1.Suppression of Glioblastoma Stem Cell Potency and Tumor Growth via LRRK2 Inhibition
Saewhan PARK ; Kyung-Hee KIM ; Yun-Hee BAE ; Young Taek OH ; Hyemi SHIN ; Hyung Joon KWON ; Chan Il KIM ; Sung Soo KIM ; Hwan-Geun CHOI ; Jong Bae PARK ; Byoung Dae LEE
International Journal of Stem Cells 2024;17(3):319-329
Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson’s disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors.Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.
2.The Results of the Ultrasonographic Evaluation for the Contralateral Achilles Tendon in Patients with Acute Achilles Tendon Rupture
Dae-Geun KIM ; Jun-Beom KIM ; Byeong-Seop PARK
The Korean Journal of Sports Medicine 2023;41(3):147-152
Purpose:
This study was performed to evaluate changes in Achilles tendon (AT) characteristics of asymptomatic tendons in patients with acute AT ruptures on the contralateral side by using ultrasonography.
Methods:
From January 2016 to December 2018, 31 patients were enrolled. The contralateral asymptomatic ATs were assessed: (1) fluid collection of paratenon, (2) echogenicity, and (3) thickness. The ATs were divided into the distal, middle, and proximal thirds for evaluation and were assessed before the surgery, as well as at 6 weeks, 3 months, 6 months, and 12 months after the surgery. At each time, pain in the tendons was recorded.
Results:
In all cases, it was observed that there was a hypoechoic lesion or fluid collection of the paratenon, which did not show a significant change over time. There was no significant difference in tendon thickness according to the period in the distal and proximal areas, and significant differences were observed only in the middle area (p< 0.05). A new pain around the tendon occurred most often at 6 weeks after surgery (eight cases of 31 cases, 25.8%). Eight cases of pain (47.1%) remained at 12 months after surgery.
Conclusion
In patients with acute AT rupture, ultrasonographic hypoechoic lesions or fluid collections of the paratenon were initially observed on the contralateral tendon, but this did not show significant changes over time. A significant change in tendon thickness was observed in the middle area, but this did not show a close association with pain.
3.Variance of the COVID-19 occurrence in the community: influence on the emergency medical service and the survival of out-of-hospital cardiac arrest patients
Geun Chang KIM ; Sin Young KIM ; Jong Won KIM ; Dae Young HONG ; Kyeong Ryong LEE ; Kwang Je BAEK ; Sang O PARK
Journal of the Korean Society of Emergency Medicine 2023;34(2):96-104
Objective:
This study evaluates the impact of the coronavirus disease 2019 (COVID-19) pandemic on emergency medical service (EMS) responses and out-of-hospital cardiac arrest (OHCA) outcomes.
Methods:
This is a retrospective comparison study analyzing the OHCA data of a university medical center in Seoul during the COVID-19 pandemic period (January 2020-January 2021) and non-pandemic period (January 2019-January 2020). The EMS response time and OHCA outcomes were compared between both periods. Based on the weekly mean number of confirmed cases and their EMS response time, patients were classified into six groups and OHCA outcomes were compared.
Results:
This study evaluated 309 OHCA patients (non-pandemic period of 146, pandemic period of 163). Significant delays in the EMS response and transport time were observed during the pandemic period. However, no significant differences were obtained in the rate of return of spontaneous circulation (ROSC) and survival at discharge (12.4% in pandemic vs. 13.8% in non-pandemic; P=0.722). According to the weekly mean COVID-19 incidence when patients were over 100, there was a significant increase in the EMS response and transport time, whereas ROSC and survival rate were dramatically decreased.
Conclusion
During the pandemic, the EMS service for OHCA patients was worse than before, with delayed and reduced survival for OHCA patients. We further determined that an increase in the number of COVID-19 cases (especially when weekly mean numbers were over 100) dramatically delayed the EMS response time. This resulted in a very low survival rate of OHCA patients.
