1.Tumor Spheroids of an Aggressive Form of Central Neurocytoma Have Transit-Amplifying Progenitor Characteristics with Enhanced EGFR and Tumor Stem Cell Signaling
Hye Young SHIN ; Kyung-Seok HAN ; Hyung Woo PARK ; Yun Hwa HONG ; Yona KIM ; Hyo Eun MOON ; Kwang Woo PARK ; Hye Ran PARK ; C. Justin LEE ; Kiyoung LEE ; Sang Jeong KIM ; Man Seung HEO ; Sung-Hye PARK ; Dong Gyu KIM ; Sun Ha PAEK
Experimental Neurobiology 2021;30(2):120-143
Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as KLF4 and TPD5L1, when compared to their differentiated cells and human NSCs. Importantly, Gene Set Enrichment Analysis showed that gene sets of GBM-Spheroids, EGFR Signaling, and Packaging of Telomere Ends are enriched in CN-spheroids in comparison with their differentiated cells. We speculate that CN tumor stem cells have TAP and RGC characteristics, and upregulation of EGFR signaling as well as downregulation of eph-ephrin signaling have critical roles in tumorigenesis of CN. And their ephemeral nature of TAPs destined to neuroblasts, might reflect benign nature of CN.
2.Long-term Outcome of Microscopic Transsphenoidal Surgery for Prolactinomas as an Alternative to Dopamine Agonists
Kawngwoo PARK ; Kwang Hyon PARK ; Hye Ran PARK ; Jae Meen LEE ; Yong Hwy KIM ; Dong-Young KIM ; Tae-Bin WON ; Sung Hye KONG ; Jung Hee KIM ; Chan Soo SHIN ; Sun Ha PAEK
Journal of Korean Medical Science 2021;36(15):e97-
Background:
Although long-term dopamine agonist (DA) therapy is recommended as a first-line treatment for prolactinoma, some patients may prefer surgical treatment because of the potential adverse effects of long-term medication, or the desire to become pregnant. This study aimed to determine whether surgical treatment of prolactinomas could be an alternative to DA therapy.
Methods:
In this retrospective study, 96 consecutive patients (74 female, 22 male) underwent primary pituitary surgery without long-term DA treatment for prolactinomas at a single institution from 1990 to 2010. All patients underwent primary surgical treatment in the microscopic transsphenoidal approach (TSA).
Results:
The median age and median follow-up period were 31 (16–73) years and 139.1 (12.2–319.6) months, respectively. An initial overall remission was accomplished in 47.9% (46 of 96 patients, 33 macroadenomas, and 13 microadenomas) of patients. DA dose reduction was achieved in all patients after TSA. A better remission rate was independently predicted by lower diagnostic prolactin levels and by a greater extent of surgical resection. Overall remission at the last follow-up was 33.3%, and the overall recurrence rate was 30.4%. The permanent complication rate was 3.1%, and there was no mortality.
Conclusion
TSA can be considered a safe and potentially curative treatment for selective microprolactinomas as an alternative to treatment with a long-term DA.
3.How to Treat Peripheral Arteriovenous Malformations
Ran KIM ; Young Soo DO ; Kwang Bo PARK
Korean Journal of Radiology 2021;22(4):568-576
Arteriovenous malformations (AVMs) are direct communications between primitive reticular networks of dysplastic vessels that have failed to mature into capillary vessels. Based on angiographic findings, peripheral AVMs can be classified into six types: type I, type IIa, type IIb, type IIc, type IIIa, and type IIIb. Treatment strategies vary with the types. Type I is treated by embolizing the fistula between the artery and the vein with coils. Type II (IIa, IIb, and IIc) AVM is treated as follows:first, reduce the blood flow velocity in the venous segment of the AVM with coils; second, perform ethanol embolotherapy of the residual shunts. Type IIIa is treated by transarterial catheterization of the feeding arteries and injection of diluted ethanol. Type IIIb is treated by transarterial or direct puncture approaches. A high concentration of ethanol is injected through the transarterial catheter or direct puncture needle. When the fistula is large, coil insertion is required to reduce the amount of ethanol. Type I and type II AVMs showed the best clinical results; type IIIb showed a satisfactory response rate. However, type IIIa showed the poorest response rate, either alone or in combination with other types. Clinical success can be achieved by using different treatment strategies for different angiographic AVM types.
