Establishing Patient-Derived Cancer Cell Cultures and Xenografts in Biliary Tract Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Biliary tract cancers (BTCs) are rare and show a dismal prognosis with limited treatment options. To improve our understanding of these heterogeneous tumors and develop effective therapeutic agents, suitable preclinical models reflecting diverse tumor characteristics are needed. We established and characterized new patient-derived cancer cell cultures and patient-derived xenograft (PDX) models using malignant ascites from five patients with BTC. @*Materials and Methods@#Five patient-derived cancer cell cultures and three PDX models derived from malignant ascites of five patients with BTC, AMCBTC-01, -02, -03, -04, and -05, were established. To characterize the models histogenetically and confirm whether characteristics of the primary tumor were maintained, targeted sequencing and histopathological comparison between primary tissue and xenograft tumors were performed. @*Results@#From malignant ascites of five BTC patients, five patient-derived cancer cell cultures (100% success rate), and three PDXs (60% success rate) were established. The morphological characteristics of three primary xenograft tumors were compared with those of matched primary tumors, and they displayed a similar morphology. The mutated genes in samples (models, primary tumor tissue, or both) from more than one patient were TP53 (n=2), KRAS (n=2), and STK11 (n=2). Overall, the pattern of commonly mutated genes in BTC cell cultures was different from that in commercially available BTC cell lines. @*Conclusion@#We successfully established the patient-derived cancer cell cultures and xenograft models derived from malignant ascites in BTC patients. These models accompanied by different genetic characteristics from commercially available models will help better understand BTC biology.

The incidence and characteristics of patients admitted to the hospital after a fall by the life cycle and risk factor for death

Objective@#This study aimed at identifying the incidence rate and characteristics of patients who had suffered falls, classifying them by life cycle and factors that affect mortality. @*Methods@#The Korean National Hospital Discharge In-depth Injury Surveys (KNHDIS) from 2007 to 2016 were used to investigate the sex, age, place, season, payment method, underlying disease, and the death of hospitalized patients due to falls. @*Results@#The number of hospitalized patients increased with age. In all life cycles except old age, men were hospitalized more than women. The payment method for treatment was 66.1% through national health insurance, 6.6% through medical aid, and 27.3% through other sources. Falls were most common in winter and occurred frequently at home and on the road. In terms of the number of patients, the compound annual growth rate was 0.9% for men and 3.7% for women. In terms of the number of deaths in hospitals, the compound annual growth rate was -1.9% for men and -7.2% for women. Mortality risk was high in men in middle adulthood and old age, in patients with underlying diseases, and in patients who suffered a fall in their homes. @*Conclusion@#The number of patients from falls is increasing, but the deaths of hospitalized fall patients are decreasing. Mortality risk was high in men in middle adulthood and old age, in patients with underlying diseases, and in patients who suffered falls in their homes.

The incidence and characteristics of patients admitted to the hospital after a fall by the life cycle and risk factor for death

Objective@#This study aimed at identifying the incidence rate and characteristics of patients who had suffered falls, classifying them by life cycle and factors that affect mortality. @*Methods@#The Korean National Hospital Discharge In-depth Injury Surveys (KNHDIS) from 2007 to 2016 were used to investigate the sex, age, place, season, payment method, underlying disease, and the death of hospitalized patients due to falls. @*Results@#The number of hospitalized patients increased with age. In all life cycles except old age, men were hospitalized more than women. The payment method for treatment was 66.1% through national health insurance, 6.6% through medical aid, and 27.3% through other sources. Falls were most common in winter and occurred frequently at home and on the road. In terms of the number of patients, the compound annual growth rate was 0.9% for men and 3.7% for women. In terms of the number of deaths in hospitals, the compound annual growth rate was -1.9% for men and -7.2% for women. Mortality risk was high in men in middle adulthood and old age, in patients with underlying diseases, and in patients who suffered a fall in their homes. @*Conclusion@#The number of patients from falls is increasing, but the deaths of hospitalized fall patients are decreasing. Mortality risk was high in men in middle adulthood and old age, in patients with underlying diseases, and in patients who suffered falls in their homes.

Expression of Immunoproteasome Subunit LMP7 in Breast Cancer and Its Association with Immune-Related Markers / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: In the presence of interferon, proteasome subunits are replaced by their inducible counterparts to form an immunoproteasome (IP) plays a key role in generation of antigenic peptides presented by MHC class I molecules, leading to elicitation of a T cell‒mediated immune response. Although the roles of IP in other cancers, and inflammatory diseases have been extensively studied, its significance in breast cancer is unclear. MATERIALS AND METHODS: We investigated the expression of LMP7, an IP subunit, and its relationship with immune system components in two breast cancer cohorts. RESULTS: In 668 consecutive breast cancer cohort, 40% of tumors showed high level of LMP7 expression, and tumors with high expression of LMP7 had more tumor-infiltrating lymphocytes (TILs) in each subtype of breast cancer. In another cohort of 681 triple-negative breast cancer patients cohort, the expression of LMP7 in tumor cells was significantly correlated with the amount of TILs and the expression of interferon-associated molecules (MxA [p < 0.001] and PKR [p < 0.001]), endoplasmic reticulum stress-associated molecules (PERK [p=0.012], p-eIF2a [p=0.001], and XBP1 [p < 0.001]), and damage-associated molecular patterns (HMGN1 [p < 0.001] and HMGB1 [p < 0.001]). Patients with higher LMP7 expression had better disease-free survival outcomes than those with no or low expression in the positive lymph node metastasis group (p=0.041). CONCLUSION: Close association between the TIL levels and LMP7 expression in breast cancer indicates that better antigen presentation through greater LMP7 expression might be associated with more TILs.

Predictive Value of Tertiary Lymphoid Structures Assessed by High Endothelial Venule Counts in the Neoadjuvant Setting of Triple-Negative Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The tertiary lymphoid structure (TLS) is an important source of tumor-infiltrating lymphocytes (TILs), which have a strong prognostic and predictive value in triple-negative breast cancer (TNBC). A previous study reported that the levels of CXCL13 mRNA expression were associated with TLSs, but measuring the gene expression is challenging in routine practice. Therefore, this study evaluated the MECA79-positive high endothelial venule (HEV) densities and their association with the histopathologically assessed TLSs in biopsy samples. In addition, the relationship of TLSs with the CXCL13 transcript levels and clinical outcomes were examined. MATERIALS AND METHODS: A total of 108 TNBC patients treated with neoadjuvant chemotherapy (NAC) were studied. The amounts of TILs and TLSs were measured histopathologically using hematoxylin and eosin–stained slides. The HEV densities and TIL subpopulations were measured by immunohistochemistry for MECA79, CD3, CD8, and CD20. CXCL13mRNA expression levels using a NanoString assay (NanoString Technologies). RESULTS: The mean number of HEVs in pre-NAC biopsies was 12 (range, 0 to 72). The amounts of TILs and TLSs, HEV density, and CXCL13 expression showed robust correlations with each other. A lower pre-NAC clinical T stage, higher TIL and TLS levels, a higher HEV density, CD20-positive cell density, and CXCL13 expression were significant predictors of a pathologic complete response (pCR). Higher CD8-positive cell density and levels of CXCL13 expression were significantly associated with a better disease-free survival rate. CONCLUSION: MECA79-positive HEV density in pre-NAC biopsies is an objective and quantitative surrogate marker of TLS and might be a valuable tool for predicting pCR of TNBC in routine pathology practice.