Our aim was to analyze the clinical and survival differences among patients who underwent the two main treatment modalities, endoscopic ablation and radical nephroureterectomy. This study examined ...all patients who had undergone endoscopic management and RNU between Jul. 1988 and Mar. 2019 from the Taiwan UTUC registry. The inclusion criteria were low stage UTUC in RNU and all cases in endoscopic managed UTUC with a curative intent. The demographic and clinical characteristics were included for analysis. In total, 84 cases in the endoscopic group and 272 cases in the RNU group were enrolled for final analysis. The median follow-up period were 33.5 and 42.0 months in endoscopic and RNU group, respectively (p = 0.082). Comparison of Kaplan-Meier estimated survival curves between groups, the endoscopic group was associated with similar overall survival (OS), cancer specific survival (CSS), and intravesical recurrence free survival (IVRS) but demonstrated inferior disease free survival (DFS) (p = 0.188 for OS, p = 0.493 for CSS and p < 0.001 for DFS). Endoscopic management of UTUC was as safe as RNU in UTUC endemic region.
Effects of electronic and atomic structures of V‐doped 2D layered SnS2 are studied using X‐ray spectroscopy for the development of photocatalytic/photovoltaic applications. Extended X‐ray absorption ...fine structure measurements at V K‐edge reveal the presence of VO and VS bonds which form the intercalation of tetrahedral OVS sites in the van der Waals (vdW) gap of SnS2 layers. X‐ray absorption near‐edge structure (XANES) reveals not only valence state of V dopant in SnS2 is ≈4+ but also the charge transfer (CT) from V to ligands, supported by V Lα,β resonant inelastic X‐ray scattering. These results suggest V doping produces extra interlayer covalent interactions and additional conducting channels, which increase the electronic conductivity and CT. This gives rapid transport of photo‐excited electrons and effective carrier separation in layered SnS2. Additionally, valence‐band photoemission spectra and S K‐edge XANES indicate that the density of states near/at valence‐band maximum is shifted to lower binding energy in V‐doped SnS2 compare to pristine SnS2 and exhibits band gap shrinkage. These findings support first‐principles density functional theory calculations of the interstitially tetrahedral OVS site intercalated in the vdW gap, highlighting the CT from V to ligands in V‐doped SnS2.
The interstitially tetrahedral O–V–S site in the vdW gap of V‐doped 2D SnS2 establishes the origin of the charge transfer mechanism between metal ion V4+ 3d and ligand O2‐ 2p/S2‐ 3p states and the decrease in the band gap by studying synchrotron‐based techniques and first‐principles density functional theory.
Lung cancer is the most frequent cause of cancer-related death around the world. With the recent introduction of low-dose lung computed tomography for lung cancer screening, there has been an ...increasing number of smoking- and non-smoking-related lung cancer cases worldwide that are manifesting with subsolid nodules, especially in Asian populations. However, the pros and cons of lung cancer screening also follow the implementation of lung cancer screening programs. Here, we review the literature related to radiomics for early lung cancer diagnosis. There are four main radiomics applications: the classification of lung nodules as being malignant/benign; determining the degree of invasiveness of the lung adenocarcinoma; histopathologic subtyping; and prognostication in lung cancer prediction models. In conclusion, radiomics offers great potential to improve diagnosis and personalized risk stratification in early lung cancer diagnosis through patient-doctor cooperation and shared decision making.
Since chemotherapy is a main strategy to treat triple-negative breast cancer (TNBC) patients currently, identifying a biomarker to predict chemotherapeutic responses is urgently needed for patients ...to avoid suffering through unnecessary chemotherapeutic treatments. Here, we found that the endogenous expression of
TNFSF13
in a panel of TNBC cell lines highly correlates with paclitaxel (PTX) and doxorubicin IC
50
concentrations. Whereas knocking down
TNFSF13
enhances PTX effectiveness in PTX-insensitive MDA-MB231 cells, recombinant TNFSF13 (recTNFSF13) desensitizes PTX-sensitive HCC1806 cells to PTX treatment. Moreover, Kaplan-Meier analysis revealed that higher TNFSF13 mRNA expression significantly predicts an increased risk for cancer recurrence in estrogen receptor (ER)-negative breast cancer patients receiving an anthracycline-based treatment. Accordingly, immunohistochemistry experiments indicated that higher levels of TNFSF13 protein are detected in TNBC patients who do not respond to an anthracycline-based treatment. The in silico analysis and Western blotting demonstrated that
TNFSF13
expression inversely associates with the activity of the Akt-mTOR pathway, which acts as a negative regulator of autophagy activity. Significantly, the pharmaceutical inhibition of autophagy activity restores the therapeutic effectiveness of PTX in TNFSF13-treated HCC1806 cells. These findings suggest that TNFSF13 can serve as a predictive biomarker for TNBC patients, who can use it to decide whether to receive chemotherapy.
