Development of an AI-based image/ultrasonic convergence camera system for accurate gas leak detection in petrochemical plants.

Outdoor pipeline leaks are difficult to accurately measure using existing concentration measurement systems installed in petrochemical plants owing to external air currents. Besides, leak detection is only possible for a specific gas. The purpose of this study was to develop an image/ultrasonic convergence camera system that incorporates artificial intelligence (AI) to improve pipe leak detection and establish a real-time monitoring system. Our system includes an advanced ultrasonic camera coupled with a deep learning-based object-detection algorithm trained on pipe image data from petrochemical plants. The collected data improved the accuracy of detected gas leak localization through deep learning. Our detection model achieves an mAP50 (Mean average precision calculated at an intersection over union (IoU) threshold of 0.50)score of 0.45 on our data and is able to detect the majority of leak points within a system. The petrochemical plant environment was simulated by visiting petrochemical plants and reviewing drawings, and an outdoor experimental demonstration site was established. Scenarios such as flange connection failure were set under medium-/low-pressure conditions, and the developed product was experimented under gas leak conditions that simulated leakage accidents. These experiments enabled the removal of potentially confounding surrounding noise sources, which led to the false detection of actual gas leaks using the AI piping detection technique.

Effect of Laser Peening on the Corrosion Properties of 304L Stainless Steel.

Dry canisters used in nuclear power plants can be subject to localized corrosion, including stress corrosion cracking. External and residual tensile stress can facilitate the occurrence of stress corrosion cracking. Residual stress can arise from welding and plastic deformation. Mitigation methods of residual stress depend upon the energy used and include laser peening, ultrasonic peening, ultrasonic nanocrystal surface modification, shot peening, or water jet peening. Among these, laser peening technology irradiates a continuous laser beam on the surface of metals and alloys at short intervals to add compressive residual stress as a shock wave is caused. This research studied the effect of laser peening with/without a thin aluminum layer on the corrosion properties of welded 304L stainless steel. The intergranular corrosion rate of the laser-peened specimen was a little faster than the rate of the non-peened specimen. However, laser peening enhanced the polarization properties of the cross-section of 304L stainless steel, while the properties of the surface were reduced by laser peening. This behavior was discussed on the basis of the microstructure and residual stress.

Genetic Characteristics of Canine Adenovirus Type 2 Detected in Wild Raccoon Dogs (Nyctereutes procyonoides) in Korea (2017-2020).

Adenovirus has been detected in a wide range of hosts like dogs, foxes, horses, bats, avian animals, and raccoon dogs. Canine adenoviruses with two serotypes host mammals and are members of the mastadenovirus family. Canine adenovirus type 1 (CAdV-1) and canine adenovirus type 2 (CAdV-2) cause infectious canine hepatitis and infectious bronchial disease, respectively. In this study, we investigated the prevalence of CAdV-1 and 2 in wild Nyctereutes procyonoides in Korea in 2017-2020 from 414 tissue samples, including the liver, kidney, lung, and intestine, collected from 105 raccoon dog carcasses. Only CAdV-2 was detected in two raccoon dogs, whereas CAdV-1 was not detected. Tissue samples from raccoon dogs were screened for CAdV-1 and CAdV-2 using conventional PCR. Adenovirus was successfully isolated from PCR positive samples using the Vero cell line, and the full-length gene sequence of the isolated viruses was obtained through 5' and 3' rapid amplification of cDNA ends (RACE). The major genes of the isolated CAdV-2/18Ra54 and CAdV-2/18Ra-65 strains showed the closest relationship with that of the CAdV-2 Toronto A26/61 strain isolated from Canada in 1976. There is no large mutation between CAdV-2, which is prevalent worldwide, and CAdV-2, which is prevalent in wild animals in Korea. In addition, it is still spreading and causing infections. The Toronto A26/61 strain, which showed the most similarity to CAdV-2/18Ra-54, was likely transmitted to wild animals through vaccinated companion animals, suggesting that further research is needed on safety measures surrounding animal vaccination. This study provides information on the genetic characteristics and prevalence of canine adenovirus in domestic wild animals and provides a better understanding of canine adenovirus.

Effect of Laser Peening on Microstructural Changes in GTA-Welded 304L Stainless Steel.

