1.Activation of DDR2 Involved in Atherosclerosis by Oxidative Stress.
Journal of the Korean Geriatrics Society 2007;11(4):181-188
BACKGROUND: Reactive Oxygen species have been known to be a key factor to promote atherosclerosis. DDR2(Discoidin Domain Receptor 2) is a cell surface receptor tyrosine kinase which is activated by fiber collagen. Recently, DDR2 was suggested to be involved in activation of smooth muscle cell in blood vessel of atherosclerosis. METHODS: The effect of antioxidant, N-acetyl cysteine and H2O2(Hydrogen peroxide) in the activation of DDR2 by collagen was studied using HEK293 cells expressing DDR2. The direct activation of DDR2 tyrosine kinase domain by tyrosine phosphorylation upon the treatment of H2O2 was analysed after the kinase domain was expressed in sf9 cells. RESULTS: H2O2 enhanced DDR2 auto-phosphorylation and its cellular signaling to induce MMP-1 expression. However N-acetyl cysteine suppressed the DDR2 activation. The reactive oxygen induced tyrosine phosphorylation in DDR2 tyrosine kinase domain to activate its tyrosine kinase activity. CONCLUSIONS: DDR2 activity can be up-regulated by oxidative stress and this provides a mechanism that DDR2 plays a critical role when reactive oxygen species promote atherosclerosis. Therefore inhibition of the activated DDR2 could be a new therapeutic strategy for atherosclerosis.
Atherosclerosis*
;
Blood Vessels
;
Collagen
;
Cysteine
;
HEK293 Cells
;
Myocytes, Smooth Muscle
;
Oxidative Stress*
;
Oxygen
;
Phosphorylation
;
Phosphotransferases
;
Protein-Tyrosine Kinases
;
Reactive Oxygen Species
;
Sf9 Cells
;
Tyrosine
2.Biochemical characterizations reveal different properties between CDK4/cyclin D1 and CDK2/cyclin A.
Dong Myung KIM ; Kyungmi YANG ; Beom Seok YANG
Experimental & Molecular Medicine 2003;35(5):421-430
CDK2 and CDK4 known promoter of cell cycling catalyze phosphorylation of RB protein. Enzyme specificity between two CDKs that work at a different cell cycle phase is not clearly understood. In order to define kinase properties of CDK2 and CDK4 in complex with cycline A or cycline D1 in relation to their respective role in cell cycling regulation, we examined enzymatic properties of both CDK4/cycline D1 and CDK2/cycline A in vitro. Association constant, Km for ATP in CDK4/cyclin D1 was found as 418 micrometer, a value unusually high whereas CDK2/cyclin A was 23 micrometer, a value close to most of other regulatory protein kinases. Turnover value for both CDK4/cyclin D1 and CDK2/cyclin A were estimated as 3.4 and 3.9 min(-1)respectively. Kinetic efficiency estimation indicates far over one order magnitude less efficiency for CDK4/cyclin D1 than the value of CDK2/cycline A (9.3 pM(-1)min(-1)and 170 pM(-1)min(-1)respectively). In addition, inhibition of cellular CDK4 caused increase of cellular levels of ATP, even though inhibition of CDK2 did not change it noticeably. These data suggest cellular CDK4/cyclin D1 activity is tightly associated with cellular ATP concentration. Also, analysis of phosphorylated serine/threonine sites on RB catalyzed by CDK4/cyclin D1 and CDK2/cyclin A showed significant differences in their preference of phosphorylation sites in RB C-terminal domain. Since RB is known to regulate various cellular proteins by binding and this binding is controlled by its phosphorylation, these data shown here clearly indicate significant difference in their biochemical properties between CDK4/cyclin D1 and CDK2/cyclin A affecting regulation of cellular RB function.
Adenosine Triphosphate/metabolism
;
Amino Acid Sequence
;
Baculoviridae/genetics
;
CDC2-CDC28 Kinases/genetics/isolation&purification/*metabolism
;
Cyclin A/genetics/isolation&purification/*metabolism
;
Cyclin D1/genetics/isolation&purification/*metabolism
;
Cyclin-Dependent Kinases/antagonists&inhibitors/genetics/isolation&purification/*metabolism
;
Human
;
Kinetics
;
Molecular Sequence Data
;
Phosphorylation
;
Protein Conformation
;
Protein p16/metabolism
;
Recombinant Proteins/genetics/isolation&purification/metabolism
3.Patterns of Proton Beam Therapy Use in Clinical Practice between 2007 and 2019 in Korea
Sung Uk LEE ; Kyungmi YANG ; Sung Ho MOON ; Yang-Gun SUH ; Gyu Sang YOO
Cancer Research and Treatment 2021;53(4):935-943
Purpose:
Proton beam therapy (PBT) is a state-of-the-art technology employed in radiotherapy (RT) for cancer patients. This study characterized how PBT has been used in clinical practice in Korea.
Materials and Methods:
Patients who received any type of RT between 2007 and 2019 were identified from the radiation oncology registry of the two PBT facilities operating in Korea (National Cancer Center and Samsung Medical Center). The chi-square test was used to identify patient- and treatment-related characteristics associated with the receipt of PBT.
Results:
A total of 54,035 patients had been treated with some form of RT in the two institutions, of whom 5,398 received PBT (10.0%). The number of patients who receive PBT has gradually increased since PBT first started, from 162 patients in 2007 to 1,304 patients in 2019. Among all types of cancer, PBT use in liver cancer has been steadily increasing from 20% in 2008-2009 to 32% in 2018-2019. In contrast, that in prostate cancer has been continuously decreasing from 20% in 2008-2009 to < 10% in 2018-2019. Male sex, very young or old age, stage I-II disease, residency in non-capital areas, a definitive setting, a curative treatment aim, enrollment in a clinical trial, re-irradiation and insurance coverage were significantly associated with the receipt of PBT (all p < 0.05).
Conclusion
Since PBT started in Korea, the number of patients receiving PBT has increased to more than 1,000 per year and treatment indications have expanded. Liver cancer is the most common primary tumor among all PBT cases in Korea.
4.Intracranial Vasospasm without Intracranial Hemorrhage due to Acute Spontaneous Spinal Subdural Hematoma.
Jung Hwan OH ; Seung Joo JWA ; Tae Ki YANG ; Chang Sub LEE ; Kyungmi OH ; Ji Hoon KANG
Experimental Neurobiology 2015;24(4):366-370
Spontaneous spinal subdural hematoma (SDH) is very rare. Furthermore, intracranial vasospasm (ICVS) associated with spinal hemorrhage has been very rarely reported. We present an ICVS case without intracranial hemorrhage following SDH. A 41-year-old woman was admitted to our hospital with a complaint of severe headache. Multiple intracranial vasospasms were noted on a brain CT angiogram and transfemoral cerebral angiography. However, intracranial hemorrhage was not revealed by brain MRI or CT. On day 3 after admission, weakness of both legs and urinary incontinence developed. Spine MRI showed C7~T6 spinal cord compression due to hyperacute stage of SDH. After hematoma evacuation, her symptoms gradually improved. We suggest that spinal cord evaluation should be considered in patients with headache who have ICVS, although intracranial hemorrhage would not be visible in brain images.
Adult
;
Brain
;
Cerebral Angiography
;
Female
;
Headache
;
Hematoma
;
Hematoma, Subdural, Spinal*
;
Hemorrhage
;
Humans
;
Intracranial Hemorrhages*
;
Leg
;
Magnetic Resonance Imaging
;
Spinal Cord
;
Spinal Cord Compression
;
Spine
;
Subarachnoid Hemorrhage
;
Urinary Incontinence
;
Vasospasm, Intracranial*
5.The senior anesthesiologists and their medical profession in Korea: based on a survey
Kyungmi KIM ; Sungwoon BAEK ; In-Cheol CHOI ; Hong-Seuk YANG
Anesthesia and Pain Medicine 2021;16(2):205-212
Background:
The number of aging physicians is increasing as the global population ages. With aging, anesthesiologists would be expected to experience changes in their professional position. Therefore, we aimed to investigate the current professional status of Korean anesthesiologists aged over 60 years.
Methods:
Registered anesthesiologists aged over 60 years in Korea were invited for a survey. The questionnaire addressed 10 subjects with 40 questions that focused on demographics, practical activities, work conditions, difficulties experienced due to physical changes caused by aging, and economic status.
Results:
In total, 122 anesthesiologists responded to the survey (response rate: 15.7%). Of them, 30.3% were working in honorary and advisory positions at tertiary hospitals, while 19.7% were working as pain physicians. Majority of the respondents were working for 5 days a week (41.8%) and 6–8 hours/day (48.4%). Majority of them (79.5%) were generally satisfied with their present life.
Conclusions
Majority of the senior anesthesiologists were working at general hospitals and they reported being “satisfied” with the current status of their life. However, the clinical practice and retirement strategies of senior anesthesiologists need to be evaluated systematically to prepare for the continuing gradual increase in the number of senior anesthesiologists.
