Comparison of Proliferative Activity in Each Histological Subtypes of Benign and Atypical Intracranial Meningiomas by PCNA and Ki-67 Immunolabeling

최승진,장은덕,권성오,계대곤,박춘근,이상원,강준기,Choi, Seung Jin,Chang, Eun Deok,Kwon, Seung Oh,Kye, Dae Kon,Park, Choon Keun,Lee, Sang Won,Kang, Joon Ki The Korean Neurosurgical Society 2000 Journal of Korean neurosurgical society Vol.29 No.9

목 적 : 양성 뇌수막종에 비하여 이형성 및 악성 뇌수막종이 나쁜 임상적인 예후 및 양상을 보이는 것은 잘 알려져 있으나, 양성 뇌수막종에 있어서 각각의 병리조직학적 아형에 따른 생물학적 양상의 차이에 대해서는 잘 알려지지 않거나 일부 논란이 되고있다. 본 연구에서는 이형성 뇌수막종 및 양성 뇌수막종의 각각의 병리조직학적 아형에 따른 증식능의 차이여부를 알아보고자 PCNA와 Ki-67표지지수를 분석하였다. 방 법 : 본원에서 뇌수막종으로 수술을 시행하여 얻은, 재발을 보여 재수술을 시행한 2례를 포함하여, 파라핀에 포매시킨 27개의 조직을 대상으로 병리학적인 증식능을 분석하기 위해, PCNA에 대한 단일항체 및 MIB-1 단일항체를 이용한 면역조직화학적 염색을 시행하였다. 조직학적 분류상 meningothelial type이 8례, transitional type이 9례, fibroblastic type이 5례였으며, 이형성 수막종이 5례였다. 결 과 : PCNA표지지수의 평균값은 양성 수막종에서 meningothelial type이 $4.82{\pm}5.10%$, transitional type이 $9.01{\pm}4.25%$, fibroblastic type이 $5.66{\pm}5.32%$를 보였으나 이형성 수막종에서는 $27.62{\pm}19.67%$의 높은 지수를 나타냈고, Ki-67 표지지수의 평균값은 양성 수막종의 아형에서 각각 $0.43{\pm}0.85%$, $0.44{\pm}1.08%$, $0.24{\pm}0.18%$를 보이고, 역시 이형성 수막종에서는 $0.84{\pm}0.59%$의 높은 지수를 보였다. 즉, 양성 수막종에서 각각의 아형에 따른 PCNA 및 Ki-67 표지지수는 통계학적으로 의미있는 차이는 없었으나(p>0.05), 이형성 수막종에서는 의미있는 높은 표지지수를 보여(p<0.05) 양성 수막종에서 보다 높은 증식능을 보임을 알 수 있었다. 결 론 : PCNA 및 Ki-67 표지지수를 이용한 증식능의 비교결과, 양성 뇌수막종에서는 각각의 아형에 따른 생물학적 양상이나 예후는 차이가 없을것으로 생각되나, 이형성 수막종에서는 높은 증식능을 보여 이에 대한 예후를 예상할 수 있을것으로 생각되며, 또한 이러한 표지지수가 병리조직학적으로 양성과 이형성의 감별에 많은 도움이 될것으로 사료된다. Objective : The clinical prognosis and biological behavior of atypical and especially malignant meningiomas are well known to be worse than benign meningioma, but the degree of biological aggressiveness in each classical subtypes of benign meningioma is controversy. This study was performed to see whether there is a difference in the proliferative activity between each different histological subtypes of benign meningioma as well as atypical meningioma. Methods : Paraffin-embedded surgical specimens of 27 meningiomas, including two recurrent tumors, were studied to evaluate proliferative activity by immunohistochemical method with monoclonal antibodies to proliferating cell nuclear antigen(PCNA) and MIB-1. The specimens consisted of 8 cases of meningothelial, 9 cases of transitional, 5 cases of fibroblastic subtypes and 5 cases of atypical meningiomas. Results : Mean PCNA labeling indices of meningothelial, transitional and fibroblastic meningiomas were $4.82{\pm}5.10%$, $9.01{\pm}4.25%$ and $5.66{\pm}5.32%$, but that of atypical meningiomas was $27.62{\pm}19.67%$, noting a higher value compared to all three subtypes of benign meningiomas. Mean Ki-67 labeling indices of the above 3 subtypes were $0.43{\pm}0.85%$, $0.44{\pm}1.08%$ and $0.24{\pm}0.18%$, and that of atypical meningiomas was also revealed to be of higher value ($0.84{\pm}0.59%$). PCNA and Ki-67 labeling indices were not statistically different between histological subtypes of benign meningioma(p>0.05), but the differences of both immunolabeling between benign and atypical meningiomas were statistically significant(p<0.05). Conclusion : Immunolabeling of PCNA and Ki-67 in intracranial meningiomas reveals no prognostic difference between meningothelial, transitional and fibroblastic subtypes in classical benign meningiomas by measuring expression of PCNA and Ki-67, but it seems to be helpful in differentiating benign and atypical meningioma, later showing more proliferative activity and biological aggressiveness.

