Feasibility of intraoperative pathologic examination for sentinel lymph nodes during sentinel node navigation surgery in early gastric cancer: results of pathologic protocol for SENORITA trial.

BACKGROUND: During sentinel node navigation surgery in patients with gastric cancer, intraoperative pathologic examination of sentinel nodes is crucial in determining the extent of surgery. In this study, we evaluated the feasibility and accuracy of intraoperative pathologic protocols using data from a prospective, multicenter, randomized trial. METHODS: A retrospective analysis was conducted using data from the SEntinel Node ORIented Tailored Approach trials from 2013 to 2016. All sentinel lymph nodes were evaluated during surgery with hematoxylin-eosin (HE) staining using a representative section at the largest plane for lymph nodes. For permanent histologic evaluation, sentinel basin nodes were stained with HE and cytokeratin immunohistochemistry in formalin-fixed, paraffin-embedded (FFPE) sections and examined with HE for three deeper-step sections at 200-µm intervals. The failure rate of identification by frozen section and the metastasis rate in non-sentinel basins were investigated. RESULTS: Of the 237 patients who underwent sentinel node basin dissection, 30 had lymph node metastases on permanent pathology. Thirteen patients had macrometastasis confirmed in frozen sections as well as FFPE sections (failure rate: 0%). Patients with negative sentinel nodes in frozen sections but micrometastasis in FFPE sections had no lymph node recurrence during the follow-up period (0%, 0/6). However, in cases with tumor-positive nodes in frozen sections, metastases in non-sentinel basins were detected in the paraffin blocks (8.3%, 2/24). CONCLUSIONS: The single-section HE staining method is sufficient for detecting macrometastasis via intraoperative pathological examination. If a negative frozen-section result is confirmed, sentinel basin dissection can be performed safely. Otherwise, standard surgery is required.

Exosome-mediated secretion of miR-127-3p regulated by RAB27A accelerates metastasis in renal cell carcinoma.

BACKGROUND: The exosome-mediated extracellular secretion of miRNAs occurs in many cancers, and RAB27A is a potent regulator of exosome secretion. For metastatic renal cell carcinoma (RCC), this study examines the mechanisms of cancer metastasis via the RAB27A-regulated secretion of specific miRNAs. METHODS: RAB27A knockdown (KD) and overexpressing (OE) RCC cells were used to examine cell migration and adhesion. The particle counts and sizes of exosomes in RAB27A OE cells were analyzed using Exoview, and those of intraluminal vesicles (ILV) and multivesicular bodies (MVB) were measured using an electron microscope. Analysis of RNA sequences, protein-protein interaction networks, and the competing endogenous RNA (ceRNA) network were used to identify representative downregulated miRNAs that are likely to undergo cargo-sorting into exosomes and subsequent secretion. A molecular beacon of miR-137-3p, one of the most representatively downregulated genes with a fold change of 339, was produced, and its secretion was analyzed using Exoview. RAB27A OE and control cells were incubated in an exosome-containing media to determine the uptake of tumor suppressor miRNAs that affect cancer cell metastasis. RESULTS: Migration and cell adhesion were higher in RAB27A OE cells than in RAB27A KD cells. Electron microscopy revealed that the numbers of multivesicular bodies and intraluminal vesicles per cell were higher in RAB27A OE cells than in control cells, suggesting their secretion. The finding revealed that miR-127-3p was sorted into exosomes and disposed of extracellularly. Protein-protein interaction analysis revealed MYCN to be the most significant hub for RAB27A-OE RCC cells. ceRNA network analysis revealed that MAPK4 interacted strongly with miR-127-3p. CONCLUSION: The disposal of miR-127-3p through exosome secretion in RAB27A overexpressing cells may not inhibit the MAPK pathway to gain metastatic potential by activating MYCN. The exosomes containing miRNAs are valuable therapeutic targets for cancer treatment.

AVEN: a novel oncogenic biomarker with prognostic significance and implications of AVEN-associated immunophenotypes in lung adenocarcinoma.

