NEK2 (NIMA‐related expressed kinase 2) is a serine/threonine centrosomal kinase that acts as a critical regulator of centrosome structure and function. Aberrant NEK2 activities lead to failure in ...regulating centrosome duplication. NEK2 overexpression promotes tumorigenesis and is associated with poor prognosis in several cancers. Increased NEK2 expression during the late pathological stage has been detected in the Oncomine liver dataset and hepatocellular carcinoma (HCC) specimens. Elevated NEK2 protein is associated with poor overall survival in patients with HCC. However, the precise roles and mechanisms of NEK2 in liver cancer progression remain largely unknown. An earlier functional study revealed that NEK2 mediates drug resistance (cisplatin or lipo‐doxorubicin) via expression of an ABCC10 transporter. Active angiogenesis and metastasis underlie the rapid recurrence and poor survival of HCC. Results from the current study showed that NEK2 mediates tumor growth, metastasis and angiogenesis in vivo. NEK2‐mediated drug resistance was blocked by a specific PI3K or AKT inhibitor. Moreover, NEK2 mediated liver cancer cell migration via pAKT/NF‐κB signaling and matrix metalloproteinase (MMP) activation. Angiogenesis was induced via the same signaling pathway and IL‐8 stimulation. Our findings collectively indicate that NEK2 modulates hepatoma cell functions, including growth, drug resistance, metastasis and angiogenesis via downstream genes activation.
What's new?
Hepatocellular carcinoma (HCC) is an aggressive disease that tends to spread extensively within the liver, resulting in a high frequency of disease recurrence and poor survival, despite treatment. According to the present study, the invasive nature of HCC is fueled in part by NEK2, an oncogenic serine/threonine centrosomal kinase. Experiments in a hepatoma xenograft mouse model show that NEK2 overexpression contributes to tumor growth, metastasis, and angiogenesis. In hepatoma cells, NEK2 overexpression was associated with drug resistance and decreased apoptosis. Analyses of clinical HCC specimens reveal additional links between NEK2 overexpression and increased vascular invasion.
Monocytic myeloid-derived suppressor cells (MDSCs), particularly the S100A9+ subset, has been shown initial clinical relevance. However, its role in EGFR-mutated lung adenocarcinoma, especially to ...EGFR-tyrosine kinase inhibitor (EGFR-TKI) is not clear. In a clinical setting of EGFR mutated lung adenocarcinoma, a role of the MDSC apart from T cell suppression was also investigated.
Blood monocytic S100A9
MDSC counts were higher in lung cancer patients than healthy donors, and were associated with poor treatment response and shorter progression-free survival (PFS). S100A9
MDSCs in PBMC were well correlated to tumor infiltrating CD68
and S100A9
cells, suggesting an origin of TAMs. Patient's MDMs, mostly from S100A9
MDSC, similar to primary alveolar macrophages from patients, both expressed S100A9 and CD206, attenuated EGFR-TKI cytotoxicity. Microarray analysis identified up-regulation of the
signaling genes, confirmed by Western blotting and functionally by
knockdown.
In conclusion, blood S100A9
MDSC is a predictor of poor treatment response to EGFR-TKI, possibly via its derived TAMs through activation of the non-canonical NF-κB
pathway.
Patients with activating EGFR mutation lung adenocarcinoma receiving first line EGFR TKIs were prospectively enrolled. Peripheral blood mononuclear cells (PBMCs) were collected for MDSCs analysis and for monocyte-derived macrophages (MDMs) and stored tissue for TAM analysis by IHC. A transwell co-culture system of MDMs/macrophages and H827 cells was used to detect the effect of macrophages on H827 and microarray analysis to explore the underlying molecular mechanisms, functionally confirmed by RNA interference.
Diabetes with co-existing bone fragility or osteoporosis is common in elderly patients, whereas is frequently underestimated.
We conducted dual-energy x-ray absorptiometry (DXA) with 7-site skinfold ...(SF) and dominant hand grip strength measurements among patients with type 2 diabetes (T2DM) to assess their gender-specific associations. A total of 103 patients with T2DM (60 females and 43 males), aged between 50 and 80 years (median 68.0 years) were enrolled and 45 non-DM females were also included to compare with T2DM females.