4.The Role of Adjuvant Therapy Following Surgical Resection of Small Cell Lung Cancer: A Multi-Center Study
Seong Yong PARK ; Samina PARK ; Geun Dong LEE ; Hong Kwan KIM ; Sehoon CHOI ; Hyeong Ryul KIM ; Yong-Hee KIM ; Dong Kwan KIM ; Seung-Il PARK ; Tae Hee HONG ; Yong Soo CHOI ; Jhingook KIM ; Jong Ho CHO ; Young Mog SHIM ; Jae Ill ZO ; Kwon Joong NA ; In Kyu PARK ; Chang Hyun KANG ; Young-Tae KIM ; Byung Jo PARK ; Chang Young LEE ; Jin Gu LEE ; Dae Joon KIM ; Hyo Chae PAIK
Cancer Research and Treatment 2023;55(1):94-102
Purpose:
This multi-center, retrospective study was conducted to evaluate the long-term survival in patients who underwent surgical resection for small cell lung cancer (SCLC) and to identify the benefit of adjuvant therapy following surgery.
Materials and Methods:
The data of 213 patients who underwent surgical resection for SCLC at four institutions were retrospectively reviewed. Patients who received neoadjuvant therapy or an incomplete resection were excluded.
Results:
The mean patient age was 65.29±8.93 years, and 184 patients (86.4%) were male. Lobectomies and pneumonectomies were performed in 173 patients (81.2%), and 198 (93%) underwent systematic mediastinal lymph node dissections. Overall, 170 patients (79.8%) underwent adjuvant chemotherapy, 42 (19.7%) underwent radiotherapy to the mediastinum, and 23 (10.8%) underwent prophylactic cranial irradiation. The median follow-up period was 31.08 months (interquartile range, 13.79 to 64.52 months). The 5-year overall survival (OS) and disease-free survival were 53.4% and 46.9%, respectively. The 5-year OS significantly improved after adjuvant chemotherapy in all patients (57.4% vs. 40.3%, p=0.007), and the survival benefit of adjuvant chemotherapy was significant in patients with negative node pathology (70.8% vs. 39.7%, p=0.004). Adjuvant radiotherapy did not affect the 5-year OS (54.6% vs. 48.5%, p=0.458). Age (hazard ratio [HR], 1.032; p=0.017), node metastasis (HR, 2.190; p < 0.001), and adjuvant chemotherapy (HR, 0.558; p=0.019) were associated with OS.
Conclusion
Adjuvant chemotherapy after surgical resection in patients with SCLC improved the OS, though adjuvant radiotherapy to the mediastinum did not improve the survival or decrease the locoregional recurrence rate.
6.Consideration for Coronavirus Disease 2019 Drug Treatment in Patients with Epilepsy on Antiepileptic Drugs
Jung-Ick BYUN ; Jun-Sang SUNWOO ; Kyung Wook KANG ; Keun Tae KIM ; Daeyoung KIM ; Dong Wook KIM ; Saeyoon KIM ; Se Hee KIM ; Woojun KIM ; Hye-Jin MOON ; Hea Ree PARK ; Jong-Geun SEO ; Min Kyung CHU ; Kyoung Jin HWANG ; Dae-Won SEO ;
Journal of the Korean Neurological Association 2022;40(2):121-126
Several medications are approved to treat coronavirus disease 2019 (COVID-19) in Korea including nirmatrelvir/ritonavir, remdesivir, and regdanvimab. There is potential drug-drug interaction between antiepileptic drugs (AEDs) and the medications used to treat COVID-19. Several AEDs such as phenytoin, carbamazepine, phenobarbital, and primidone are strong cytochrome P450 inducers and can inhibit the drugs used for COVID-19. Particularly, these drugs are contraindicated with nirmatrelvir/ritonavir (Paxlovid®). There is a weaker drug-drug interaction between the AEDs and remdesivir. No significant interaction has been reported between the AEDs and molnupiravir. Pharmacokinetic interactions of the AEDs are important in effective management of COVID-19 in patients with epilepsy.
7.Hearing Impairment Increases Economic Inequality
So Young KIM ; Chanyang MIN ; Dae Myoung YOO ; Jiwon CHANG ; Hyo-Jeong LEE ; Bumjung PARK ; Hyo Geun CHOI
Clinical and Experimental Otorhinolaryngology 2021;14(3):278-286
Objectives:
. We evaluated changes in income levels in a hearing-impaired population.