한의진단명과 진단요건의 표준화 연구 III : 3차년도 연구결과 보고

최선미,양기상,최승훈,박경모,박종현,심범상,김성우,노석선,이인선,정진홍,이진용,김달래,임형호,김윤범,박성식,송태원,김종우,이승기,최윤정,신순식 한국한의학연구원 1997 한국한의학연구원논문집 Vol.3 No.1

The diagnostic requirements were suggested and explained regarding the systems of differentiation of symptoms and signs in the third year study of standardization and unification of the terms and conditions used for diagnosis in oriental medicine. The systems were as follows : - analyzing and differentiating of epidemic febrile disease - analyzing and differentiating in accordance with the Sasang constitution medicine based on four-type recognition - differentiation of disease according to pathological changes of Chong and Ren channels - standards for diagnosis of women's disease - standards for diagnosis of children's disease - standards for diagnosis of motor and sensor disturbance (-muscle. born, joint, etc.) - standards for diagnosis of neuropsychiatric disease - standards for diagnosis of five sense organ disease - standards for diagnosis of external disease The indivisual diagnosis pattern was arranged by the diagnostic requirements in the following order : another name, notion of diagnosis pattern, index of differentiation of symptoms and signs, the main point of diagnosis, analysis of diagnosis pattern, discrimination of diagnosis pattern, prognosis, a way of curing a disease, prescription, herbs in common use, disease appearing the diagnosis pattern, documents. The standards for diagnosis of each disease was arranged by the diagnostic requirements in the following order : another name, notion of disease, the main point of diagnosis, analyzing and differentiating of disease, analysis of disease, discrimination of disease, prognosis, a way of curing and prescription of disease, disease in western medicine appearing the disease in oriental medicine, documents.

Clinicopathological and molecular analysis of multinodular and vacuolating neuronal tumors of the cerebrum

Choi, Euno,Kim, Seonk-Ik,Won, Jae-Kyung,Chung, Chun Kee,Kim, Seung Ki,Choi, Seung-Hong,Choi, Seongmin,Han, Bome,Ahn, Bokyung,Im, Sun-Wha,Park, Sung-Hye Elsevier 2019 Human pathology Vol.86 No.-

<P><B>Summary</B></P> <P>Multinodular and vacuolating neuronal tumor (MVNT) of the cerebrum is a recently recognized rare neuronal tumor, and its pathogenesis is unclear. We analyzed 7 cases of histologically typical MVNT: 6 were adults (mean age, 43.0 years [range, 23-56 years]) and 1 was a child (age, 10 years). The most common symptoms were seizures (n = 4) and headache (n = 2). The tumors were supratentorial (temporal, 5; frontal lobes, 2) in origin as reported. Vacuolated tumor cells were robustly positive for α-INA and Olig2 and at least partly positive for synaptophysin and MAP2, but negative for Neu-N, nestin and CD34. GFAP and vimentin were expressed in reactive astrocytes but not in tumor cells. Negative results were obtained for p53, IDH-1, BRAF<SUP>V600E</SUP>, H3 K27M, EGFR, Lin28A, and L1CAM. ATRX, BRG1, INI-1, and TMHH were retained. The Ki-67 labeling index was very low (<1%), and pHH3 revealed no mitotic figure. Ultrastructural features of tumor cells were comparable with those of immature neuronal cells, with several intracytoplasmic myelin-like autophagosomes and pericellular vacuolization. No <I>IDH1</I>/<I>IDH2</I> and <I>BRAF</I> <SUP> <I>V600E</I> </SUP> mutations were found upon direct sequencing. Whole-exome sequencing revealed <I>FGFR2</I>-<I>ZMYND11</I> gene fusion in 1 case. After gross total resection, all patients were alive without seizures. There was no tumor recurrence during an average period of 68 months (range, 23-101 months). The analysis of 7 typical cases of MVNT suggested that these lesions may be clonal tumors because <I>FGFR2</I>-<I>ZMYND11</I> fusion was found (1 case).</P> <P><B>Highlights</B></P> <P> <UL> <LI> “MVNT” of the cerebrum is a recently recognized rare epileptogenic neuronal tumor. </LI> <LI> Whole-exome sequencing revealed <I>FGFR2</I>-<I>ZMYND11</I> gene fusion in one of our MVNT cases. </LI> <LI> The tumor cell is robustly positive for α-INA and Olig2, but negative for Neu-N. </LI> <LI> Ultrastructurally, tumor cells have autophagolysosomes with pericellular vacuolization. </LI> <LI> There was no tumor recurrence during an average period of 68 months. </LI> </UL> </P>

