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.

Ki-67 Expression Gives Additional Prognostic Information on St. Gallen 2007 and Adjuvant! Online Risk Categories in Early Breast Cancer

Jung, So-Youn,Han, Wonshik,Lee, Jong Won,Ko, Eunyoung,Kim, Eunkyu,Yu, Jong-Han,Moon, Hyeong-Gon,Park, In Ae,Oh, Do-Youn,Im, Seock-Ah,Kim, Tae-You,Hwang, Ki-Tae,Kim, Sung-Won,Noh, Dong-Young Springer - Society of Surgical Oncology 2009 Annals of Surgical Oncology Vol.16 No.5

Growth Inhibition of Colon Cancer through Inactivation of STAT3 Pathway by IL-10 and IL-1ra Released from Murine Macrophage

Jin Tae Hong, Dohee Won1, Mi Hee Park, Sun Mi Kown, Miran Jo, Sang-Yoon Nam, Beom Jun Lee, Young Won Yun, Ki-Wan Oh, Sang Bae Han 충북대학교 동물의학연구소 2011 Journal of Biomedical and Translational Research Vol.12 No.4

The objective of this study was to determine the effect of macrophages on growth of human colon cancer cells. The results showed that co-culture of colon cancer cells with macrophages inhibited the growth of colon cancer cells (HCT116 and SW620) depending on the number of macrophages, RAW 264.7 cells, and activated THP-1 cells accompanied by down regulation of pSTAT3 in cancer cells. We also found that expression and release of cancer cell growth inhibitory cytokines, IL-1 receptor antagonist (IL-1ra) and IL-10, was increased in macrophages. Blocking of the STAT3 pathway with specific inhibitor and siRNA of STAT3 abolished the growth of colon cancer cells and expression of IL-1ra and IL-10. In addition, neutralization of IL-1ra and IL-10 with antibodies resulted in reversal of macrophage-induced inhibition of cancer cell growth. These data showed that IL-1ra and IL-10 released from macrophages inhibit growth of colon cancer cells through inhibition of the STAT3 pathway

The impact of pathologic differentiation (well/ poorly) and the degree of Ki-67 index in patients with metastatic WHO grade 3 GEP-NECs.

Kim, Seung Tae,Lee, Su Jin,Lee, Jeeyun,Park, Joon Oh,Park, Young Suk,Lim, Ho Yeong,Kang, Won Ki Grune & Stratton 2017 Journal of clinical oncology Vol.35 No._suppl15

<P> e15686 </P><P> Background: Herein, we investigated the impact of pathologic differentiation (well or poorly differentiated) in metastatic grade 3 GEP-NEC patients receiving etoposide and platinum-based therapy. Simultaneously, we evaluated a more exact Ki67 index cut-off point to select patients with grade 3 GEP-NEC who might benefit from etoposide plus platinum (EP)-based therapy. Methods: Among patients pathologically diagnosed with metastatic grade 3 GEP-NECs at Samsung Medical Center between June 2013 and March 2016, 31 GEP-NEC patients receiving etoposide and platinum-based therapy were included in this study. Results: Primary sites included 13 foregut-derived GEP-NECs [stomach (n = 4), duodenum (n = 4), and pancreas (n = 5)] and 2 hindgut-derived GEP-NECs of the rectum. Sixteen unclassified GEP-NECs originated from 7 gall-bladder (GB), 6 liver and 3 unknown primary sites. According to pathologic differentiation, 14 patients had well differentiated and 17 had poorly differentiated grade 3 GEP-NECs. Between well differentiated and poorly differentiated grade 3 GEP-NECs, there was a significant difference in the distribution of Ki67 index. There was no significant difference of treatment efficacy between well and poorly differentiated grade 3 GEP-NECs (RR; 35.7% vs. 41.2%, p = 0.525). Tumor response to EP occurred in 5 of 7 patients with Ki67 > 60% and 7 of 24 with Ki67≤60%, which was significantly different (RR; 71.4% vs. 29.2%, P = 0.043). There was no significant difference in PFS according to pathologic differentiation (well differentiated vs. poorly differentiated) and Ki67 index ( > 60% vs ≤60%). Conclusions: Grade 3 GEP-NECs could be morphologically classified into well and poorly differentiated NETs. Additionally, among grade 3 GEP-NECs, there was a significant difference in ranges of Ki67 index between well and poorly differentiated NECs. Higher levels ( > 60%) of Ki67 index might be a predictive marker for efficacy of EP as a standard regimen in grade 3 GEP-NECs. </P>

수족냉증(手足冷症) 환자(患者)에 대(對)한 컴퓨터 적외선(赤外線) 체열촬영(體熱撮影)의 의의(意義)

