A full-length translational product of the trophinin gene, KIAA1114, is a distinctive marker of cancer stem cells in human hepatocellular carcinoma, and a mAb, Kiatomab, is specific to KIAA1114 antigen. In this study, we addressed the therapeutic potential of Kiatomab for treating both metastatic and solid tumors in mouse models. Kiatomab recognizes the linear epitope of KIAA1114, which is expressed on cell surfaces of various murine cancer cell lines. Kiatomab treatment induced potent antitumor responses in pulmonary metastasis models. Antitumor activity was mediated by the fragment crystallizable portion of Kiatomab and dependent on the host immune system. The use of Kiatomab alone as an antitumor therapy was ineffective in solid tumor models. However, in combination with cyclophosphamide, or by switching the isotype of the mAb, improved antitumor effects of Kiatomab were observed. These results suggest that Kiatomab can be used as a novel mAb for cancer immunotherapy.
Animals ; Carcinoma, Hepatocellular ; Cell Line ; Cyclophosphamide ; Humans ; Immune System ; Immunotherapy ; Mice ; Neoplasm Metastasis ; Neoplastic Stem Cells

In the era of immunotherapeutic control of cancers, many advances in biotechnology, especially in Ab engineering, have provided multiple new candidates as therapeutic immunooncology modalities. Bispecific Abs (BsAbs) that recognize 2 different antigens in one molecule are promising drug candidates and have inspired an upsurge in research in both academia and the pharmaceutical industry. Among several BsAbs, T cell engaging BsAb (TCEB), a new class of therapeutic agents designed to simultaneously bind to T cells and tumor cells via tumor cell specific antigens in immunotherapy, is the most promising BsAb.Herein, we are providing an overview of the current status of the development of TCEBs. The diverse formats and characteristics of TCEBs, in addition to the functional mechanisms of BsAbs are discussed. Several aspects of a new TCEB-Blinatumomab-are reviewed, including the current clinical data, challenges of patient treatment, drawbacks regarding toxicities, and resistance of TCEB therapy. Development of the next generation of TCEBs is also discussed in addition to the comparison of TCEB with current chimeric antigen receptor-T therapy.

Background: Atomic bombs dropped on Hiroshima and Nagasaki in Japan in August 1945 were estimated to have killed approximately 70,000 Koreans. In Japan, studies on the health status and mortality of atomic bomb survivors compared with the non-exposed population have been conducted. However, there have been no studies related to the mortality of Korean atomic bomb survivors. Therefore, we aimed to study the cause of death of atomic bomb survivors compared to that of the general population. Methods: Of 2,299 atomic bomb survivors registered with the Korean Red Cross, 2,176 were included in the study. In the general population, the number of deaths by age group was calculated from 1992 to 2019, and 6,377,781 individuals were assessed. Causes of death were categorized according to the Korean Standard Classification of Diseases. To compare the proportional mortality between the two groups, the P value for the ratio test was confirmed, and the Cochran-Armitage trend test and χ 2 test were performed to determine the cause of death according to the distance from the hypocenter. Results: Diseases of the circulatory system were the most common cause of death (25.4%), followed by neoplasms (25.1%) and diseases of the respiratory system (10.6%) in atomic bomb survivors who died between 1992 and 2019. The proportional mortality associated with respiratory diseases, nervous system diseases, and other diseases among atomic bomb survivors was higher than that of the general population. Of the dead people between 1992 and 2019, the age at death of survivors who were exposed at a close distance was younger than those who were exposed at a greater distance. Conclusion Overall, proportional mortality of respiratory diseases and nervous system diseases was high in atomic bomb survivors, compared with the general population. Further studies on the health status of Korean atomic bomb survivors are needed.

PURPOSE: The association between tobacco smoking and thyroid cancer remains uncertain. We evaluated the associations of active and passive smokingwith the risk of papillary thyroid cancer (PTC), the most common type of thyroid cancer, and with the BRAF(V600E) mutation, the most common oncogenic mutation in PTC related to poor prognosis. MATERIALS AND METHODS: We conducted this study with newly diagnosed PTC patients (n=2,142) and community controls (n=21,420) individually matched to cases for age and sex. Information on active and passive smoking and potential confounders were obtained from structured questionnaires, anthropometric measurements, and medical records. BRAF(V600E) mutation status was assessed in PTC patients. We evaluated the associations of active and passive smoking with PTC and BRAF(V600E) mutation risk using conditional and unconditional logistic regression models, respectively. RESULTS: We did not find associations between exposure indices of active and passive smoking and PTC risk in both men and women, except for the association between current smoking and lower PTC risk. Cumulative smoking ≥ 20 pack-years was associated with lower BRAF(V600E) mutation risk in male PTC patients (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.30 to 1.00). The CI for the association was wider in female PTC patients (OR, 0.23; 95% CI, 0.02 to 2.62), possibly owing to a smaller sample size in this stratum. CONCLUSION: We did not find consistent associations between active and passive smoking and PTC risk. Cumulative smoking ≥ 20 pack-years was associated with lower BRAF(V600E) mutation risk in male PTC patients.
Case-Control Studies ; Female ; Humans ; Logistic Models ; Male ; Medical Records ; Prognosis ; Sample Size ; Smoke ; Smoking ; Thyroid Gland ; Thyroid Neoplasms ; Tobacco Smoke Pollution

In the publication by Kang et al., typographical error has been detected in acknowledgements.

