APE1 Promotes Pancreatic Cancer Proliferation through GFRα1/Src/ERK Axis-Cascade Signaling in Response to GDNF

Pancreatic cancer is the worst exocrine gastrointestinal cancer leading to the highest mortality. Recent studies reported that aberrant expression of apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is involved in uncontrolled cell growth. However, the molecular mechanism of APE1 biological role remains unrevealed in pancreatic cancer progression. Here, we demonstrate that APE1 accelerates pancreatic cancer cell proliferation through glial cell line-derived neurotrophic factor (GDNF)/glial factor receptor α1 (GFRα1)/Src/ERK axis-cascade signaling. The proliferation of endogenous APE1 expressed-MIA PaCa-2, a human pancreatic carcinoma cell line, was increased by treatment with GDNF, a ligand of GFRα1. Either of downregulated APE1 or GFRα1 expression using small interference RNA (siRNA) inhibited GDNF-induced cancer cell proliferation. The MEK-1 inhibitor PD98059 decreased GDNF-induced MIA PaCa-2 cell proliferation. Src inactivation by either its siRNA or Src inhibitor decreased ERK-phosphorylation in response to GDNF in MIA PaCa-2 cells. Overexpression of GFRα1 in APE1-deficient MIA PaCa-2 cells activated the phosphorylation of Src and ERK. The expression of both APE1 and GFRα1 was gradually increased as progressing pancreatic cancer grades. Our results highlight a critical role for APE1 in GDNF-induced pancreatic cancer cell proliferation through APE1/GFRα1/Src/ERK axis-cascade signaling and provide evidence for future potential therapeutic drug targets for the treatment of pancreatic cancer

Resection of individually identified high-rate high-frequency oscillations region is associated with favorable outcome in neocortical epilepsy

Objectives: High-frequency oscillations (HFOs) represent a novel electrophysiologic marker of endogenous epileptogenicity. Clinically, this propensity can be utilized to more accurately delineate the resection margin before epilepsy surgery. Currently, prospective application of HFOs is limited because of a lack of an exact quantitative measure to reliably identify HFO-generating areas necessary to include in the resection. Here, we evaluated the potential of a patient-individualized approach of identifying high-rate HFO regions to plan the neocortical resection. Methods: Fifteen patients with neocortical seizure-onset zones (SOZs) underwent intracranial electroencephalographic monitoring. To identify interictal HFOs, we applied an automated, hypersensitive HFO-detection algorithm followed by post hoc processing steps to reject false detections. The spatial relationship between HFO distribution and the SOZ was evaluated. To address high interpatient variability in HFO properties, we evaluated the high-rate HFO region, an unbiased statistical parameter, in each patient. The relationship between resection of the high-rate HFO region and postoperative outcome was examined. Results: Grouped data demonstrated that the rate of ripple (60–200 Hz) and fast ripple (200–500 Hz) was increased in the SOZ (both p < 0.01). Intrapatient analysis of the HFO distribution localized the SOZ in 11 patients. High-rate HFO regions were determined in all patients by an individually adjusted threshold. Resection of high-rate HFO regions was significantly associated with a seizure-free outcome (p < 0.01). The extent/ratio of SOZ or spiking region resection did not differ between seizure-free and seizure-persistent groups. Significance: Intrapatient analysis of high-rate HFOs provides more detailed description of HFO-generating areas and can mark the areas of clinically significant epileptogenicity—a crucial component of the neocortical epileptic network that should be removed to achieve a good outcome. Validating and adopting an unbiased quantitative HFO parameter has the potential to propel wider and prospective utilization of HFOs in the surgical treatment of neocortical epilepsy and to improve its outcome

The First Case of Familial Mediterranean Fever Associated with Renal Amyloidosis in Korea

Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterized by periodic episodes of fever and recurrent polyserositis. It is caused by a dysfunction of pyrin (or marenostrin) as a result of a mutation within the MEFV gene. It occurs mostly in individuals of Mediterranean origin; however, it has also been reported in non-Mediterranean populations. In this report, we describe the first case of FMF in a Korean child. As eight-year-old boy presented recurrent febrile attacks from an unknown cause, an acute scrotum and renal amyloidosis. He also showed splenomegaly, lymphadenopathy, pleural effusion, ascites and elevated acute phase reactants. After MEFV gene analysis, he was diagnosed as FMF combined with amyloidosis

The Spread of Pandemic H1N1 2009 by Age and Region and the Comparison among Monitoring Tools

This report describes the pattern of the spread of the pandemic H1N1 2009 and compares 3 monitoring tools until the 57th week or January 31, 2010. The 1st week was from December 28th, 2008 to January 3rd, 2009. A total of 740,835 patients were reported to be infected with pandemic H1N1 2009 and 225 patients were reported to have died of pandemic H1N1 2009. The number of patients aged from 7 to 12 was the largest (183,363 patients in total) but the virus spread and then was suppressed most quickly among the children between 13 and 18. The region-determinant incidence of patients showed diverse patterns according to regions. The peak of the ILI per thousand was at the 45th week, the number of antiviral prescriptions reached its peak at the 44th week, and the peak based on reported patients was the 46th week. As of February 3 2010, the outbreak passed through the peak and has gradually subsided. Now it is time for the government and the academic world to review this outbreak, efficacy of vaccination, and further preparation and response for the next pandemic