The introduction of tensile residual stress has led to the induction of damage such as fatigue, corrosion fatigue, and stress corrosion cracking (SCC) in stainless steel in association with the influence of environments, components, surface defects, and corrosive factors during its use. Compressive residual stress can be achieved through various techniques. Among several methods, laser peening can be more attractive as it creates regularity on the surface with a high-quality surface finish. However, there is very little research on heavily peened surface and cross-section of stainless steel with very deep compressive residual stress. This work focused on welding and laser peening and the influence of Al coating on the microstructural changes in 304L stainless steel. The specimen obtained by laser peening had a very deep compressive residual stress of over 1 mm and was evaluated based on microstructural and hardness analysis. Therefore, a model for microstructural change by laser peening on welded 304L stainless steel was proposed.

Significance of Altered Fatty Acid Transporter Expressions in Uterine Cervical Cancer and Its Precursor Lesions.

BACKGROUND: High-risk human papilloma virus (HR HPV) infection is a major factor leading to the development of uterine cervical cancer. Data suggest that alterations in lipid metabolism are related to the pathogenesis of cervical cancer. Specifically, the uptake of exogenous fatty acids and their intracellular storage in lipid droplets enables cancer cells to survive and adapt to the changing tumor environment. MATERIALS AND METHODS: We compared the immunohistochemical expression of fatty acid transport protein 4 (FATP4), and cluster of differentiation 36/fatty acid translocase (CD36/FAT) in normal cervical epithelium, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and squamous cell carcinoma (SCC) tissues of the uterine cervix. We also investigated the clinicopathological implications of these fatty acid transporters in SCC. RESULTS: Compared with that in normal cervical tissues, the expression of FATP4 was lower in LSIL (p=0.002), HSIL (p=0.006), and SCC (p=0.001). In contrast, CD36 expression was higher in SCC tissues than in normal cervical tissues (p<0.001). In normal cervical tissues, HR HPV-infected lesions exhibited a decrease in FATP4 (p<0.001) and an increase of CD36 (p=0.134), compared to those that were not infected with HR HPV. High CD36 expression was associated with a shorter recurrence-free survival (p<0.001). However, high FATP4 levels showed no significant correlation with the clinicopathological parameters of SCC. CONCLUSION: Altered expression levels of FATP4 and CD36 are unique features that might be related to HR HPV infection and promote tumorigenesis and progression of cervical cancer.

Coexpression of MCT1 and MCT4 in ALK-positive Anaplastic Large Cell Lymphoma: Diagnostic and Therapeutic Implications.

In solid tumors, glycolytic cancer or stromal cells export lactates through monocarboxylate transporter (MCT) 4, while oxidative cancer or stromal cells take up lactates as metabolic fuels or signaling molecules through MCT1. CD147 acts as a chaperone of MCT1 or MCT4. Unlike solid tumors, malignant lymphomas have a peculiar tumor microenvironment. To investigate the metabolic phenotype of malignant lymphoma associated with lactate transport, we analyzed immunohistochemical expressions of MCT1, MCT4, and CD147 in 247 cases of various malignant lymphomas. Surprisingly, both MCT1 and MCT4 were diffusely expressed on tumor cell membranes in all cases (11/11, 100%) of anaplastic lymphoma kinase (ALK) (+) anaplastic large cell lymphoma (ALCL). In contrast, only MCT1 was diffusely expressed in tumor cells of ALK(-) ALCL, as well as in B-cell, natural killer/T-cell, T-cell, and classic Hodgkin lymphomas. In these lymphomas, MCT4 expression was mostly localized to adjacent stromal cells. The pattern of diffuse membranous MCT1 and partial MCT4 expressions in tumor cells was observed in 1 case each of peripheral T-cell lymphoma (1/15, 6.7%) and multiple myeloma (1/34, 2.9%). CD147 was diffusely expressed in all types of lymphoma tumor and/or stromal cells. In conclusion, ALK(+) ALCL has a unique metabolism showing high coexpression of MCT1 and MCT4 in tumor cells. Because only ALK(+) ALCL overexpresses MCT4, immunostaining for MCT4 together with ALK is very useful for differential diagnosis from ALK(-) ALCL or peripheral T-cell lymphoma. Moreover, dual targeting against MCT1 and MCT4 would be an appropriate therapeutic approach for ALK(+) ALCL.

Dissection of PD-L1 promoter reveals differential transcriptional regulation of PD-L1 in VHL mutant clear cell renal cell carcinoma.