Introduction: AVEN, an apoptosis and caspase activation inhibitor, has been associated with adverse clinical outcomes and poor prognosis in Acute myeloid leukemia (AML). Targeting AVEN in AML improves apoptosis sensitivity and chemotherapy efficacy, making it a promising therapeutic target. However, AVEN's role has not been studied in solid tumors. Therefore, our study investigated AVEN as a prognostic biomarker in a more comprehensive manner and developed an AVEN-derived prognostic model in Lung adenocarcinoma (LUAD). Method: Pan-cancer analysis was performed to examine AVEN expression in 33 cancer types obtained from the TCGA database. GEPIA analysis was used to determine the predictive value of AVEN in each cancer type with cancer-specific AVEN expression. Lung Adenocarcinomas (LUAD) patients were grouped into AVENhigh and AVENlow based on AVEN expression level. Differentially expressed genes (DEGs) and pathway enrichment analysis were performed to gain insight into the biological function of AVEN in LUAD. In addition, several deconvolution tools, including Timer, CIBERSORT, EPIC, xCell, Quanti-seq and MCP-counter were used to explore immune infiltration. AVEN-relevant prognostic genes were identified by Random Survival Forest analysis via univariate Cox regression. The AVEN-derived genomic model was established using a multivariate-Cox regression model and GEO datasets (GSE31210, GSE50081) were used to validate its prognostic effect. Results: AVEN expression was increased in several cancer types compared to normal tissue, but its impact on survival was only significant in LUAD in the TCGA cohort. High AVEN expression was significantly correlated with tumor progression and shorter life span in LUAD patients. Pathway analysis was performed with 838 genes associated with AVEN expression and several oncogenic pathways were altered such as the Cell cycle, VEGFA-VEGFR2 pathway, and epithelial-mesenchymal-transition pathway. Immune infiltration was also analyzed, and less infiltrated B cells was observed in AVENhigh patients. Furthermore, an AVEN-derived genomic model was established, demonstrating a reliable and improved prognostic value in TCGA and GEO databases. Conclusion: This study provided evidence that AVEN is accumulated in LUAD compared to adjacent tissue and is associated with poor survival, high tumor progression, and immune infiltration alteration. Moreover, the study introduced the AVEN-derived prognostic model as a promising prognosis tool for LUAD.

Unraveling Connective Tissue Growth Factor as a Therapeutic Target and Assessing Kahweol as a Potential Drug Candidate in Triple-Negative Breast Cancer Treatment.

Triple-negative breast cancer (TNBC) is characterized by aggressive behavior and limited treatment options, necessitating the identification of novel therapeutic targets. In this study, we investigated the clinical significance of connective tissue growth factor (CTGF) as a prognostic marker and explored the potential therapeutic effects of kahweol, a coffee diterpene molecule, in TNBC treatment. Initially, through a survival analysis on breast cancer patients from The Cancer Genome Atlas (TCGA) database, we found that CTGF exhibited significant prognostic effects exclusively in TNBC patients. To gain mechanistic insights, we performed the functional annotation and gene set enrichment analyses, revealing the involvement of CTGF in migratory pathways relevant to TNBC treatment. Subsequently, in vitro experiments using MDA-MB 231 cells, a representative TNBC cell line, demonstrated that recombinant CTGF (rCTGF) administration enhanced cell motility, whereas CTGF knockdown using CTGF siRNA resulted in reduced motility. Notably, rCTGF restored kahweol-reduced cell motility, providing compelling evidence for the role of CTGF in mediating kahweol's effects. At the molecular level, kahweol downregulated the protein expression of CTGF as well as critical signaling molecules, such as p-ERK, p-P38, p-PI3K/AKT, and p-FAK, associated with cell motility. In summary, our findings propose CTGF as a potential prognostic marker for guiding TNBC treatment and suggest kahweol as a promising antitumor compound capable of regulating CTGF expression to suppress cell motility in TNBC. These insights hold promise for the development of targeted therapies and improved clinical outcomes for TNBC patients.

Perilipin1 Expression as a Prognostic Factor in Patients with Squamous Cell Carcinoma of the Lung.

