What Findings on Chest CTs Can Delay Diagnosis of Pleuropulmonary Paragonimiasis?

PURPOSE: The purpose of this study was to investigate which findings were delayed in diagnosis with respect to chest CT findings of paragonimiasis. METHODS: This retrospective, informed questionnaire study was conducted to evaluate chest CT scans of 103 patients (58 men and 45 women; mean age 46.1 ± 14.6 years). The patients were diagnosed with paragonimiasis from 2003 to 2008 in four tertiary hospitals. Statistical analysis was performed using the chi-square test to identify differences between an initially correct diagnosis and an incorrect one of paragonimiasis on chest CT scans, for which we evaluated such variables as the location of lesion, type of parenchymal lesions, and worm migration track. RESULTS: Nodular opacities on chest CT scans were the most common findings (53/94, 56.4%). The sign of worm migration tracks was only present in 18.1% of cases (17/94). Although statistically insignificant, the form of consolidation (18/25, 72%) and mass (6/8, 75%) on CT was common in correct diagnostics, and the form of the worm migration track (12/17, 70.6%) was high in correct diagnostics. CONCLUSION: A delayed diagnosis of paragonimiasis may often be made in patients with non-nodular, parenchymal lesions who are negative for worm migration track on chest CT scans.

Performance of Diabetes and Kidney Disease Screening Scores in Contemporary United States and Korean Populations.

BACKGROUND: Risk assessment tools have been actively studied, and they summarize key predictors with relative weights/importance for a disease. Currently, standardized screening scores for type 2 diabetes mellitus (DM) and chronic kidney disease (CKD)-two key global health problems-are available in United States and Korea. We aimed to compare and evaluate screening scores for DM (or combined with prediabetes) and CKD, and assess the risk in contemporary United States and Korean populations. METHODS: Four (2×2) models were evaluated in the United States-National Health and Nutrition Examination Survey (NHANES 2015-2018) and Korea-NHANES (2016-2018)-8,928 and 16,209 adults. Weighted statistics were used to describe population characteristics. We used logistic regression for predictors in the models to assess associations with study outcomes (undiagnosed DM and CKD) and diagnostic measures for temporal and cross-validation. RESULTS: Korean adult population (mean age 47.5 years) appeared to be healthier than United States counterpart, in terms of DM and CKD risks and associated factors, with exceptions of undiagnosed DM, prediabetes and prehypertension. Models performed well in own country and external populations regarding predictor-outcome association and discrimination. Risk tests (high vs. low) showed area under the curve >0.75, sensitivity >84%, specificity >45%, positive predictive value >8%, and negative predictive value >99%. Discrimination was better for DM, compared to the combined outcome of DM and prediabetes, and excellent for CKD due to age. CONCLUSION: Four easy-to-use screening scores for DM and CKD are well-validated in contemporary United States and Korean populations. Prevention of DM and CKD may serve as first-step in public health, with these self-assessment tools as basic tools to help health education and disparity.

Erratum: Correction of Text in the Article "Evidence of Long-Distance Droplet Transmission of SARS-CoV-2 by Direct Air Flow in a Restaurant in Korea".

This corrects the article on p. e415 in vol. 35, PMID: 33258335.

Evidence of Long-Distance Droplet Transmission of SARS-CoV-2 by Direct Air Flow in a Restaurant in Korea.

BACKGROUND: The transmission mode of severe acute respiratory syndrome coronavirus 2 is primarily known as droplet transmission. However, a recent argument has emerged about the possibility of airborne transmission. On June 17, there was a coronavirus disease 2019 (COVID-19) outbreak in Korea associated with long distance droplet transmission. METHODS: The epidemiological investigation was implemented based on personal interviews and data collection on closed-circuit television images, and cell phone location data. The epidemic investigation support system developed by the Korea Disease Control and Prevention Agency was used for contact tracing. At the restaurant considered the site of exposure, air flow direction and velocity, distances between cases, and movement of visitors were investigated. RESULTS: A total of 3 cases were identified in this outbreak, and maximum air flow velocity of 1.2 m/s was measured between the infector and infectee in a restaurant equipped with ceiling-type air conditioners. The index case was infected at a 6.5 m away from the infector and 5 minutes exposure without any direct or indirect contact. CONCLUSION: Droplet transmission can occur at a distance greater than 2 m if there is direct air flow from an infected person. Therefore, updated guidelines involving prevention, contact tracing, and quarantine for COVID-19 are required for control of this highly contagious disease.