Programmed death-ligand 1 (PD-L1) is constitutively expressed by hypoxia-inducible factor 2α (HIF2α). It can be induced by interferon gamma (IFNγ) signaling in clear cell renal cell carcinoma (ccRCC). Clinical trials of metastatic ccRCCs have suggested that a canonical IFNγ signature is a better biomarker for therapeutic response to immune checkpoint inhibitors (ICIs) than PD-L1 expression levels in tumor cells. To understand the therapeutic response to ICIs according to PD-L1 expression levels, we analyzed transcriptional regulation of the PD-L1 promoter by HIF2α and IFNγ-inducible interferon regulatory factor-1 (IRF-1) in ccRCC cells. Here, we present two ccRCC cell models showing differential PD-L1 expression levels in response to IFNγ and hypoxia. Analysis of The Cancer Genome Atlas RNA-sequencing data revealed that PD-L1 expression correlated with JAK2 and STAT1 expression of the canonical IFNγ signature in ccRCC tissues. Upon IFNγ stimulation, PD-L1 was induced by sequential activation of JAK2/STAT1/IRF-1 signaling in both WT- and Mut- VHL ccRCC cells. IFNγ activated the IRF-1α site of the PD-L1 promoter. The IFNγ-mediated increase of PD-L1 expression in Mut-VHL cells was 4.8-fold greater than that in WT-VHL cells. Under normoxia condition, PD-L1 expression in Mut-VHL cells was significantly higher than that in WT-VHL cells due to high basal HIF2α expression. Under hypoxia condition, PD-L1 expression in WT-VHL cells was induced up to 1.8-fold through activation of hypoxia-response elements 2 and 3. In contrast, although PD-L1 in Mut-VHL cells was already highly expressed in the basal state through activation of hypoxia-response elements 2, 3, and 4, it was no longer induced by hypoxia. In conclusion, Mut-VHL ccRCC cells displayed higher PD-L1 expression due to high basal HIF2α expression and a stronger response to IFNγ stimulation than WT-VHL cells. The fact that HIF2α antagonists can potentially reduce PD-L1 expression levels should be considered in ICI combination therapy.

Inhibition of Hepatic Stellate Cell Activation Suppresses Tumorigenicity of Hepatocellular Carcinoma in Mice.

Transdifferentiation (or activation) of hepatic stellate cells (HSCs) to myofibroblasts is a key event in liver fibrosis. Activated HSCs in the tumor microenvironment reportedly promote tumor progression. This study analyzed the effect of an inhibitor of HSC activation, retinol-binding protein-albumin domain III fusion protein (R-III), on protumorigenic functions of HSCs. Although conditioned medium collected from activated HSCs enhanced the migration, invasion, and proliferation of the hepatocellular carcinoma cell line Hepa-1c1c7, this effect was not observed in Hepa-1c1c7 cells treated with conditioned medium from R-III-exposed HSCs. In a subcutaneous tumor model, larger tumors with increased vascular density were formed in mice transplanted with Hepa-1c1c7+HSC than in mice transplanted with Hepa-1c1c7 cells alone. Intriguingly, when Hepa-1c1c7+HSC-transplanted mice were injected intravenously with R-III, a reduction in vascular density and extended tumor necrosis were observed. In an orthotopic tumor model, co-transplantation of HSCs enhanced tumor growth, angiogenesis, and regional metastasis accompanied by increased peritumoral lymphatic vessel density, which was abolished by R-III. In vitro study showed that R-III treatment affected the synthesis of pro-angiogenic and anti-angiogenic factors in activated HSCs, which might be the potential mechanism underlying the R-III effect. These findings suggest that the inhibition of HSC activation abrogates HSC-induced tumor angiogenesis and growth, which represents an attractive therapeutic strategy.

Upregulation of Fatty Acid Transporters is Associated With Tumor Progression in Non-Muscle-Invasive Bladder Cancer.

