Despite ionizing radiation (IR) is being widely used as a standard treatment for lung cancer, many evidences suggest that IR paradoxically promotes cancer malignancy. However, its molecular ...mechanisms underlying radiation-induced cancer progression remain obscure. Here, we report that exposure to fractionated radiation (2 Gy per day for 3 days) induces the secretion of granulocyte-colony-stimulating factor (G-CSF) that has been commonly used in cancer therapies to ameliorate neutropenia. Intriguingly, radiation-induced G-CSF promoted the migratory and invasive properties by triggering the epithelial-mesenchymal cell transition (EMT) in non-small-cell lung cancer cells (NSCLCs). By irradiation, G-CSF was upregulated transcriptionally by β-catenin/TCF4 complex that binds to the promoter region of G-CSF as a transcription factor. Importantly, irradiation increased the stability of β-catenin through the activation of PI3K/AKT (phosphatidylinositol 3-kinase/AKT), thereby upregulating the expression of G-CSF. Radiation-induced G-CSF is recognized by G-CSFR and transduced its intracellular signaling JAK/STAT3 (Janus kinase/signal transducers and activators of transcription), thereby triggering EMT program in NSCLCs. Taken together, our findings suggest that the application of G-CSF in cancer therapies to ameliorate neutropenia should be reconsidered owing to its effect on cancer progression, and G-CSF could be a novel therapeutic target to mitigate the harmful effect of radiotherapy for the treatment of NSCLC.
L-ascorbate (L-ascorbic acid, vitamin C) clearly has an inhibitory effect on cancer cells. However, the mechanism underlying differential sensitivity of cancer cells from same tissue to L-ascorbate ...is yet to be clarified. Here, we demonstrate that L-ascorbate has a selective killing effect, which is influenced by sodium-dependent vitamin C transporter 2 (SVCT-2) in human breast cancer cells. Treatment of human breast cancer cells with L-ascorbate differentially induced cell death, dependent on the SVCT-2 protein level. Moreover, knockdown of endogenous SVCT-2 via RNA interference in breast cancer cells expressing high levels of the protein induced resistance to L-ascorbate treatment, whereas transfection with SVCT-2 expression plasmids led to enhanced L-ascorbate chemosensitivity. Surprisingly, tumor regression by L-ascorbate administration in mice bearing tumor cell xenograft also corresponded to the SVCT-2 protein level. Interestingly, SVCT-2 expression was absent or weak in normal tissues, but strongly detected in tumor samples obtained from breast cancer patients. In addition, enhanced chemosensitivity to L-ascorbate occurred as a result of caspase-independent autophagy, which was mediated by beclin-1 and LC3 II. In addition, treatment with N-acetyl-L-cysteine, a reactive oxygen species (ROS) scavenger, suppressed the induction of beclin-1 and LC3 II, implying that the differential SVCT-2 protein-dependent L-ascorbate uptake was attributable to intracellular ROS induced by L-ascorbate, subsequently leading to autophagy. These results suggest that functional SVCT-2 sensitizes breast cancer cells to autophagic damage by increasing the L-ascorbate concentration and intracellular ROS production and furthermore, SVCT-2 in breast cancer may act as an indicator for commencing L-ascorbate treatment.
The RENO experiment has observed the disappearance of reactor electron antineutrinos, consistent with neutrino oscillations, with a significance of 4.9 standard deviations. Antineutrinos from six 2.8 ... GW(th) reactors at the Yonggwang Nuclear Power Plant in Korea, are detected by two identical detectors located at 294 and 1383 m, respectively, from the reactor array center. In the 229 d data-taking period between 11 August 2011 and 26 March 2012, the far (near) detector observed 17102 (154088) electron antineutrino candidate events with a background fraction of 5.5% (2.7%). The ratio of observed to expected numbers of antineutrinos in the far detector is 0.920±0.009(stat)±0.014(syst). From this deficit, we determine sin(2)2θ(13)=0.113±0.013(stat)±0.019(syst) based on a rate-only analysis.