Gintonin facilitates catecholamine secretion from the perfused adrenal medulla

Seung-Yeol Na,Ki-Hwan Kim,Mi-Sung Choi,Kang-Su Ha,Dong-Yoon Lim 대한생리학회-대한약리학회 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.6

The present study was designed to investigate the characteristics of gintonin, one of components isolated from Korean Ginseng on secretion of catecholamines (CA) from the isolated perfused model of rat adrenal gland and to clarify its mechanism of action. Gintonin (1 to 30 μg/ml), perfused into an adrenal vein, markedly increased the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. The gintonin-evoked CA secretion was greatly inhibited in the presence of chlorisondamine (1 μM, an autonomic ganglionic bloker), pirenzepine (2 μM, a muscarinic M₁ receptor antagonist), Ki14625 (10 μM, an LPA_1/3 receptor antagonist), amiloride (1 mM, an inhibitor of Na⁺/Ca²⁺ exchanger), a nicardipine (1 μM, a voltage-dependent Ca²⁺ channel blocker), TMB-8 (1 μM, an intracellular Ca²⁺antagonist), and perfusion of Ca²⁺-free Krebs solution with 5mM EGTA (a Ca²⁺chelater), while was not affected by sodium nitroprusside (100 μM, a nitrosovasodialtor). Interestingly, LPA (0.3~3 μM, an LPA receptor agonist) also dose-dependently enhanced the CA secretion from the adrenal medulla, but this facilitatory effect of LPA was greatly inhibited in the presence of Ki 14625 (10 μM). Moreover, acetylcholine (AC)-evoked CA secretion was greatly potentiated during the perfusion of gintonin (3 μg/ml). Taken together, these results demonstrate the first evidence that gintonin increases the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. This facilitatory effect of gintonin seems to be associated with activation of LPA- and cholinergic-receptors, which are relevant to the cytoplasmic Ca²⁺ increase by stimulation of the Ca²⁺ influx as well as by the inhibition of Ca²⁺ uptake into the cytoplasmic Ca²⁺ stores, without the increased nitric oxide (NO). Based on these results, it is thought that gintonin, one of ginseng components, can elevate the CA secretion from adrenal medulla by regulating the Ca²⁺ mobilization for exocytosis, suggesting facilitation of cardiovascular system. Also, these findings show that gintonin might be at least one of ginseng-induced hypertensive components.

한의진단명과 진단요건의 표준화 연구 II (표준화 실례) : 2차년도 연구결과 중간 보고

양기상,최선미,최승훈,안규석,박경모,박종현,김성우,신승호,정우열,전병훈,고현,김정범,신상우,김성훈,김동희,권영규,엄현섭,장혜옥 한국한의학연구원 1996 한국한의학연구원논문집 Vol.2 No.1

The diagnostic requirements were suggested and explained regarding the systems of differentiation of symptoms and signs in the second year study of standardization and unification of the terms and conditions used for diagnosis in oriental medicine. The systems were as follows; - differential diagnosis according to condition of body fluid, differentiation of syndromes according to the state of qi and blood, differential diagnosis according to relative excessiveness or deficiency of yin and yang(氣血陰陽津液辨證) - differentiation of diseases according to pathological changes of the viscera and their interrelation - analyzing and differentiating of febrile diseases in accordance with the theory of the six channels(傷寒辨證) The individual diagnosis pattern was arranged by the diagnostic requirements in the following order : another name(異名), notion of diagnosis pattern, index of differentiation of symptoms and signs(辨證指標), the main point of diagnosis, analysis of diagnosis pattern(證候分析), discrimination of diagnosis pattern(證候鑑別), a way of curing a diseases(治法), prescription(處方), herb in common use(常用藥物), diseases appearing the diagnosis pattern(常見疾病), documents(文獻調査). This study was carried out on the basis of the Chinese documents and references.