Key messages
TNFSF13 upregulation correlates with a poor response to chemotherapy in TNBCs.
TNFSF13 promotes autophagy initiation in chemotherapeutic resistant TNBCs.
Therapeutic targeting of autophagy initiation overcomes the TNFSF13-related chemoresistance.
TNFSF13 could be a predictive biomarker for TNBC patients receiving chemotherapy.
Radiotherapy is the first-line regimen for treating oral squamous cell carcinoma (OSCC) in current clinics. However, the development of therapeutic resistance impacts the anticancer efficacy of ...irradiation in a subpopulation of OSCC patients. As a result, discovering a valuable biomarker to predict radiotherapeutic effectiveness and uncovering the molecular mechanism for radioresistance are clinical issues in OSCC.
Three OSCC cohorts from The Cancer Genome Atlas (TCGA), GSE42743 dataset and Taipei Medical University Biobank were enrolled to examine the transcriptional levels and prognostic significance of neuronal precursor cell-expressed developmentally downregulated protein 8 (NEDD8). Gene set enrichment analysis (GSEA) was utilized to predict the critical pathways underlying radioresistance in OSCC. The colony-forming assay was used to estimate the consequences of irradiation sensitivity after the inhibition or activation of the NEDD8-autophagy axis in OSCC cells.
NEDD8 upregulation was extensively found in primary tumors compared to normal adjacent tissues and potentially served as a predictive marker for the therapeutic effectiveness of irradiation in OSCC patients. NEDD8 knockdown enhanced radiosensitivity but NEDD8 overexpression reduced it in OSCC cell lines. The inclusion of MLN4924, a pharmaceutical inhibitor for NEDD8-activating enzyme, dose-dependently restored the cellular sensitivity to irradiation treatment in irradiation-insensitive OSCC cells. Computational simulation by GSEA software and cell-based analyses revealed that NEDD8 upregulation suppresses Akt/mTOR activity to initiate autophagy formation and ultimately confers radioresistance to OSCC cells.
These findings not only identify NEDD8 as a valuable biomarker to predict the efficacy of irradiation but also offer a novel strategy to overcome radioresistance via targeting NEDD8-mediated protein neddylation in OSCC.
With the popularization of lung cancer screening, many persistent subsolid nodules (SSNs) have been identified clinically, especially in Asian non-smokers. However, many studies have found that SSNs ...exhibit heterogeneous growth trends during long-term follow ups. This article adopted a narrative approach to extensively review the available literature on the topic to explore the definitions, rationale, and clinical application of different interval growths of subsolid pulmonary nodule management and follow-up strategies. The development of SSN growth thresholds with different growth patterns could support clinical decision making with follow-up guidelines to reduce over- and delayed diagnoses. In conclusion, using different SSN growth thresholds could optimize the follow-up management and clinical decision making of SSNs in lung cancer screening programs. This could further reduce the lung cancer mortality rate and potential harm from overdiagnosis and over management.
In this study, ultrasound-assisted extraction (UAE) and other methods of extracting flavonoid compounds and ferulic acid (FA) from S. sinensis were investigated. Five different extraction methods, ...including water extraction (W), water extraction using UAE (W+U), 75% ethanol extraction (E), 75% ethanol extraction using UAE (E+U), and supercritical CO2 extraction (SFE) were applied in the extraction of bioactive compounds (flavonoids and ferulic acid) in order to compare their efficiency. The highest yield of flavonoids (4.28 mg/g) and ferulic acid (4.13 mg/g) content was detected in the E+U extract. Furthermore, S. sinensis extracts obtained by E+U show high antioxidant activity, and IC50 values of 0.47 mg/mL for DPPH radicals and 0.205 mg/mL for metal chelating activity. The total antioxidant assay shows superoxide radical scavenging capacity and in vitro mushroom tyrosinase inhibition in a dose-dependent manner, suggesting that E+U can be used for extraction of bioactive compounds from S. sinensis.