Perilipin (PLIN) is a major structural protein located on the surface of lipid droplets. PLIN plays an important role in human metabolism and is associated with metabolic diseases, such as obesity, diabetes, hypertension, and endocrine disorders. The dysregulation of lipid metabolism is one of the most prominent metabolic changes observed in cancers. Therefore, the PLIN protein family has recently attracted attention owing to its role in lipid metabolism and cancer. To date, no studies have addressed the association between the prognosis of lung cancer and PLIN1 expression. For the first time, we found that high PLIN1 expression was significantly correlated with worse disease-free survival (DFS) in lung squamous cell carcinoma (SCC). We examined PLIN1 expression by the immunohistochemical analysis of surgical lung SCC specimens obtained from 94 patients. We analyzed the correlation between PLIN1 expression, clinicopathological data, and patient survival, using a chi-squared test, Kaplan-Meier analysis with log-rank tests, and the multivariate Cox proportional hazards regression test. High PLIN1 expression was significantly correlated with lower DFS in the Kaplan-Meier analysis and the multivariate Cox proportional hazards regression model. High PLIN1 expression was significantly correlated with worse prognosis in lung SCC.

The Genome of the Korean Island-Originated Perilla citriodora 'Jeju17' Sheds Light on Its Environmental Adaptation and Fatty Acid and Lipid Production Pathways.

Perilla is a key component of Korean food. It contains several plant-specialized metabolites that provide medical benefits. In response to an increased interest in healthy supplement food from the public, people are focusing on the properties of Perilla. Nevertheless, unlike rice and soybeans, there are few studies based on molecular genetics on Perilla, so it is difficult to systematically study the molecular breed. The wild Perilla, Perilla citriodora 'Jeju17', was identified a decade ago on the Korean island of Jeju. Using short-reads, long-reads, and Hi-C, a chromosome-scale genome spanning 676 Mbp, with high contiguity, was assembled. Aligning the 'Jeju17' genome to the 'PC002' Chinese species revealed significant collinearity with respect to the total length. A total of 31,769 coding sequences were predicted, among which 3331 were 'Jeju17'-specific. Gene enrichment of the species-specific gene repertoire highlighted environment adaptation, fatty acid metabolism, and plant-specialized metabolite biosynthesis. Using a homology-based approach, genes involved in fatty acid and lipid triacylglycerol biosynthesis were identified. A total of 22 fatty acid desaturases were found and comprehensively characterized. Expression of the FAD genes in 'Jeju17' was examined at the seed level, and hormone signaling factors were identified. The results showed that the expression of FAD genes in 'Jeju17' at the seed level was high 25 days after flowering, and their responses of hormones and stress were mainly associated with hormone signal transduction and abiotic stress via cis-elements patterns. This study presents a chromosome-level genome assembly of P. citriodora 'Jeju17', the first wild Perilla to be sequenced from the Korean island of Jeju. The analyses provided can be useful in designing ALA-enhanced Perilla genotypes in the future.

Development of an SNP marker set for marker-assisted backcrossing using genotyping-by-sequencing in tetraploid perilla.

High-quality molecular markers are essential for marker-assisted selection to accelerate breeding progress. Compared with diploid species, recently diverged polyploid crop species tend to have highly similar homeologous subgenomes, which is expected to limit the development of broadly applicable locus-specific single-nucleotide polymorphism (SNP) assays. Furthermore, it is particularly challenging to make genome-wide marker sets for species that lack a reference genome. Here, we report the development of a genome-wide set of kompetitive allele specific PCR (KASP) markers for marker-assisted recurrent selection (MARS) in the tetraploid minor crop perilla. To find locus-specific SNP markers across the perilla genome, we used genotyping-by-sequencing (GBS) to construct linkage maps of two F2 populations. The two resulting high-resolution linkage maps comprised 2326 and 2454 SNP markers that spanned a total genetic distance of 2133 cM across 16 linkage groups and 2169 cM across 21 linkage groups, respectively. We then obtained a final genetic map consisting of 22 linkage groups with 1123 common markers from the two genetic maps. We selected 96 genome-wide markers for MARS and confirmed the accuracy of markers in the two F2 populations using a high-throughput Fluidigm system. We confirmed that 91.8% of the SNP genotyping results from the Fluidigm assay were the same as the results obtained through GBS. These results provide a foundation for marker-assisted backcrossing and the development of new varieties of perilla.

Mebendazole Increases Anticancer Activity of Radiotherapy in Radiotherapy-Resistant Triple-Negative Breast Cancer Cells by Enhancing Natural Killer Cell-Mediated Cytotoxicity.