As patients with non-muscle-invasive bladder cancer (NMIBC) show a high degree of heterogeneity in tumor recurrence or progression, many clinicians demand a detailed risk stratification. Although modified fatty acid metabolism in cancer cells is reported to reflect malignant phenotypes such as metastasis, the impact of fatty acid transporters on NMIBC has never been investigated. This study examined the clinicopathologic implications of fatty acid transporters such as fatty acid transport protein 4 (FATP4), cluster of differentiation 36/fatty acid translocase (CD36/FAT), and long chain acyl CoA synthetase 1 (ACSL1) in 286 NMIBC cases. This study revealed that FATP4, CD36, and ACSL1 were overexpressed in 123 (43.0%), 43 (15.0%), and 35 (12.2%) NMIBC cases, respectively. High FATP4 in tumor cells was associated with high grade (p = 0.004) and high stage (p = 0.039). High CD36 was related to high grade (p < 0.001), high stage (p = 0.002), and non-papillary growth type (p = 0.004). High ACSL1 showed an association with high grade (p < 0.001), high stage (p = 0.01), non-papillary growth type (p = 0.002), and metastasis (p = 0.033). High FATP4 was an independent factor predicting short overall survival (OS) (hazard ratio = 3.32; 95% confidence interval, 1.07-10.31; p = 0.038). In conclusion, upregulation of FATP4, CD36, and ACSL1 might promote the NMIBC progression and could be exploited in clinical risk stratification and targeted therapy.

Increased expression levels of AURKA and KIFC1 are promising predictors of progression and poor survival associated with gastric cancer.

Increased cell proliferation is a critical hallmark of cancer development and progression. The proliferation of tumor cells depends on mitotic deregulation. Here, we identified the differentially expressed genes (DEGs) in gastric cancer (GC) through RNA sequencing data and bioinformatics analysis. Subsequent functional and pathway enrichment analyses showed that the screened DEGs were enriched in the mitosis-associated pathway. Based on the analysis results, we selected two signatures (aurora kinase A [AURKA] and kinesin family member C1 [KIFC1]) to determine their clinicopathological significance. The results showed a significant positive correlation between AURKA and KIFC1 expression both at the mRNA and protein levels. AURKA expression was positively correlated with distant metastases (p = 0.032) and tumor-node-metastasis (TNM) stage (p = 0.001). Elevated KIFC1 expression was significantly associated with tumor size (p = 0.029), depth of invasion (p < 0.001), lymph node metastasis (p < 0.001), distant metastasis (p = 0.023), and TNM stage (p < 0.001). Higher AURKA (hazard ratio [HR] = 1.3, p < 0.001) and KIFC1 (HR = 1.41, p < 0.001) mRNA levels were also significantly correlated with poor overall survival. Thus, AURKA and KIFC1 could serve as potential prognostic markers and therapeutic targets for GC.

Cyclic Loading Performance of Radius-Cut Double Coke-Shaped Strip Dampers.

Conventional slit dampers are widely used for the purpose of seismic retrofitting, however, the structure of these dampers is susceptible to fractures, due to stress concentration at the ends of the strips in the event of large earthquakes. To address this issue, a novel radius-cut coke-shaped strip damper featuring improved ductility is proposed herein. This damper was developed based on the moment distribution over the strip when both its ends were constrained. The height-to-width ratio of the strip was increased to induce bending rather than shear deformation, and the reduced beam section method was employed. A radius-cut section was used to intentionally focus the stress to induce the plastic hinge. This reduced the fracture fragility of the specimen, resulting in an increased inelastic deformation capacity. Cyclic loading tests were conducted to verify damping performance against earthquakes. Experiments and finite element analyses proved that the coke-shaped damper exhibits improved ductility. The final fracture occurred in the radius-cut section after sufficient energy dissipation during cyclic loading. The results also indicated further improvements in strength due to the membrane effect under cyclic loading, caused by the tensile resistance of the strip due to its constrained ends.

Increased HOXC6 mRNA expression is a novel biomarker of gastric cancer.

In this study, we aimed to investigate the molecular biomarkers that are pivotal for the development and progression of gastric cancer (GC). We analyzed clinical specimens using RNA sequencing to identify the target genes. We found that the expression of HOXC6 mRNA was upregulated with the progression of cancer, which was validated by quantitative real time PCR and RNA in-situ hybridization. To compare the protein expression of HOXC6, we evaluated GC and normal gastric tissue samples using western blot analysis and immunohistochemistry. We detected significantly higher levels of HOXC6 in the GC tissues than in the normal controls at both mRNA and protein levels. The expression levels of HOXC6 mRNA in patients with advanced gastric cancer (AGC) were significantly higher than those in patients with early gastric cancer (EGC). Kaplan-Meier curves showed that high expression of HOXC6 mRNA is significantly associated with poor clinical prognosis. Our findings suggest that HOXC6 mRNA may be a novel biomarker and can be potentially valuable in predicting the prognosis of GC patients. Especially, HOXC6 mRNA in-situ hybridization may be a diagnostic tool for predicting prognosis of individual GC patients.

Protein expression profiles and prognostic value of E2F family members in clear cell renal cell carcinoma.

The derangement of the cell cycle facilitates uncontrolled cell proliferation and acquisition of genetic alterations favorable for malignancy. However, the protein expression profiles of E2 F family cell cycle regulators in clear cell renal cell carcinoma (ccRCC) have not yet been thoroughly investigated. In this study, we aimed to examine the protein expression profiles and prognostic value of E2 F1, E2 F3, and E2 F4 in ccRCC cases. The immunohistochemical expression of E2 F1, E2 F3, and E2 F4 was quantitatively scored in 180 ccRCC tumor tissues and 79 normal kidney tissues. The prognostic implications of these E2 F members were determined. We found that ccRCC tumor cells showed higher nuclear expression of E2 F1, E2 F3 and E2 F4 than normal kidney samples. High E2 F1 and E2 F3 expression in tumor cells was associated with poor prognostic factors of ccRCC, whereas high E2 F4 correlated with beneficial prognostic factors. High expression of E2 F1 and E2 F3 in tumor cells was correlated with a poor overall and recurrence-free survival, while high E2 F4 expression did not. In conclusion, E2 F1, E2 F3 and E2 F4 may function as oncogenes during tumorigenesis of ccRCC, although they contribute to the progression of ccRCC in different ways. Additional studies are required to clarify the conflicting role of E2 F4 in the tumor evolution of ccRCC.

High Membranous Expression of Fatty Acid Transport Protein 4 Is Associated with Tumorigenesis and Tumor Progression in Clear Cell Renal Cell Carcinoma.

The increased requirement of fatty acids forces cancer cells to enhance uptake of fatty acids from the extracellular milieu, in addition to de novo lipogenesis. Coexpression of cluster of differentiation 36 (CD36) with fatty acid transport protein 4 (FATP4) or long-chain acyl CoA synthetase 1 (ACSL1) synergistically activated fatty acid uptake in experimental models. In this study, we investigated the immunohistochemical expression of CD36, FATP4, and ACSL1 in 180 cases of clear cell renal cell carcinoma (RCC) in comparison with 80 specimens of the normal kidney. We also examined the clinical implication of these three fatty acid transporters in RCC, which was validated by an open-access The Cancer Genome Atlas data analysis. Both CD36 and FATP4 revealed higher membranous expressions in RCC tumor cells than in normal cells. In contrast, ACSL1 expression was remarkably reduced in RCC tumor cells compared to normal cells. CD36, FATP4, and ACSL1 showed high expressions in 74 (41.1%), 85 (47.2%), and 72 (40.0%) out of 180 RCC cases, respectively. Clinically, high FATP4 in tumor cells was associated with female gender (p = 0.05), high TNM stage (p = 0.039), tumor necrosis (p = 0.009), and tumor recurrence (p = 0.037), while high ACSL1 was only related to female gender (p = 0.023). CD36 expression revealed no correlation with the clinicopathologic parameters of RCC. Increased FATP4 expression displayed an association with short recurrence-free survival (p = 0.003). In conclusion, the high FATP4 expression was clinically associated with poor prognostic factors of RCC. Overexpression of membranous FATP4 and CD36 combined with reduced cytoplasmic expression of ACSL1 might be a tumor-specific feature of RCC, contributing to the tumorigenesis and tumor progression.

Spindle assembly checkpoint MAD2 and CDC20 overexpressions and cell-in-cell formation in gastric cancer and its precursor lesions.