An exclusively dopamine secreting paraganglioma in the retroperitoneum: a first clinical case in Korea

Exclusively dopamine producing retroperitoneal paragangliomas are extremely rare. We have experienced the first Korean case managed successfully based on the proper evaluation. A 26-year-old female patient came to our attention after the accidental detection of an adrenal mass. She had no symptoms and denied any family history. Laboratory evaluations were normal but serum dopamine (425 ng/L) and 24-hour urine dopamine levels (1,565.3 µg/day) were elevated. She underwent laparoscopic right adrenalectomy. Histopathological diagnosis was a paraganglioma. After operation, dopamine levels in serum and 24-hour urine dropped to 0.09 ng/L and 388.4 µg/day. Dopamine producing paraganglioma elicit no clinical symptoms. Only the dopamine level is elevated in serum and 24-hour urine samples. Surgical resection without using preoperative alpha blockage is the treatment of choice. The prognosis for patients with this tumor tends to be poor because the diagnosis is usually delayed due to lack of symptoms

High-dose Chemotherapy and Autologous Stem Cell Rescue in Patients with High-risk Stage 3 Neuroblastoma: 10-Year Experience at a Single Center

High-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) was applied to improve the prognosis of patients with high-risk stage 3 neuroblastoma. From January 1997 to December 2006, 28 patients were newly diagnosed as stage 3 neuroblastoma. Nine of 11 patients with N-myc amplification and 5 of 17 patients without N-myc amplification (poor response in 2 patients, persistent residual tumor in 2 and relapse in 1) underwent single or tandem HDCT/ASCR. Patients without high-risk features received conventional treatment modalities only. While 8 of 9 patients underwent single HDCT/ASCR and the remaining one patient underwent tandem HDCT/ASCR during the early study period, all 5 patients underwent tandem HDCT/ASCR during the late period. Toxicities associated with HDCT/ASCR were tolerable and there was no treatment-related mortality. While the tumor relapsed in two of eight patients in single HDCT/ASCR group, all six patients in tandem HDCT/ASCR group remained relapse free. The 5-yr event-free survival (EFS) from diagnosis, in patients with N-myc amplification, was 71.6±14.0%. In addition, 12 of 14 patients who underwent HDCT/ASCR remained event free resulting in an 85.1±9.7% 5-yr EFS after the first HDCT/ASCR. The present study demonstrates that HDCT/ASCR may improve the survival of patients with high-risk stage 3 neuroblastoma

Severe pulmonary edema occurred during endobronchial ultrasound under monitored anesthesia care - A case report -

Background Endobronchial ultrasound (EBUS) is widely used to diagnose lung cancer. Monitored anesthesia care (MAC) can enhance patient comfort and procedural conditions during EBUS. EBUS under MAC is usually safe but can lead to various complications. Case A 34-year-old male who had increased sputum for two months showed an enlarged paratracheal lymph node and planned for lymph node biopsy by EBUS. During EBUS under MAC, an unexpected oxygen saturation decline required intervention. After intubation, copious frothy fluid was suctioned from the bronchi, and oxygenation was recovered. A narrowed trachea and the EBUS bronchoscope might have resulted in upper airway obstruction, and suction performed under these conditions might have caused pulmonary edema. The patient received non-invasive ventilation and high-flow nasal cannula and recovered without complications. Conclusions When there is an expected risk of upper airway obstruction during EBUS, careful preoperative evaluation and preparation are essential to prevent negative pressure pulmonary edema

Impact of a delirium prevention project among older hospitalized patients who underwent orthopedic surgery: a retrospective cohort study

Background Postoperative delirium (POD) is a common clinical syndrome with significant negative outcomes. Thus, we aimed to evaluate the feasibility and effectiveness of a delirium screening tool and multidisciplinary delirium prevention project. Methods A retrospective cohort study was conducted at a single teaching center in Korea. A cohort of patients who underwent a delirium prevention program using a simple delirium screening tool from December 2018 to February 2019 (intervention group, N = 275) was compared with the cohort from the year before implementation of the delirium prevention program (December 2017 to February 2018) (control group, N = 274). Patients aged ≥65 years who were admitted to orthopedic wards and underwent surgery were included. The incidence rates of delirium before and after implementation of the delirium prevention program, effectiveness of the delirium screening tool, change in the knowledge score of nurses, and length of hospital stay were assessed. Results The sensitivity and specificity of the screening tool for the incidence of POD were 94.1 and 72.7%, respectively. The incidence rates of POD were 10.2% (control group) and 6.2% (intervention group). The odds ratio for the risk reduction effect of the project related to the incidence of POD was 0.316 (95% confidence interval: 0.125–0.800, p = 0.015) after adjustment for possible confounders. The delirium knowledge test score increased from 40.52 to 43.24 out of 49 total points (p < 0.001). The median length of hospital stay in the intervention and control groups was 6.0 (interquartile range, 4–9) and 7.0 (interquartile range, 4–10) days, respectively (p = 0.062). Conclusion The screening tool successfully identified patients at a high risk of POD at admission. The POD prevention project was feasible to implement, effective in preventing delirium, and improved knowledge regarding delirium among the medical staff. Trial registration None.This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors