Deregulation of microtubules and centrosome integrity is response for the initiation and progression of human cancers. Sperm-associated antigen 5 (SPAG5) is essential for the spindle apparatus ...organization and chromosome segregation, but its role in hepatocellular carcinoma (HCC) remains undefined.
The expression of SPAG5 in HCC were examined in a large cohort of patients by RT-PCR, western blot and IHC. The clinical significance of SPAG5 was next determined by statistical analyses. The biological function of SPAG5 in HCC and the underlying mechanisms were investigated, using in vitro and in vivo models.
Here, we demonstrated that SPAG5 exhibited pro-HCC activities via the activation of PI3K/AKT signaling pathway. SPAG5 expression was increased in HCC and correlated with poor outcomes in two independent cohorts containing 670 patients. High SPAG5 expression was associated with poor tumor differentiation, larger tumor size, advanced TNM stage, tumor vascular invasion and lymph node metastasis. In vitro and in vivo data showed that SPAG5 overexpression promoted tumor growth and metastasis, whereas SPAG5 knockdown led to the opposite phenotypes. SPAG5 interacted with centrosomal protein CEP55 to trigger the phosphorylation of AKT at Ser473. Inhibition of PI3K/AKT signaling markedly attenuated SPAG5-mediated cell growth. Furthermore, SPAG5 expression was suppressed by miR-363-3p which inhibited the activity of SPAG5 mRNA 3'UTR. Ectopic expression of SPAG5 partly abolished the miR-363-3p-caused cell cycle arrest and suppression of cell proliferation and migration.
Collectively, these findings indicate that SPAG5 serves a promising prognostic factor in HCC and functions as an oncogene via CEP55-mediated PI3K/AKT pathway. The newly identified miR-363-3p/SPAG5/CEP55 axis may represent a potential therapeutic target for the clinical intervention of HCC.
Research on the science–policy interaction that happens in deliberative systems is limited. Drawing on concepts of democratisation of science and deliberation, this study used the case of dumping ...industrial waste on farmland in Taiwan to explore how local activists and non-governmental organisations contribute to knowledge production, democratising science and the epistemic–ethical–democratic functions for deliberative systems. The research methods used are documentary analysis and in-depth interviews. Local activists problematise official knowledge claims and its validation, deploy situated experiential expertise and engage directly in their own knowledge practices. Local activists and civic organisations play versatile roles in connecting the related networked institutions and intertwined spheres of deliberative systems. Civic activism engages in democratising science and participates in shaping policymaking, leading to the amendment of the Waste Disposal Act.
Background
Positron emission tomography (PET)/MRI biomarkers have been shown to have prognostic significance in patients with cervical cancer. Their associations with progression‐free survival (PFS) ...and overall survival (OS) merit further investigation.
Purpose
To evaluate the association between PET/MRI biomarkers and tumor stage, PFS, and OS in patients with cervical cancer.
Study Type
Prospective cohort study.
Population
In all, 54 patients with newly diagnosed cervical cancer and measurable tumors (>1 cm) were included in the image analysis.
Field Strength/Sequence
3.0T integrated PET/MRI including diffusion‐weighted echo‐planar imaging (b = 50 and 1000 s/mm2) and 18Ffluorodeoxyglucose PET.
Assessment
Two radiologists measured the minimum and mean apparent diffusion coefficient (ADCmin and ADCmean), maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors.
Statistical Tests
A Mann–Whitney U‐test was used to evaluate the association between the imaging biomarkers and tumor stage. A Cox proportional hazards model was used to assess the relationships between the imaging biomarkers and survival.
Results
In advanced tumors (T ≥ 1b2, M1, stage ≥ IB3), ADCmin was significantly lower and MTV, TLG, MTV/ADCmin, and TLG/ADCmin were significantly higher (P values between <0.001 and 0.036). In N1 tumors, ADCmin was significantly lower and MTV and MTV/ADCmin were significantly higher (P values between 0.005 and 0.016). In survival analysis, SUVmax was an independent predictor of PFS (hazard ratio HR = 4.57, P < 0.05), and ADCmin was an independent predictor of OS (HR = 0.02, P < 0.05). In subgroup analysis of patients with different stages, MTV/ADCmin was a predictor of PFS in stage I disease (P = 0.003), ADCmin (P = 0.038), and MTV (P = 0.020) in stage II, SUVmax (P = 0.006), and TLG (P = 0.006) in stage IV; and ADCmin was a predictor of OS in stage III disease (P = 0.008).
Data Conclusion
PET/MRI biomarkers of cervical cancer are associated with tumor stage and survival. SUVmax and ADCmin are independent predictors of PFS and OS, respectively.
Level of Evidence
1
Technical Efficacy
3
This study examined whether cerebrospinal fluid (CSF) baseline levels of the synaptic protein NPTX2 predict time to onset of symptoms of mild cognitive impairment (MCI), both alone and when ...accounting for traditional CSF Alzheimer's disease (AD) biomarker levels. Longitudinal NPTX2 levels were also examined.
CSF was collected longitudinally from 269 cognitively normal BIOCARD Study participants (mean baseline age = 57.7 years; mean follow-up = 16.3 years; n = 77 progressed to MCI/dementia). NPTX2 levels were measured from 3 correlated peptides using quantitative parallel reaction monitoring mass spectrometry. Levels of Aβ
/Aβ
, p-tau
, and t-tau were measured from the same CSF specimens using Lumipulse automated electrochemiluminescence assays.
In Cox regression models, lower baseline NPTX2 levels were associated with an earlier time to MCI symptom onset (hazard ratio HR = 0.76, SE = 0.09, p = 0.023). This association was significant for progression within 7 years (p = 0.036) and after 7 years from baseline (p = 0.001). Baseline NPTX2 levels improved prediction of time to MCI symptom onset after accounting for baseline AD biomarker levels (p < 0.01), and NPTX2 did not interact with the CSF AD biomarkers or APOE-ε4 genetic status. In linear mixed effects models, higher baseline p-tau
and t-tau levels were associated with higher baseline levels of NPTX2 (both p < 0.001) and greater rates of NPTX2 declines over time.
NPTX2 may be a valuable prognostic biomarker during preclinical AD that provides additive and independent prediction of MCI onset among individuals who are cognitively normal. We hypothesize that NPTX2-mediated circuit homeostasis confers resilience during the early phase of AD. ANN NEUROL 2023;94:620-631.
•The relative abundance of NK cells is lower in HCC than adjacent normal tissues.•The HCC subclasses showed distinct NK scores and expression patterns of NK-specific gene signatures.•The ...receptor-ligand pairs of immune checkpoint genes may be the major cause of immune evasion and immunotherapeutic targets.•Higher NK scores may be an indicator of sorafinib response and favorable prognosis.
Natural Killer (NK) cells are effector lymphocytes involved in tumor immunosurveillance, however, the specific mechanism in hepatocellular carcinoma (HCC) has not been well understood. In the present study, we estimated the relative abundances of NK cells in HCC using gene expression data, and found that NK cell abundance was lower in HCC tissues than in the adjacent normal tissues. With the common HCC subclasses, we also found that three HCC subclasses had distinct abundances of NK cells. Moreover, we also found strong association between NK cell abundances and genes encoding immune checkpoint proteins, such as KLRD1, CD96, TIGIT, CD86, HAVCR2, PDCD1 (PD-1), HLA-E, CD274 (PD-L1), and CTLA4, among which, KLRD1 vs. HLA-E, CD274 vs. PDCD1, and CTLA4 vs. CD86 were three pairs of receptors and ligands. Furthermore, we investigated the clinical significance of NK cell activities in HCC, and found that the NK cell abundances were highly associated with the response to sorafinib, and higher NK cell abundances may prolong both the recurrence-free and overall survival of HCC patients. In summary, the present study not only improved our understanding of the potential tumor immune evasion mechanism of NK cells in HCC, but also proposed the potential clinical application of NK activities in HCC treatment and risk assessment.
