Self-Entrapment of Antimicrobial Peptides in Silica Particles for Stable and Effective Antimicrobial Peptide Delivery System.

Antimicrobial peptides (AMPs) have emerged as a promising solution to tackle bacterial infections and combat antibiotic resistance. However, their vulnerability to protease degradation and toxicity towards mammalian cells has hindered their clinical application. To overcome these challenges, our study aims to develop a method to enhance the stability and safety of AMPs applicable to effective drug-device combination products. The KR12 antimicrobial peptide was chosen, and in order to further enhance its delivery and efficacy the human immunodeficiency virus TAT protein-derived cell-penetrating peptide (CPP) was fused to form CPP-KR12. A new product, CPP-KR12@Si, was developed by forming silica particles with self-entrapped CPP-KR12 peptide using biomimetic silica precipitability because of its cationic nature. Peptide delivery from CPP-KR12@Si to bacteria and cells was observed at a slightly delivered rate, with improved stability against trypsin treatment and a reduction in cytotoxicity compared to CPP-KR12. Finally, the antimicrobial potential of the CPP-KR12@Si/bone graft substitute (BGS) combination product was demonstrated. CPP-KR12 is coated in the form of submicron-sized particles on the surface of the BGS. Self-entrapped AMP in silica nanoparticles is a safe and effective AMP delivery method that will be useful for developing a drug-device combination product for tissue regeneration.

Clinical Characteristics of TZAP (ZBTB48) in Hepatocellular Carcinomas from Tissue, Cell Line, and TCGA.

Background and Objectives: ZBTB48 is a telomere-related protein that has been renamed telomeric zinc finger-associated protein (TZAP). It favorably binds to elongated telomeres to regulate their appropriate length. However, TZAP expression has not been investigated in hepatocellular carcinomas (HCC). Materials and Methods: The clinical significance of TZAP expression in 72 HCC was investigated. Additionally, its findings were supported by open big data and cancer cell lines. Results: TZAP expression level was not associated with the clinical parameters of HCC. TZAP expression induced a poorer survival result (overall survival, p = 0.020; disease-free survival, p = 0.012). TCGA data showed TZAP expression was more frequently found in HCCs with hepatitis C infection (p = 0.023). However, TCGA data revealed that TZAP expression did not predict HCC prognosis. In a cell line study, TZAP inhibition via siRNA suppressed PLC/PRF/5 cell growth; however, cell viability was increased in HepG2 cells. Conclusions: We presented the clinical and prognostic values of TZAP expression in HCC tissues and cancer cell lines. Additionally, the TCGA results also revealed a significant role for TZAP expression. TZAP expression may involve HCC progression and its prognosis.

Etiological Distribution and Morphological Patterns of Granulomatous Pleurisy in a Tuberculosis-prevalent Country.

The cause of epithelioid granulomatous inflammation varies widely depending on the affected organ, geographic region, and whether the granulomas morphologically contain necrosis. Compared with other organs, the etiological distribution and morphological patterns of pleural epithelioid granulomas have rarely been investigated. We evaluated the final etiologies and morphological patterns of pleural epithelioid granulomatous inflammation in a tuberculosis (TB)-prevalent country. Of 83 patients with pleural granulomas, 50 (60.2%) had confirmed TB pleurisy (TB-P) and 29 (34.9%) had probable TB-P. Four patients (4.8%) with non-TB-P were diagnosed. With the exception of microbiological results, there was no significant difference in clinical characteristics and granuloma patterns between the confirmed TB-P and non-TB-P groups, or between patients with confirmed and probable TB-Ps. These findings suggest that most pleural granulomatous inflammation (95.2%) was attributable to TB-P in TB-endemic areas and that the granuloma patterns contributed little to the prediction of final diagnosis compared with other organs.

Whole-exome sequencing identifies recurrent AKT1 mutations in sclerosing hemangioma of lung.