Overexpression of mitotic arrest deficient 2 (MAD2) and/or cell division cycle 20 (CDC20) in the spindle assembly checkpoint leads to chromosomal instability and aneuploidy. Cell-in-cell (CIC) structures are formed by the process where cancer or immune cells are internalized into adjacent host cancer cells. Here, we investigated the clinicopathological significances of spindle assembly checkpoint protein overexpression and CIC structures in 829 cases of normal, premalignant, and gastric cancer (GC) lesions. MAD2 and CDC20 expressions were significantly increased in intestinal metaplasia, low-grade dysplasia, high-grade dysplasia (HGD), and early GC than normal mucosa, and their expression levels were the highest in HGD. Interestingly, CDC20 immunohistochemistry specifically stained the outer cells of CIC structures, which were the most frequently observed in early GC. In univariate analyses, MAD2 and CDC20 overexpressions and CIC formation were associated with older age, intestinal histology, lower tumor-node-metastasis stage, and longer recurrence-free survival and cancer-specific survival of GC patients. In multivariate survival analyses, MAD2 and CDC20 overexpressions were associated with better recurrence-free survival (hazard ratio, 0.61; P = .012) and cancer-specific survival (hazard ratio, 0.63; P = .043), respectively. In conclusion, MAD2 and CDC20 are the most expressed in HGD, suggesting their roles in the early stage of gastric carcinogenesis, whereas their overexpressions in GC are associated with intestinal histology and favorable clinicopathological parameters, which may be useful for immunohistochemical classification of chromosomal instability-type GC. Moreover, CDC20 is a novel immunohistochemical marker for highlighting CIC structures.

Prognostic Characteristics of MACC1 Expression in Epithelial Ovarian Cancer.

Recent studies have shown that overexpression of metastasis-associated in colon cancer 1 (MACC1) is significantly associated with adverse prognoses of patients with different kinds of cancer. However, the exact survival effect of MACC1 on epithelial ovarian cancer (EOC) patients has not yet been established. Thus, the objective of this study was to explore the prognostic role of MACC1 mRNA in EOC by using Kaplan-Meier (KM) plotter and ONCOMINE database. Our results indicated that MACC1 mRNA high expression was significantly associated with unfavorable overall survival (hazard ratio (HR) = 1.51 (95% confidence interval (CI): 1.21 - 1.88), P = 0.00025) and progression-free survival (HR = 1.53 (95% CI: 1.24 - 1.89), P = 5.8e-05) in EOC patients. We also found that the expression of MACC1 mRNA in EOC was 2.5 times higher than that in normal surface ovarian epithelium, which was statistically significant (P = 2.86e-7). Our results suggest that MACC1 expression might be a biomarker for poor prognosis in individual EOC patients.

Liquid biopsy prediction of axillary lymph node metastasis, cancer recurrence, and patient survival in breast cancer: A meta-analysis.

BACKGROUND: Liquid biopsies using circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) have been developed for early cancer detection and patient monitoring. To investigate the clinical usefulness of ctDNA aberrations and cfDNA levels in patients with breast cancer (BC), we conducted a meta-analysis of 69 published studies on 5736 patients with BC. METHODS: The relevant publications were identified by searching PubMed and Embase databases. The effect sizes of outcome parameters were pooled using a random-effects model. RESULTS: The ctDNA mutation rates of TP53, PIK3CA, and ESR1 were approximately 38%, 27%, and 32%, respectively. High levels of cfDNA were associated with BCs rather than with healthy controls. However, these detection rates were not satisfactory for BC screening. Although the precise mechanisms have been unknown, high cfDNA levels were significantly associated with axillary lymph node metastasis (odds ratio [OR] = 2.148, P = .030). The ctDNA mutations were significantly associated with cancer recurrence (OR = 3.793, P < .001), short disease-free survival (univariate hazard ratio [HR] = 5.180, P = .026; multivariate HR = 3.605, P = .001), and progression-free survival (HR = 1.311, P = .013) rates, and poor overall survival outcomes (HR = 2.425, P = .007). CONCLUSION: This meta-analysis demonstrates that ctDNA mutation status predicts disease recurrence and unfavorable survival outcomes, while cfDNA levels can be predictive of axillary lymph node metastasis in patients with BC.

IFNγ induces PD-L1 overexpression by JAK2/STAT1/IRF-1 signaling in EBV-positive gastric carcinoma.

