Although intravesical instillation of Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the most successful cancer immunotherapy for superficial bladder cancer, the serious side effects are frequently arisen by using live mycobacteria. To allow less toxic and more potent immunotherapeutic agents following intravesical BCG treatment for superficial bladder cancer, noninfectious immunotherapeutic drug instead of live BCG would be highly desirable. Recently, immune-enhancing adjuvants are considered an effective vaccine immunotherapy for cancer, providing enhanced antitumor effects and boosted immunity. The BCG-cell wall skeleton (BCG-CWS), the main immune active center of BCG, is a potent candidate as a noninfectious immunotherapeutic drug instead of live BCG against bladder cancer. However, the most limited application for anticancer therapy, it is difficult to formulate a water-soluble BCG-CWS due to the aggregation of BCG-CWS in both aqueous and nonaqueous solvents. To overcome the insolubility and improve the internalization of BCG-CWS into bladder cancer cells, it should be developed the lipid nanoparticulation of BCG-CWS, resulting in improved dispensability, stability, and small size. In addition, powerful technology of delivery systems should be applied to enhance the internalization of BCG-CWS, such as encapsulated into lipid nanoparticles using novel packaging methods. Here, we describe the progress in research on effects of BCG-CWS for cancer immunotherapy, development of lipid-based solvent, and packaging method using nanoparticles with drug delivery system.
Administration, Intravesical ; Bacillus ; Cell Wall Skeleton ; Drug Delivery Systems ; Immunotherapy ; Methods ; Mycobacterium bovis ; Nanoparticles ; Product Packaging ; Skeleton ; Solvents ; Urinary Bladder Neoplasms ; Urinary Bladder

Interstitial lung disease (ILD) is often observed in connective tissue diseases (CTDs), frequently in rheumatoid arthritis, systemic sclerosis, primary Sjögren’s syndrome, and inflammatory myositis. Early detection of ILDs secondary to rheumatic diseases is important as timely initiation of proper management affects the prognosis. Among many imaging modalities, high-resuloution computed tomography (HRCT) serves the gold standard for finding early lung inflammatory and fibrotic changes as well as monitoring afterwards because of its superior spatial resolution. Additionally, lung ultrasound (LUS) and magnetic resonance imaging (MRI) are the rising free-radiation imaging tools that can get images of lungs of CTD-ILD. In this review article, we present the subtypes of ILD images found in each CTD acquired by HRCT as well as some images taken by LUS and MRI with comparative HRCT scans. It is expected that this discussion would be helpful in discussing recent advances in imaging modalities for CTDILD and raising critical points for diagnosis and tracing of the images from the perspective of rheumatologists.

BACKGROUND: Stem cell engineering is appealing consideration for regenerating damaged endothelial cells (ECs) because stem cells can differentiate into EC-like cells. In this study, we demonstrate that tonsil-derived mesenchymal stem cells (TMSCs) can differentiate into EC-like cells under optimal physiochemical microenvironments.METHODS: TMSCs were preconditioned with Dulbecco's Modified Eagle Medium (DMEM) or EC growth medium (EGM) for 4 days and then replating them on Matrigel to observe the formation of a capillary-like network under light microscope. Microarray, quantitative real time polymerase chain reaction, Western blotting and immunofluorescence analyses were used to evaluate the expression of gene and protein of EC-related markers.RESULTS: Preconditioning TMSCs in EGM for 4 days and then replating them on Matrigel induced the formation of a capillary-like network in 3 h, but TMSCs preconditioned with DMEM did not form such a network. Genome analyses confirmed that EGM preconditioning significantly affected the expression of genes related to angiogenesis, blood vessel morphogenesis and development, and vascular development. Western blot analyses revealed that EGM preconditioning with gelatin coating induced the expression of endothelial nitric oxide synthase (eNOS), a mature EC-specific marker, as well as phosphorylated Akt at serine 473, a signaling molecule related to eNOS activation. Gelatin-coating during EGM preconditioning further enhanced the stability of the capillary-like network, and also resulted in the network more closely resembled to those observed in human umbilical vein endothelial cells.CONCLUSION: This study suggests that under specific conditions, i.e., EGM preconditioning with gelatin coating for 4 days followed by Matrigel, TMSCs could be a source of generating endothelial cells for treating vascular dysfunction.
Blood Vessels ; Blotting, Western ; Eagles ; Endothelial Cells ; Fluorescent Antibody Technique ; Gelatin ; Genome ; Human Umbilical Vein Endothelial Cells ; Mesenchymal Stromal Cells ; Morphogenesis ; Nitric Oxide Synthase Type III ; Palatine Tonsil ; Real-Time Polymerase Chain Reaction ; Serine ; Stem Cells

Transarterial chemoembolization (TACE) is reportedly a useful palliative treatment in patients with unresectable or recurred hepatocellular carcinoma. Post-TACE complications are common; however, acute cholecystitis after TACE is rare. We herein report a case of a 73-year-old woman who presented with emphysematous cholecystitis and pneumobilia following TACE. Computed tomography performed for evaluation of her tumor status before TACE incidentally showed gallbladder and common bile duct stones. After TACE, she complained of severe epigastric pain with a positive Murphy's sign. Computed tomography showed emphysematous cholecystitis and pneumobilia. She was successfully treated with emergent biliary stone removal by endoscopic retrograde cholangiopancreatography.
Aged ; Carcinoma, Hepatocellular ; Chemoembolization, Therapeutic ; Cholangiopancreatography, Endoscopic Retrograde ; Cholecystitis, Acute ; Common Bile Duct ; Emphysematous Cholecystitis ; Female ; Gallbladder ; Humans ; Palliative Care

Background and Objectives: Vitamin D modulates immunity, including that of allergic diseases, and plays its roles through contact with vitamin D receptors (VDR). Recent studies have shown that patients with allergic rhinitis have low systemic serum vitamin D level. However, the expression of VDR in local tissue such as human nasal mucosa has not been investigated. Our study demonstrated that, in nasal mucosa of normal controls and patients with allergic rhinitis. Materials and Methods: Nasal mucosa were harvested from twenty-five patients who had normal nasal mucosa and twenty-five patients with allergic rhinitis. After the total RNA isolation, we performed reverse transcriptase-polymerase chain reaction, immunohistochemical staining and western blot analysis. Results: VDR were expressed in submucosal glands and the superficial layer of epithelial cell, and that inflammatory cells are expressed more highly in the nasal mucosa of patients with allergic rhinitis compared to those without. In the mucosa of patients with allergic rhinitis, VDR expression level was upregulated compared to that in normal nasal mucosa. Conclusion This findings suggest that VDR plays a role in the pathogenesis of allergic rhinitis. Additional research is needed to determine the mechanism and consequences of VDR upregulation.

Background: We analyzed the differences between clinical characteristics and computed tomography (CT) findings in patients with coronavirus disease 2019 (COVID-19) to establish potential relationships with mediastinal lymphadenopathy and clinical outcomes. Methods: We compared the clinical characteristics and CT findings of COVID-19 patients from a nationwide multicenter cohort who were grouped based on the presence or absence of mediastinal lymphadenopathy. Differences between clinical characteristics and CT findings in these groups were analyzed. Univariate and multivariate analyses were performed to determine the impact of mediastinal lymphadenopathy on clinical outcomes. Results: Of the 344 patients included in this study, 53 (15.4%) presented with mediastinal lymphadenopathy. The rate of diffuse alveolar damage pattern pneumonia and the visual CT scores were significantly higher in patients with mediastinal lymphadenopathy than in those without (P < 0.05). A positive correlation between the number of enlarged mediastinal lymph nodes and visual CT scores was noted in patients with mediastinal lymphadenopathy (Spearman’s ρ = 0.334, P < 0.001). Multivariate analysis showed that mediastinal lymphadenopathy was independently associated with a higher risk of intensive care unit (ICU) admission (odds ratio, 95% confidence interval; 3.25, 1.06-9.95) but was not significantly associated with an increased risk of in-hospital death in patients with COVID-19. Conclusion COVID-19 patients with mediastinal lymphadenopathy had a larger extent of pneumonia than those without. Multivariate analysis adjusted for clinical characteristics and CT findings revealed that the presence of mediastinal lymphadenopathy was significantly associated with ICU admission.

Purpose: Identification of type I protein arginine methyltransferase (PRMT) substrates and their functional significance during tumorigenesis is becoming more important. The present study aimed to identify target substrates for type I PRMT using 2-dimensional (2D) gel electrophoresis (GE) and 2D Western blotting (WB). Methods: Using immunoblot analysis, we compared the expression of type I PRMTs and endogenous levels of arginine methylation between the primary colorectal cancer (CRC) and adjacent noncancerous tissues paired from the same patient. To identify arginine-methylated proteins in HCT116 cells, we carried out 2D-GE and 2D-WB with a type I PRMT product-specific antibody (anti-dimethyl-arginine antibody, asymmetric [ASYM24]). Arginine-methylated protein spots were identified by mass spectrometry, and messenger RNA (mRNA) levels corresponding to the identified proteins were analyzed using National Center for Biotechnology Information (NCBI) microarray datasets between the primary CRC and noncancerous tissues. Results: Type I PRMTs and methylarginine-containing proteins were highly maintained in CRC tissues compared to noncancerous tissues. We matched 142 spots using spot analysis software between a Coomassie blue (CBB)-stained 2D gel and 2D-WB, and we successfully identified 7 proteins that reacted with the ASYM24 antibody: CACYBP, GLOD4, MAPRE1, CCT7, TKT, CK8, and HSPA8. Among these proteins, the levels of 4 mRNAs including MAPRE1, CCT7, TKT, and HSPA8 in CRC tissues showed a statistically significant increase compared to noncancerous tissues from patients using the NCBI microarray datasets. Conclusion Our results indicate that the method shown here is useful in identifying arginine-methylated proteins, and significance of arginine modification in the proteins identified here should be further identified during CRC development.