Pulmonary sclerosing hemangioma (PSH) is a benign tumor with two cell populations (epithelial and stromal cells), for which genomic profiles remain unknown. We conducted exome sequencing of 44 PSHs and identified recurrent somatic mutations of AKT1 (43.2%) and ß-catenin (4.5%). We used a second subset of 24 PSHs to confirm the high frequency of AKT1 mutations (overall 31/68, 45.6%; p.E17K, 33.8%) and recurrent ß-catenin mutations (overall 3 of 68, 4.4%). Of the PSHs without AKT1 mutations, two exhibited AKT1 copy gain. AKT1 mutations existed in both epithelial and stromal cells. In two separate PSHs from one patient, we observed two different AKT1 mutations, indicating they were not disseminated but independent arising tumors. Because the AKT1 mutations were not found to co-occur with ß-catenin mutations (or any other known driver alterations) in any of the PSHs studied, we speculate that this may be the single-most common driver alteration to develop PSHs. Our study revealed genomic differences between PSHs and lung adenocarcinomas, including a high rate of AKT1 mutation in PSHs. These genomic features of PSH identified in the present study provide clues to understanding the biology of PSH and for differential genomic diagnosis of lung tumors.

The clinical significance of fascin expression in a newly diagnosed primary glioblastoma.

The actin-binding protein fascin has been associated with clinically aggressive tumors and poor prognosis. The purpose of this study was to investigate possibility of fascin expression as a prognostic factor in a newly diagnosed primary glioblastoma (GBM). Between July 2007 and December 2013, 37 out of 126 patients diagnosed with GBM satisfied the following inclusion criteria: (1) the presence of immunohistochemically-available tissue, (2) a new primary GBM, (3) gross-total resection, and (4) standardized adjuvant treatment, known as the Stupp regimen. The median follow-up period was 18 months (range 5-95). According to the staining intensity of fascin, progression-free survival (PFS) in the low-intensity fascin group (median PFS 9.0 months; 95 % CI 6.0-12.0) was longer than PFS in the high-intensity fascin group (median PFS 7.0 months; 95 % CI 5.6-10.4; p = 0.024). Overall survival (OS) in the low-intensity fascin group (median OS 20.0 months; 95 % CI 17.7-22.4) was longer than OS in the high-intensity fascin group (median OS 13.0 months; 95 % CI 8.2-17.8; p = 0.031). And, the staining intensity of fascin was a statistically significant factor in PFS and OS according to univariate and multivariate analyses (univariate analysis p = 0.043 and p = 0.043; multivariate analysis p = 0.041 and p = 0.044). Our clinical study showed that fascin expression intensity may be correlated with clinical outcomes of a newly diagnosed primary GBM, especially with regard to PFS and OS.

Fluorometric and Colorimetric Method for SARS-CoV-2 Detection Using Designed Aptamer Display Particles.

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has spurred the urgent need for practical diagnostics with high sensitivity and selectivity. Although advanced diagnostic tools have emerged to efficiently control pandemics, they still have costly limitations owing to their reliance on antibodies or enzymes and require high-tech equipment. Therefore, there is still a need to develop rapid and low-cost diagnostics with high sensitivity and selectivity. In this study, we generated aptamer display particles (AdP), enabling easy fabrication of a SARS-CoV-2 detection matrix through particle PCR, and applied it to diagnosis using fluorometric and colorimetric assays. We designed two AdPs, C1-AdP and C4-AdP, displayed with SpS1-C1 and SpS1-C4 aptamers, respectively, and showed their high binding ability against SARS-CoV-2 spike protein with a concentration-dependent fluorescence increase. This enabled detection even at low concentrations (0.5 nM). To validate its use as a diagnostic tool for SARS-CoV-2, we designed a sandwich-type assay using two AdPs and high-quality aptamers targeting SARS-CoV-2 pseudoviruses. The fluorometric assay achieved a detection limit of 3.9 × 103 pseudoviruses/mL. The colorimetric assay using an amplification approach exhibited higher sensitivity, with a detection limit of 1 × 101 pseudoviruses/mL, and a broad range of over four orders of magnitude was observed.