Colorectal cancer (CRC) is one of the most common cancers and results in high mortality worldwide, owing to cancer progression, i.e., metastasis. However, the molecular mechanism underlying the ...metastatic evolution of CRC remains largely unknown. Here, we find that the upregulation of Ral Guanine Nucleotide Dissociation Stimulator Like 2 (RGL2) is commonly detected in primary tumors compared normal tissues and is significantly associated with a poorer prognosis in CRC patients. Moreover, RGL2 expression appeared to positively correlate with the metastatic potentials of CRC cells. Whereas RGL2 knockdown dramatically suppresses the metastatic potentials of CRC cells in vitro and in vivo, RGL2 overexpression in the poorly metastatic CRC cells and reconstitution in the RGL2-silenced CRC cells enhanced and rescued the cellular metastatic ability, respectively. Computational simulation using Gene Set Enrichment Analysis program and cell-based assays demonstrated that RGL2 expression causally associated with the activity of Wnt/β-catenin signaling axis and Kirsten ras (KRAS)S, as well as the progression of epithelial-mesenchymal transition (EMT) in the detected CRC cells. Importantly, RGL2 upregulation was capable of preventing the protein degradation of β-catenin and KRAS in CRC cells. These findings suggest that RGL2 acts as a driver to promote the metastatic progression of CRC and also serves as a poor prognostic biomarker in CRC patients.
We proposed a modification of the ACR Lung Imaging Reporting and Data System (Lung-RADS) to clarify the characteristics of subsolid nodules with categories 1-11, and to compare the diagnostic ...accuracy with Lung-RADS and National Lung Screening Trial criteria in an Asian population with high prevalence of adenocarcinoma.
We analyzed a retrospective cohort of 1978 consecutive healthy subjects (72.8% nonsmoker) who underwent low-dose computed tomography from August 2013 to October 2014 (1084 men, 894 women). Lung-RADS categories 2 and 3 were modified to include subcategories of 2A/2B/2C and 3A/3B/3C, respectively. Clinical information and nodule characteristics were recorded. Receiver operating characteristic curves were used to compare diagnostic accuracy at different cutoffs.
Thirty-two subjects (30 nonsmokers) had pathology-proven adenocarcinoma spectrum lesions in the follow-up period (1.6 ± 0.5 years). Modified Lung-RADS, using modified Lung-RADS category 2C as cutoff, had an area under the curve (AUC) of 0.973 in predicting adenocarcinoma spectrum lesions (sensitivity of 100%, specificity of 89.3%), which was significantly higher than that of Lung-RADS (AUC = 0.815, P < .001) and National Lung Screening Trial (AUC = 0.906, P < .001). Furthermore, modified Lung-RADS showed an AUC of 0.992 in predicting invasive adenocarcinoma (sensitivity of 95%, specificity of 97.8%) when category 3B was used as cutoff.
Modified Lung-RADS may substantially improve sensitivity while maintaining specificity for detection of adenocarcinoma spectrum lesions in an Asian population. Compared to Lung-RADS, it has enhanced ability to differentiate invasive from indolent adenocarcinoma by more refined subclassification of subsolid nodules using two cutoff values of category 2C and 3B. The effect of using modified Lung-RADS in clinical practice must be carefully studied in prospective large cohort studies.
Glass-ceramics for low-temperature co-fired-ceramic 5G wireless devices exhibit excellent microwave properties. However, silver diffusion and interdiffusion of the electrode decreases the ...high-frequency conductivity. In this work, the inhibition of the silver diffusion mechanism in CaO-MgO-SiO2 glass-ceramics was investigated. Specimens without SiO2 were found to exhibit both Ag diffusion and Zn, Mg, and Ca interdiffusion. In contrast, samples with SiO2 show much less diffusion and a Ag6O2 phase at the diffusive boundary layer, indicating that the SiO2 addition inhibits Ag diffusion and interdiffusion. Elemental mapping indicated the presence of a concentration gradient-reaction between the SiO2 particles and the glass-ceramic. This reaction enhances the glass viscosity and inhibits Ag diffusion and interdiffusion. SiO2-added glass-ceramics co-fired with an Ag electrode show improved 5G-patch-antenna microwave characteristics, with an enhanced conductivity at ~8.2 GHz and a return loss of S11 = -23 dB at ~28.3 GHz.
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