Methods:
. The study subjects were selected from the Korean National Health Insurance Service-Health Screening Cohort data from 2002 to 2015 of Koreans ≥40 years old. In total, 5,857 hearing-impaired subjects were matched with 23,428 comparison participants. Differences between the initial income level and income levels at 1, 2, 3, 4, and 5 years post-enrollment were compared between the hearing-impaired and comparison groups. The interaction of time and hearing impairment/comparison was estimated.
Results:
. Both the hearing-impaired group and the comparison group showed increased income levels over time. In the hearing-impaired group, the income levels at 4 and 5 years post-enrollment were higher than the initial income level (each P<0.001). In the comparison group, the income levels of all the participants after 1–5 years were higher than the initial income level (each P<0.001). The interaction of time and hearing impairment was statistically significant (P=0.021).
Conclusion
. The increase in income over time was relatively lower in the hearing-impaired adult population; therefore, the income gap widened between this population and the normal-hearing population.
8.Gastric Angiolipoma Resected with Endoscopic Submucosal Dissection
Sang Myung YEO ; Jae Kwang LEE ; Hyun Soo KIM ; Chang Geun PARK ; Jae Kwon JUNG ; Dae Jin KIM ; Yun Jin CHUNG ; Han Jun RYU
Clinical Endoscopy 2021;54(3):432-435
Angiolipoma is a benign fatty neoplasm that has components of proliferating blood vessels. These types of lesions commonly occur in the subcutaneous tissue of the limbs and trunk. Angiolipoma in the gastrointestinal tract is extremely rare, and the final diagnosis generally depends on histological examination of the excised biopsy. In most previously reported cases, the lesions were diagnosed and treated with surgical management. In this study, we report a case of gastric angiolipoma of approximately 4 cm in size that was diagnosed and treated with endoscopic submucosal dissection.
9.Hearing Impairment Increases Economic Inequality
So Young KIM ; Chanyang MIN ; Dae Myoung YOO ; Jiwon CHANG ; Hyo-Jeong LEE ; Bumjung PARK ; Hyo Geun CHOI
Clinical and Experimental Otorhinolaryngology 2021;14(3):278-286
Objectives:
. We evaluated changes in income levels in a hearing-impaired population.
Methods:
. The study subjects were selected from the Korean National Health Insurance Service-Health Screening Cohort data from 2002 to 2015 of Koreans ≥40 years old. In total, 5,857 hearing-impaired subjects were matched with 23,428 comparison participants. Differences between the initial income level and income levels at 1, 2, 3, 4, and 5 years post-enrollment were compared between the hearing-impaired and comparison groups. The interaction of time and hearing impairment/comparison was estimated.
Results:
. Both the hearing-impaired group and the comparison group showed increased income levels over time. In the hearing-impaired group, the income levels at 4 and 5 years post-enrollment were higher than the initial income level (each P<0.001). In the comparison group, the income levels of all the participants after 1–5 years were higher than the initial income level (each P<0.001). The interaction of time and hearing impairment was statistically significant (P=0.021).
Conclusion
. The increase in income over time was relatively lower in the hearing-impaired adult population; therefore, the income gap widened between this population and the normal-hearing population.
10.Gastric Angiolipoma Resected with Endoscopic Submucosal Dissection
Sang Myung YEO ; Jae Kwang LEE ; Hyun Soo KIM ; Chang Geun PARK ; Jae Kwon JUNG ; Dae Jin KIM ; Yun Jin CHUNG ; Han Jun RYU
Clinical Endoscopy 2021;54(3):432-435
Angiolipoma is a benign fatty neoplasm that has components of proliferating blood vessels. These types of lesions commonly occur in the subcutaneous tissue of the limbs and trunk. Angiolipoma in the gastrointestinal tract is extremely rare, and the final diagnosis generally depends on histological examination of the excised biopsy. In most previously reported cases, the lesions were diagnosed and treated with surgical management. In this study, we report a case of gastric angiolipoma of approximately 4 cm in size that was diagnosed and treated with endoscopic submucosal dissection.

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