Breast cancer is the most commonly diagnosed cancer worldwide and ranks first in terms of both prevalence and cancer-related mortality in women. In this study, we aimed to evaluate the anticancer effect of mebendazole (MBZ) and radiotherapy (RT) concomitant use in triple-negative breast cancer (TNBC) cells and elucidate the underlying mechanisms of action. Breast cancer mouse models and several types of breast cancer cells, including TNBC-derived RT-resistant (RT-R) MDA-MB-231 cells, were treated with MBZ and/or RT. In mice, changes in body weight, renal and liver toxicity, tumor volume, and number of lung metastases were determined. In cells, cell viability, colony formation, scratch wound healing, Matrigel invasion, and protein expression using western blotting were determined. Our findings showed that MBZ and RT combined treatment increased the anticancer effect of RT without additional toxicity. In addition, we noted that cyclin B1, PH2AX, and natural killer (NK) cell-mediated cytotoxicity increased following MBZ + RT treatment compared to unaided RT. Our results suggest that MBZ + RT have an enhanced anticancer effect in TNBC which acquires radiation resistance through blocking cell cycle progression, initiating DNA double-strand breaks, and promoting NK cell-mediated cytotoxicity.

Fc Receptor Expression as a Prognostic Factor in Patients With Non-small-cell Lung Cancer.

BACKGROUND/AIM: The neonatal Fc receptor (FcRn) is a major histocompatibility class I-like molecule responsible for the transfer of passive humoral immunity from a mother to her newborn. Recent research revealed that FcRn is involved in antigen-presentation, humoral immunity and antitumor immunity of various types of cancer, such as lung, colon and breast. Lung cancer is the leading cause of cancer-related death and non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer. NSCLC is a highly heterogeneous disease and this affects the prognosis. Therefore, many studies have tried to identify factors that are associated with prognosis. The lungs are a major organ expressing FcRn. We aimed to evaluate FcRn expression in surgical specimens of NSCLC and determine its correlation with patient prognosis. MATERIALS AND METHODS: We analyzed 140 NSCLC surgical specimens for FcRn expression using immunohistochemistry and correlated positivity with clinicopathology and survival of these patients. A chi-squared test and Kaplan-Meier analysis with log-rank tests were performed for statistical evaluation. RESULTS: The FcRn-positive group had a significantly higher disease-free survival and a tendency towards increased disease-specific survival in patients with tumor-node-metastasis stage I NSCLC. CONCLUSION: Our study supports the hypothesis that FcRn down-regulation is associated with NSCLC progression.

Pyoderma Gangrenosum Mimicking Necrotizing Fasciitis on Magnetic Resonance Imaging: A Case Report and Literature Review.

BACKGROUND Pyoderma gangrenosum (PG) is a sterile neutrophilic dermatosis that can be associated with systemic diseases, such as ulcerative colitis, polyarthritis, diabetes mellitus, myelodysplastic syndrome, and/or myeloid leukemia, and is often misdiagnosed as a necrotizing infection. Few reports have described imaging studies of PG; however, necrotizing fasciitis (NF) exhibits distinct imaging characteristics. If deep fascial involvement is not demonstrated on magnetic resonance imaging (MRI), NF is excluded. CASE REPORT We present a case of PG mimicking NF on MRI in a 67-year-old woman with acute myeloblastic leukemia. After undergoing a second cycle of decitabine therapy, she was admitted for pain in her lower left leg. The condition was initially misdiagnosed as NF because MRI findings demonstrated signal intensity in the fascia. MRI revealed fasciitis that exhibited linear fluid signal intensity in the fascia of lower left leg. Despite broad-spectrum antibiotics, the lesion rapidly progressed to a swollen hemorrhagic patch with bullae and an ulcer. Skin biopsy results ultimately led to the diagnosis of PG, based on histopathological findings. The patient was treated with intravenous steroids and regular wound dressing. The skin lesion on the lower left leg exhibited a good response. CONCLUSIONS Despite the presence of a lesion that invaded the fascia on MRI, our patient was diagnosed with PG following a skin biopsy and completely recovered with steroid treatment. To distinguish PG from NF, it is more important to identify the characteristic clinical features than to rely solely on imaging findings.

Mucoepidermoid carcinoma of the breast: A case report and literature review focused on radiological findings.

