NTRK oncogenic fusions are exclusively associated with the serrated neoplasia pathway in the colorectum and begin to occur in sessile serrated lesions.

Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are emerging tissue-agnostic drug targets in malignancies including colorectal carcinomas (CRCs), but their detailed landscape in the context of various colorectal carcinogenesis pathways remains to be investigated. In this study, pan-tropomyosin receptor kinase (TRK) protein expression was assessed by immunohistochemistry (IHC) in retrospectively collected colorectal epithelial tumor tissues, including 441 CRCs [133 microsatellite instability-high (MSI-high) and 308 microsatellite stable (MSS)] and 595 premalignant colorectal lesions (330 serrated lesions and 265 conventional adenomas). TRK-positive cases were then subjected to next-generation sequencing and/or fluorescence in situ hybridization to confirm NTRK rearrangements. TRK IHC positivity was not observed in any of the MSS CRCs, conventional adenomas, traditional serrated adenomas, or hyperplastic polyps, whereas TRK positivity was observed in 11 of 58 (19%) MLH1-methylated MSI-high CRCs, 4 of 23 (17%) sessile serrated lesions with dysplasia (SSLDs), and 5 of 132 (4%) sessile serrated lesions (SSLs). The 11 TRK-positive MSI-high CRCs commonly harbored CpG island methylator phenotype-high (CIMP-high), MLH1 methylation, BRAF/KRAS wild-type, and NTRK1 or NTRK3 fusion (TPM3-NTRK1, TPR-NTRK1, LMNA-NTRK1, SFPQ-NTRK1, ETV6-NTRK3, or EML4-NTRK3). Both NTRK1 or NTRK3 rearrangement and BRAF/KRAS wild-type were detected in all nine TRK-positive SSL(D)s, seven of which demonstrated MSS and/or CIMP-low. TRK expression was selectively observed in distorted serrated crypts within SSLs and was occasionally localized at the base of serrated crypts. NTRK fusions were detected only in SSLs of patients aged ≥50 years, whereas BRAF mutation was found in younger age-onset SSLs. In conclusion, NTRK-rearranged colorectal tumors develop exclusively through the serrated neoplasia pathway and can be initiated from non-dysplastic SSLs without BRAF/KRAS mutations prior to full occurrence of MSI-high/CIMP-high. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

IRS2 Amplification as a Predictive Biomarker in Response to Ceritinib in Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is a fast-growing and malignant cancer that responds well to chemotherapy; however, the survival rate is less than 15% after 2 years of diagnosis. Therefore, novel therapeutic agents for treating SCLC patients need to be evaluated. This study aims to identify the therapeutic targets based on the comprehensive genomic profiling of SCLC patients. Among the molecular-profiled SCLC samples obtained using targeted sequencing, the array-based comparative genomic hybridization (array CGH) identified focal insulin receptor substrate 2 (IRS2) amplification in the SCLC patients. IRS2 amplification was confirmed in 5% of 73 SCLC patients. To determine whether IRS2 amplification could act as a therapeutic target, we generated a patient-derived xenograft (PDX) model and subsequently screened 43 targeted agents using the PDX-derived cells (PDCs). Ceritinib significantly inhibited the cell growth and impaired the tumor sphere formation in IRS2-expressing PDCs. Its effects were confirmed in various in vitro assays and were further validated in the mouse xenograft models. In this study, we present that IRS2 amplification and/or expression serve as preclinical implications for a novel therapeutic target in SCLC progression. Furthermore, we suggest that insulin-like growth factor-1 (IGF-1) receptor inhibitor-based therapy could be used for treating SCLC with IRS2 amplification.

Correlations between dietary taurine intake and life stress in Korean college students.

The purpose of this study was to investigate the relationship between dietary taurine intake and life stress in Korean college students. The subjects were 320 college students (164 male and 156 female). A three day-recall method was used to assess dietary status (2 weekdays and 1 weekend). Life stress scores were determined using a self-administered life stress questionnaire. The higher stress scores indicate a high frequency and importance of the stress. Average dietary intake of taurine in male and female subjects was 124.1 +/- 78.8 mg/day and 96.9 +/- 71.7 mg/day, respectively. There were significant negative correlations between taurine intake and the frequency (p < 0.01), importance (p < 0.05) and total scores (p < 0.05) of life stress in female subjects while there were no significant correlations between taurine intake and the frequency, importance and total scores of life stress in male subjects. In female subjects a correlation existed between taurine intake and professor problems, friend problems and future problems (p < 0.05). These results suggest that dietary taurine intake may play an important role in reducing life stress.

