The epithelial-mesenchymal transition (EMT) and endoplasmic reticulum (ER) stress induced by urinary protein, particularly albumin, play an important role in tubulointerstitial injury. However, signaling pathways regulating both albumin-induced EMT and ER stress are not precisely known. We postulated that reactive oxygen species (ROS), c-Src kinase, and mammalian target of rapamysin (mTOR) would act as upstream signaling molecules. We further examined the effect of imatinib mesylate on these processes. All experiments were performed using HK-2 cells, a human proximal tubular cell line. Protein and mRNA expression were measured by Western blot analysis and real-time PCR, respectively. Exposure of tubular cells to albumin (5 mg/ml) for up to 5 days induced EMT in a time-dependent manner, as shown by conversion to the spindle-like morphology, loss of E-cadherin protein, and upregulation of α-smooth muscle actin mRNA and protein. Albumin also induced ER stress as evidenced by phosphorylation of eukaryotic translation initiation factor-2α and increased expression of GRP78 mRNA and protein. Albumin induced ROS, c-Src kinase, and mTOR as well. Antioxidants, c-Src kinase inhibitor (PP2), and mTOR inhibitor (rapamycin) suppressed the albumin-induced EMT and ER stress. Antioxidants and PP2 inhibited the albumin-induced c-Src kinase and mTOR, respectively. Imatinib suppressed the albumin-induced EMT and ER stress via inhibition of ROS and c-Src kinase. Imatinib also inhibited the albumin-induced mRNA expression of MCP-1, VCAM-1, transforming growth factor (TGF)-β1, and collagen I (α1). In conclusion, the ROS-c-Src kinase-mTOR pathway played a central role in the signaling pathway that linked albumin to EMT and ER stress. Imatinib might be beneficial in attenuating the albumin-induced tubular injury.

Background/AimsHelicobacter pylori is a major risk factor for atrophic gastritis (AG) and gastric cancer. The correlation between H. pylori, AG and colorectal neoplasm (CRN) has only been examined in a limited number of studies, and findings have been inconclusive. We aimed to investigate the association between H. pylori infection status, AG and advanced CRN.MethodsThis cross-sectional study investigated the relationship between the presence of serum anti-H. pylori IgG antibodies, AG, and advanced CRN in 6,351 consecutive asymptomatic subjects who underwent a screening colonoscopy.ResultsA total of 316 participants (5.0%) had advanced CRN. H. pylori seropositivity was 61.3%. In a univariate analysis, the presence of H. pylori infection was associated with advanced CRN (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.17 to 1.91; p=0.001). H. pylori infection was associated with an increased risk of advanced CRN after adjusting for clinically relevant confounders (OR, 1.34; 95% CI, 1.04 to 1.72; p=0.023). H. pylori-related AG was significantly associated with the risk of advanced CRN (OR, 1.40; 95% CI, 1.03 to 1.91; p=0.030), whereas H. pylori infection without AG was not.ConclusionsH. pylori infection increased the risk of advanced CRN, especially when it was combined with AG. Strict colonoscopy screening and surveillance may be warranted in those with H. pylori-positive AG.

Background/AimsBecause of the poor prognosis of diffuse-type gastric cancer, early detection is important. We investigated the clinical characteristics and prognosis of diffuse-type early gastric cancer (EGC) diagnosed in subjects during health check-ups.MethodsAmong 121,111 subjects who underwent gastroscopy during a routine health check-up, we identified 282 patients with 286 EGC lesions and reviewed their clinical and tumor-specific parameters.ResultsPatients with diffuse-type EGC were younger, and 48.1% of them were female. Serum anti-Helicobacter pylori IgG (Hp-IgG) was positive in 90.7% of diffuse-type EGC patients (vs 75.9% of intestinal-type EGC, p=0.002), and the proportion of diffuse-type EGC cases increased significantly with increasing Hp-IgG serum titers (p<0.001). Diffuse-type EGC had pale discolorations on the tumor surface (26.4% vs 4.0% in intestinal-type EGC, p<0.001) and were often located in the middle third of the stomach. Submucosal invasion or regional nodal metastasis was observed more commonly in patients with diffuse-type EGC. However, during the median follow-up period of 50 months, 5-year disease-free survival rates did not differ between the groups.ConclusionsDiffuse-type EGC shows different clinical and endoscopic characteristics. Diffuse-type EGC is more closely associated with Hp-IgG seropositivity and a higher serum titer. Early detection results in excellent prognosis.