FAM83H and SCRIB stabilize ß-catenin and stimulate progression of gastric carcinoma.

FAM83H primarily is known for its function in tooth development. Recently, a role for FAM83H in tumorigenesis, conjunction with MYC and ß-catenin, has been suggested. Analysis of public data indicates that FAM83H expression is closely associated with SCRIB expression in human gastric cancers. Therefore, this study investigated the roles of FAM83H and SCRIB in 200 human gastric cancers and gastric cancer cells. In human gastric carcinomas, both the individual and combined expression patterns of the nuclear FAM83H and SCRIB were independent indicators of shorter survival of gastric carcinoma patients. In MKN-45 and NCI-N87 gastric cancer cells, the expression of FAM83H and SCRIB were associated with proliferation and invasiveness of cells. FAM83H-mediated in vivo tumor growth was attenuated with knock-down of SCRIB. Moreover, immunoprecipitation indicates that FAM83H, SCRIB, and ß-catenin, form a complex, and knock-down of either FAM83H or SCRIB accelerated proteasomal degradation of ß-catenin. In conclusion, this study has found that the individual and combined expression patterns of nuclear FAM83H and SCRIB are prognostic indicators of gastric carcinomas and further suggests that FAM83H and SCRIB are involved in the progression of gastric carcinomas by stabilizing ß-catenin.

The Expression Patterns of FAM83H and PANX2 Are Associated With Shorter Survival of Clear Cell Renal Cell Carcinoma Patients.

FAM83H is primarily known for its role in amelogenesis; however, recent reports suggest FAM83H might be involved in tumorigenesis. Although the studies of FAM83H in kidney cancer are limited, a search of the public database shows a significant association between FAM83H and pannexin-2 (PANX2) in clear cell renal cell carcinomas (CCRCCs). Therefore, we evaluated the clinicopathological significance of the immunohistochemical expression of FAM83H and PANX2 in 199 CCRCC patients. The expression of FAM83H and PANX2 were significantly associated with each other. In univariate analysis, individual, and co-expression pattern of FAM83H and PANX2 was significantly associated with shorter overall survival (OS) and relapse-free survival (RFS) of CCRCC patients: nuclear expression of FAM83H (OS; P < 0.001, RFS; P < 0.001), cytoplasmic expression of FAM83H (OS; P < 0.001, RFS; P < 0.001), nuclear expression of PANX2 (OS; P < 0.001, RFS; P < 0.001), cytoplasmic expression of PANX2 (OS; P < 0.001, RFS; P < 0.001), co-expression pattern of nuclear FAM83H and nuclear PANX2 (OS; P < 0.001, RFS; P < 0.001). In multivariate analysis, nuclear expression of FAM83H (OS; P < 0.001, RFS; P = 0.003) and the co-expression pattern of nuclear FAM83H and PANX2 (OS; P < 0.001, RFS; P < 0.001) were independent indicators of shorter survival of CCRCC patients. Cytoplasmic expression of FAM83H was associated with shorter RFS (P = 0.030) in multivariate analysis. In Caki-1 and Caki-2 CCRCC cells, knock-down of FAM83H decreased PANX2 expression and cell proliferation, and overexpression of FAM83H increased PANX2 expression and cell proliferation. These results suggest that FAM83H and PANX2 might be involved in the progression of CCRCC in a co-operative manner, and their expression might be used as novel prognostic indicators for CCRCC patients.

