G-protein-coupled receptor 81 promotes a malignant phenotype in breast cancer through angiogenic factor secretion

G-protein-coupled receptor 81 (GPR81) functions as a receptor for lactate and plays an important role in the regulation of anti-lipolytic effects in adipocytes. However, to data, a role for GPR81 in the tumor microenvironment has not been clearly defined. Here, GPR81 expression in breast cancer patients and several breast cancer cell lines was significantly increased compared with normal mammary tissues and cells. GPR81 knockdown resulted in impaired breast cancer growth and led to apoptosis both in vitro and in vivo. Furthermore, the inhibition of GPR81 signaling suppressed angiogenesis through a phosphoinositide 3-OH kinase (PI3K)/Akt-cAMP response element binding protein (CREB) pathway, which led to decreased production of the pro-angiogenic mediator amphiregulin (AREG). Overall, these findings identify GPR81 as a tumor-promoting receptor in breast cancer progression and suggest a novel mechanism that regulates GPR81-dependent activation of the PI3K/Akt signaling axis in tumor microenvironment.open

Effect of coronavirus disease 2019 on febrile children’s visits to the emergency department of a tertiary hospital

Purpose During the coronavirus disease 2019 pandemic, many countries have reported sharp drops in the numbers of patients, especially children, seeking emergency care unrelated to the disease. The author investigated the patterns of febrile children’s visits to the emergency department (ED) of a tertiary hospital from 2017 through 2020. Methods We compared the data of febrile children aged 15 years or younger who visited the ED in 2017-2019 and in 2020 (February through August, each year). Information on the children’s baseline characteristics, the Korean Triage and Acuity Scale 1-2 indicating a high severity, and ED disposition, such as hospitalization, were collected. In addition, we determined the number of children who underwent cancellation, defined as the leave of children without treatment, and the rates of respiratory virus polymerase chain reaction performance and its positivity. Results In 2020, we noted decreases in the median monthly fever-related ED visits (2017-2019, 326 [interquartile range, 292-425] vs. 2020, 149 [132-182]; P < 0.001) with a shorter median fever duration (2017-2019, 11 [3-27] days vs. 2020, 9 [2-23] days; P < 0.001). However, in the same year, we noted increases in rates of the Korean Triage and Acuity Scale 1-2 (2017-2019, 5.7% vs. 2020, 16.4%; P < 0.001) and hospitalization (2017-2019, 23.5% vs. 2020, 35.7%; P < 0.001). We also noted increases in the number of cancellation and the rate of respiratory virus polymerase chain reaction performance rate, along with a decrease in its positive rate in 2020. Conclusion During the pandemic, the febrile children’s visits to the ED decreased in number. However, the severity remarkably increased, requiring more medical attention

Korean Studies on Blood Stasis: An Overview

Blood stasis is one of the important pathological concepts in Korean medicine. We analyzed the Korean studies concerning blood stasis. We searched for articles in eight electronic databases from their inception to September, 2014. We included reviews, clinical studies, and preclinical studies that had studied blood stasis and excluded articles in which blood stasis was not mentioned or in which the original authors had not explained blood stasis. Of 211 total included studies, 19 were reviews, 52 were clinical studies, and 140 were preclinical articles. “Stagnant blood within the body” was the most frequently mentioned phrase of the traditional concept of blood stasis. Traumatic injury was the most frequently studied disease/condition in the clinical studies. In the preclinical studies, coagulopathy was studied most frequently, followed by hyperviscosity, hyperlipidemia, inflammation, neoplasm, ischemic brain injury, and atherosclerosis. Hyeolbuchukeo-tang and Angelicae Gigantis Radix were the most frequent formula and single herb, respectively, used in the blood stasis researches. The results showed that blood stasis was mainly recognized as disorder of circulation and many studies showed the effectiveness of activating blood circulating herbs for diseases and pathologies such as traumatic injury or coagulopathy. Further studies are needed in the pathologic mechanisms and various diseases of blood stasis

Retrospective Analysis of Peripheral Blood Stem Cell Transplantation for the Treatment of High-Risk Neuroblastoma

Disease relapse after autologous peripheral blood stem cell transplantation (APBSCT) is the main cause of treatment failure in high-risk neuroblastoma (NBL). To reduce relapse, various efforts have been made such as CD34+ selection and double APBSCT. Here the authors reviewed the clinical features and outcomes of high-risk NBL patients and analyzed their survival. The medical records of 36 patients with stage III or IV NBL who underwent APBSCT at Seoul National University Children's Hospital between May 1996 and May 2004 were reviewed. Total 46 APBSCTs were performed in 36 patients. Disease free survival (DFS) and overall survival of all patients were 47.7% and 68.8%, respectively. The patients were allocated to three groups according to the APBSCT type. The DFS of CD34+ non-selected single APBSCT patients (N=13), CD34+ selected single APBSCT patients (N=14), and CD34+ selected double APBSCT patients (N=9) were 55.6%, 40.6%, and 50.0%, respectively, which were not significantly different. Thus the survival was not found to be affected by CD34+ selection or transplantation number. To improve long-term survival, various efforts should be made such as chemotherapy dose intensification, more effective tumor purging, and control of minimal residual disease via the use of differentiating and immune-modulating agents

Therapeutic Co-targeting of WEE1 and ATM Downregulates PD-L1 Expression in Pancreatic Cancer

Purpose Pancreatic cancer (PC) is one of the most lethal cancers worldwide, but there are currently no effective treatments. The DNA damage response (DDR) is under investigation for the development of novel anti-cancer drugs. Since DNA repair pathway alterations have been found frequently in PC, the purpose of this study was to test the DDR-targeting strategy in PC using WEE1 and ATM inhibitors. Materials and Methods We performed in vitro experiments using a total of ten human PC cell lines to evaluate antitumor effect of AZD1775 (WEE1 inhibitor) alone or combination with AZD0156 (ATM inhibitor). We established Capan-1-mouse model for in vivo experiments to confirm our findings. Results In our research, we found that WEE1 inhibitor (AZD1775) as single agent showed anti-tumor effects in PC cells, however, targeting WEE1 upregulated p-ATM level. Here, we observed that co-targeting of WEE1 and ATM acted synergistically to reduce cell proliferation and migration, and to induce DNA damage in vitro. Notably, inhibition of WEE1 or WEE1/ATM downregulated programmed cell death ligand 1 expression by blocking glycogen synthase kinase-3 beta serine 9 phosphorylation and decrease of CMTM6 expression. In Capan-1 mouse xenograft model, AZD1775 plus AZD0156 (ATM inhibitor) treatment reduced tumor growth and downregulated tumor expression of programmed cell death ligand 1, CMTM6, CD163, and CXCR2, all of which contribute to tumor immune evasion. Conclusion Dual blockade of WEE1 and ATM might be a potential therapeutic strategy for PC. Taken together, our results support further clinical development of DDR-targeting strategies for PC.