Aptamers and Nanobodies as New Bioprobes for SARS-CoV-2 Diagnostic and Therapeutic System Applications.

The global challenges posed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have underscored the critical importance of innovative and efficient control systems for addressing future pandemics. The most effective way to control the pandemic is to rapidly suppress the spread of the virus through early detection using a rapid, accurate, and easy-to-use diagnostic platform. In biosensors that use bioprobes, the binding affinity of molecular recognition elements (MREs) is the primary factor determining the dynamic range of the sensing platform. Furthermore, the sensitivity relies mainly on bioprobe quality with sufficient functionality. This comprehensive review investigates aptamers and nanobodies recently developed as advanced MREs for SARS-CoV-2 diagnostic and therapeutic applications. These bioprobes might be integrated into organic bioelectronic materials and devices, with promising enhanced sensitivity and specificity. This review offers valuable insights into advancing biosensing technologies for infectious disease diagnosis and treatment using aptamers and nanobodies as new bioprobes.

Prognostic significance of tetraspanin CD151 in newly diagnosed glioblastomas.

BACKGROUND: Tetraspanin CD151 is a positive effector of cancer invasion and metastasis. METHODS: We investigated the expression of CD151 by immunohistochemistry in 211 cases of grade I to IV gliomas. Additionally, we performed O6-methylguanin-DNA methyltransferase (MGMT) methylation analysis using real-time methylation-specific PCR in 36 patients with glioblastoma, and the prognostic significance of these biomarkers in glioblastomas was evaluated. RESULTS: Overexpression of CD151 was observed in a significant proportion (55.6%) of glioblastomas, while CD151 was rarely overexpressed in most of grade I to III glial tumors. CD151 overexpression was closely associated with MGMT methylation (P = 0.014), and it was a prognostic factor for predicting worse overall survival (OS; P = 0.002) and progression-free survival (PFS; P = 0.043). We also found that combination of CD151 overexpression and MGMT methylation better stratified the patients' OS (P = 0.001) and PFS (P = 0.009). In multivariate analysis, CD151 overexpression was an independent prognostic factor for predicting OS over MGMT methylation (P = 0.012). CONCLUSIONS: CD151 seems to have a critical role for high-grade progression in astroglial tumors. Furthermore, CD151 is a good tissue marker that can be used easily in a daily practice for predicting worse prognosis in patients with glioblastoma.

Biomimetic Silica Particles with Self-Loading BMP-2 Knuckle Epitope Peptide and Its Delivery for Bone Regeneration.

Biomimetic silica deposition is an in-situ immobilization method for bioactive molecules under biocompatible conditions. The osteoinductive P4 peptide derived from the knuckle epitope of bone morphogenetic protein (BMP), which binds to BMP receptor-II (BMPRII), has been newly found to contain silica formation ability. We found that the two lysine residues at the N-terminus of P4 played a vital role in silica deposition. The P4 peptide co-precipitated with silica during P4-mediated silicification, yielding P4/silica hybrid particles (P4@Si) with a high loading efficiency of 87%. P4 was released from P4@Si at a constant rate for over 250 h, representing a zero-order kinetic model. In flow cytometric analysis, P4@Si showed a 1.5-fold increase in the delivery capacity to MC3T3 E1 cells than the free form of P4. Furthermore, P4 was found anchored to hydroxyapatite (HA) through a hexa-glutamate tag, followed by P4-mediated silicification, yielding P4@Si coated HA. This suggested a superior osteoinductive potential compared to silica or P4 alone coated HA in the in vitro study. In conclusion, the co-delivery of the osteoinductive P4 peptide and silica by P4-mediated silica deposition is an efficient method for capturing and delivering its molecules and inducing synergistic osteogenesis.

Ultra-sensitive label-free SERS biosensor with high-throughput screened DNA aptamer for universal detection of SARS-CoV-2 variants from clinical samples.

COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an ongoing global pandemic with economic and social disruption. Moreover, the virus has persistently and rapidly evolved into novel lineages with mutations. The most effective strategy to control the pandemic is suppressing virus spread through early detection of infections. Therefore, developing a rapid, accurate, easy-to-use diagnostic platform against SARS-CoV-2 variants of concern remains necessary. Here, we developed an ultra-sensitive label-free surface-enhanced Raman scattering-based aptasensor as a countermeasure for the universal detection of SARS-CoV-2 variants of concern. In this aptasensor platform, we discovered two DNA aptamers that enable binding to SARS-CoV-2 spike protein via the Particle Display, a high-throughput screening approach. These showed high affinity that exhibited dissociation constants of 1.47 ± 0.30 nM and 1.81 ± 0.39 nM. We designed a combination with the aptamers and silver nanoforest for developing an ultra-sensitive SERS platform and achieved an attomolar (10-18 M) level detection limit with a recombinant trimeric spike protein. Furthermore, using the intrinsic properties of the aptamer signal, we demonstrated a label-free aptasensor approach, enabling use without the Raman tag. Finally, our label-free SERS-combined aptasensor succeeded in detecting SARS-CoV-2 with excellent accuracy, even in clinical samples with variants of concern, including the wild-type, delta, and omicron variants.

EML4-ALK fusion gene in Korean non-small cell lung cancer.

A fusion gene between echinoderm microtubule-associated protein-like 4 (EML4) and the anaplastic lymphoma kinase (ALK) has been identified in non-small cell lung cancers (NSCLCs). Although a few studies have evaluated EML4-ALK fusion genes in Korean NSCLCs, the prevalence of different EML4-ALK fusion variants has yet to be clearly assessed. Herein, we have examined the profiles of EML4-ALK fusion gene variants in Korean patients of NSCLCs. EML4-ALK fusion genes have been detected in 10 (6.0%) of 167 patients of NSCLCs and in 9 (7.4%) of 121 patients of adenocarcinoma. Of the 10 patients with fusion genes identified, 8 (80%) were E13;A20 (variant 1) and 2 (20%) were E6;A20, with an additional 33-bp sequence derived from intron 6 of EML4 (variant 3b). These results indicate that the profiles of EML4-ALK fusion gene variants in Korean patients of NSCLC may differ from those in other ethnic populations. Herein, we describe for the first time the profiles of EML4-ALK fusion variants of Korean patients with NSCLCs.

Relationship between gallstones and interstitial cells of Cajal in the gallbladder.

INTRODUCTION: A high percentage of patients with gallstones exhibit abnormalities in gallbladder emptying, and gallstones are often associated with gallbladder contraction. Interstitial cells of Cajal (ICC) in the gallbladder are involved in the generation and spreading of spontaneous contractions of the gallbladder. This study examined the relationship among the number of gallbladder ICC, gallbladder contractility, and gallstones. MATERIALS AND METHODS: Forty-six patients, who underwent cholecystectomy within 3 months of enduring a gallbladder ejection fraction scan, were enrolled in this study. ICC were identified using a microscope after immunohistochemical staining for CD117/c-kit. Five high-power field (magnification 400×) units were randomly assigned, and the number of ICC in the mucosal and muscular layers was counted. These counts were compared according to the sex, age, reason for cholecystectomy, presence of gallstone, presence of gallbladder polyp, gallbladder ejection fraction, and gallbladder size for each patient. RESULTS: The number of ICC in the mucosal layer was increased in the male participants (154.4 ± 73.9) compared with the female participants (107.3 ± 75.2); however, the ICC in the muscular layer was not different between the 2 groups. Additionally, the ICC in the mucosal and muscular layers did not differ according to age, cause of cholecystectomy, number of stones, stone character, stone diameter, or the presence of polyps. A larger gallbladder size was correlated with a decreased number of ICC in the muscular layer of the gallbladder. Additionally, when the number of gallbladder stones was increased, the number of ICC in the muscular layer of the gallbladder was decreased; however, there was no significant correlation between the number of ICC in the mucosal layer of the gallbladder and any of the following factors: age, GBEF, gallbladder size, stone number, or diameter. Furthermore, there was no significant correlation between the number of ICC in the muscular layer of the gallbladder, regardless of age, GBEF, and stone diameter. CONCLUSION: Although we were unable to achieve significant results regarding the relationship between GBEF and ICC, this is the first human study to reveal the relationship among ICC, gallbladder size, and the number of gallstones.

Effect of Cadherin-11 Expression on the Prognosis of a Newly Diagnosed Primary Glioblastoma.

BACKGROUND: Cadherin-11, a cell-to-cell adhesion molecule, is associated with higher tumor grade and decreased patient survival. The purpose of this study was to investigate the clinical significance of cadherin-11 expression in the progression and prognosis of a newly diagnosed primary glioblastoma (GBL). METHODS: Between 2007 and 2016, 52 out of 178 patients diagnosed with a GBL and satisfied the following criteria: 1) a new primary GBL, 2) gross-total resection, 3) immunohistochemically-available tissue, and 4) standardized adjuvant treatment. RESULTS: In terms of staining intensity, the low-intensity cadherin-11 group showed longer progression-free survival (PFS) than the high-intensity cadherin-11 group (median PFS, 12.0 months [95% CI, 11.1-12.9] vs. median PFS, 6.0 months [95% CI, 3.7-8.3]; p<0.001). The low-intensity cadherin-11 group revealed longer overall survival (OS) than the high-intensity cadherin-11 group (median OS, 20.0 months [95% CI, 11.8-16.6] vs. median OS, 15.0 months [95% CI, 11.8-18.2]; p=0.003). The staining intensity of cadherin-11 was a statistically significant factor in PFS and OS in terms of univariate and multivariate analyses (univariate analysis: p<0.001 and p=0.005; multivariate analysis: p<0.001 and p=0.005). CONCLUSION: Our clinical study demonstrates high cadherin-11 expression may be associated with poor PFS and OS for a newly diagnosed primary GBL.

Development of Spinal Tuberculosis in an Adolescent With Crohn's Disease After Infliximab Therapy: A Case Report With Literature Review.

INTRODUCTION: Tuberculosis (TB) spondylitis, also known as Pott's disease, is a severe form of extrapulmonary TB. Infliximab treatment for Crohn's disease (CD) patients increases the risk of TB, and is likely to increase the risk of TB spondylitis as well. CASE PRESENTATION: We report a rare case of TB spondylitis development in a 16-year-old female with CD. She had a close household contact of active pulmonary TB and received contact investigation. She was diagnosed with latent TB 1 month before the diagnosis of CD, and had started a latent TB treatment regimen with isoniazid for 9 months. At 5 months from the start of latent TB treatment, infliximab was started. Approximately 1 year after infliximab treatment, her infusion interval was shortened from every 8 weeks to every 4 weeks owing to secondary loss of response due to nonimmunogenic pharmacokinetic failure. One month later, miliary TB developed and infliximab was stopped. She received a miliary TB treatment regimen for 6 months, curing the disease. Three months later, spinal TB was incidentally detected on abdominal computed tomography. She received a TB treatment regimen for 12 months, curing spinal TB. Currently, she is receiving vedolizumab to treat CD and is in clinical remission. Although this patient has sufficiently been treated at each stage of TB development, particularly for latent TB and miliary TB, TB spondylitis still developed. CONCLUSION: Considering that TB spondylitis developed despite sufficient treatment at each stage, pediatric gastroenterologists should stay cautious when using anti-tumor necrosis factor agents in patients with inflammatory bowel disease with a history of latent TB.

Clinical implication of minimal presence of solid or micropapillary subtype in early-stage lung adenocarcinoma.

BACKGROUND: We investigated the clinical features and surgical outcomes of lung adenocarcinoma with minimal solid or micropapillary (S/MP) components, with a focus on stage IA. METHODS: We enrolled 506 patients with lung adenocarcinoma who underwent curative resection in this study. Clinical features and surgical outcomes were compared between the groups with and without the S/MP subtype (S/MP+ and S/MP-, respectively), and between the group with an S/MP proportion of ≤5% (S/MP5) and the S/MP-. RESULTS: The S/MP subtype was present in 247 patients (48.8%); 129 (25.5%) were grouped as the S/MP5 group. The S/MP+ and S/MP5 groups had larger tumors, higher frequency of lymph node metastasis, and more advanced stages of disease than the S/MP- group (P < 0.001, all comparisons). Pleural, lymphatic, and vascular invasions occurred more frequently in the S/MP+ and S/MP5 groups (P < 0.001, all comparisons for S/MP+ vs. S/MP-; P ≤ 0.01, all comparisons for S/MP5 vs. S/MP-). The S/MP+ and S/MP5 groups showed a shorter time to recurrence and cancer-related death than the S/MP- group(P < 0.001, both comparisons). For stage I, the presence or absence of the S/MP subtype defined prognostic subgroups better than the stage IA/IB classification. Notably, in the multivariate analysis, the minimal S/MP component was a significant predictor of recurrence, even in stage IA. CONCLUSIONS: The presence of the minimal S/MP component was a significant predictor of poor prognosis after surgery, even in stage IA patients. Clinical trials to evaluate the advantages of adjuvant chemotherapy for this subset of patients and further investigations to understand underlying biological mechanisms of poor prognosis are needed. KEY POINTS: Significant findings of the study: We demonstrated that only minimal presence of solid or micropapillary component was profoundly associated with aggressive clinicopathological features and poor prognosis after complete resection even in stage IA lung adenocarcinoma. WHAT THIS STUDY ADDS: Our results suggest that minimal presence of these subtypes is a strong prognostic factor which should be taken into account in the risk assessment for adjuvant chemotherapy in lung adenocarcinoma.

Polymorphisms in apoptosis-related genes and survival of patients with early-stage non-small-cell lung cancer.

PURPOSE: This study was conducted to determine the association between single-nucleotide polymorphisms (SNPs) in apoptosis-related genes and survival outcomes of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: Three hundred ten consecutive patients with surgically resected NSCLC were enrolled. Twenty-five SNPs in 17 apoptosis-related genes were genotyped by a sequenome mass spectrometry-based genotyping assay. The genotype associations with overall survival (OS) and disease-free survival (DFS) were analyzed. RESULTS: Three SNPs (TNFRSF10B rs1047266, TNFRSF1A rs4149570, and PPP1R13L rs1005165) were significantly associated with survival outcomes on multivariate analysis. When the three SNPs were combined, OS and DFS were decreased as the number of bad genotypes increased (P (trend) for OS and DFS = 7 × 10(-5) and 1 × 10(-4), respectively). Patients with one bad genotype, and patients with two or three bad genotypes had significantly worse OS and DFS compared with those with no bad genotypes [adjusted hazard ratio (aHR) for OS = 2.27, 95% confidence interval (CI) = 1.22-4.21, P = 0.01, aHR for DFS = 1.74, 95% CI = 1.08-2.81, P = 0.02; aHR for OS = 4.11, 95% CI = 2.03-8.29, P = 8 × 10(-5); and aHR for DFS = 2.89, 95% CI = 1.64-5.11, P = 3 × 10(-4), respectively]. CONCLUSION: Three SNPs in apoptosis-related genes were identified as possible prognostic markers of survival in patients with early-stage NSCLC. The SNPs, and particularly their combined genotypes, can be used to identify patients at high risk for poor disease outcome.

Polymorphisms in the FAS and FASL genes and survival of early stage non-small cell lung cancer.