Expression of oxidized protein tyrosine phosphatase and γH2AX predicts poor survival of gastric carcinoma patients.

BACKGROUND: Oxidative stress induces various intracellular damage, which might be correlated with tumorigenesis. Accumulated oxidative stresses might inactivate protein tyrosine phosphatase (PTP) by oxidizing it, and inducing the phosphorylation of H2AX (γH2AX) in response to DNA damage. METHODS: We evaluated the clinical significance of the expression of oxidized-PTP and γH2AX in 169 gastric carcinomas. RESULTS: Immunohistochemical expression of nuclear oxidized-PTP, cytoplasmic oxidized-PTP, and γH2AX expression were significantly associated with each other, and their expressions predicted shorter survival of gastric carcinoma patients. In multivariate analysis, nuclear oxidized-PTP (overall survival; p <  0.001, relapse-free survival; P <  0.001) was an independent indicator of poor prognosis of gastric carcinoma patients. In addition, co-expression patterns of nuclear oxidized-PTP and γH2AX were independent indicators of poor prognosis of gastric carcinoma patients (overall survival; P <  0.001, relapse-free survival; P <  0.001). CONCLUSIONS: This study suggests that oxidative stress-mediated oxidation of PTP might be involved in the progression of gastric carcinomas. In addition, this study suggests that individual and co-expression pattern of nuclear oxidized-PTP and γH2AX might be used as a prognostic marker of gastric carcinomas.

Expression of ANO1/DOG1 is associated with shorter survival and progression of breast carcinomas.

The expression of ANO1 is considered to have diagnostic specificity for gastrointestinal stromal tumors. However, its function as a calcium-activated chloride channel suggests that the expression of ANO1 is not restricted to gastrointestinal stromal tumors. Recently, it has been reported that ANO1 has roles in the progression of human malignant tumors. However, the role of ANO1 in breast carcinoma has been controversial. Therefore, we investigated the expression of ANO1 in 139 breast carcinoma patients and the role of ANO1 in vitro. The immunohistochemical expression of ANO1 was significantly associated with the expression of ß-catenin, cyclin D1, MMP9, snail, and E-cadherin. Especially, ANO1 expression was an independent indicator of poor prognosis of shorter overall survival and relapse-free survival of breast carcinoma patients by multivariate analysis. In MCF7 and MDA-MB-231 breast carcinoma cells, inhibition of ANO1 with T16Ainh-A01 or siRNA for ANO1 significantly suppressed the proliferation of cells. Knock-down of ANO1 with siRNA induced G0/G1 cell cycle arrest and significantly inhibited the invasiveness of breast carcinoma cells. Knock-down of ANO1 decreased the expression of ß-catenin, cyclin D1, MMP9, snail, and N-cadherin, and increased the expression of E-cadherin. In conclusion, this study demonstrates that ANO1 expression is an indicator of poor prognosis of breast carcinoma patients and suggests that ANO1 might be a therapeutic target for breast carcinoma patients with ANO1-positive tumors and poor prognosis.

Effect of greater trochanteric epiphysiodesis after femoral varus osteotomy for lateral pillar classification B and B/C border Legg-Calvé-Perthes disease: A retrospective observational study.