조유경,오수완,조남희,김동묵,김진성,류봉하,박동원,류기원,Cho, Yu-Kyung,Oh, Su-Wan,Cho, Nam-Hee,Kim, Dong-Mook,Kim, Jin-Seong,Ryu, Bong-Ha,Park, Dong-Won,Ryu, Ki-Won 대한한방내과학회 1998 大韓韓方內科學會誌 Vol.19 No.2

To make a objective diagnosis of the syndrome of cold-limbs, We investigated the 20 patients with cold limbs and GI trouble and 20 normal people as a control group. And we compared the thermal difference between Chon-jung(CV17) and Chung-wan(CV12 中脘), Chon-jung(CV17) and Ki-hae(氣海 CV6) and we compared the thermal differences of No-gung(PE8 勞宮) and Yong-chon(湧泉 KI1), too. The results were as follows. 1. All 20 patients had GI trouble and cold limbs. They had the symptom-Indigestion(16 cases-80%) with heart burn, tympanites, abdominal distention, hiccup, belching. Beside that symptom they also had constipation(6 cases-30%), diarrhea(3 cases-15%), headache & dizziness(6 cases-30%). And some had the menstrual syndrome, chronic fatigue, palpitation, insomnia, edema, arthralgia. 2. The thermal difference of the palms between the patients group and the control group were $25.70^{\circ}C,\;25.82^{\circ}C$, but they were not significant. 3. The thermal difference of the soles between the patients group and the control group were $23.58^{\circ}C,\;24.42^{\circ}C$ and the significancy was P=0.020 so it was significant(P<0.05). 4. The thermal difference of the palms and Chon-jung(CV17) between the patients group and the control group were $1.08^{\circ}C,\;0.76^{\circ}C$, but they were not significant. 5. The thermal difference of the sales and Chon-jung(CV17) between the patients group and the control group were $3.01^{\circ}C,\;1.90^{\circ}C$ and the significancy was P=0.003 so it was significant(P<0.05). 6. The thermal difference of Chon-jung(CV17) and Chung-wan(CV12 中脘) between the patients group and the control group was $0.30^{\circ}C,\;0.62^{\circ}C$ and the significancy was P=0.793 so it was significant(P<0.05). 7. The thermal difference of Chon-jung(CV17) and Ki-hae(CV6 氣海) between the patients group and the control group was $0.53^{\circ}C,\;0.68^{\circ}C$, but they were not significant. From the above, I could find the significance of D.I.T.I to diagnose the cold-feet not the cold-hands and the thermal difference between the trunk and limbs was more significant on cold-feet than on cold-hand, either.

Benzyl Isothiocyanate Inhibits Prostate Cancer Development in the Transgenic Adenocarcinoma Mouse Prostate (TRAMP) Model, Which Is Associated with the Induction of Cell Cycle G1 Arrest

Cho, Han Jin,Lim, Do Young,Kwon, Gyoo Taik,Kim, Ji Hee,Huang, Zunnan,Song, Hyerim,Oh, Yoon Sin,Kang, Young-Hee,Lee, Ki Won,Dong, Zigang,Park, Jung Han Yoon MDPI 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.2

<P>Benzyl isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin, a compound found in cruciferous vegetables, and has been shown to have anti-tumor properties. In the present study, we investigated whether BITC inhibits the development of prostate cancer in the transgenic adenocarcinoma mouse prostate (TRAMP) mice. Five-week old, male TRAMP mice and their nontransgenic littermates were gavage-fed with 0, 5, or 10 mg/kg of BITC every day for 19 weeks. The weight of the genitourinary tract increased markedly in TRAMP mice and this increase was suppressed significantly by BITC feeding. H and E staining of the dorsolateral lobes of the prostate demonstrated that well-differentiated carcinoma (WDC) was a predominant feature in the TRAMP mice. The number of lobes with WDC was reduced by BITC feeding while that of lobes with prostatic intraepithelial neoplasia was increased. BITC feeding reduced the number of cells expressing Ki67 (a proliferation marker), cyclin A, cyclin D1, and cyclin-dependent kinase (CDK)2 in the prostatic tissue. <I>In vitro</I> cell culture results revealed that BITC decreased DNA synthesis, as well as CDK2 and CDK4 activity in TRAMP-C2 mouse prostate cancer cells. These results indicate that inhibition of cell cycle progression contributes to the inhibition of prostate cancer development in TRAMP mice treated with BITC.</P>

A New Pea Cultivar, Cheongmi with Short Stem Height, Lodging Resistance and High Yield

Won Young Han,Sang Ouk Shin,Myoung Gun Choung,Chan Sik Jung,Doo Chull Shin,Sea Kwan Oh,Sung Taeg Kang,In Youl Baek,Duck Yong Suh,Soon Chul Kim,Dong Kwan Kim,Chang Ki Son 한국육종학회 2004 한국육종학회지 Vol.36 No.5

