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>

직장 카르시노이드 종양에서 Ki-67 발현의 예후적 중요성

홍수민 ( Su Min Hong ),김유선 ( You Sun Kim ),문정섭 ( Jung Seop Moon ),김진남 ( Jin Nam Kim ),오명기 ( Myoung Ki Oh ),권선옥 ( Sun Ok Kwon ),정성연 ( Seong Yeon Jeong ),홍성우 ( Seong Woo Hong ),강윤경 ( Yun Kyung Kang ) 대한소화기학회 2013 대한소화기학회지 Vol.61 No.2

Background/Aims: Rectal carcinoid tumors can be resected with endoscopy, and it is important to assess their prognostic factors. We evaluated the potential of Ki-67 expression as a prognostic factor in rectal carcinoid tumors. Methods: We retrospectively reviewed the medical records of 37 patients with rectal carcinoid tumors who got endoscopic resection from January 2001 to January 2011 at Inje University Seoul Paik Hospital. We analyzed their endoscopic and histologic findings, Ki-67 expression, clinical outcome, and prognosis. Results: The mean age (±SD) of the patients was 56.3±10.7 years, and the male : female ratio was 3.6:1. The mean tumor size was 0.5±0.4 cm, 33 patients showed grade 1 tumors (89.2%) and the average Ki-67 expression was 0.7±1.2%. Thirty five patients underwent endoscopic mucosal resection, and two required endoscopic submucosal dissection. Eight patients had positive margins after resection, but no cases of lymphovascular invasion were identified. The median follow-up duration was 21.4±25.4 months, and no recurrences were observed. Conclusions: In low grade rectal carcinoid tumors which are lack of central depression on colonoscopy, the expression of a molecular marker of malignant potential, Ki-67, was low. Therefore, endoscopic resection seemed to be a safe and effective treatment for these tumors.

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

Ki - 1 임파종 1 예

강민모(Min Mo Kang),김경재(Kyoung Jae Kim),이지현(Ji Hyun Lee),최석문(Seog Mun Choi),안기성(Ki Sung Ahn),황기석(Kee Suk Whang),김용진(Yong Jin Kim),박재복(Jae Bok Park) 대한내과학회 1993 대한내과학회지 Vol.45 No.4

A 60-year-old man was admitted to our hospital complaining of fever with chillness and anarexia for 12 weeks. Physical examination revealed supraclavicular lymphadenopathy and left inguinal lymphadenopathy. Abdominal CT scan showed the evidence of maked lymphadenopathy on retraperitoneal, external iliac, obturator, left inguinal, and celiac lymph nodes. A pathologic diagnosis of Ki-1(+) lymphoma was made by the biopsed supraclavicular lymph node because the node consisted of large cells with pleomorphic nuclei, scanty cytoplasm, large basophilic nucleoli, atypical vacuoli and large cells were positive for leukocyte common antigen, Ber-H2, marker, and B-cell marker.

Expression of Wnt Target Genes in Solid Pseudopapillary Tumor of the Pancreas: A Pilot Study

Kang, Chang Moo,Kim, Hyun Ki,Kim, Hoguen,Choi, Gi Hong,Kim, Kyung Sik,Choi, Jin Sub,Lee, Woo Jung Lippincott Williams Wilkins, Inc. 2009 PANCREAS Vol.38 No.2

OBJECTIVES:: Solid pseudopapillary tumor (SPT) of the pancreas is very rare. This study was performed to analyze the expression of Wnt signal target genes (matrix metalloproteinase-7 [MMP-7], cyclin-D1, and c-myc) and Ki-67 in resected SPTs to determine their clinicopathologic characteristics according to their expression. METHODS:: From January 1995 to December 2005, 23 patients underwent pancreatic resections for SPT of the pancreas. Among 23 formalin-fixed, paraffin-embedded tissues, 12 were evaluated as a pilot study. Immunohistochemistry was performed using various detection and antigen retrieval methods to detect MMP-7, cyclin-D1, c-myc, and Ki-67. The expression of Wnt target genes was correlated with clinicopathologic features of the patients. RESULTS:: Solid pseudopapillary tumors of the pancreas always showed cytoplasmic/nuclear accumulation of &bgr;-catenin, frequent expression of cyclin-D1, and low proliferation index. MMP-7, cyclin-D1, c-myc, and Ki-67 were not correlated with microscopic features suggesting malignant potential (P > 0.05). Tumor size was closely related to microscopic features of malignant potential and apparently has an inverse relationship with the expression of cyclin-D1 and Ki-67 (P < 0.05). CONCLUSIONS:: Low proliferative index and associated MMP-7 expression may cause an unpredictable clinical course in this tumor. Subtle changes in the intracellular environment, not pathologic (morphologic) changes, may elucidate the unpredictable clinical course of this tumor.