Mutation in PTEN has not yet been detected, but its function as a tumor suppressor is inactivated in many cancers. In this study we determined that, activated Notch signaling disables PTEN by ...phosphorylation and thereby contributes to gastric tumorigenesis. Notch inhibition by small interfering RNA or γ-secretase inhibitor (GSI) induced mitotic arrest and apoptosis in gastric cancer cells. Notch inhibition induced dephosphorylation in the C-terminal domain of PTEN, which led to PTEN nuclear localization. Overexpression of activated Notch1-induced phosphorylation of PTEN and reversed GSI-induced mitotic arrest. Dephosphorylated nuclear PTEN caused prometaphase arrest by interaction with the cyclin B1-CDK1 complex, resulting in their accumulation in the nucleus and subsequent apoptosis. We found a correlation between high expression levels of Notch1 and low survival rates and, similarly, between reduced nuclear PTEN expression and increasing the TNM classification of malignant tumours stages in malignant tissues from gastric cancer patients. The growth of Notch1-depleted gastric tumors was significantly retarded in xenografted mice, and in addition, PTEN deletion restored growth similar to control tumors. We also demonstrated that combination treatment with GSI and chemotherapeutic agents significantly reduced the orthotopically transplanted gastric tumors in mice without noticeable toxicity. Overall, our findings suggest that inhibition of Notch signaling can be employed as a PTEN activator, making it a potential target for gastric cancer therapy.
Background
Periostin is a matricellular protein, and its synthesis in airway epithelial cells and lung fibroblasts is induced by interleukin (IL)‐4 and IL‐13. The significance of periostin as a ...biomarker of TH2‐induced airway inflammation, and (importantly) as a measure of the response to TH2‐targeted therapy, has recently been emphasized. We explored the relationship between periostin and airway hyperresponsiveness (AHR) in asthmatic children.
Methods
The study included 83 children aged 6–15 years in an asthmatic group (n = 54) and healthy controls (n = 29). We measured the periostin levels in serum and performed methacholine and mannitol provocation challenges. The responses to mannitol were expressed as the provocative dose causing a 15% fall in the FEV1 (the PD15 dose).
Results
Of the 54 subjects with asthma, all had positive methacholine bronchial provocation test (BPT) results and 38 had positive mannitol BPT results. Children with asthma had significantly higher periostin levels than controls 76.0 (65.0–91.8) vs 71.0 (57.5–80.0) ng/mL; P = 0.017. Periostin levels were significantly correlated with both the methacholine PC20 and mannitol PD15 values.
Conclusion
Serum levels of periostin, a new biomarker induced by IL‐13, were higher in asthmatic children, and were associated with AHR to methacholine and mannitol.
Gliomas are associated with high mortality because of their exceedingly invasive character. As these tumors acquire their invasiveness from low-grade tumors, it is very important to understand the ...detailed molecular mechanisms of invasion onset. Recent evidences suggest the significant role of microRNAs in tumor invasion. Thus, we hypothesized that deregulation of microRNAs may be important for the malignant progression of gliomas. We found that the aberrant expression of miR-21 is responsible for glioma invasion by disrupting the negative feedback circuit of Ras/MAPK signaling, which is mediated by Spry2. Upregulation of miR-21 was triggered by tumor microenvironmental factors such as hyaluronan and growth factors in glioma cells lacking functional phosphatase and tensin homolog (PTEN), but not harboring wild-type PTEN. Consistently with these in vitro results, Spry2 protein levels were significantly decreased in 79.7% of invasive WHO grade II-IV human glioma tissues, but not in non-invasive grade I and normal tissues. The Spry2 protein levels were not correlated with their mRNA levels, but inversely correlated with miR-21 levels. Taken together, these results suggest that the post-transcriptional regulation of Spry2 by miR-21 has an essential role on the malignant progression of human gliomas. Thus, Spry2 may be a novel therapeutic target for treating gliomas.