This is a retrospective observational study. Greater trochanteric epiphysiodesis (GTE) has been recommended to prevent Trendelenburg gait and limitation of the hip joint motion due to trochanteric overgrowth after femoral varus osteotomy (FVO) in Legg-Calvé-Perthes disease (LCPD). However, capital femoral physeal arrest frequently occurs in patients with severe disease (lateral pillar C), so GTE might not be as effective in these patients. The aim of this study was to compare trochanteric growth inhibition due to GTE after FVO between 2 age groups (<8 or >8 years) in patients with lateral pillar B and B/C border LCPD and evaluate the effectiveness of GTE compared with the normal, unaffected hip.This study included 19 children with lateral pillar B and B/C border LCPD in 1 leg who underwent FVO followed by GTE. Of the 19 children, 9 underwent GTE before the age of 8 years and 10 underwent GTE after 8 years of age. On radiographs taken at the immediate postoperative period and at skeletal maturity, the articulo-trochanteric distance (ATD), center-trochanteric distance (CTD), and neck-shaft angle (NSA) were compared between the 2 age groups. The amount of correction was compared between groups. The contralateral, unaffected hip was used as a control for trochanteric growth. The patients were clinically evaluated with Iowa hip score at the final follow-up.There was no significant difference between the 2 age groups in terms of time to GTE, length of follow-up, or lateral pillar classification. In the affected hip, the amount of correction of the ATD, CTD, and NSA was significantly greater in patients < 8 years than in patients > 8 years. However, in the unaffected hip, the change in the ATD, CTD, and NSA did not differ significantly between the 2 groups.We suggest that FVO followed by GTE for lateral pillar B and B/C border LCPD in patients under the age of 8 years can affect growth of the greater trochanter. However, effective growth inhibition due to GTE was not achieved after 8 years of age.

FAM83H is involved in the progression of hepatocellular carcinoma and is regulated by MYC.

Recently, the roles of FAM83H in tumorigenesis have been interested and increased expression of FAM83H and MYC in hepatocellular carcinoma (HCC) have been reported. Therefore, we investigated the expression and role of FAM83H in 163 human HCCs and further investigated the relationship between FAM83H and oncogene MYC. The expression of FAM83H is elevated in liver cancer cells, and nuclear expression of FAM83H predicted shorter survival of HCC patients. In HLE and HepG2 HCC cells, knock-down of FAM83H inhibited proliferation and invasive activity of HCC cells. FAM83H induced expression of cyclin-D1, cyclin-E1, snail and MMP2 and inhibited the expression of P53 and P27. In hepatic tumor cells derived from Tet-O-MYC mice, the expression of mRNA and protein of FAM83H were dependent on MYC expression. Moreover, a chromatin immunoprecipitation assay demonstrated that MYC binds to the promotor of FAM83H and that MYC promotes the transcription of FAM83H, which was supported by the results of a dual-luciferase reporter assay. In conclusion, we present an oncogenic role of FAM83H in liver cancer, which is closely associated with the oncogene MYC. In addition, our results suggest FAM83H expression as a poor prognostic indicator of HCC patients.

CK2α/CSNK2A1 Phosphorylates SIRT6 and Is Involved in the Progression of Breast Carcinoma and Predicts Shorter Survival of Diagnosed Patients.

Recently, the roles of sirtuins (SIRTs) in tumorigenesis have been of interest to oncologists, and protein kinase CK2 α1 (CSNK2A1) has been shown to be involved in tumorigenesis by phosphorylating various proteins, including SIRT1. Therefore, we evaluated the roles of CSNK2A1, SIRT6, and phosphorylated SIRT6 and their relationships in breast carcinoma. Nuclear expression of CSNK2A1 and SIRT6 predicted shorter overall survival and relapse-free survival by multivariate analysis. Inhibition of CSNK2A1 decreased the proliferative and invasive activity of cancer cells. In addition, CSNK2A1 was bound to SIRT6 and phosphorylated SIRT6; evidence for this is provided from immunofluorescence staining, co-immunoprecipitation of CSNK2A1 and SIRT6, a glutathione S-transferase pull-down assay, an in vitro kinase assay, and transfection of mutant CSNK2A1. Knockdown of SIRT6 decreased the proliferation and invasiveness of cancer cells. Overexpression of SIRT6 increased proliferation, but mutation at the Ser338 phosphorylation site of SIRT6 inhibited the proliferation of MCF7 cells. Moreover, both knockdown of SIRT6 and a mutation at the phosphorylation site of SIRT6 decreased expression of matrix metallopeptidase 9, ß-catenin, cyclin D1, and NF-κB. Especially, SIRT6 expression was associated with the nuclear localization of ß-catenin. This study demonstrates that CSNK2A1 and SIRT6 are indicators of poor prognosis for breast carcinomas and that CSNK2A1-mediated phosphorylation of SIRT6 might be involved in the progression of breast carcinoma.

Differentiating Smoking-Related Interstitial Fibrosis (SRIF) from Usual Interstitial Pneumonia (UIP) with Emphysema Using CT Features Based on Pathologically Proven Cases.

OBJECTIVE: To differentiate smoking-related interstitial fibrosis (SRIF) from usual interstitial pneumonia (UIP) with emphysema on CT in combined pulmonary fibrosis and emphysema (CPFE) patients. MATERIALS AND METHODS: This study was approved by the institutional review board and informed consent was waived. We included 65 patients who underwent lung biopsy under the suspicion of UIP pattern on HRCT, and after radiologic-pathologic correlation, they were divided into three groups: UIP without emphysema (n = 30), UIP with emphysema (n = 26), and SRIF (n = 9). The quantitative extent of emphysema in the entire lung was visually assessed and fibrotic patterns were qualitatively analyzed based on six characteristics (asymmetry, juxta-subpleural sparing, emphysema beside the honeycombing area, absence of ground grass attenuation/reticulation in honeycombing area, inhomogeneous honeycombing, and absence of honeycombing in the upper lobes). Kaplan-Meier analysis was used for survival analysis, and logistic regression with a receiver operating characteristic curve was used to predict the possibility of SRIF. RESULTS: In qualitative analysis of fibrotic patterns, SRIF tended to exhibit more than three of six fibrotic features, whereas UIP with emphysema demonstrated about two of these characteristics (p = 0.035). In addition, SRIF had a higher extent of emphysema than UIP with emphysema when they have same amount of fibrosis (p = 0.014). In patients with SRIF, 5-year survival rate was 85.7%, while it was 40.7% in UIP with emphysema patients (p = 0.035). CONCLUSION: Fibrotic CT patterns and survival rate differed between SRIF and UIP with emphysema among CPFE patients, which explains the variable prognosis of CPFE.

Individual and Combined Expression of DNA Damage Response Molecules PARP1, γH2AX, BRCA1, and BRCA2 Predict Shorter Survival of Soft Tissue Sarcoma Patients.

DNA damage response (DDR) molecules are protective against genotoxic stresses. DDR molecules are also involved in the survival of cancer cells in patients undergoing anti-cancer therapies. Therefore, DDR molecules are potential markers of cancer progression in addition to being potential therapeutic targets. In this study, we evaluated the immunohistochemical expression of PARP1, γH2AX, BRCA1, and BRCA2 and their prognostic significance in 112 cases of soft tissue sarcoma (STS). The expression of PARP1, γH2AX, BRCA1, and BRCA2 were significantly associated with each other and were associated with higher tumor stage and presence of distant metastasis. The expression of PARP1, γH2AX, and BRCA2 were significantly associated with shorter disease-specific survival (DSS) and event-free survival (EFS) by univariate analysis. BRCA1 expression was associated with shorter DSS. Multivariate analysis revealed the expression of PARP1 and γH2AX to be independent indicators of poor prognosis of DSS and EFS. BRCA2 expression was an independent indicator of poor prognosis of DSS. In addition, the combined expressional patterns of PARP1, γH2AX, BRCA1, and BRCA2 (CSddrm) were independent prognostic predictors of DSS (P < 0.001) and EFS (P = 0.016). The ten-year DSS rate of the CSddrm-low, CSddrm-intermediate, and CSddrm-high subgroups were 81%, 26%, and 0%, respectively. In conclusion, this study demonstrates that the individual and combined expression patterns of the DDR molecules PARP1, γH2AX, BRCA1, and BRCA2 could be predictive of the prognosis of STS patients and suggests that controlling the activity of these DDR molecules could be employed in new therapeutic stratagems for the treatment of STS.

Enhanced M2 macrophage polarization in high n-3 polyunsaturated fatty acid transgenic mice fed a high-fat diet.

SCOPE: Diet-induced obesity and consequent insulin resistance are caused, in part, by macrophage polarization and accumulation in peripheral tissues. Here, we examined the effects of endogenously synthesized n-3 PUFAs on macrophage chemotaxis and polarization. METHODS AND RESULTS: Fat-1 mice and wild-type (WT) littermates were fed a 60% calorie high-fat diet (HFD) for 10 weeks. Bone marrow macrophages (BMMs) from fat-1 and WT mice were used in in vitro chemotaxis assays and macrophage polarization studies. WT mice fed a HFD exhibited glucose intolerance, insulin resistance, and lipid accumulation and macrophage infiltration in liver and adipose tissue. However, these metabolic and inflammatory phenotypes were not observed in HFD-fed fat-1 mice. In flow cytometric analysis, M1 macrophage infiltration into adipose tissue was markedly attenuated in fat-1 mice. Consistently, results from in vitro experiments indicated that n-3 PUFAs prevented adipocyte conditioned medium-mediated macrophage chemotaxis, stimulated M2 polarization, and suppressed M1 polarization. The inhibition of macrophage migration by n-3 PUFAs was associated with suppression of multiple kinases, such as IκB kinase, AKT, and focal adhesion kinase. CONCLUSION: Our results indicate that n-3 PUFAs play a crucial role in macrophage polarization and chemotaxis, and thus regulate the development of HFD-induced tissue inflammation and metabolic derangements.

Factors associated with abnormal pulmonary function test among subjects with normal chest radiography: The Korean National Health and Nutrition Examination Survey.

Determinants of abnormal lung function among subjects with normal chest radiography have not been widely evaluated. We investigated 12 109 participants with normal chest radiographs from the Korean National Health and Nutrition Examination Survey. Factors associated with abnormal pulmonary function were male gender, age ≥50, smoking history and a clinical history of cough or sputum production. Pulmonary function tests should be considered in population-based screening, especially in men over 50 years old with a smoking history.

Tumor suppressive effect of PARP1 and FOXO3A in gastric cancers and its clinical implications.

Poly (ADP-ribose) polymerase1 (PARP1) has been reported as a possible target for chemotherapy in many cancer types. However, its action mechanisms and clinical implications for gastric cancer survival are not yet fully understood. Here, we investigated the effect of PARP1 inhibition in the growth of gastric cancer cells. PARP1 inhibition by Olaparib or PARP1 siRNA could significantly attenuate growth and colony formation of gastric cancer cells, and which were mediated through induction of G2/M cell cycle arrest but not apoptosis. FOXO3A expression was induced by PARP1 inhibition, suggesting that FOXO3A might be one of downstream target of the PARP1 effect on gastric cancer cell growth. In addition, by performing tissue microarrays on the 166 cases of gastric cancer patients, we could observe that the expression status of PARP1 and FOXO3A were significantly associated with overall survival (OS) and relapse-free survival (RFS). Strikingly, combined expression status of PARP1 and FOXO3A showed better prediction for patient's clinical outcomes. The patient group with PARP1+/FOXO3A- expression had the worst prognosis while the patient group with PARP1-/FOXO3A+ had the most favorable prognosis (OS: P = 6.0 × 10(-9), RFS: P = 2.2 × 10(-8)). In conclusion, we suggest that PARP1 and FOXO3A play critical roles in gastric cancer progression, and might have therapeutic and/or diagnostic potential in clinic.

The NLRP3 inflammasome is dispensable for ER stress-induced pancreatic ß-cell damage in Akita mice.