Our results revealed osteoporosis was negatively correlated with grip strength in both genders, negatively correlated with lean mass solely in males and negatively correlated with fat mass (particular the gynoid fat mass and thigh SF thickness) in females. Via performing multivariable stepwise logistic regression, we identified grip strength in both genders and thigh SF thickness in females as predictors for osteoporosis. Receiver operating characteristic curve analysis further disclosed 20.5 mm female thigh skinfold thickness, 18.1 kg female grip strength and 29.0 kg male grip strength as reasonable cutoff levels for predicting osteoporosis in the Taiwanese patients with T2DM.
Patients with T2DM presented gender-specific associations between osteoporosis, body composition and grip strength. Grip strength and thigh SF thickness might serve as predictors for detection of osteoporosis in patients with T2DM.
Racial and ethnic disparities exist for hepatitis C virus (HCV) treatment and hepatocellular carcinoma (HCC) survival.
To evaluate the impact of HCV treatment on such disparities.
In a retrospective ...cohort study, we analysed 6069 patients with HCV-related HCC (54.2% Asian, 30.1% White, 8.5% Black, and 7.3% Hispanic) from centres in the United States and Asia.
The mean age was 61, 60, 59 and 68, respectively, for White, Black, Hispanic and Asian patients. Black patients were most likely to have Barcelona Clinic Liver Cancer stage D, vascular invasion and distant metastasis (23% vs. 5%-15%, 20% vs. 10%-17% and 10% vs. 5%-7%, respectively; all p < 0.0001). Treatment rate with direct-acting antiviral agents (DAA) was 35.9% for Asian, 34.9% for White, 30.3% for Hispanic (30.3%), and 18.7% for Black patients (p < 0.0001). Among those untreated or without sustained virologic response (SVR), 10-year survival rates were 35.4, 27.5, 19.3 and 14.0, respectively, for Asian, Hispanic, White and Black patients (p < 0.0001). There were no statistically significant differences among those with SVR (p = 0.44). On multivariable analysis adjusted for relevant confounders, there was no statistically significant association between survival and being Hispanic (aHR: 0.68, p = 0.26) or Black (aHR: 1.18, p = 0.60) versus White. There was a significant association between being Asian American and survival (aHR: 0.24, p = 0.001; non-U.S. Asian: aHR: 0.66, p = 0.05), and for SVR (aHR: 0.30, p < 0.0001).
DAA treatment rates were suboptimal. Racial and ethnic disparities resolved with HCV cure. Early diagnosis and improved access to HCV treatment is needed for all patients with HCV infection.
The development of rapid and sensitive methods for the detection of immunogenic tumor-associated antigen is important not only for understanding their roles in cancer immunology but also for the ...development of clinical diagnostics. α-Enolase (ENO1), a p48 molecule, is widely distributed in a variety of tissues, whereas γ-enolase (ENO2) and β-enolase (ENO3) are found exclusively in neuron/neuroendocrine and muscle tissues, respectively. Because ENO1 has been correlated with small cell lung cancer, nonsmall cell lung cancer, and head and neck cancer, it can be used as a potential diagnostic marker for lung cancer. In this study, we developed a simple, yet novel and sensitive, electrochemical sandwich immunosensor for the detection of ENO1; it operates through physisorption of anti-ENO1 monoclonal antibody on polyethylene glycol-modified disposable screen-printed electrode as the detection platform, with polyclonal secondary anti-ENO1-tagged, gold nanoparticle (AuNP) congregates as electrochemical signal probes. The immunorecognition of the sample ENO1 by the congregated AuNP@antibody occurred on the surface of the electrodes; the electrochemical signal from the bound AuNP congregates was obtained after oxidizing them in 0.1 M HCl at 1.2 V for 120 s, followed by the reduction of AuCl4− in square wave voltammetry (SWV) mode. The resulting sigmoidally shaped dose−response curves possessed a linear dynamic working range from 10−8 to 10−12 g/mL. This AuNP congregate-based assay provides an amplification approach for detecting ENO1 at trace levels, leading to a detection limit as low as 11.9 fg (equivalent to 5 μL of a 2.38 pg/mL solution).