6.Recent Trends of Medical Expenses Associated with Radiation Therapy in Korea Based on HIRA Big Data
Jeong Eun LEE ; Kyungmi YANG ; Yong Chan AHN ; Won PARK ; Seung Jae HUH
Cancer Research and Treatment 2023;55(3):758-765
Purpose:
We aimed to determine the trends in the use of radiotherapy (RT) and the expenses associated with it in South Korea.
Materials and Methods:
The statistical data of the claims and reimbursement records provided on the Health and Insurance Review and Assessment Service website were utilized. This included information such as the number of patients, fractions, medical expenses according to treatment codes, in/outpatient, sex, age, and regions of hospitals. We analyzed data from 2016 to 2020.
Results:
With a growing RT infrastructure and an increase in the number of radiation oncologists, the expenses for RT were 605.5 million USD in 2020, which had increased 1.5 times from 394.7 million USD in 2016. This growth was mainly because of the increased usage of advanced RT techniques. Furthermore, the proportion of intensity-modulated radiation therapy (IMRT) expenses in the total expenses increased by 1.6 times from 48.8% in 2016 to 76.9% in 2020. Advanced techniques were used more commonly in older individuals or children. However, the proportion of IMRT expenses increased mostly in young women. Additionally, geographical differences in RT use and expense were observed, although the gap in the IMRT fractions decreased among the regions.
Conclusion
Recent medical expenses associated with RT in Korea have increased in tandem with technological advances and changes in demographics.
7.Re-irradiation with Moderate Hypo-fractionation Using Intensity Modulated Photon or Proton Radiation Therapy in Locally Recurrent Squamous Cell Carcinoma of Nasopharynx
Heerim NAM ; Yong Chan AHN ; Kyungmi YANG ; Dongryul OH ; Jae Myoung NOH
Cancer Research and Treatment 2022;54(1):96-108
Purpose:
This study aimed to analyze the treatment outcomes of locally recurrent nasopharyngeal cancer (NPC) patients following moderate hypo-fractionation re-irradiation (re-RT).
Materials and Methods:
Sixty locally recurrent NPC patients underwent hypo-fractionation re-RT. Forty-eight point three percentage had rT3-4, and 30.0% did keratinizing squamous cell carcinoma. Intensity-modulated radiation therapy (IMRT), with or without intensity-modulated proton therapy (IMPT), was used in 66.7% of patients.
Results:
With the median follow-up of 22 months (range, 2 to 254 months), 31 patients (51.7%) died, 38 (63.3%) developed further treatment failure, and 30 (50.0%) developed ≥ grade 3 toxicity (including seven grade 5) at time of analysis. The 2- and 5-year rates of overall survival, local failure-free survival, and ≥ grade 3 toxicity-free survival were 57.9% and 45.8%, 64.1% and 52.5%, and 54.8% and 44.9%, respectively. In multivariate analyses, worse factors for overall survival (OS) were iT3-4 (p=0.010) and age at re-RT ≥ 53 years (p=0.003), those for local failure-free survival (LFFS) were rT3-4 (p=0.022) and rN0-1 (p=0.035), and those for toxicity-free survival (TFS) were iT3-4 (p=0.020) and re-IMRT/IMPT (p=0.030), respectively. Cumulative dose or fraction size ≥ 3 Gy at re-RT, however, showed no significance for OS, LFFS and TFS.
Conclusion
Current re-RT with modern RT techniques by moderate hypo-fractionation scheme seemed feasible in treating locally recurrent NPC patients.
8.The senior anesthesiologists and their medical profession in Korea: based on a survey
Kyungmi KIM ; Sungwoon BAEK ; In-Cheol CHOI ; Hong-Seuk YANG
Anesthesia and Pain Medicine 2021;16(2):205-212
Background:
The number of aging physicians is increasing as the global population ages. With aging, anesthesiologists would be expected to experience changes in their professional position. Therefore, we aimed to investigate the current professional status of Korean anesthesiologists aged over 60 years.
Methods:
Registered anesthesiologists aged over 60 years in Korea were invited for a survey. The questionnaire addressed 10 subjects with 40 questions that focused on demographics, practical activities, work conditions, difficulties experienced due to physical changes caused by aging, and economic status.
Results:
In total, 122 anesthesiologists responded to the survey (response rate: 15.7%). Of them, 30.3% were working in honorary and advisory positions at tertiary hospitals, while 19.7% were working as pain physicians. Majority of the respondents were working for 5 days a week (41.8%) and 6–8 hours/day (48.4%). Majority of them (79.5%) were generally satisfied with their present life.