임상 증상이 심하지 않은 심낭 삼출 환자의 장기 추적 결과

배장호,김기식,강미숙,남명희,김미정,김민수,김기영,님창욱,김윤년,김권배,정시전,김여희 대한순환기학회 1999 Korean Circulation Journal Vol.29 No.7

Associations of serotonergic genes with poststroke emotional incontinence

Kim, Jae‐,Min,Stewart, Robert,Kang, Hee‐,Ju,Bae, Kyung‐,Yeol,Kim, Sung‐,Wan,Shin, Il‐,Seon,Kim, Joon‐,Tae,Park, Man‐,Seok,Cho, Ki‐,Hyun,Yoon, Jin‐ John Wiley Sons, Ltd 2012 INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Vol.27 No.8

<P><B>Objectives</B></P><P>Poststroke emotional incontinence (PSEI) has been associated with serotonergic dysfunction. Polymorphisms of serotonin transporter (5‐HTT) and serotonin 2a receptor (5‐HTR2a) genes may regulate serotonergic signaling at brain synapses, and this study was to investigate associations with PSEI in an East Asian population.</P><P><B>Methods</B></P><P>In 276 stroke cases, PSEI was diagnosed by Kim's criteria. Covariates included age, gender, education, history of depression or stroke, current depression, and stroke severity and location. Genotypes were ascertained for 5‐HTT gene‐linked promoter region (5‐HTTLPR), serotonin transporter intron 2 variable number tandem repeat, 5‐HTR2a 1438A/G, and 5‐HTR2a 102 T/C. Associations with PSEI were estimated by using logistic regression models, and gene–gene interactions were investigated by using the generalized multifactor dimensionality reduction method.</P><P><B>Results</B></P><P>PSEI was present in 37 (13.4%) patients. The 5‐HTT gene‐linked promoter region <I>s</I>/<I>s</I> genotype was independently associated with PSEI. No associations with STin2 VNTR and 5‐HTR2a genes were found, and no significant gene–gene interactions were identified.</P><P><B>Conclusions</B></P><P>Stroke patients with 5‐HTTLPR <I>s</I> allele had higher susceptibility to PSEI, which underlines the potential role of serotonergic pathways in its etiology. Copyright © 2011 John Wiley & Sons, Ltd.</P>

담낭암의 발생에서 담췌관합류이상의 역할 규명과 암화과정에 관한 연구

한기준,송시영,정재복,이세준,김호근,강진경 大韓消化器病學會 1998 大韓消化器病學會誌 Vol.32 No.4

Hair growth promoting effects of different alternating- current parameter settings are mediated by the activation of Wnt/β-catenin and MAPK pathway

( Ki Min Sohn ),( Kwan Ho Jeong ),( Jung Eun Kim ),( Young Min Park ),( Hoon Kang ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: There are clinical studies demonstrating the positive effect of electrical stimuli on hair regrowth. However, the underlying mechanism and optimal parameter settings are not clarified. Objectives: To investigate the effects of different parameter settings of electrical stimuli on hair growth by examining changes in human dermal papilla cells (hDPCs) in vitro and by observing molecular changes in animal tissue. Methods: In vitro, cultured hDPCs were electrically stimulated with different parameter settings. Cell proliferation was measured by MTT assay. The Ki67 expression was measured by immunofluorescence. Hair growth-related gene expressions were measured by RT-PCR. In animal model, different parameter settings were applied to the shaved dorsal skin of rabbit for 8 weeks. Expression of hair-related genes in the skin of rabbit was examined by RT-PCR.Results: At low voltage power (3.5V) and low frequency (1MHz or 2MHz) alterating current, in vitro proliferation of hDPCs was successfully induced. A significant increase in Wnt/モ-catenin, Ki67, p-ERK and p-AKT expression was observed. In animal model, hair regrowth was observed in the entire stimulated areas and expression of hair-related genes in the skin significantly increased. Conclusion: There are optimal conditions for electric stimulated hair growth and they might be different in the cells, animal, and human tissue. Electric stimuli induces mechanisms such as activation of Wnt/モ-catenin and MAPK pathway in hair follicles.

P196 : Effects of different electrical parameter settings on hair growth: the changes of dermal papilla cell in vitro and at microscopic level in animal tissue

( Ki Min Sohn ),( Kwan Ho Jeong ),( Joo Hyun Lee ),( Jung Eun Kim ),( Hoon Kang ) 대한피부과학회 2014 대한피부과학회 학술발표대회집 Vol.66 No.2

Background: Frequency electrical stimulation is clinically being used in variable skin therapeutic conditions such as skin rejuvenation and hair disorder. There have been several clinical studies demonstrating the positive effect of electrical stimuli on hair regrowth. However, its exact mechanism is yet to be clarified. Objectives: The objective of this study is to investigate effects of different electrical parameter settings on hair growth by revealing the changes of dermal papilla cell in vitro and at microscopic level in animal tissue. Methods: Cultured dermal papilla cells (DPCs) and dorsal skin of rabbit were electrically stimulated with different parameter settings at alternating-current to find the optimal condition for hair growth. Cell viability and proliferation were measured by MTT. In addition, Ki67, proliferation marker, expression was measured by immunofluorescence. Hair growth-related gene expression in DPCs and the skin of rabbit were measured by RT-PCR. Results: At certain electrical settings, DPCs responded well and their proliferation was successfully induced. Wnt/β -catenin, Ki67, p-ERK and p-AKT expressions in DPCs increased at certain frequency settings. Dermal thickness and hair related genes (PDGF, VEGF, SOX9 and KGF) expressions in the skin of rabbit also significantly increased. Conclusion: These data suggest that electrical stimulations at certain electrical settings, may give more effective therapeutic outcomes for hair growth.