Gliomas are solid tumors that originate from glial cells in the brain or spine and account for 74.6% of malignant primary central nervous system tumors worldwide. As patient-derived primary cells are ...important tools for drug screening and new therapy development in glioma, we aim to understand the genomic similarity of the primary cells to their parental tumors by comparing their whole-genome copy number variations and expression profile of glioma clinicopathologic factors. We found that the primary cells from grade II/III gliomas lost most of the gene copy number alterations (CNAs), which were mainly located on chromosome 1p and 19q in their parental tumors. The glioblastoma (GBM) primary cells preserved 83.7% of the gene CNAs in the parental GBM tumors, including chromosome 7 gain and 10q loss. The CNA gains of
and
and the chromosome 16p11 loss were reconstituted in primary cells from both grade II/III gliomas and GBMs. Interestingly, we found these CNAs were correlated to overall survival (OS) in glioma patients using the Merged Cohort LGG and GBM dataset from cBioPortal. The gene CNAs preserved in glioma primary cells often predicted poor survival, whereas the gene CNAs lost in grade II/III primary cells were mainly associated to better prognosis in glioma patients. Glioma prognostic factors that predict better survival, such as
mutations and 1p/19q codeletion in grade II/III gliomas, were lost in their primary cells, whereas methylated
promoters as well as
promoter mutations were preserved in GBM primary cells while lost in grade II/III primary cells. Our results suggest that GBM primary cells tend to preserve CNAs in their parental tumors, and these CNAs are correlated to poor OS and predict worse prognosis in glioma patients.
Cephalic arch stenosis (CAS) is a common cause of AV dialysis access failure and is notoriously difficult to treat with conventional venoplasty. Although stent graft (SG) placement has improved ...patency rate, they are prone to stent failure caused by edge stenosis. We investigate the effect of SG diameter relative to cephalic vein on patency rate among hemodialysis patients with dysfunctional arteriovenous access caused by CAS. We identified 22 patients with recalcitrant cephalic arch stenosis or post-venoplasty vessel rupture and received SG placement. Patients were divided into two groups based on the stent-to-vessel diameter (S/V) ratio: undersized group, < 1; and apposed group, 1-1.2. Outcomes were assessed through follow-up angiography. S/V ratio was significant smaller in the undersized patient group (p < 0.001). Placement of undersized SG demonstrated higher primary stent (p = 0.001) and access patency rates (p = 0.021) and a reduced number of post-treatment reinterventions per access year (p = 0.021). A decreased number of lateral edge stenosis was noted in undersized SG (p = 0.005). Increased S/V ratio was significantly associated with lateral edge stenosis (OR = 5.19; p = 0.027). Undersized SG is associated with higher primary stent and access patency rate, and decreased number of post-SG interventions, and are suggested in the treatment of cephalic arch stenosis.
In recent years, novel Al secondary batteries with Al anodes, natural graphite cathodes, and ionic liquid electrolytes have received more attention. However, most research on Al secondary batteries ...used lower graphite loading (<8 mg/cm2), which will inhibit the batteries from commercialization in the future. Here, we prepared Al secondary batteries using Al anode, low-cost natural graphite cathode, and cheaper ionic liquid electrolyte. The effects of loading (7–12 mg/cm2) on performance were investigated. Based on our observations, graphite-based Al secondary batteries (GABs) using 10 mg/cm2 graphite electrodes had better performance of 82 mAh/g and 6.5 Wh/L at a current density of 100 mA/g. Moreover, the 10 mg/cm2 GABs showed a long life of 250 charge–discharge cycles with a high coulombic efficiency of 98% and excellent performance rate up to 1000 mA/g.
To explore symptom clusters (SCs) in lymphoma survivors before, during, and after chemotherapy. .
61 lymphoma survivors from a medical center in central Taiwan were enrolled in the study. .
A ...prospective observational study design was adopted. The MD Anderson Symptom Inventory was used to measure symptoms. The 13 symptoms assessed by the MD Anderson Symptom Inventory were evaluated after diagnosis and before chemotherapy (T1), after the fourth cycle of chemotherapy (T2), and after completion of chemotherapy (T3). Data were analyzed using mean, frequency, and latent profile analysis. .
Three SCs were identified at T1, four at T2, and three at T3. Fatigue was the predominant symptom in each SC for the participants over time. Fatigue, disturbed sleep, and numbness constituted an SC at T2 and T3. An SC consisting of multiple psychological symptoms was found only at T1.
This study describes methods for grouping SCs. An SC of fatigue, disturbed sleep, and numbness was identified at T2 and T3. By familiarizing themselves with this SC, clinicians can be attentive to patients' concurrent symptoms and implement early prevention measures and timely symptom management.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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