RATIONALE: Mucoepidermoid carcinoma (MEC) of the breast is a rare entity, with an estimated incidence of only 0.2% to 0.3% of all primary breast tumors. The radiological features of breast MEC have scarcely been investigated mainly because of its rarity. In this article, we present a case of breast MEC diagnosed at our hospital and review the literature, focusing on radiological findings and radiologic-pathologic correlations that could improve clinical management of this entity. To the best of our knowledge, our study is the first review of the literature that focuses on the radiological features of breast MEC. PATIENT CONCERNS: A 47-year-old premenopausal woman presented with a painless palpable mass in the right breast. DIAGNOSIS: Mammography and ultrasonography revealed a mass with suspicious malignant features, which was categorized as Breast Imaging Reporting and Data System category 4c. A 14-gauge core-needle biopsy revealed an intermediate-grade MEC of the breast. The patient underwent breast magnetic resonance imaging and chest computed tomography for preoperative evaluation. Postoperative histopathological examination confirmed a diagnosis of intermediate-grade MEC. The clinical staging was T2N0M0. INTERVENTIONS: The patient underwent breast-conserving surgery, adjuvant chemotherapy, radiotherapy, and hormonal therapy. OUTCOMES: No evidence of recurrence has been reported over 37 months. LESSONS: The imaging characteristics of breast MEC were variable, and there were no specific radiological features for diagnosis. The presence of cystic components on radiological imaging is likely to be an indicator of a low-grade tumor and better prognosis, although the number of reported cases is limited.

Cyclin D1 Serves as a Poor Prognostic Biomarker in Stage I Gastric Cancer.

TNM stage still serves as the best prognostic marker in gastric cancer (GC). The next step is to find prognostic biomarkers that detect subgroups with different prognoses in the same TNM stage. In this study, the expression levels of epidermal growth factor receptor (EGFR) and cyclin D1 were assessed in 96 tissue samples, including non-tumorous tissue, adenoma, and carcinoma. Then, the prognostic impact of EGFR and cyclin D1 was retrospectively investigated in 316 patients who underwent R0 resection for GC. EGFR positivity increased as gastric tissue became malignant, and cyclin D1 positivity was increased in all the tumorous tissues. However, there was no survival difference caused by the EGFR positivity, while the cyclin D1-postive group had worse overall survival (OS) than the cyclin D1-negative group in stage I GC (10-year survival rate (10-YSR): 62.8% vs. 86.5%, p = 0.010). In subgroup analyses for the propensity score-matched (PSM) cohort, there were also significant differences in the OS according to the cyclin D1 positivity in stage I GC but not in stage II and III GC. Upon multivariate analysis, cyclin D1 positivity was an independent prognostic factor in stage I GC. In conclusion, cyclin D1 may be a useful biomarker for predicting prognosis in stage I GC.

A Novel Approach on Deep Learning-Based Decision Support System Applying Multiple Output LSTM-Autoencoder: Focusing on Identifying Variations by PHSMs' Effect over COVID-19 Pandemic.

Following the outbreak of the COVID-19 pandemic, the continued emergence of major variant viruses has caused enormous damage worldwide by generating social and economic ripple effects, and the importance of PHSMs (Public Health and Social Measures) is being highlighted to cope with this severe situation. Accordingly, there has also been an increase in research related to a decision support system based on simulation approaches used as a basis for PHSMs. However, previous studies showed limitations impeding utilization as a decision support system for policy establishment and implementation, such as the failure to reflect changes in the effectiveness of PHSMs and the restriction to short-term forecasts. Therefore, this study proposes an LSTM-Autoencoder-based decision support system for establishing and implementing PHSMs. To overcome the limitations of existing studies, the proposed decision support system used a methodology for predicting the number of daily confirmed cases over multiple periods based on multiple output strategies and a methodology for rapidly identifying varies in policy effects based on anomaly detection. It was confirmed that the proposed decision support system demonstrated excellent performance compared to models used for time series analysis such as statistical models and deep learning models. In addition, we endeavored to increase the usability of the proposed decision support system by suggesting a transfer learning-based methodology that can efficiently reflect variations in policy effects. Finally, the decision support system proposed in this study provides a methodology that provides multi-period forecasts, identifying variations in policy effects, and efficiently reflects the effects of variation policies. It was intended to provide reasonable and realistic information for the establishment and implementation of PHSMs and, through this, to yield information expected to be highly useful, which had not been provided in the decision support systems presented in previous studies.