Gintonin facilitates catecholamine secretion from the perfused adrenal medulla

Na, Seung-Yeol,Kim, Ki-Hwan,Choi, Mi-Sung,Ha, Kang-Su,Lim, Dong-Yoon The Korean Society of Pharmacology 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.6

The present study was designed to investigate the characteristics of gintonin, one of components isolated from Korean Ginseng on secretion of catecholamines (CA) from the isolated perfused model of rat adrenal gland and to clarify its mechanism of action. Gintonin (1 to $30{\mu}g/ml$), perfused into an adrenal vein, markedly increased the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. The gintonin-evoked CA secretion was greatly inhibited in the presence of chlorisondamine ($1{\mu}M$, an autonomic ganglionic bloker), pirenzepine ($2{\mu}M$, a muscarinic $M_1$ receptor antagonist), Ki14625 ($10{\mu}M$, an $LPA_{1/3}$ receptor antagonist), amiloride (1 mM, an inhibitor of $Na^+/Ca^{2+}$ exchanger), a nicardipine ($1{\mu}M$, a voltage-dependent $Ca^{2+}$ channel blocker), TMB-8 ($1{\mu}M$, an intracellular $Ca^{2+}$ antagonist), and perfusion of $Ca^{2+}$-free Krebs solution with 5mM EGTA (a $Ca^{2+}$chelater), while was not affected by sodium nitroprusside ($100{\mu}M$, a nitrosovasodialtor). Interestingly, LPA ($0.3{\sim}3{\mu}M$, an LPA receptor agonist) also dose-dependently enhanced the CA secretion from the adrenal medulla, but this facilitatory effect of LPA was greatly inhibited in the presence of Ki 14625 ($10{\mu}M$). Moreover, acetylcholine (AC)-evoked CA secretion was greatly potentiated during the perfusion of gintonin ($3{\mu}g/ml$). Taken together, these results demonstrate the first evidence that gintonin increases the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. This facilitatory effect of gintonin seems to be associated with activation of LPA- and cholinergic-receptors, which are relevant to the cytoplasmic $Ca^{2+}$ increase by stimulation of the $Ca^{2+}$ influx as well as by the inhibition of $Ca^{2+}$ uptake into the cytoplasmic $Ca^{2+}$ stores, without the increased nitric oxide (NO). Based on these results, it is thought that gintonin, one of ginseng components, can elevate the CA secretion from adrenal medulla by regulating the $Ca^{2+}$ mobilization for exocytosis, suggesting facilitation of cardiovascular system. Also, these findings show that gintonin might be at least one of ginseng-induced hypertensive components.

Therapeutic Effects of Recombinant Human Epidermal Growth Factor (rhEGF) in a Murine Model of Concurrent Chemo- and Radiotherapy-Induced Oral Mucositis

RYU, Seung-Hee,KANG, Ki Mun,MOON, Soo Young,CHAI, Gyu Young,HONG, Joon Pio,CHO, Kyoung-Oh,KANG, Mun-Il,CHOI, Eun Kyung,LEE, Sang-wook Journal of Radiation Research Editorial Committee 2010 JOURNAL OF RADIATION RESEARCH Vol.51 No.5

