Natural killer (NK) cells with mismatched killer cell immunoglobulin-like receptor-ligand pairs have shown efficacy and been proven safe in treatment of cancer patients. Ex vivo-expanded and highly activated NK cells (MG4101) had been generated under good manufacturing practice conditions, which demonstrated potent anticancer activity in vitro and in vivo in preclinical studies. The current phase I clinical trial was designed to evaluate safety and possible clinical efficacy of repetitive administrations of MG4101 derived from random unrelated healthy donors into patients with malignant lymphoma or advanced, recurrent solid tumors. The maximum dose (3 × 10(7) cells/kg, triple infusion) was tolerable without significant adverse events. Of 17 evaluable patients, 8 patients (47.1%) showed stable disease and 9 (52.9%) showed progressive disease. We also evaluated the capacity of MG4101 to influence host immune responses. Administration of MG4101 augmented NKG2D expression on CD8(+) T cells and upregulated chemokines that recruit T cells. In contrast, administration of MG4101 reduced regulatory T cells and myeloid-derived suppressor cells and suppressed TGFβ production. In conclusion, administration of a large number of MG4101 cells was not only safe and feasible, but also exhibited efficacy in maintaining the effector arm of the host immune response.
The purpose of this study was to report age- and gender-specific distribution of the hand grip strength (HGS) using data from the Korea National Health and Nutrition Examination Survey (KNHANES) VI-3 (2015) survey and determine cut-off values for low muscle strength of HGS of Koreans. Of a total of 7,380 participants, 4,553 were subjected to measurements of HGS, including 1,997 men and 2,556 women with a mean age of 49.3 years (range, 19–80 years). The mean ages of men and women were 49.0 and 49.5 years, respectively. HGS was measured using a digital hand dynamometer. It was defined as maximal measured grip strength of the dominant hand. The cut-off value for low muscle strength was defined as the lower 20th percentile of HGS of the study population. Maximum grip strength of men was significantly higher than that of women (40.2 kg in men vs. 24.2 kg in women, P < 0.001). The mean HGS was increased from the age of 19 to 39 years. It was peaked in the age of 35 to 39 years range for both men and women. It was then decreased after 39 years. The cut-off values of HGS in male and female elderly healthy populations were 28.6 and 16.4 kg, respectively. These data might be used as reference values when evaluating sarcopenia and assessing hand injuries.
The aim of this study was to determine the distribution of known oncogenic driver mutations in female never-smoker Asian patients with lung adenocarcinoma. We analyzed 214 mutations across 26 lung cancer-associated genes and three fusion genes using the MassARRAY® LungCarta Panel and the ALK, ROS1, and RET fusion assays in 198 consecutively resected lung adenocarcinomas from never-smoker females at a single institution. EGFR mutation, which was the most frequent driver gene mutation, was detected in 124 (63%) cases. Mutation of ALK, KRAS, PIK3CA, ERBB2, BRAF, ROS1, and RET genesoccurred in 7%, 4%, 2.5%, 1.5%, 1%, 1%, and 1% of cases, respectively. Thus, 79% of lung adenocarcinomas from never-smoker females harbored well-known oncogenic mutations. Mucinous adenocarcinomas tended to have a lower frequency of known driver gene mutations than other histologic subtypes. EGFR mutation was associated with older age and a predominantly acinar pattern, while ALK rearrangement was associated with younger age and a predominantly solid pattern. Lung cancer in never-smoker Asian females is a distinct entity, with the majority of these cancers developing from oncogenic mutations.
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