4.How to Treat Peripheral Arteriovenous Malformations
Ran KIM ; Young Soo DO ; Kwang Bo PARK
Korean Journal of Radiology 2021;22(4):568-576
Arteriovenous malformations (AVMs) are direct communications between primitive reticular networks of dysplastic vessels that have failed to mature into capillary vessels. Based on angiographic findings, peripheral AVMs can be classified into six types: type I, type IIa, type IIb, type IIc, type IIIa, and type IIIb. Treatment strategies vary with the types. Type I is treated by embolizing the fistula between the artery and the vein with coils. Type II (IIa, IIb, and IIc) AVM is treated as follows:first, reduce the blood flow velocity in the venous segment of the AVM with coils; second, perform ethanol embolotherapy of the residual shunts. Type IIIa is treated by transarterial catheterization of the feeding arteries and injection of diluted ethanol. Type IIIb is treated by transarterial or direct puncture approaches. A high concentration of ethanol is injected through the transarterial catheter or direct puncture needle. When the fistula is large, coil insertion is required to reduce the amount of ethanol. Type I and type II AVMs showed the best clinical results; type IIIb showed a satisfactory response rate. However, type IIIa showed the poorest response rate, either alone or in combination with other types. Clinical success can be achieved by using different treatment strategies for different angiographic AVM types.
5.Tumor Spheroids of an Aggressive Form of Central Neurocytoma Have Transit-Amplifying Progenitor Characteristics with Enhanced EGFR and Tumor Stem Cell Signaling
Hye Young SHIN ; Kyung-Seok HAN ; Hyung Woo PARK ; Yun Hwa HONG ; Yona KIM ; Hyo Eun MOON ; Kwang Woo PARK ; Hye Ran PARK ; C. Justin LEE ; Kiyoung LEE ; Sang Jeong KIM ; Man Seung HEO ; Sung-Hye PARK ; Dong Gyu KIM ; Sun Ha PAEK
Experimental Neurobiology 2021;30(2):120-143
Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as KLF4 and TPD5L1, when compared to their differentiated cells and human NSCs. Importantly, Gene Set Enrichment Analysis showed that gene sets of GBM-Spheroids, EGFR Signaling, and Packaging of Telomere Ends are enriched in CN-spheroids in comparison with their differentiated cells. We speculate that CN tumor stem cells have TAP and RGC characteristics, and upregulation of EGFR signaling as well as downregulation of eph-ephrin signaling have critical roles in tumorigenesis of CN. And their ephemeral nature of TAPs destined to neuroblasts, might reflect benign nature of CN.
6.Long-term Outcome of Microscopic Transsphenoidal Surgery for Prolactinomas as an Alternative to Dopamine Agonists
Kawngwoo PARK ; Kwang Hyon PARK ; Hye Ran PARK ; Jae Meen LEE ; Yong Hwy KIM ; Dong-Young KIM ; Tae-Bin WON ; Sung Hye KONG ; Jung Hee KIM ; Chan Soo SHIN ; Sun Ha PAEK
Journal of Korean Medical Science 2021;36(15):e97-
Background:
Although long-term dopamine agonist (DA) therapy is recommended as a first-line treatment for prolactinoma, some patients may prefer surgical treatment because of the potential adverse effects of long-term medication, or the desire to become pregnant. This study aimed to determine whether surgical treatment of prolactinomas could be an alternative to DA therapy.
Methods:
In this retrospective study, 96 consecutive patients (74 female, 22 male) underwent primary pituitary surgery without long-term DA treatment for prolactinomas at a single institution from 1990 to 2010. All patients underwent primary surgical treatment in the microscopic transsphenoidal approach (TSA).
Results:
The median age and median follow-up period were 31 (16–73) years and 139.1 (12.2–319.6) months, respectively. An initial overall remission was accomplished in 47.9% (46 of 96 patients, 33 macroadenomas, and 13 microadenomas) of patients. DA dose reduction was achieved in all patients after TSA. A better remission rate was independently predicted by lower diagnostic prolactin levels and by a greater extent of surgical resection. Overall remission at the last follow-up was 33.3%, and the overall recurrence rate was 30.4%. The permanent complication rate was 3.1%, and there was no mortality.
Conclusion
TSA can be considered a safe and potentially curative treatment for selective microprolactinomas as an alternative to treatment with a long-term DA.
7.EEG Revealed That Fragrances Positively Affect Menopausal Symptoms in Mid-life Women
Sun Ae MOON ; Jis ub BAE ; Kwang su KIM ; Si Young CHO ; Gu sang KWON ; Ran LEE ; Seung Ho KO ; Soy eon LIM ; Che il MOON
Experimental Neurobiology 2020;29(5):389-401
During mid-life, women experienced not only physical but also neurological transition. Because of this, many women suffer from physiological and/or psychological menopausal symptoms. Although hormone therapy (HT) was broadly used to alleviate menopausal symptoms, HT showed inconsistent effects in case of psychological symptoms. Moreover, mid-life women’s brains have distinct characteristics than in other periods of life, it is needed to study psychological symptoms in shifted brain network of mid-life women. As an alternative, inhalation of fragrances may alleviate psychological menopausal symptoms. To characterize the alleviation mechanism by fragrances, we tested the effect of fragrances on menopausal symptoms using electroencephalographic (EEG) methods. We hypothesized that fragrance could restore mid-life women’s brain response to stressful situations. We tested six fragrance conditions, including no-odor condition (solvent only) in twenty-eight mid-life women (49.75 years±3.49).Our results showed that fragrances increased alpha power and decreased β/α ratio depending on the severity of menopausal symptoms in a stressful situation. Our study would be helpful in psychological menopausal symptom alleviation as well as fragrance screening for well-being in mid-life.
8.Higher Morbidity of Monogenic Inflammatory Bowel Disease Compared to the Adolescent Onset Inflammatory Bowel Disease
Kwang Yeon KIM ; Eun Joo LEE ; Ju Whi KIM ; Jin Soo MOON ; Ju Young JANG ; Hye Ran YANG ; Jae Sung KO
Pediatric Gastroenterology, Hepatology & Nutrition 2018;21(1):34-42
PURPOSE: Monogenic inflammatory bowel disease (IBD) patients do not respond to conventional therapy and are associated with a higher morbidity. We summarized the clinical characteristics of monogenic IBD patients and compared their clinical outcomes to that of non-monogenic IBD patients. METHODS: We performed a retrospective cohort study of all children <18 years old who were diagnosed with IBD between 2005 and 2016. A total of 230 children were enrolled. Monogenic IBD was defined as a presentation age less than 6 years old with confirmation of a genetic disorder. We subdivided the groups into monogenic IBD (n=18), non-monogenic very early-onset IBD (defined as patients with a presentation age <6 years old without a confirmed genetic disorder, n=12), non-monogenic IBD (defined as all patients under 18 years old excluding monogenic IBD, n=212), and severe IBD (defined as patients treated with an anti-tumor necrosis factor excluding monogenic IBD, n=92). We compared demographic data, initial pediatric Crohn disease activity index/pediatric ulcerative colitis activity index (PCDAI/PUCAI) score, frequency of hospitalizations, surgical experiences, and height and weight under 3rd percentile among the patients enrolled. RESULTS: The initial PCDAI/PUCAI score (p < 0.05), incidence of surgery per year (p < 0.05), and hospitalization per year (p < 0.05) were higher in the monogenic IBD group than in the other IBD groups. Additionally, the proportion of children whose weight and height were less than the 3rd percentile (p < 0.05 and p < 0.05, respectively) was also higher in the monogenic IBD group. CONCLUSION: Monogenic IBD showed more severe clinical manifestations than the other groups.