Correlation between myoferlin expression and lymph node metastasis in papillary thyroid carcinoma.

BACKGROUND: Myoferlin is a multifunctional protein expressed in various normal and cancer cells, with novel oncogenic roles being newly discovered. Recently, correlations have been found between myoferlin expression and unfavorable prognosis in various carcinomas. This study investigated the prognostic role of myoferlin expression in papillary thyroid carcinoma (PTC), specifically that associated with nodal metastasis. METHODS: We collected clinicopathological data and PTC tissues from 116 patients who had been admitted to Gyeongsang National University Hospital in 2010. Immunohistochemical analysis was performed on surgical specimen-derived tissue microarray blocks. Myoferlin expression was graded, and the relationship between expression level and pathological features of tumors based on the American Joint Committee on Cancer staging system was evaluated. RESULTS: Of the 116 patient samples, 100 cases exhibited positive myoferlin expression. Higher grade of myoferlin expression was correlated with lower T category group (p = .010). Presence of lymph node metastasis was determined to be significantly correlated with low-grade myoferlin expression (p = .019), with no significant difference between pN1a and pN1b tumors. CONCLUSIONS: Our study revealed an adverse correlation between myoferlin expression and pathological features of PTC, evidence of the potential prognostic role of myoferlin in PTC lymph node metastasis.

Human cytomegalovirus lytic infection inhibits replication-dependent histone synthesis and requires stem loop binding protein function.

Replication-dependent (RD) histones are deposited onto human cytomegalovirus (HCMV) genomes at the start of infection. We examined how HCMV affects the de novo production of RD histones and found that viral infection blocked the accumulation of RD histone mRNAs that normally occurs during the S phase. Furthermore, RD histone mRNAs present in HCMV-infected cells did not undergo the unique 3' processing required for their normal nuclear export and translation. The protein that orchestrates processing in the nucleus, stem loop­binding protein (SLBP), was found predominantly in the cytoplasm, and RD histone proteins were not de novo synthesized in HCMV-infected cells. Intriguingly, however, we found that SLBP was required for the efficient synthesis and assembly of infectious progeny virions. We conclude that HCMV infection attenuates RD histone mRNA accumulation and processing and the de novo protein synthesis of the RD histones, while utilizing SLBP for an alternative purpose to support infectious virion production.

Effect of the Interaction between Dietary Patterns and the Gastric Microbiome on the Risk of Gastric Cancer.

We aimed to observe the combined effects of Gaussian graphical model (GGM)-derived dietary patterns and the gastric microbiome on the risk of gastric cancer (GC) in a Korean population. The study included 268 patients with GC and 288 healthy controls. Food intake was assessed using a 106-item semiquantitative food frequency questionnaire. GGMs were applied to derive dietary pattern networks. 16S rRNA gene sequencing was performed using DNA extracted from gastric biopsy samples. The fruit pattern network was inversely associated with the risk of GC for the highest vs. lowest tertiles in the total population (odds ratio (OR): 0.47; 95% confidence interval (CI): 0.28-0.77; p for trend = 0.003) and in females (OR: 0.38; 95% CI: 0.17-0.83; p for trend = 0.021). Males who had a low microbial dysbiosis index (MDI) and high vegetable and seafood pattern score showed a significantly reduced risk of GC (OR: 0.44; 95% CI: 0.22-0.91; p-interaction = 0.021). Females who had a low MDI and high dairy pattern score showed a significantly reduced risk of GC (OR: 0.23; 95% CI: 0.07-0.76; p-interaction = 0.018). Our novel findings revealed that vegetable and seafood pattern might interact with dysbiosis to attenuate the risk of GC in males, whereas the dairy pattern might interact with dysbiosis to reduce the GC risk in females.

A Comparison of the Transcriptomes of Cowpeas in Response to Two Different Ionizing Radiations.