Uncontrolled endoplasmic reticulum (ER) stress activates members of the NOD-like receptor family, which are involved in the pyrin domain containing 3 (NLRP3) inflammasome pathway. This pathway has been proposed to contribute to ß-cell dysfunction and death. However, the connection between ER stress and NLRP3 inflammasome activation remains controversial. Here we generated Akita/KO (Ins2(+/C96Y); NLRP3(-/-)) mice by crossing Akita (Ins2(+/C96Y); NLRP3(+/+)) mice with NLRP3 KO (Ins2(+/+); NLRP3(-/-)) mice. We then compared the metabolic phenotypes of the different strains. Knockout of the NLRP3 inflammasome did not affect the onset or the severity of diabetes in Akita/KO mice at any point of the study. Histological observations of pancreatic islets supported these findings. Tunicamycin-exposed islets from NLRP3 KO mice exhibited similar levels of ER stress and apoptosis induction as islets from WT (Ins2(+/+); NLRP3(+/+)) mice. Furthermore, NLRP3 deletion did not prevent tunicamycin-mediated reduction of glucose-stimulated insulin secretion. In conclusion, deletion of the NLRP3 inflammasome did not protect against ER stress-induced diabetes development or ß-cell damage, indicating that ß cell death in Akita mice is not mediated via activation of the NLRP3 inflammasome.

Visually stratified CT honeycombing as a survival predictor in combined pulmonary fibrosis and emphysema.

OBJECTIVE: To determine whether visually stratified CT findings and pulmonary function variables are helpful in predicting mortality in patients with combined pulmonary fibrosis and emphysema (CPFE). METHODS: We retrospectively identified 113 patients with CPFE who underwent high-resolution CT between January 2004 and December 2009. The extent of emphysema and fibrosis on CT was visually assessed using a 6- or 5-point scale, respectively. Univariate and multivariate Cox proportional regression analyses were performed to determine the prognostic value of visually stratified CT findings and pulmonary function variables in patients with CPFE. Differences in 5-year survival rates in patients with CPFE according to the extent of honeycombing were calculated using Kaplan-Meier analysis. RESULTS: An increase in the extent of visually stratified honeycombing on CT [hazard ratio (HR), 1.95; p = 0.018; 95% confidence interval (CI), 1.12-3.39] and reduced diffusing capacity of lung for carbon monoxide (DLCO) (HR, 0.97; p = 0.017; 95% CI, 0.94-0.99) were independently associated with increased mortality. In patients with CPFE, the 5-year survival rate was 78.5% for <5% honeycombing, 55.7% for 5-25% honeycombing, 32% for 26-50% honeycombing and 33.3% for >50% honeycombing on CT. CONCLUSION: The >50% honeycombing on CT and reduced DLCO are important prognostic factors in CPFE. ADVANCES IN KNOWLEDGE: Visual estimation of honeycombing extent on CT can help in the prediction of prognosis in CPFE.

DBC1/CCAR2 is involved in the stabilization of androgen receptor and the progression of osteosarcoma.

Deleted in breast cancer 1 (DBC1/CCAR2) is a protein of interest because of its diverse roles in tumorigenesis and its possible role as an androgen receptor (AR) co-activator. However, there are limited studies on the role of DBC1 in osteosarcoma. Therefore, we investigated the role of DBC1 and AR and their relationship in osteosarcoma. Immunohistochemical expression of DBC1 and AR was significantly associated with higher clinical stage and higher histologic grade, and predicted shorter survival. Especially, DBC1 expression was an independent prognostic indicator of overall survival (p = 0.005) and relapse-free survival (p = 0.004) by multivariate analysis. In osteosarcoma cell lines, U2OS and SaOS2, the knock down of DBC1 and AR with siRNA significantly reduced cellular proliferation and inhibited proliferation-related signaling. In addition, the knock down of DBC1 and AR decreased the invasion activity and inhibited invasion-related signaling of osteosarcoma cells. Interestingly, DBC1 affects the stabilization of AR protein via a mechanism involving the ubiquitination of AR. Proteosome-mediated degradation and poly-ubiquitination of AR were increased with the knock-down of DBC1. In conclusion, this study has shown that DBC1 is involved in the stabilization of AR protein and DBC1-AR pathways might be involved in the progression of osteosarcoma.