Dietary taurine and nutrients intake and anthropometric and body composition data by abdominal obesity in Korean male college students.

The purpose of this study was to investigate the relationship between abdominal obesity and dietary taurine intake, nutrient intake, anthropometric data and body composition in Korean male college students. One hundred seventy four subjects were divided into 2 groups based on abdominal obesity as estimated by waist circumference (cm) (Lee et al. 2006): normal group (waist circumference (cm): < 90 cm, n = 141), obese group (waist circumference (cm): > or = 90 cm, n = 33). A three day-recall method was used to assess diet (2 weekdays and 1 weekend). Anthropometric data and body composition were measured with Inbody 3.0 (Bioelectrical Impedance Fatness Analyzer). Average dietary intake of taurine in the normal and obese groups was 123.1 +/- 78.8 mg/day and 128.4 +/- 79.6 mg/day, respectively. There was no significant difference in dietary taurine and nutrient intake between the normal and obese groups. However, data of anthropometric measurements and body composition in the obese group were significantly elevated compared to those of the normal group. In the normal group, dietary taurine intake was positively correlated with nutrient intake (p < 0.01), the exception being the intake of plant lipid and of animal calcium. In the obese group, dietary taurine intake was positively correlated with the intake of energy foods and of animal lipid (p < 0.05). There were positive correlations between dietary taurine intake, weight and hip circumference (p < 0.05) in the normal group. However, there was no significant correlation between dietary taurine intake and anthropometric and body composition data in the obese group. Therefore, the data suggest that further study is warranted to examine the relationship between dietary taurine intake and abdominal obesity.

Evaluation of 8-week body weight control program including sea tangle (Laminaria japonica) supplementation in Korean female college students.

This study was conducted to evaluate the effects of a body weight control program with supplementation of sea tangle (20 g/day) on 22 female college students. The contents of the program for 8 weeks contained diet therapy, exercise and behavioral modification through nutrition education. Body composition, dietary habit scores, serum lipid profiles, daily nutrient intakes and the quality of life were assessed at the beginning and at the end of the program. Average age of subjects and height were 20.8 years and 161.9 cm, respectively. After 8 weeks, there were significant reductions in body weight, body fat mass, percent body fat, waist-hip ratio and BMI. The dietary habit score such as a balanced diet, regularity of mealtime, overeating, eating while watching TV or using the computer and eating salty food were increased significantly. Serum lipid levels such as total cholesterol level, LDL-cholesterol level and triglyceride level were decreased but not significantly. There were decreases in intake of energy, protein and fat and increases in intakes of dietary fiber, folic acid, calcium and potassium from the beginning to the end of the program. There were significant improvements on subcomponents of quality of life; physical functioning, general-health and vitality. The limitation of this study was the fact that there was no control group, but an overall evaluation suggests the 8-week body weight control program consisting of diet therapy, exercise and behavioral modification with supplementation of sea tangle would be helpful to improve the body composition, dietary habits, daily nutrient intakes and quality of life in Korean female college students.

Kikuchi-Fujimoto disease of 16 children in a single center of Korea.

Kikuchi-Fujimoto disease (KFD) is subacute necrotizing lymphadenitis characterized by fever, leukopenia and cervical lymphadenopathy. There are few reports on the clinical characteristics and laboratory findings of KFD in the pediatric literature. In this study, we evaluate the characteristics and outcome of KFD in children. A total of 412 patients were studied with fever and peripheral lymphadenopathy at Pusan National University Hospital from January 1998 to December 2003. Among the total 412 there were 16 patients diagnosed with KFD by lymph node biopsy. We analyze the clinical, laboratory and outcome after review of the medical records retrospectively. The mean age of the patients was 10.6 +/- 3.4 yr (range: 4-17 yr). The male to female ratio was 1:1. Almost all patients, except two, had cervical lymph node swelling. The size of the involved lymph node was less than 4 cm in the greatest dimension in 75% of the patients. All the children had fever as the chief complaint and the mean duration of the fever was 17.7 +/- 11.2 days (range: 2-122 days). Approximately 87% of the patients had leukopenia (WBC < 4000/mm(3)) and 43.8% of the patients had a mild increase in the transaminases on liver function testing. A total of 8 out of the 16 patients were initially misdiagnosed as an infectious disease and treated with antibiotics which caused prolonged hospitalization for most patients. Six patients were treated with prednisone and the prolonged fever subsided immediately after steroid therapy. KFD should be considered in the differential diagnosis of prolonged fever in children with cervical lymphadenopathy. Early cervical lymph node biopsy is necessary to minimize inappropriate examinations and treatments in such cases.