Adolescent
;
Child
;
Cohort Studies
;
Colitis, Ulcerative
;
Crohn Disease
;
Hospitalization
;
Humans
;
Immunologic Deficiency Syndromes
;
Incidence
;
Inflammatory Bowel Diseases
;
Interleukin-10
;
Necrosis
;
Retrospective Studies
9.Prevalence of Malnutrition in Hospitalized Patients: a Multicenter Cross-sectional Study
Min Chang KANG ; Ji Hoon KIM ; Seung Wan RYU ; Jae Young MOON ; Je Hoon PARK ; Jong Kyung PARK ; Jong Hoon PARK ; Hyun Wook BAIK ; Jeong Meen SEO ; Myoung Won SON ; Geun Am SONG ; Dong Woo SHIN ; Yeon Myung SHIN ; Hong yup AHN ; Han Kwang YANG ; Hee Chul YU ; Ik Jin YUN ; Jae Gil LEE ; Jae Myeong LEE ; Jung Hwa LEE ; Tae Hee LEE ; Haejun YIM ; Hyun Jeong JEON ; Kyuwhan JUNG ; Mi Ran JUNG ; Chi Young JEONG ; Hee Sook LIM ; Suk Kyung HONG ;
Journal of Korean Medical Science 2018;33(2):e10-
BACKGROUND: Malnutrition is associated with many adverse clinical outcomes. The present study aimed to identify the prevalence of malnutrition in hospitalized patients in Korea, evaluate the association between malnutrition and clinical outcomes, and ascertain the risk factors of malnutrition. METHODS: A multicenter cross-sectional study was performed with 300 patients recruited from among the patients admitted in 25 hospitals on January 6, 2014. Nutritional status was assessed by using the Subjective Global Assessment (SGA). Demographic characteristics and underlying diseases were compared according to nutritional status. Logistic regression analysis was performed to identify the risk factors of malnutrition. Clinical outcomes such as rate of admission in intensive care units, length of hospital stay, and survival rate were evaluated. RESULTS: The prevalence of malnutrition in the hospitalized patients was 22.0%. Old age (≥ 70 years), admission for medical treatment or diagnostic work-up, and underlying pulmonary or oncological disease were associated with malnutrition. Old age and admission for medical treatment or diagnostic work-up were identified to be risk factors of malnutrition in the multivariate analysis. Patients with malnutrition had longer hospital stay (SGA A = 7.63 ± 6.03 days, B = 9.02 ± 9.96 days, and C = 12.18 ± 7.24 days, P = 0.018) and lower 90-day survival rate (SGA A = 97.9%, B = 90.7%, and C = 58.3%, P < 0.001). CONCLUSION: Malnutrition was common in hospitalized patients, and resulted in longer hospitalization and associated lower survival rate. The rate of malnutrition tended to be higher when the patient was older than 70 years old or hospitalized for medical treatment or diagnostic work-up compared to elective surgery.
Cross-Sectional Studies
;
Hospitalization
;
Humans
;
Intensive Care Units
;
Korea
;
Length of Stay
;
Logistic Models
;
Malnutrition
;
Multivariate Analysis
;
Nutrition Assessment
;
Nutritional Status
;
Prevalence
;
Risk Factors
;
Survival Rate
10.A Report on Diabetic Foot and Amputation from the Korean Health Insurance Review & Assessment Service Data.
Jong Kil KIM ; Young Ran JUNG ; Kyung Tae KIM ; Chung Shik SHIN ; Kwang Bok LEE
Journal of Korean Foot and Ankle Society 2017;21(2):66-69
PURPOSE: This study reports on limb amputations in diabetic patients according to gender, age, and region based on the data from the Korean Health Insurance Review & Assessment Service. MATERIALS AND METHODS: The number of amputations was compared by region, age, gender, and year, as well as by femoral region, lower leg, foot, and toe in diabetic patients who received limb amputation. This analysis was performed based on the data from the Korean Health Insurance Review & Assessment Service, between January 2009 and December 2014. RESULTS: The total number of amputations between the study period was 9,155. The number of patients who were treated at hospitals for diabetes in 2009 was 1.9 million, among which, 1,214 patients underwent amputation. In 2014, the incidence of diabetes was 1,747 in 2.58 million individuals. With this rising incidence of diabetes, the amputation of limbs due to diabetes is increasing every year. In particular, the following regions were amputated more often: femoral region, 2.3%; lower legs, 19.6%; feet, 18.1%; and toes 60.0%. Regarding gender differences, males showed a higher amputation rate than females for all body parts. With respect to region, Seoul was the highest with 30.2%, followed by Gyeonggi with 19.9%, and Busan with 8.8%. According to age, older age showed greater diabetic amputation rate. CONCLUSION: In accordance with the rising incidence of diabetes, the diabetic amputation is also increasing. Here, we showed that toes were amputated with the highest percentage and males had greater amputation rate than females for all body parts. Moreover, amputation rate was highest in older diabetic patients, especially for those in their seventies. Additionally, Seoul was the region with highest amputation rate.
Amputation*
;
Busan
;
Diabetes Mellitus
;
Diabetic Foot*
;
Extremities
;
Female
;
Foot
;
Gyeonggi-do
;
Human Body
;
Humans
;
Incidence
;
Insurance, Health*
;
Korea
;
Leg
;
Male
;
Seoul
;
Sex Factors
;
Toes

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