Histone Deacetylase as a Valuable Predictive Biomarker and Therapeutic Target in Immunotherapy for Non-Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Histone deacetylase inhibitors (HDACis) are epigenetic regulators and used clinically for hematopoietic malignancies. Recently, HDACis have received attention as a factor that modulates the immune system. In this study, the role of histone deacetylase (HDAC) expression as a predictive marker in lung cancer patients who were treated with immune checkpoint inhibitors (ICIs) and the role of HDACi and ICI combination treatment in the mouse tumor model were analyzed. @*Materials and Methods@#The overall response rate (ORR) and progression-free survival (PFS) were analyzed by the expression of HDAC. In vitro assay, the mRNA and protein expression levels of cytokines and programmed death-ligand 1 (PD-L1) were analyzed after HDACi treatment. In vivo assay, TC-1 tumor-bearing mice were treated with HDACi and mouse programmed cell death 1 (PD-1) inhibitor. @*Results@#The HDAC6 low expression group showed high ORR and prolonged PFS. When the selective HDAC6 inhibitor was administered to the A549 cell line, the levels of interleukin-1β and interleukin-6 decreased and the expression of PD-L1 was reduced. Mice that received both the mouse PD-1 inhibitor and pan-HDACi had a smaller tumor size than that of the mice from the control group. Moreover, mice treated with the mouse PD-1 inhibitor and pan-HDACi generated greater numbers of E7-specific CD8+ T cells. @*Conclusion@#HDAC6 expression can predict the prognosis of non–small cell lung cancerpatients who were treated with ICIs. Furthermore, co-treatment with HDACi and PD-1 inhibitor was shown to decrease the tumor growth rate and create a favorable tumor microenvironment for cytotoxic T lymphocytes in the TC-1 mouse model.

Intramural Gastric Hematoma after Acute Necrotizing Pancreatitis: A Case Report and Review of Imaging Findings

Intramural hematoma of the gastrointestinal tract is a rare disease entity. Pancreatitis-induced intramural gastric hematoma (IGH) is far more seldom reported. Here, we report a rare case of a giant IGH occurring as a delayed complication of pancreatitis in a 51-year-old man. The diagnosis was made using computed tomography (CT) and endoscopic ultrasonography. The patient was conservatively managed, and follow-up abdominal CT showed marked decreases in the size of the IGH.

Effects of Instability Tools on Muscles Activities in Lunge Exercise in Healthy Adult Males

PURPOSE@#This study was to investigate the effect of instability on the activation of lower limb muscles during lunge exercise.@*METHODS@#The study subjects were healthy twenties and were selected to have no orthopedic or neurological diseases. 1) Flat lunge exercise (Lunge 1, 2) Lunge exercise on TOGU (Lunge 2, 3) Holding the olympic bar and moving the lunge on TOGU (Lunge 3, 4) Holding the Surge and moving the lunge on TOGU (Lunge 4). Through the above four actions, we can see how the top-down instability influences the lower limb unlike the Bottom-up instability. EMG attachment sites were gluteus medius, vastus medialis, gastrocnemius, tibialis anterior.@*RESULTS@#These result suggest that exercise using Lunge 4 activity was the highest in muscle activity compared to other exercises, but vastus medialis showed the highest muscle activity in Lunge 2 exercise(p<0.05).@*CONCLUSION@#This study showed the muscular activity of the lower extremities according to the lunge exercise using the instability tools.

Optimization of RNA Extraction from Formalin-Fixed Paraffin-Embedded Blocks for Targeted Next-Generation Sequencing / 한국유방암학회지

PURPOSE: Breast cancer has a high prevalence in Korea. To achieve personalized therapy for breast cancer, long-term follow-up specimens are needed for next-generation sequencing (NGS) and multigene analysis. Formalin-fixed paraffin-embedded (FFPE) samples are easier to store than fresh frozen (FF) samples. The objective of this study was to optimize RNA extraction from FFPE blocks for NGS. METHODS: RNA quality from FF and FFPE tissues (n=5), expected RNA amount per unit area, the relationship between archiving time and quantity/quality of FFPE-extracted RNA (n=14), differences in quantitative real-time polymerase chain reaction (qRT-PCR) and NGS results, and comparisons of both techniques with tissue processing at different institutions (n=96) were determined in this study. RESULTS: The quality of RNA did not show any statistically significant difference between paired FF and FFPE specimens (p=0.49). Analysis of tumor cellularity gave an expected RNA amount of 33.25 ng/mm2. Archiving time affected RNA quality, showing a negative correlation with RNA integrity number and a positive correlation with threshold cycle. However, RNA from samples as old as 10 years showed a 100% success rate in qRT-PCR using short primers, showing that the effect of archiving time can be overcome by proper experiment design. NGS showed a higher success rate than qRT-PCR. Specimens from institution B (n=46), which were often stored in a refrigerator for more than 6 hours and fixed without slicing, showed lower success rates and worse results than specimens from the other institutes. CONCLUSION: Archived FFPE tissues can be used to extract RNA for NGS if they are properly processed before fixation. The expected amount of RNA per unit size calculated in this study will be useful for other researchers.

Detection of Human Papillomavirus in Korean Breast Cancer Patients by Real-Time Polymerase Chain Reaction and Meta-Analysis of Human Papillomavirus and Breast Cancer

BACKGROUND: Human papillomavirus (HPV) is a well-established oncogenic virus of cervical, anogenital, and oropharyngeal cancer. Various subtypes of HPV have been detected in 0% to 60% of breast cancers. The roles of HPV in the carcinogenesis of breast cancer remain controversial. This study was performed to determine the prevalence of HPV-positive breast cancer in Korean patients and to evaluate the possibility of carcinogenic effect of HPV on breast. METHODS: Meta-analysis was performed in 22 case-control studies for HPV infection in breast cancer. A total of 123 breast cancers, nine intraductal papillomas and 13 nipple tissues of patients with proven cervical HPV infection were tested by real-time polymerase chain reaction to detect 28 subtypes of HPV. Breast cancers were composed of 106 formalin-fixed and paraffin embedded (FFPE) breast cancer samples and 17 touch imprint cytology samples of breast cancers. RESULTS: The overall odds ratio between breast cancer and HPV infection was 5.43 (95% confidence interval, 3.24 to 9.12) with I2 = 34.5% in meta-analysis of published studies with case-control setting and it was statistically significant. HPV was detected in 22 cases of breast cancers (17.9%) and two cases of intaductal papillomas (22.2%). However, these cases had weak positivity. CONCLUSIONS: These results failed to serve as significant evidence to support the relationship between HPV and breast cancer. Further study with larger epidemiologic population is merited to determine the relationship between HPV and breast cancer.