As an important source of drugs, natural products play an important role in the discovery and development of new drugs. More than 60% of anti-tumor drugs are closely related to natural products. At ...the same time, as the main cause of tumors, the abnormal activity of tyrosine kinase has become an important target for clinical treatment. Although, small molecule targeted drugs dominate the cancer treatment. Natural active products are driving the development of new tyrosine kinase inhibitors with their unique mode of action and molecular structure diversity. Obtaining new chemical entities with tyrosine kinase inhibitory activity from natural active products will bring new breakthroughs in the research of anticancer drugs. In this paper, different tyrosine kinases are mainly classified as targets, and natural products and derivatives which have been found to inhibit tyrosine kinase activity have been described. It is hoped that by analyzing the different aspects of the source, structural characteristics, mechanism of action and biological activity of these natural products, we will find new members that can be developed into drugs and promote the development of anti-tumor drugs.
Display omitted
•Tyrosine Kinases are key target of anti-tumor medicines.•Natural products are most important resource of new drug.•All the natural products with significant Tyrosine Kinases inhibition activity are classified and discussed.•This review will be more useful in developing the new drugs as a tyrosine kinase inhibitor based on these natural compounds.
This study examined whether the causal relationships of protection motivation theory (PMT) can be applied to explain and predict the public's behavioural intentions for safe food choice through ...protection motivation of health and well-being promotion in Taiwan. In addition, the public's perceived food risk management quality and perceived product safety liability of food providers involved in food safety scandals were considered in the PMT model. The results of structural equation modelling indicated that, compared with the original PMT model, the extended PMT model demonstrates higher explanatory and predictive power of a person's protection motivation to mitigate food safety problems, but lower explanatory and predictive power of a person's behavioural intentions to make safe food choices. The empirical results drawn from the extended PMT model revealed that in addition to perceived vulnerability regarding the threat of food safety scandals and perceived self-efficacy, a person's perceived product safety liability of food providers involved in food safety scandals is a significant predictor of his or her protection motivation, which subsequently influences his or her behavioural intentions regarding safe food choices.
•Perceived vulnerability and self-efficacy affects protection motivation.•Perceived product safety liability also influences protection motivation.•The extended PMT model has higher predictive power of protection motivation.
RNA methylation is emerging as an important regulator of gene expression. Dysregulation of methyltransferase that is essential for RNA modification contributes to the development and progression of ...human cancers. Here we show that methyltransferase-like 1 (METTL1) is upregulated in hepatocellular carcinoma (HCC) and exhibits oncogenic activities via PTEN/AKT signaling pathway. High expression of METTL1 is correlated with larger tumor size, higher serum AFP level, tumor vascular invasion, and poor prognosis in two independent cohorts containing 892 patients with HCC. Multivariate analyses suggest METTL1 as an independent factor for unfavorable overall survival. In vitro studies demonstrate that METTL1 overexpression promotes cell proliferation and migration, whereas its knockdown results in opposite phenotypes. Gene set enrichment analysis (GSEA) indicates PTEN pathway is activated in patients with low METTL1 expression. Ectopic expression of PTEN or inhibition of AKT activity significantly attenuates the METTL1-mediated malignant phenotypes. In clinical samples, METTL1 expression is reversely associated with PTEN expression. Combination of low METTL1 expression and high PTEN expression is significantly correlated with overall survival, more so than either METTL1 or PTEN expression alone. Collectively, our data suggest that METTL1 serves as a promising prognostic biomarker and that targeting METTL1/PTEN axis may provide therapeutic potential in HCC intervention.
Key messages
METTL1 is upregulated in HCC and correlated with poor outcomes.
METTL1 promotes cell proliferation and migration in HCC.
METTL1 exerts oncogenic activities via suppression of PTEN signaling.
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