<P>Concurrent chemotherapy with radiotherapy (CCRT) has been applied for the treatment of advanced stage of head and neck cancer patients. However CCRT is associated with several complications including mucositis, dermatitis, stomatitis, etc. This study was conducted to evaluate the therapeutic effect of systemically administrated recombinant human epidermal growth factor (rhEGF) in CCRT-induced oral mucositis in a mouse model. Oral mucositis was induced in male BALB/c mice through combination treatment with cisplatin (11 mg/kg, i.p.) and irradiation (17 Gy) of the head and neck area. rhEGF (1.0 mg/kg/day for consecutive 3 days) was administered systemically, and the therapeutic effect was determined by histological evaluation of the oral mucosa. To elucidate optimal dose of rhEGF on CCRT-induced mucositis, various concentrations (0.04–3 mg/kg) of rhEGF were injected for 3 days. Systemic rhEGF administration accelerated the recovery of body weight. Histologically, rhEGF-treated mice showed significantly increased epithelial cell layer thickness, basal cell number, and expression of Ki-67 compared to control mice. Most effective dose was 1 mg/kg among other doses tested. Systemic administration of 1 mg/kg of rhEGF reduces the severity of oral mucositis induced by CCRT in a mouse model, suggesting that rhEGF can be used for treating CCRT-induced mucositis during the cancer treatment.</P>

Synchronous double primary cancers associated with a choledochal cyst and anomalous pancreaticobiliary ductal union

Kang Kook Choi,Sae Byeol Choi,Seung Woo Park,Hyun Ki Kim,Young Nyun Park,Kyung Sik Kim 대한외과학회 2011 Annals of Surgical Treatment and Research(ASRT) Vol.81 No.4

A 60-year-old female was admitted with epigastric pain lasting a month. Preoperative diagnosis was choledochal cyst with anomalous pancreaticobiliaryductal union (APBDU), C-P type. A papillary mass measuring 2.5 × 1.9 cm was found adjacent to the pancreaticocholedochal junction. Gallbladder (GB) cancer was also observed. Pyloric-preserving pancreaticoduodenectomy (PPPD) was performed. The patient received adjuvant chemotherapy/radiation therapy on the tumor bed. The gallbladder cancer showed serosal invasion, while the bile duct cancer extended into the pancreas. Although common bile duct (CBD) cancer lesion showed focally positive for p53 and the gallbladder cancer lesion showed negative for p53, the Ki-67 labeling index of the CBD cancer and GB cancer were about 10% and 30%, respectively. Nine months after curative resection, a stricture on the subhepatic colon developed due to adjuvant radiation therapy. Localized peritoneal seedings were incidentally found during a right hemicolectomy. The patient underwent chemotherapy and had no evidence of tumor recurrence for two years after PPPD.

관동맥질환에서 저밀도 지단백 입자 크기의 분포

임효영,김인숙,승기배,강동헌,전두수,장기육,박준철,이수영,홍순조,최규보 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.8

A subpopulation of cancer stem cells identifies radiographic characteristics in glioblastoma

Kim, Ja Eun,Kim, Sung Kwon,Shin, Jaekyung,Se, Young-Bem,Choi, Seung Hong,Park, Sung-Hye,Choi, Seung Ah,Lee, Ji Yeoun,Phi, Ji Hoon,Wang, Kyu-Chang,Park, Chul-Kee,Kim, Seung-Ki D.A. Spandidos 2017 Oncology letters Vol.13 No.3

<P>Cancer stem cells (CSCs), defined by CD133 expression, harbor heterogeneous subpopulations of cells, including endothelial progenitor cells (EPCs). This study aimed to investigate whether a subpopulation of CSCs could affect the radiographic characteristics of glioblastoma. Tissue samples from 10 patients newly diagnosed with glioblastoma were selected according to the radiographic characteristics of their tumors. The patients were divided into two groups based on preoperative magnetic resonance imaging demonstrating contrast enhancement, necrosis and infiltrative patterns: the enhancement/necrosis group (E/N, n=5) and the non-enhancement/infiltration group (NE/I, n=5). Flow cytometry was used to assess the CSCs while immunohistochemistry was used to study microvessel density and the proliferation index. The EPC (CD34<SUP>+</SUP>/CD133<SUP>+</SUP>) fraction in CSCs (CD133<SUP>+</SUP>) was larger in the NE/I group. However, there was little difference in the angiogenic activity assessed using microvessel density between the two groups. The proliferation index (assessed using the antibody Ki-67) was higher in the E/N group and was negatively correlated with the EPC fraction. The non-EPC (CD34<SUP>−</SUP>/CD133<SUP>+</SUP>) fraction is a major factor responsible for radiographic characteristics of contrast enhancement, thus establishing an association between a subpopulation fraction of CSCs and radiographic characteristics in glioblastoma. Therefore, the simple non-invasive assessment of studying contrast enhancement lesions in glioblastomas may be used to estimate CSC subpopulations.</P>