Background: The Korean Society of Thoracic Radiology (KSTR) recently constructed a nation-wide coronavirus disease 2019 (COVID-19) database and imaging repository, referred to the Korean imaging cohort of COVID-19 (KICC-19) based on the collaborative efforts of its members. The purpose of this study was to provide a summary of the clinico-epidemiological data and imaging data of the KICC-19. Methods: The KSTR members at 17 COVID-19 referral centers retrospectively collected imaging data and clinical information of consecutive patients with reverse transcription polymerase chain reaction-proven COVID-19 in respiratory specimens from February 2020 through May 2020 who underwent diagnostic chest computed tomography (CT) or radiograph in each participating hospital. Results: The cohort consisted of 239 men and 283 women (mean age, 52.3 years; age range, 11–97 years). Of the 522 subjects, 201 (38.5%) had an underlying disease. The most common symptoms were fever (n = 292) and cough (n = 245). The 151 patients (28.9%) had lymphocytopenia, 86 had (16.5%) thrombocytopenia, and 227 patients (43.5%) had an elevated CRP at admission. The 121 (23.4%) needed nasal oxygen therapy or mechanical ventilation (n = 38; 7.3%), and 49 patients (9.4%) were admitted to an intensive care unit.Although most patients had cured, 21 patients (4.0%) died. The 465 (89.1%) subjects underwent a low to standard-dose chest CT scan at least once during hospitalization, resulting in a total of 658 CT scans. The 497 subjects (95.2%) underwent chest radiography at least once during hospitalization, which resulted in a total of 1,475 chest radiographs. Conclusion The KICC-19 was successfully established and comprised of 658 CT scans and 1,475 chest radiographs of 522 hospitalized Korean COVID-19 patients. The KICC-19 will provide a more comprehensive understanding of the clinical, epidemiological, and radiologic characteristics of patients with COVID-19.

PURPOSE: Little is known about the clinical value of peripheral blood immune profiling. Here, we aimed to identify colorectal cancer (CRC)-related peripheral blood immune cells and develop liquid biopsy-based immune profiling models for CRC diagnosis. METHODS: Peripheral blood from 131 preoperative patients with CRC and 174 healthy controls was analyzed by flow cytometry and automated hematology. CRC-related immune factors were identified by comparing the mean values of immune cell percentages and counts. Subsequently, CRC diagnostic algorithms were constructed using binary logistic regression. RESULTS: Significant differences were observed in percentages and counts of white blood cells, lymphocytes, neutrophils, regulatory T cells, and myeloid-derived suppressor cells (MDSCs) of patients and controls. The neutrophil/lymphocyte and Th1/Th2 ratios were also significantly different. Likewise, the percentages and counts of peripheral blood programed death 1, cytotoxic T lymphocyte antigen 4, B-and T-lymphocyte attenuator, and lymphocyte activation gene-3 were higher in patients with CRC. The binary logistic regression model included 12 variables, age, CD3+%, NK%, CD4+CD279+%, CD4+CD25+%, CD4+CD152+%, CD3+CD366+%, CD3+CD272+%, CD3+CD223+%, CD158b−CD314+CD3−CD56+%, Th2%, and MDSCs cells/µL, for the prediction of cancer. Results of retrospective and prospective evaluation of the area under the curve, sensitivity, and specificity were 0.980 and 0.940, 91.53% and 85.80%, and 93.50% and 86.20%, respectively. CONCLUSION: Peripheral blood immune profiling may be valuable in evaluating the immunity of CRC patients. Our liquid biopsy-based immune diagnostic method and its algorithms may serve as a novel tool for CRC diagnosis. Future largescale studies are needed for better characterization of its diagnostic value and potential for clinical application.
Blood Cells ; Colorectal Neoplasms* ; CTLA-4 Antigen ; Diagnosis ; Early Detection of Cancer ; Flow Cytometry ; Hematology ; Humans ; Immunologic Factors ; Leukocytes ; Logistic Models ; Lymphocyte Activation ; Lymphocytes ; Methods ; Neutrophils ; Prospective Studies ; Retrospective Studies ; Sensitivity and Specificity ; T-Lymphocytes ; T-Lymphocytes, Regulatory