Despite intense studies into silicon anode materials, the large volume expansion of silicon remains a significant problem that reduces battery performance and shortens battery life. In this paper, a ...procedure to increase the cycle life of the silicon anode in full-cell configuration using a simple pre-lithiation method is proposed. By precisely controlling the thickness of the pre-deposited lithium through evaporation, the volume change of the silicon-containing anodes can be effectively reduced during discharge. A coin-cell fabricated with a high-capacity cathode and the pre-lithiated silicon–graphite anode shows improvements in cycling performance, as well as a higher discharge capacity. Electrochemical and microscopic analysis confirm that pre-lithiation successfully suppresses the volumetric changes. Thus, this work provides an effective method for the preparation of long-cycle-life Li-ion batteries containing silicon-based anodes.
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•The mechanism for improving cycle life through pre-lithiation was proposed and proved.•A pre-lithiation method is proposed by lithium evaporation on a Si-Gr anode.•Precisely controlled pre-lithiated cells prevent complete shrinkage of the silicon.•Enhanced cycle life and a high areal capacity were achieved at a high current densities.
Identifying the extent of environmental contamination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for infection control and prevention. The extent of environmental ...contamination has not been fully investigated in the context of severe coronavirus disease (COVID-19) patients.
To investigate environmental SARS-CoV-2 contamination in the isolation rooms of severe COVID-19 patients requiring mechanical ventilation or high-flow oxygen therapy.
Environmental swab samples and air samples were collected from the isolation rooms of three COVID-19 patients with severe pneumonia. Patients 1 and 2 received mechanical ventilation with a closed suction system, while patient 3 received high-flow oxygen therapy and non-invasive ventilation. Real-time reverse transcription–polymerase chain reaction (rRT–PCR) was used to detect SARS-CoV-2; viral cultures were performed for samples not negative on rRT–PCR.
Of the 48 swab samples collected in the rooms of patients 1 and 2, only samples from the outside surfaces of the endotracheal tubes tested positive for SARS-CoV-2 by rRT–PCR. However, in patient 3's room, 13 of the 28 environmental samples (fomites, fixed structures, and ventilation exit on the ceiling) showed positive results. Air samples were negative for SARS-CoV-2. Viable viruses were identified on the surface of the endotracheal tube of patient 1 and seven sites in patient 3's room.
Environmental contamination of SARS-CoV-2 may be a route of viral transmission. However, it might be minimized when patients receive mechanical ventilation with a closed suction system. These findings can provide evidence for guidelines for the safe use of personal protective equipment.
We conducted a population-based retrospective cohort study to investigate the influence of hospital volume, delay of surgery, and both together on the long-term survival of postoperative cancer ...patients.
Using information from the Korea Central Cancer Registry from 2001 through 2005 and the National Health Insurance claim database, we determined survival for 147 682 patients who underwent definitive surgery for any of six cancers.
Regardless of cancer site, surgical patients in low- to medium-volume hospitals showed significantly worse survival adjusted hazard ratio (aHR) = 1.36–1.86 than those in high-volume hospitals in multivariable analyses. Among the latter, treatment delays > 1 month were not associated with worse survival for stomach, colon, pancreatic, or lung cancer but were for rectal aHR = 1.28; 95% confidence interval (CI), 1.17–1.40 and breast (aHR = 1.59; 95% CI, 1.37–1.84) cancer. For patients in low- to medium-volume hospitals, treatment delay was associated with worse survival for all types of cancer (aHR = 1.78–3.81).
Our findings suggest that the effect of hospital volume and surgical treatment delay on overall survival of cancer patients should be considered in formulating or revising national health policy.
Thin, soft, and elastic electronics with physical properties well matched to the epidermis can be conformally and robustly integrated with the skin. Materials and optimized designs for such devices ...are presented for surface electromyography (sEMG). The findings enable sEMG from wide ranging areas of the body. The measurements have quality sufficient for advanced forms of human‐machine interface.
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