Developing a novel vaccine that can be applied against multiple strains of influenza virus is of utmost importance to human health. Previously, we demonstrated that the intranasal introduction of Fc-fused IL-7 (IL-7-mFc), a long-acting cytokine fusion protein, confers long-lasting prophylaxis against multiple strains of influenza A virus (IAV) by inducing the development of lung-resident memory-like T cells, called T(RM)-like cells. Here, we further investigated the mechanisms of IL-7-mFc-mediated protective immunity to IAVs. First, we found that IL-7-mFc treatment augments the accumulation of pulmonary T cells in 2 ways: recruiting blood circulating T cells into the lung and expanding T cells at the lung parenchyma. Second, the blockade of T cell migration from the lymph nodes (LNs) with FTY720 treatment was not required for mounting the protective immunity to IAV with IL-7-mFc, suggesting a more important role of IL-7 in T cells in the lungs. Third, IL-7-mFc treatment also recruited various innate immune cells into the lungs. Among these cells, plasmacytoid dendritic cells (pDCs) play an important role in IL-7-mFc-mediated protective immunity through reducing the immunopathology and increasing IAV-specific cytotoxic T lymphocyte (CTL) responses. In summary, our results show that intranasal treatment with IL-7-mFc modulates pulmonary immune responses to IAV, affecting both innate and adaptive immune cells.
Cell Movement ; Dendritic Cells* ; Fingolimod Hydrochloride ; Humans ; Influenza A virus ; Influenza, Human* ; Interleukin-7* ; Lung ; Lymph Nodes ; Lymphocytes ; Orthomyxoviridae* ; T-Lymphocytes

Chalcone, (2E)-1,3-Diphenylprop-2-en-1-one, and its synthetic derivatives are known to possess anti-oxidative and anti-inflammatory properties. In the present study, we prepared a novel synthetic chalcone compound, (E)-1-(4-hydroxyphenyl)-3-(2-(trifluoromethoxy)phenyl)prop-2-en-1-one name (YJI-7), and investigated its inhibitory effects on endotoxin-stimulated production of reactive oxygen species (ROS) and expression of inflammatory mediators in macrophages. We demonstrated that treatment of RAW 264.7 macrophages with YJI-7 significantly suppressed lipopolysaccharide (LPS)-stimulated ROS production. We also found that YJI-7 substantially decreased NADPH oxidase activity stimulated by LPS, indicating that YJI-7 regulates ROS production via modulation of NADPH oxidase in macrophages. Furthermore, YJI-7 strongly inhibited the expression of a number of inflammatory mediators in a gene-selective manner, suggesting that YJI-7 possesses potent anti-inflammatory properties, as well as anti-oxidative activity. In continuing experiments to investigate the mechanisms that could underlie such biological effects, we revealed that YJI-7 suppressed phosphorylation of p38MAPK and JNK stimulated by LPS, whereas no significant effect on ERK was observed. Furthermore, LPS-stimulated production of ROS, activation of NADPH oxidase and expression of inflammatory mediators were markedly suppressed by treatment with selective inhibitor of p38MAPK (SB203580) and JNK (SP600125). Taken together, these results demonstrated that YJI-7, a novel synthetic chalcone derivative, suppressed LPS-stimulated ROS production via modulation of NADPH oxidase and diminished expression of inflammatory mediators, at least in part, via down-regulation of p38MAPK and JNK signaling in macrophages.
Chalcone ; Down-Regulation ; Macrophages* ; NADPH Oxidase ; Phosphorylation ; Reactive Oxygen Species