PURPOSE: This study was conducted to investigate the impact of functional polymorphisms in the FAS and FASL genes on the survival of early stage non-small cell lung cancer (NSCLC) patients. EXPERIMENTAL DESIGN: Three hundred and thirty-eight consecutive patients with surgically resected NSCLC were enrolled. The FAS -1377G>A (rs2234767) and -670A>G (rs1800682) and FASL -844C>T (rs763110) polymorphisms were investigated. Immunohistochemistry was used to assess FAS protein expression in tumors. The genotype and haplotype associations with survival were analyzed using Cox proportional hazards model, Kaplan-Meier method, and the log-rank test. RESULTS: Patients with the GG and combined AG+GG genotypes of the FAS -670A>G locus had a significantly decreased survival when compared with patients with the AA genotype [adjusted hazard ratio=1.71, 95% confidence interval (95% CI)=1.06-2.77, and P=0.03; and adjusted hazard ratio=1.48, 95% CI=1.01-2.20, and P=0.047, respectively]. In addition, the FAS -1377G/-670G and -1377A/-670G haplotypes exhibited a significantly lower survival compared with the -1377G/-670A haplotype (adjusted hazard ratio=1.87, 95% CI=1.20-2.91, and P=0.006; and adjusted hazard ratio=1.31, 95% CI=1.05-1.65, P=0.02, respectively). Strongly positive FAS immunostaining was significantly less frequent in patients with the FAS -670 AG+GG genotype than in patients with the -670 AA genotype (4.5% versus 10.8%; P=0.04). CONCLUSION: The FAS -670A>G polymorphism may affect survival in early-stage NSCLC. The analysis of the FAS -670A>G polymorphism can help identify patients at high risk for a poor disease outcome.

TP53 mutations in Korean patients with non-small cell lung cancer.

Although TP53 mutations have been widely studied in lung cancer, the majority of studies have focused on exons 5-8 of the gene. In addition, TP53 mutations in Korean patients with lung cancers have not been investigated. We searched for mutations in the entire coding exons, including splice sites of the gene, in Korean patients with non-small cell lung cancer (NSCLC). Mutations of the gene were determined by direct sequencing in 176 NSCLCs. Sixty-nine mutations (62 different mutations) were identified in 65 tumors. Of the 62 mutations, 12 were novel mutations. TP53 mutations were more frequent in males, ever-smokers and squamous cell carcinomas than in females, never-smokers and adenocarcinomas, respectively (all comparisons, P<0.001). Missense mutations were most common (52.2%), but frameshift, nonsense, and splice-site mutations were frequently observed at frequencies of 18.8%, 15.9% and 10.1%, respectively. Of the 69 mutations, 9 (13.0%) were found in the oligomerization domain. In addition, the proportion of mutations in the oligomerization domain was significantly higher in adenocarcinomas than in squamous cell carcinomas (23.5% vs. 2.9%, P=0.01). Our study provides clinical and molecular characteristics of TP53 mutations in Korean patients with NSCLCs.

Comprehensive Analysis and Clinical Implication of PD-L1 Expression Considering HPV Status in Oropharyngeal Squamous Cell Carcinoma.

BACKGROUND/AIM: This study was conducted to comprehensively evaluate programmed cell death ligand 1 (PD-L1) expression, and analyze the clinical and prognostic implications of PD-L1 expression in oropharyngeal squamous cell carcinoma (OPSCC). PATIENTS AND METHODS: We evaluated the expression of PD-L1 using the antibodies SP263 and SP142 in 106 patients with OPSCC, using immunohistochemistry. PD-L1 expression was subdivided into tumor cell score (TC), immune cell score (IC), and combined score (CS). Correlations between each PD-L1 expression and HPV status, clinicopathological features, and survival were analyzed. RESULTS: The expression levels of PD-L1 SP263 and SP142 were significantly correlated. High PD-L1 SP263 TC and CS and SP142 IC and CS were associated with HPV positivity. PD-L1 expression showed no effect on survival in all patients' group. However, in the subgroup analysis, high TC and CS of both PD-L1 SP263 and SP142 were correlated with shorter time to recurrence in the HPV positive group. CONCLUSION: High expression of PD-L1 was associated with HPV positivity in OPSCC. In addition, high expression of PD-L1 might suggest a poorer outcome, especially in the HPV positive subgroup. PD-L1 could be a useful predictive and prognostic biomarker in OPSCC.