<b><i>Background:</i></b> Most of children with cow’s milk (CM) and hen’s egg allergies are known to outgrow their diseases with time, but recent studies have demonstrated that children tend to continue to have allergic symptoms in adolescence and adulthood. The aim of this study was to investigate the natural course of CM and egg allergies in Korean children and analyze prognostic factors. <b><i>Methods:</i></b> In this retrospective study, we reviewed data of children with CM allergy and with egg allergy using medical records and parental telephone interviews. Diagnosis of CM or egg allergy was based on positive oral food challenge test or convincing history of allergic symptoms in combination with positive allergen-specific IgE. Acquisition of tolerance was defined by the absence of allergic symptoms after reintroduction of the offending foods. <b><i>Results:</i></b> Half of the children outgrew CM allergy at a median age of 8.7 years. CM-specific IgE level at the first reaction was a significant prognostic factor for oral tolerance in CM allergy (<i>p</i> &#x3c; 0.05). The median age to acquire oral tolerance in 50% of patients with egg allergy was 5.6 years. Egg-specific IgE level at the first reaction and family history of allergic diseases significantly affected the prognosis in children with egg allergy (<i>p</i> &#x3c; 0.05). <b><i>Conclusions:</i></b> Half of Korean children with CM and egg allergies had symptom resolution at 8.7 and 5.6 years of age, respectively. Our results also suggest that CM- and egg-specific IgE levels at the first reaction are the most significant prognostic factors in predicting acquisition of oral tolerance.

Individuals aged 40-49 years had a lower prevalence of colorectal neoplasms than those aged 50-59 years, but some 40- to 49-year-olds showed a similar prevalence to those aged 50-59 years. Age, current smoking habits, and metabolic syndrome are associated with an increased risk of advanced neoplasms in subjects aged 40-49 years. Further studies are needed to stratify the risks of colon cancer and guide targeted screening in persons younger than 50 years old.

Objective:To evaluate the efficacy of taxane and platinum-based chemotherapy guided by extreme drug resistance assay (EDRA) in patients with epithelial ovarian cancer. Methods: Thirty-nine patients were enrolled, who were diagnosed as epithelial ovarian cancer, tubal cancer or primary peritoneal carcinoma and received both debulking surgery and EDRA in Asan Medical Center between August 2004 and August 2006. Another thirty-nine patients were enrolled, who did not receive EDRA as control. Paclitaxel 175 mg/m 2 and carboplatin AUC 5 were administered as primary combination chemotherapy to both EDRA group and the control group. In the EDRA group, paclitaxel was replaced by docetaxel 75 mg/m 2 if a patient showed extreme drug resistance (EDR) to paclitaxel and not to docetaxel. Carboplatin was replaced by cisplatin 75 mg/m 2 if a patient showed EDR to carboplatin and not to cisplatin. If only one drug showed low drug resistance (LDR), it was allowed to add another drug which showed LDR such as gemcitabine 1,000 mg/m 2 . CT scan was performed every three cycles and CA-125 was checked at each cycle. Results: There was no significant difference in overall response rate between EDRA group and the control group (84.5% vs. 71.8%, p=0.107). However, 93.8% of patients in EDRA group did not show EDR to at least one drug and its response rate was significantly higher than that of the control group (93.3% vs. 71.8%, p=0.023). Conclusion: we could choose a combination of taxane and platinum which did not show EDR and could obtain a good response in the patients with ovarian cancer.

Background: Expression of the proto-oncogene Pim-1 is post-transcriptionally controlled in cancer cells. Results: Tristetraprolin (TTP) enhances the decay of Pim-1 mRNA by binding to the AU-rich element in its 3Ј-UTR. Conclusion: TTP contributes to tumor suppression in part by down-regulating Pim-1 expression. Significance: This work explains the mechanisms by which Pim-1 expression is regulated in cancer cells.

Background Respiratory infections among children, particularly community-acquired pneumonia (CAP), is a major disease with a high frequency among outpatient and inpatient visits. The causes of CAP vary depending on individual susceptibility, the epidemiological characteristics of the community, and the season. We performed this study to establish a nationwide surveillance network system and identify the causative agents for CAP and antibiotic resistance in Korean children with CAP. Methods The monitoring network was composed of 28 secondary and tertiary medical institutions. Upper and lower respiratory samples were assayed using a culture or polymerase chain reaction (PCR) from August 2018 to May 2020. Results A total of 1023 cases were registered in patients with CAP, and PCR of atypical pneumonia pathogens revealed 422 cases of M. pneumoniae (41.3%). Respiratory viruses showed a positivity rate of 65.7% by multiplex PCR test, and human rhinovirus was the most common virus, with 312 cases (30.5%). Two hundred sixty four cases (25.8%) were isolated by culture, including 131 cases of S. aureus (12.8%), 92 cases of S. pneumoniae (9%), and 20 cases of H. influenzae (2%). The cultured, isolated bacteria may be colonized pathogen. The proportion of co-detection was 49.2%. The rate of antibiotic resistance showed similar results as previous reports. Conclusions This study will identify the pathogens that cause respiratory infections and analyze the current status of antibiotic resistance to provide scientific evidence for management policies of domestic respiratory infections. Additionally, in preparation for new epidemics, including COVID-19, monitoring respiratory infections in children and adolescents has become more important, and research on this topic should be continuously conducted in the future.