In this study, gene expression changes in cowpea plants irradiated by two different types of radiation: proton-beams and gamma-rays were investigated. Seeds of the Okdang cultivar were exposed to 100, 200, and 300 Gy of gamma-rays and proton-beams. In transcriptome analysis, the 32, 75, and 69 differentially expressed genes (DEGs) at each dose of gamma-ray irradiation compared with that of the control were identified. A total of eight genes were commonly up-regulated for all gamma-ray doses. However, there were no down-regulated genes. In contrast, 168, 434, and 387 DEGs were identified for each dose of proton-beam irradiation compared with that of the control. A total of 61 DEGs were commonly up-regulated for all proton-beam doses. As a result of GO and KEGG analysis, the ranks of functional categories according to the number of DEGs were not the same in both treatments and were more diverse in terms of pathways in the proton-beam treatments than gamma-ray treatments. The number of genes related to defense, photosynthesis, reactive oxygen species (ROS), plant hormones, and transcription factors (TF) that were up-/down-regulated was higher in the proton beam treatment than that in gamma ray treatment. Proton-beam treatment had a distinct mutation spectrum and gene expression pattern compared to that of gamma-ray treatment. These results provide important information on the mechanism for gene regulation in response to two ionizing radiations in cowpeas.

PD-1 Expression and its Correlation With Prognosis in Clear Cell Renal Cell Carcinoma.

BACKGROUND/AIM: Programmed death ligand-1 (PD-L1) and programmed death protein 1 (PD-1) expression levels in many tumors and their correlation with prognosis have been actively studied. However, studies on PD-1 expression and its prognostic value in clear cell renal cell carcinoma (ccRCC) are limited and controversial. In this study, we describe the expression of PD-1 and its prognostic significance and association with clinical features in patients with ccRCC. MATERIALS AND METHODS: We obtained clinicopathological data from 166 patients with ccRCC who were treated at Gyeongsang National University Hospital, Jinju, Korea between January 2000 and December 2009. Tissue microarray blocks were made using representative paraffin blocks of ccRCC specimens. Two pathologists analyzed PD-L1 and PD-1 expression in both tumor and inflammatory cells. RESULTS: PD-1 expression in tumor-infiltrating inflammatory cells was significantly correlated with unfavorable disease-free survival (DFS) (p<0.001) and disease-specific survival (DSS) (p=0.002) in the univariate analysis. A statistically significant correlation between PD-1 expression and unfavorable DFS (p=0.025) was observed in the multivariate analysis. CONCLUSION: PD-1 expression in tumor-infiltrating inflammatory cells serves as an independent prognostic factor for unfavorable DSS in patients with ccRCC.

Kahweol, a Diterpenoid Molecule, Inhibits CTGF-Dependent Synthetic Phenotype Switching and Migration in Vascular Smooth Muscle Cells.

Vascular smooth muscle cell (VSMC) phenotype switching from contractile to synthetic is essential for proliferation and migration in vascular pathophysiology. Connective tissue growth factor (CTGF) is a matricellular protein involved in cell adhesion, migration, and proliferation. Kahweol, a diterpene molecule in arabica coffee beans, has been reported to have anti-inflammatory, antiproliferative, and apoptotic effects in many cells. However, in VSMCs, the effects of kahweol on CTGF activities have not been investigated. Thus, in this study, the effects and associated mechanisms of kahweol in CTGF-dependent phenotype switching and migration in VSMCs were examined. Experiments were performed on primary rat aortic smooth muscle cells and a rat VSMC line, A7r5. Western blot analysis was used to determine the protein levels. The mRNA levels of synthetic markers were measured by qRT-PCR. Migration of VSMCs was evaluated by wound healing and transwell assays. Kahweol reduced the angiotensin II (Ang II)-induced CTGF expression. Further, kahweol inhibited expressions of synthetic phenotype markers of VSMC. The kahweol-reduced synthetic marker protein levels were reversed by the administration of rCTGF. However, expressions of contractile phenotype markers of VSMC were not affected. Kahweol suppressed Ang II-stimulated VSMC migration. Moreover, kahweol downregulated Ang II-induced p-FAK, p-Erk, and Yes-associated protein (YAP) protein expressions. Taken together, in Ang II-stimulated VSMCs, kahweol inhibited CTGF-dependent synthetic phenotype switching and migration, with focal adhesion kinase (FAK), Erk, and YAP involved in the underlying mechanisms of the kahweol effects. These results suggest that kahweol has a potential as a therapeutic agent to inhibit CTGF, which is a molecular target in sclerogenic vascular disease.