PURPOSE: This study was performed to investigate the effectiveness of gastric cancer (GC) screening methods in a community-based prospective cohort of the Korean Multi-center Cancer Cohort (KMCC) with over a 10-year follow-up. MATERIALS AND METHODS: A total 10,909 and 4,773 subjects from the KMCC with information on gastroendoscopy (GE) and upper gastrointestinal series (UGIS) were included in this study. Cox proportional hazard model adjusted for age, sex, Helicobacter pylori infection, cigarette smoking, and alcohol drinking was used to estimate the hazard ratios (HRs) and 95% confidence interval (CI). RESULTS: The GE screened subjects had almost half the risk of GC-specific death than that of unscreened subjects (HR, 0.58; 95% CI, 0.36 to 0.94). Among the GC patients, GE screenees had a 2.24-fold higher survival rate than that of the non-screenees (95% CI, 1.61 to 3.11). In particular, GE screenees who underwent two or more screening episodes had a higher survival rate than that of the non-screenees (HR, 13.11; 95% CI, 7.38 to 23.30). The effectiveness of GE screening on reduced GC mortality and increased survival rate of GC patients was better in elderly subjects (≥ 65 years old) (HR, 0.47; 95% CI, 0.24 to 0.95 and HR, 8.84; 95% CI, 3.63 to 21.57, respectively) than that in younger subjects (< 65 years old) (HR, 0.66; 95% CI, 0.34 to 1.29 and HR, 1.83; 95% CI, 1.24 to 2.68, respectively). In contrast, UGIS screening had no significant relation to GC mortality and survival. CONCLUSION: The findings of this study suggest that a decreased GC-specific mortality and improved survival rate in GC patients can be achieved through GE screening.
Aged ; Alcohol Drinking ; Cohort Studies* ; Endoscopy, Gastrointestinal ; Follow-Up Studies ; Gastroscopy ; Helicobacter pylori ; Humans ; Incidence* ; Mass Screening* ; Mortality* ; Proportional Hazards Models ; Prospective Studies* ; Smoking ; Stomach Neoplasms* ; Survival Rate

PURPOSE: Aster glehnii (AG) and Aster yomena (AY) are medicinal plants that belong to the family Compositea and grow widely in Korea. Plants in the genus Aster have been used to treat snakebite wounds or bruises in oriental medicine. This study compared the effects of anti-oxidants and anti-adipocyte differentiation according to the species (the aerial parts of AG and AY). METHODS: AG and AY were extracted using 70% ethanol (−E) and water (−W) at room temperature. The anti-oxidant activities were measured by total phenol contents (TPC), total flavonoid contents (TFC), DPPH and ABTS+ assay. In addition, correlation analysis was performed for the anti-oxidant compounds and effect. The level of anti-adipocyte differentiation was assessed using an oil red O assay on pre-adipocytes. RESULTS: AG-W showed higher TPC (6.92 µg/mL) and AG-E presented higher TFC (8.22 µg/mL) than the other extracts. Furthermore, AG-E exhibited higher radical scavenging activity in the DPPH and ABTS+ assay (IC50: 104.88 and 30.06 µg/mL). In the cytotoxicity assay, AG and AY extracts at concentrations less than 100µg/mL were non toxic. AG-W reduced the lipid accumulation of 3T3-L1 cells significantly after differentiation (70.49%) compared to the other extracts. CONCLUSION: These results show that the water extract of AG has anti-oxidant effects and reduces the differentiation of 3T3-L1 cells. Therefore, AG has utility as a functional food material for its anti-oxidant activities and ability to prevent lipid accumulation.
3T3-L1 Cells ; Adipocytes ; Antioxidants ; Contusions ; Ethanol ; Functional Food ; Humans ; Korea ; Medicine, East Asian Traditional ; Phenol ; Plants, Medicinal ; Snake Bites ; Water ; Wounds and Injuries

PURPOSE: Few studies investigated roles of body mass index (BMI) on gastric cancer (GC) risk according to Helicobacter pylori infection status. This study was conducted to evaluate associations between BMI and GC risk with consideration of H. pylori infection information. MATERIALS AND METHODS: We performed a case-cohort study (n=2,458) that consists of a subcohort, (n=2,193 including 67 GC incident cases) randomly selected from the Korean Multicenter Cancer Cohort (KMCC) and 265 incident GC cases outside of the subcohort. H. pylori infection was assessed using an immunoblot assay. GC risk according to BMI was evaluated by calculating hazard ratios (HRs) and their 95% confidence intervals (95% CIs) using weighted Cox hazard regression model. RESULTS: Increased GC risk in lower BMI group (< 23 kg/m²) with marginal significance, (HR, 1.32; 95% CI, 0.98 to 1.77) compared to the reference group (BMI of 23-24.9 kg/m²) was observed. In the H. pylori non-infection, both lower (< 23 kg/m²) and higher BMI (≥ 25 kg/m²) showed non-significantly increased GC risk (HR, 10.82; 95% CI, 1.25 to 93.60 and HR, 11.33; 95% CI, 1.13 to 113.66, respectively). However, these U-shaped associations between BMI and GC risk were not observed in the group who had ever been infected by H. pylori. CONCLUSION: This study suggests the U-shaped associations between BMI and GC risk, especially in subjects who had never been infected by H. pylori.
Body Mass Index ; Cohort Studies ; Helicobacter pylori ; Helicobacter ; Stomach Neoplasms