A new pea cultivar, Cheongmi was developed at the Yeongnam Agricultural Research Institute (YARI) in 2003. It was selected from a cross YP303 (Frescoloy / Upton) // YP113 (Sparkle/Early Bird) /3/ YP115 (Sparkle / Euiseongjaerae) in 1992. The preliminary,

Homocysteine, Folate and Methylenetetrahydrofolate Reductase Polymorphism in Korean Normal Subjects

Oh, Ki-Won,Kang, Moo-Il,Lee, Woon-Young,Ahn, Yoo-Bae,Song, Ki-Ho,Yoo, Soon-Jib,Yoon, Kun-Ho,Cha, Bong-Yun,Lee, Kwang-Woo,Son, Ho-Young,Kang, Sung-Koo 가톨릭대학교 2000 Bulletin of The Catholic Research Institutes of Me Vol.28 No.-

Objective : Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Recently, a mutatin (677C→T) was identified in the methylenetetrahydrofolate reductase gene leading to the substitution of valine(V) for alanine(A). This mutation causes a reduced folate-dependent enzyme activity which leads to increased serum homocysteine. In this study, we examined the association between the V allele of the methylenetetrahydrofolate reductase gene and serum total homocysteine and folate concentrations in Korean healthy subjects. Methods : In 198 healthy subjects, the methylenetetrahydrofolate reductase gene genotypes were analyzed by polymerase chain reaction followed by HinfI digestion. Serum total homocysteine and folate concentrations were measured in age- and sex-matched 14 healthy subjects in each of the three methylenetetrahydrofolate reductase genotypes. Results : Homozygosity for 677C→T mutation in the methylenetetrahydrofolate reductase gene was found in 31 (15.7%) of 198 healthy subjects. In healthy subjects, those bearing the VV genotype tend to have higher serum total homocysteine concentrations than AA genotype but this was not statistically significant. Correlation between serum total homocysteine concentrations and other clinical variables showed that serum folate and creatinine were significant. Conclusion : We conclude that although the frequency of VV genotype in Korean healthy subjects is higher than that of other reports, this mutation is not associated with increased serum total homocysteine concentrations in Korean healthy subjects. (The Korean Journal of Internal Medicine 57(6):1030-1036, 1999)

The Effect of Simvastatin on the Proliferation and Differentiation of Human Bone Marrow Stromal Cells

Oh Ki Won,Lee Jung Min,Kang Moo Il,Lee Kwang Woo,Baek Ki Hyun,Lee Won Young,Tae Hyun Jung,Lee En Jung,Han Je Ho,Cha Bong Yun,Son Ho Young,Kang Sung Koo 대한의학회 2005 Journal of Korean medical science Vol.20 No.3

Methylenetetrahydrofolate Reductase Polymorphism in Korean Type 2 Diabetic Patients with Macroangiopathy

Oh, Ki-Won,Kang, Moon-Il,Lee, Young-Won,Ahn, Yoo-Bae,Song, Ki-Ho,Yoo, Soon-Jib,Yoon, Kun-Ho,Cha, Bong-Yun,Lee, Kwang-Woo,Son, Ho-Young,Kang, Sung-Koo 가톨릭대학교 2000 Bulletin of The Catholic Research Institutes of Me Vol.28 No.-

Background : Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Recently, a mutation (677C→T) was identified in the methylenetetrahydrofolate reductase (MTHFR) gene leading to the substitution of valine (V) for alanine (A). This mutation causes a reduced folate-dependent enzyme activity which leads to increased serum homocysteine. In this study, we examined the association between the V allele of the methylenetetrahydrofolate reductase gene and macroangiopathy in Korean patients with type 2 diabetes mellitus. Methods : In 54 type 2 diabetic patients with macroangiopathy and 198 normal subjects, the MTHFR genotypes were analyzed by polymerase chain reaction (PCR) followed by HinfI digestion. To confirm the detection of the MTHFR polymorphism by the PCR-restriction fragment length polymorphism (RFLP) analysis, DNA Sequencing was performed on the PCR products. Results : The allele frequency of the V mutation was slightly higher in the patients than in the normal subjects but that was not statistically significant. The crude Ors and 95% Cis for the allele frequency of the V mutation were 1.16 (0.76-1.79). Genotype frequencies were 35.9% for AA, 48.4% for AV, and 15.7% for VV in the normal subjects and 31.5% for AA, 50.0% for AV, and 18.5% for VV in the patients. The crude Ors and 95% Cis for the VV genotype were 1,22 (0.56-2.67). In multiple regression model, the VV genotype was not associated with diabetic macroangiopathy. Conclusion : Although the frequencies of VV genotype in Korean normals (□16%) are higher than those of other ethical populations (□12%), this mutation is not associated with macroangiopathy in type 2 diabetic patients. But, our sample size was to small and larger Cohort studies will be needed to confirm the effect of MTHFR polymorphism on the development of macroangiopathy in diabetic patients. (The Journal of Korean Diabetes Association 23(5):625-634, 1999)