmicutes, and reduce the proportion of harmful microbial taxa. Furthermore, dietary DE improved intestinal morphology and immunity by increasing intestinal goblet cells numbers and decreasing epithelial lymphocyte numbers. In conclusion, dietary 1.00 g/kg DE supplementation was clearly beneficial for golden pompano by improving growth performance, gut morphology and microbiota and it could use as a functional feed additive in aquaculture.
The prognostic value of the copy number (GCN) and protein expression of the mesenchymal-epithelial transition (MET) gene for survival of patients with non-small cell lung cancer (NSCLC) remains ...controversial. This study aims to comprehensively and quantitatively asses the suitability of MET GCN and protein expression to predict patients' survival.
PubMed, Embase, Web of Science and Google Scholar were searched for articles comparing overall survival in patients with high MET GCN or protein expression with those with low level. Pooled hazard ratio (HR) and 95% confidence intervals (CIs) were calculated using the random and the fixed-effects models. Subgroup and sensitivity analyses were also performed.
Eighteen eligible studies enrolling 5,516 patients were identified. Pooled analyses revealed that high MET GCN or protein expression was associated with poor overall survival (OS) (GCN: HR = 1.90, 95% CI 1.35-2.68, p<0.001; protein expression: HR = 1.52, 95% CI 1.08-2.15, p = 0.017). In Asian populations (GCN: HR = 2.22, 95% CI 1.46-3.38, p<0.001; protein expression: HR = 1.89, 95% CI 1.34-2.68, p<0.001), but not in the non-Asian subset. For adenocarcinoma, high MET GCN or protein expression indicated decreased OS (GCN: HR = 1.49, 95% CI 1.05-2.10, p = 0.025; protein expression: HR = 1.69, 95% CI 1.31-2.19, p<0.001). Results were similar for multivariate analysis (GCN: HR = 1.61, 95% CI 1.15-2.25, p = 0.005; protein expression: HR = 2.18, 95% CI 1.60-2.97, p<0.001). The results of the sensitivity analysis were not materially altered and did not draw different conclusions.
Increased MET GCN or protein expression was significantly associated with poorer survival in patients with surgically resected NSCLC; this information could potentially further stratify patients in clinical treatment.
The study of ultrasmall metal nanoclusters (NCs, ranging from subnanometer to ca 2 nm) is evidently a quickly evolving field in current nanoscience and nanotechnology research. Metal NCs, typically ...composed of several to hundreds of metal atoms, have attracted great interest in recent years owing to their unique properties including ultrasmall size and enhanced photoluminescence, together with other properties such as excellent photostability, low toxicity, and good biocompatibility desired for biological applications. This review summarizes recent advances in the field of bio‐related applications of metal NCs materials. We highlight the applications of metal NCs for biosensor development, fluorescent biological imaging, and biomedical research, and finally discuss briefly some current challenges and future work. WIREs Nanomed Nanobiotechnol 2013, 5:569–581. doi: 10.1002/wnan.1227
This article is categorized under:
Diagnostic Tools > Biosensing
Diagnostic Tools > In Vitro Nanoparticle-Based Sensing
Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
An RNA aptamer selected for binding to the fluorogenic cyanine dye, dimethylindole red (DIR), also binds and activates another cyanine, oxazole thiazole blue (OTB), giving two well-resolved emission ...colors. The aptamer binds to each dye with submicromolar K D values, and the resulting fluoromodules exhibit fluorescence quantum yields ranging from 0.17 to 0.51 and excellent photostability. The aptamer was fused to a second aptamer previously selected for binding to the epidermal growth factor receptor (EGFR) to create a bifunctional aptamer that labels cell-surface EGFR on mammalian cells. The fluorescent color of the aptamer-labeled EGFR can be switched between blue and red in situ simply by exchanging the dye in the medium. The promiscuity of the aptamer can also be used to distinguish between cell-surface and internalized EGFR on the basis of the addition of red or blue fluorogen at different times.
Pancreatic cancer, one of the deadliest cancers, is characterized by high rates of metastasis and intense desmoplasia, both of which are associated with changes in fibrillar type I collagen ...composition and microstructure. Epithelial to mesenchymal transition (EMT), a critical step of metastasis, also involves a change in extracellular matrix (ECM) context as cells detach from basement membrane (BM) and engage interstitial matrix (IM). The objective of this work was to develop and apply an in-vitro three-dimensional (3D) tumor-ECM model to define how ECM composition and biophysical properties modulate pancreatic cancer EMT. Three established pancreatic ductal adenocarcinoma (PDAC) lines were embedded within 3D matrices prepared with type I collagen Oligomer (IM) at various fibril densities to control matrix stiffness or Oligomer and Matrigel combined at various ratios while maintaining constant matrix stiffness. Evaluation of cell morphology and protein expression at both the cellular- and population-levels revealed a spectrum of matrix-driven EMT phenotypes that were dependent on ECM composition and architecture as well as initial PDAC phenotype. In general, exposure to fibrillar IM was sufficient to drive EMT, with cells displaying spindle-shaped morphology and mesenchymal markers, and non-fibrillar BM promoted more epithelial behavior. When cultured within low density Oligomer, only a subpopulation of epithelial BxPC-3 cells displayed EMT while mesenchymal MiaPaCa-2 cells displayed more uniform spindle-shaped morphologies and mesenchymal marker expression. Interestingly, as IM fibril density increased, associated changes in spatial constraints and matrix stiffness resulted in all PDAC lines growing as tight clusters; however mesenchymal marker expression was maintained. Collectively, the comparison of these results to other in-vitro tumor models highlights the role of IM fibril microstructure in guiding EMT heterogeneity and showcases the potential of standardized 3D matrices such as Oligomer to serve as robust platforms for mechanistic study of metastasis and creation of predictive drug screening models.
In the context of rapid urbanization, land has become the most valuable scarce resource, and the regeneration of urban villages is related to urban land supply for urban redevelopment. The ...redevelopment of urban villages can promote the efficient use of land resources and contribute to the sustainable development of the city. This paper examines the redevelopment of an urban village in Guangzhou from the perspective of territorialization and finds that urban villages ultimately become territories dominated by the coalition formed by the market developers and the rural collective organization of the urban village. When the local government attempts to redevelop the village, the coalition fights against the government and defends the territory, leading to the predicament of urban redevelopment. By exploring the territorialization process and the dynamics of spatial production, this paper argues that territorialization is a means of reifying and reinforcing power in a geographical space and represents a significant attempt to achieve urban redevelopment. Both the local government and the coalition can contribute to the redevelopment of urban villages. Although territorialization is an efficient way to achieve urban redevelopment, it may solidify an area and cause the straitened circumstances of city government to implement the new city strategy. This paper thus calls for a focus on the value of bottom-up territorialization and the ingenious combination of city planning and territorialization to achieve effective urban redevelopment.
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