Programmed death-ligand 1 (PD-L1) acts as an immune checkpoint inhibitor in various cancers. PD-L1 is known to be more frequently expressed in EBV (+) gastric cancer (GC). However, the mechanisms underlying the regulation of PD-L1 expression in EBV (+) GC remain unclear. We investigated the basal and inducible PD-L1 expressions in GC cells. PD-L1 expression was upregulated upon treatment with IFNγ in both EBV (-) and EBV (+) GC cells. Upon stimulation with the same concentration of IFNγ for 24 h, EBV (+) SNU-719 cells showed dramatically higher PD-L1 expression levels by activating JAK2/STAT1/IRF-1 signaling than those of EBV (-) AGS cells. PD-L1 promoter assays, chromatin immunoprecipitation, and electrophoretic mobility shift assays revealed that IFNγ-inducible PD-L1 overexpression is primarily mediated by the putative IRF-1α site of the PD-L1 promoter in EBV (+) SNU-719 cells. Moreover, EBNA1 knockdown reduced both constitutive and IFNγ-inducible PD-L1 promoter activity by decreasing the transcript and protein levels of JAK2 and subsequently STAT1/IRF-1/PD-L1 signaling. EBNA1 is suggested to be moderately enhance both constitutive and IFNγ-inducible PD-L1 expression in EBV (+) GC cells. Thus, the signaling proteins and EBNA1 that regulate PD-L1 expression are potential therapeutic targets in EBV (+) GC.

An ApoB100-mimetic vaccine prevents obesity and liver steatosis in ApoE-/- mice.

BACKGROUND: Recently, a peptide vaccine (B4T) was developed that prevents high fat diet (HFD)-induced obesity and liver steatosis in wild type mice and appears to target an epitope present in ApoB100 but not ApoB48. Here, we ask whether B4T remains effective in ApoE knockout (ApoE-ko) mice, which exhibit a greatly increased ApoB48/ApoB100 ratio and develop atherosclerosis under HFD. METHODS: HFD-fed male ApoE-ko mice were injected with B4T or vehicle 3 times between 5 and 15 weeks of age. Until 45 weeks of age, they were regularly weighed and antibody titers determined. In the end, adiposity and organ histologies were examined. RESULTS: We find that in the ApoE-ko mice, B4T prevents HFD-induced body weight increases (p<0.01) to a comparable degree as previously shown in wild type mice. Also, liver steatosis was prevented as previously shown in wild type mice. By contrast, atherosclerotic plaque formation was not prevented in any of the vaccinated mice studied, in line with the observation that antibody production paralleled the weight reduction but largely preceded atherogenesis. CONCLUSION: The findings demonstrate effectiveness of B4T despite the increased ApoB48/B100 ratio, but argue against an effect on de novo plaque formation. At least under the current vaccination schedule, the obesity- and atherosclerosis-related roles of ApoB appear to be dissociable.

Unique characteristics of ARID1A mutation and protein level in gastric and colorectal cancer: A meta-analysis.

BACKGROUND/AIM: Recently, AT-rich interactive domain-containing 1A protein (ARID1A) has been identified as a novel tumor suppressor gene in gastric cancer (GC) and colorectal cancer (CRC). However, the clinicopathologic value of ARID1A mutation or protein level in GC and CRC patients is controversial. Hence, we conducted a meta-analysis on the relationship between ARID1A aberrations and clinicopathologic parameters in GC and CRC. MATERIALS AND METHODS: Relevant published studies were selected from PubMed and EMBASE. The effect sizes of ARID1A mutation or level on the patient's clinicopathologic parameters were calculated by prevalence rate or odds ratio (OR) or hazard ratio (HR), respectively. The effect sizes were combined using a random-effects model. RESULTS: The frequency of ARID1A mutation and loss of ARID1A protein expression in GC patients was 17% and 27%, respectively. The loss of ARID1A protein expression of GC patients was significantly associated with advanced tumor depth (OR = 1.8, P = 0.004), lymph node metastasis (OR = 1.4, P = 0.001), and unfavorable adjusted overall survival (HR = 1.5, P < 0.001). ARID1A mutation of GC was significantly associated with microsatellite instability (MSI) (OR = 24.5, P < 0.001) and EBV infection (OR = 2.6, P = 0.001). The frequency of ARID1A mutation and ARID1A protein expression loss in CRC patients was approximately 12-13%. Interestingly, the loss of ARID1A protein expression in CRC patients was significantly associated with poorly differentiated grade (OR = 4.0, P < 0.001) and advanced tumor depth (OR = 1.8, P = 0.012). CONCLUSION: Our meta-analysis revealed that ARID1A alterations may be involved in the carcinogenesis of GC by EBV infection and MSI. The loss of ARID1A protein expression may be a marker of poor prognosis in GC and CRC patients.