Conclusions
Majority of the senior anesthesiologists were working at general hospitals and they reported being “satisfied” with the current status of their life. However, the clinical practice and retirement strategies of senior anesthesiologists need to be evaluated systematically to prepare for the continuing gradual increase in the number of senior anesthesiologists.
9.Comparison of radiotherapy techniques in patients with thymic epithelial tumor who underwent postoperative radiotherapy
Hyunseok LEE ; Dongryul OH ; Yong Chan AHN ; Hongryull PYO ; Kyungmi YANG ; Jae Myoung NOH
Radiation Oncology Journal 2024;42(1):43-49
Purpose:
This retrospective study aimed to compare clinical outcomes and dosimetric parameters between radiation therapy (RT) techniques in patients with thymic epithelial tumor (TET).
Materials and Methods:
From January 2016 to December 2020, 101 patients with TET received adjuvant RT (median, 52.8 Gy; range, 48.4 to 66.0). Three different RT techniques were compared: three-dimensional conformal RT (3D-CRT; n = 59, 58.4%), intensity-modulated RT (IMRT; n = 23, 22.8%), and proton beam therapy (PBT; n = 19, 18.8%).
Results:
The median age of the patients and the follow-up period were 55 years (range, 28 to 79) and 43.4 months (range, 7.7 to 77.2). Patients in the PBT group were of the youngest age (mean age, 45.4 years), while those in IMRT group had the largest clinical target volume (mean volume, 149.6 mL). Patients in the PBT group had a lower mean lung dose (4.4 Gy vs. 7.6 Gy vs. 10.9 Gy, respectively; p < 0.001), lower mean heart dose (5.4 Gy vs. 10.0 Gy vs. 13.1 Gy, respectively; p = 0.003), and lower mean esophageal dose than patients in the 3D-CRT and IMRT groups (6.3 Gy vs. 9.8 Gy vs. 13.5 Gy, respectively; p = 0.011). Twenty patients (19.8%) showed disease recurrence, and seven patients (6.9%) died. The differences in the survival rates between RT groups were not statistically significant.
Conclusion
In patients with TET who underwent adjuvant RT, PBT resulted in a lower dose of exposure to adjacent organs at risk. Survival outcomes for patients in PBT group were not significantly different from those in other groups.
10.Clinical outcomes in patients treated with radiotherapy after surgery for cervical cancer.
Kyungmi YANG ; Won PARK ; Seung Jae HUH ; Duk Soo BAE ; Byoung Gie KIM ; Jeong Won LEE
Radiation Oncology Journal 2017;35(1):39-47
PURPOSE: The purpose of this study was to analyze clinical outcomes from cervical cancer and stratify patients into risk groups for prognostic factors for early-stage disease. MATERIALS AND METHODS: We retrospectively reviewed patients with stage IB or IIA cervical cancer treated with adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) following primary surgery at Samsung Medical Center from 2001 to 2011. Adjuvant RT was added for patients with intermediate-risk factors, and adjuvant CCRT was performed on high-risk patients after surgery. RESULTS: We reviewed 247 patients—149 in the high-risk group and 98 in intermediate-risk group. The median follow-up was 62 months. Loco-regional failure (LRF) alone occurred in 7 patients (2.8%), distant metastasis alone in 37 patients (15.0%) and LRF with DM in 4 patients (1.6%). The 5-year disease-free survival (DFS) and overall survival (OS) rates for both groups were 79.7% and 87.6%, respectively. In the high-risk group, the 5-year DFS and OS probabilities were 72.5% and 81.9%, respectively. Histologic type, pathologic tumor size, and the number of pelvic lymph node (PLN) metastasis were significant prognostic factors for DFS and OS. We suggest a scoring system (0–3) using these prognostic factors to predict poor prognosis in high-risk patients. Using this system, patients with higher scores have higher recurrence and lower survival rates. CONCLUSION: In the high-risk cervical-cancer group who received primary surgery and adjuvant CCRT, non-squamous type, large tumor size and the number of PLN metastasis were significant prognostic factors, and the number of these factors was associated with survival rates.
Chemoradiotherapy
;
Chemoradiotherapy, Adjuvant
;
Disease-Free Survival
;
Follow-Up Studies
;
Humans
;
Hysterectomy
;
Lymph Nodes
;
Neoplasm Metastasis
;
Prognosis
;
Radiotherapy*
;
Radiotherapy, Adjuvant
;
Recurrence
;
Retrospective Studies
;
Survival Rate
;
Uterine Cervical Neoplasms*