BACKGROUND: Lung cancer is the most common cause of cancer-related mortality worldwide. We previously reported the identification of a new genetic marker, cellular retinoic acid binding protein 2 (CRABP2), in lung cancer tissues. The aim of this study was to assess plasma levels of CRABP2 from patients with non-small cell lung cancer (NSCLC). METHODS: Blood samples that were collected from 122 patients with NSCLC between September 2009 and September 2013 were selected for the analysis, along with samples from age- (± 5 years), sex-, and cigarette smoking history (± 10 pack-years [PY])-matched controls from the Korea Biobank Network. The control specimens were from patients who were without malignancies or pulmonary diseases. We measured plasma levels of CRABP2 using commercially available enzyme-linked immunosorbent assay kits. RESULTS: The mean age of the NSCLC patients was 71.8 ± 8.9 years, and the median cigarette smoking history was 32 PY (range, 0–150 PY). Plasma CRABP2 levels were significantly higher in patients with NSCLC than in the matched controls (37.63 ± 28.71 ng/mL vs. 24.09 ± 21.09 ng/mL, P < 0.001). Higher plasma CRABP2 levels were also correlated with lower survival rates in NSCLC patients (P = 0.014). CONCLUSION: Plasma CRABP2 levels might be a novel diagnostic and prognostic marker in NSCLC.
Biomarkers ; Carcinoma, Non-Small-Cell Lung* ; Carrier Proteins ; Enzyme-Linked Immunosorbent Assay ; Genetic Markers ; Humans ; Korea ; Lung Diseases ; Lung Neoplasms ; Mortality ; Plasma* ; Smoking ; Survival Rate ; Tretinoin

Intrathoracic involvement of immunoglobulin G4 (IgG4)-related disease has recently been reported. However, a subset of the disease presenting as interstitial lung disease is rare. Here, we report a case of a 35-year-old man with IgG4-related lung disease with manifestations similar to those of interstitial lung disease. Chest computed tomography showed diffuse ground glass opacities and rapidly progressive pleural and subpleural fibrosis in both upper lobes. Histological findings showed diffuse interstitial lymphoplasmacytic infiltration with an increased number of IgG4-positive plasma cells. Serum levels of IgG and IgG4 were also increased. The patient was diagnosed with IgG4-related lung disease, treated with anti-inflammatory agents, and showed improvement. Lung involvement of IgG4-related disease can present as interstitial lung disease and, therefore, should be differentiated when evaluating interstitial lung disease.
Adult ; Anti-Inflammatory Agents ; Fibrosis ; Glass ; Humans ; Immunoglobulin G ; Immunoglobulins ; Lung ; Lung Diseases* ; Lung Diseases, Interstitial* ; Plasma Cells ; Thorax

Purpose: To assess characteristics the application of mobile medication system and medication administration error (MAE) alerts in a general hospital. Methods: The subject hospital adopted a mobile medication system in 2016. All medication administrations in the general wards and ICUs were automatically recorded in real-time using identification barcodes, drug barcodes, and hand-held point-of-care devices. MAE alert logs were recorded from April 1st 2017 to March 31st 2018. For this study analysis was done using Pearson’s chi-squared test for potentially related factors of MAE alerts included administration time, order type, medication route, and length of nurse’s employment. Results: The total number of medications during the period of this study was 3,227,990. Among them, 2,698,317 medication doses were recorded, resulting in the system application rate of 83.6%. The system application rate was significantly correlated with all factors related to potential MAE alters. In this study 23,314 MAE alerts(0.9% of the total medication doses) were identified. The MAE alerts were related to new (OR=2.26, p<.001) and emergency (OR=2.25, p<.001) orders, and administration at a non-standard time (OR=2.032, p<.001). Medication route (p<.001), and nurse’s employment duration(p<.001) were also related. Conclusion A mobile medication system contributes to improving patient safety by preventing potential MAEs. The MAE alerts were related to administration time, order type, medication route, and duration of nurse’s employment. In order to prevent medication administration errors, it is necessary to standardize the process of medication and create an environment in which medication administration can be performed in a planned situation.

Antimalarial drugs are an urgently need and crucial tool in the campaign against malaria, which can threaten public health. In this study, we examined the cytotoxicity of the 9 antimalarial compounds chemically synthesized using SKM13-2HCl. Except for SKM13-2HCl, the 5 newly synthesized compounds had a 50% cytotoxic concentration (CC50) > 100 µM, indicating that they would be less cytotoxic than SKM13-2HCl. Among the 5 compounds, only SAM13-2HCl outperformed SKM13-2HCl for antimalarial activity, showing a 3- and 1.3-fold greater selective index (SI) (CC50/IC50) than SKM13-2HCl in vitro against both chloroquine-sensitive (3D7) and chloroquine -resistant (K1) Plasmodium falciparum strains, respectively. Thus, the presence of morpholine amide may help to effectively suppress human-infectious P. falciparum parasites. However, the antimalarial activity of SAM13-2HCl was inferior to that of the SKM13-2HCl template compound in the P. berghei NK65-infected mouse model, possibly because SAM13-2HCl had a lower polarity and less efficient pharmacokinetics than SKM13-2HCl. SAM13-2HCl was more toxic in the rodent model. Consequently, SAM13-2HCl containing morpholine was selected from screening a combination of pharmacologically significant structures as being the most effective in vitro against human-infectious P. falciparum but was less efficient in vivo in a P. berghei-infected animal model when compared with SKM13-2HCl. Therefore, SAM13-2HCl containing morpholine could be considered a promising compound to treat chloroquine-resistant P. falciparum infections, although further optimization is crucial to maintain antimalarial activity while reducing toxicity in animals.

Purpose: Cardiac radioablation is a novel, non-invasive treatment for ventricular tachycardia (VT), involving a single fractional stereotactic ablative body radiotherapy (SABR) session with a prescribed dose of 25 Gy. This complex procedure requires a detailed workflow and stringent dose constraints compared to conventional radiation therapy. This study aims to establish a consistent institutional workflow for single-fraction cardiac VT-SABR, emphasizing robust plan evaluation and quality assurance. Materials and Methods: The study developed a consistent institutional workflow for VT-SABR, including computed tomography (CT) simulation, target volume definition, treatment planning, robust plan evaluation, quality assurance, and image-guided strategy. The workflow was implemented for two patients with cardiac arrhythmia. Accurate target volume definition using planning CT images and electronic anatomical mapping was critical. A four-dimensional (4D) cone-beam CT (CBCT) and breath-hold electrocardiographic gated CT images reliably detected target motion. Results: The resulting plans exhibited a conformity index greater than 0.7 and a gradient index around G4.0. Dose constraints for the planning target volume (PTV) aimed for 95% or higher PTV dose coverage, with a maximum dose of 200% or lower. However, one case did not meet the PTV dose coverage due to the proximity of the PTV to gastrointestinal organs. Plans adhered to dose constraints for organs at risk near the heart, but meeting constraints for specific cardiac sub-structures was challenging and dependent on PTV location. Conclusion The plans demonstrated robustness against respiratory motion and patient positional uncertainty through a robust evaluation function. The 4D and intra-fractional CBCT were effective in verifying target motion and setup stability.

Purpose: Cardiac radioablation is a novel, non-invasive treatment for ventricular tachycardia (VT), involving a single fractional stereotactic ablative body radiotherapy (SABR) session with a prescribed dose of 25 Gy. This complex procedure requires a detailed workflow and stringent dose constraints compared to conventional radiation therapy. This study aims to establish a consistent institutional workflow for single-fraction cardiac VT-SABR, emphasizing robust plan evaluation and quality assurance. Materials and Methods: The study developed a consistent institutional workflow for VT-SABR, including computed tomography (CT) simulation, target volume definition, treatment planning, robust plan evaluation, quality assurance, and image-guided strategy. The workflow was implemented for two patients with cardiac arrhythmia. Accurate target volume definition using planning CT images and electronic anatomical mapping was critical. A four-dimensional (4D) cone-beam CT (CBCT) and breath-hold electrocardiographic gated CT images reliably detected target motion. Results: The resulting plans exhibited a conformity index greater than 0.7 and a gradient index around G4.0. Dose constraints for the planning target volume (PTV) aimed for 95% or higher PTV dose coverage, with a maximum dose of 200% or lower. However, one case did not meet the PTV dose coverage due to the proximity of the PTV to gastrointestinal organs. Plans adhered to dose constraints for organs at risk near the heart, but meeting constraints for specific cardiac sub-structures was challenging and dependent on PTV location. Conclusion The plans demonstrated robustness against respiratory motion and patient positional uncertainty through a robust evaluation function. The 4D and intra-fractional CBCT were effective in verifying target motion and setup stability.

Purpose: Cardiac radioablation is a novel, non-invasive treatment for ventricular tachycardia (VT), involving a single fractional stereotactic ablative body radiotherapy (SABR) session with a prescribed dose of 25 Gy. This complex procedure requires a detailed workflow and stringent dose constraints compared to conventional radiation therapy. This study aims to establish a consistent institutional workflow for single-fraction cardiac VT-SABR, emphasizing robust plan evaluation and quality assurance. Materials and Methods: The study developed a consistent institutional workflow for VT-SABR, including computed tomography (CT) simulation, target volume definition, treatment planning, robust plan evaluation, quality assurance, and image-guided strategy. The workflow was implemented for two patients with cardiac arrhythmia. Accurate target volume definition using planning CT images and electronic anatomical mapping was critical. A four-dimensional (4D) cone-beam CT (CBCT) and breath-hold electrocardiographic gated CT images reliably detected target motion. Results: The resulting plans exhibited a conformity index greater than 0.7 and a gradient index around G4.0. Dose constraints for the planning target volume (PTV) aimed for 95% or higher PTV dose coverage, with a maximum dose of 200% or lower. However, one case did not meet the PTV dose coverage due to the proximity of the PTV to gastrointestinal organs. Plans adhered to dose constraints for organs at risk near the heart, but meeting constraints for specific cardiac sub-structures was challenging and dependent on PTV location. Conclusion The plans demonstrated robustness against respiratory motion and patient positional uncertainty through a robust evaluation function. The 4D and intra-fractional CBCT were effective in verifying target motion and setup stability.

Purpose: Cardiac radioablation is a novel, non-invasive treatment for ventricular tachycardia (VT), involving a single fractional stereotactic ablative body radiotherapy (SABR) session with a prescribed dose of 25 Gy. This complex procedure requires a detailed workflow and stringent dose constraints compared to conventional radiation therapy. This study aims to establish a consistent institutional workflow for single-fraction cardiac VT-SABR, emphasizing robust plan evaluation and quality assurance. Materials and Methods: The study developed a consistent institutional workflow for VT-SABR, including computed tomography (CT) simulation, target volume definition, treatment planning, robust plan evaluation, quality assurance, and image-guided strategy. The workflow was implemented for two patients with cardiac arrhythmia. Accurate target volume definition using planning CT images and electronic anatomical mapping was critical. A four-dimensional (4D) cone-beam CT (CBCT) and breath-hold electrocardiographic gated CT images reliably detected target motion. Results: The resulting plans exhibited a conformity index greater than 0.7 and a gradient index around G4.0. Dose constraints for the planning target volume (PTV) aimed for 95% or higher PTV dose coverage, with a maximum dose of 200% or lower. However, one case did not meet the PTV dose coverage due to the proximity of the PTV to gastrointestinal organs. Plans adhered to dose constraints for organs at risk near the heart, but meeting constraints for specific cardiac sub-structures was challenging and dependent on PTV location. Conclusion The plans demonstrated robustness against respiratory motion and patient positional uncertainty through a robust evaluation function. The 4D and intra-fractional CBCT were effective in verifying target motion and setup stability.

Purpose: Cardiac radioablation is a novel, non-invasive treatment for ventricular tachycardia (VT), involving a single fractional stereotactic ablative body radiotherapy (SABR) session with a prescribed dose of 25 Gy. This complex procedure requires a detailed workflow and stringent dose constraints compared to conventional radiation therapy. This study aims to establish a consistent institutional workflow for single-fraction cardiac VT-SABR, emphasizing robust plan evaluation and quality assurance. Materials and Methods: The study developed a consistent institutional workflow for VT-SABR, including computed tomography (CT) simulation, target volume definition, treatment planning, robust plan evaluation, quality assurance, and image-guided strategy. The workflow was implemented for two patients with cardiac arrhythmia. Accurate target volume definition using planning CT images and electronic anatomical mapping was critical. A four-dimensional (4D) cone-beam CT (CBCT) and breath-hold electrocardiographic gated CT images reliably detected target motion. Results: The resulting plans exhibited a conformity index greater than 0.7 and a gradient index around G4.0. Dose constraints for the planning target volume (PTV) aimed for 95% or higher PTV dose coverage, with a maximum dose of 200% or lower. However, one case did not meet the PTV dose coverage due to the proximity of the PTV to gastrointestinal organs. Plans adhered to dose constraints for organs at risk near the heart, but meeting constraints for specific cardiac sub-structures was challenging and dependent on PTV location. Conclusion The plans demonstrated robustness against respiratory motion and patient positional uncertainty through a robust evaluation function. The 4D and intra-fractional CBCT were effective in verifying target motion and setup stability.

By changing the relative abundance of generated antigenic peptides through alterations in the proteolytic activity, interferon (IFN)-γ-induced immunoproteasomes influence the outcome of CD8⁺ cytotoxic T lymphocyte responses. In the present study, we investigated the effects of hepatitis C virus (HCV) infection on IFN-γ-induced immunoproteasome expression using a HCV infection cell culture system. We found that, although IFN-γ induced the transcriptional expression of mRNAs encoding the β1i/LMP2, β2i/MECL-1 and β5i/LMP7 immunoproteasome subunits, the formation of immunoproteasomes was significantly suppressed in HCV-infected cells. This finding indicated that immunoproteasome induction was impaired at the translational or posttranslational level by HCV infection. Gene silencing studies showed that the suppression of immunoproteasome induction is essentially dependent on protein kinase R (PKR). Indeed, the generation of a strictly immunoproteasome-dependent cytotoxic T lymphocyte epitope was impaired in in vitro processing experiments using isolated 20S proteasomes from HCV-infected cells and was restored by the silencing of PKR expression. In conclusion, our data point to a novel mechanism of immune regulation by HCV that affects the antigen-processing machinery through the PKR-mediated suppression of immunoproteasome induction in infected cells.
Cell Culture Techniques ; Epitopes, T-Lymphocyte ; Gene Silencing ; Hepacivirus ; Hepatitis C* ; Hepatitis* ; In Vitro Techniques ; Interferons ; Lymphocytes ; Peptides ; Protein Kinases* ; RNA, Messenger