A Multicenter Analysis of Clinical Features and Long-Term Outcomes of POEMS Syndrome in Korea

Kook Hye Won,Jang Ji Eun,Min Chang-Ki,Yoon Dok Hyun,Kim Kihyun,Bang Soo-Mee,Park Yong,Lee Jae Hoon,Yoon Sung-Soo,Kim Jin Seok 대한의학회 2024 Journal of Korean medical science Vol.39 No.2

Background: POEMS syndrome is a rare form of plasma cell dyscrasia characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal proteins, and skin changes. Owing to its low incidence, there are few reports regarding this syndrome. This multicenter study included 84 patients diagnosed with POEMS syndrome in South Korea. Methods: We retrospectively evaluated 84 patients diagnosed with POEMS syndrome at 8 hospitals in South Korea between January 2000 and October 2022. The clinical characteristics and treatment outcomes were analyzed. Results: The median patient age was 53 years (range, 26–77 years), and 63.1% of the patients were male. All patients had peripheral neuropathy, and 81 (96.4%) had monoclonal plasma cell proliferation. Plasma vascular endothelial growth factor levels were available for 32 patients with a median of 821 pg/mL (range, 26–12,900 pg/mL). Other common features included skin changes (54.2%), volume overload (71.4%), and organomegaly (72.6%). Of the 84 patients, 75 received initial treatment (local radiotherapy, 6 [8.0%]; chemotherapy, 17 [22.7%]; both chemotherapy and local radiotherapy, 9 [12.0%]), upfront autologous stem cell transplantation (ASCT), 43 (57.3%; with induction chemotherapy, n = 12, 16.0%; without induction chemotherapy, n = 31, 41.3%). The median follow-up duration was 40.7 months. The 5-year overall survival (OS) was 78%, and the 5-year progression-free survival (PFS) was 55%. Patients who underwent upfront ASCT and were diagnosed after 2014 had a longer OS and PFS. Conclusion: The demographics of Korean patients with POEMS syndrome were similar to those reported previously. Because of the introduction of new treatment agents and the reduced rate of transplant-related mortality related to ASCT, the treatment outcomes of Korean patients with POEMS syndrome have improved in recent years.

천연물이 간대사에 미치는 영향에 관한 연구(Ⅱ)

최기환,김순선,박윤주,안미령,서수경,신윤용,김동섭,장영섭 식품의약품안전청 1997 식품의약품안전청 연보 Vol.1 No.-

천연물이 간대사에 미치는 영향페 대한 연구의 일환으로 세계 전 지역에서 널리 사용되고 잇으며 우리나라에서도 사용빈도가 높으나 간염등 간질환 유발사레가 보고되고 있는 마황, 황금 및 샐제 임상에서 이들 생약과 복합해서 자주 사용죄고 있는 대황을 선정하여, 띠들 천연물의 투여가 간 대사에 미치는 영향을 살펴보았다. 대황,마황, 황금 수침액을 1.09/kg의 용량으로 럿드에 7일간 경구 투여하고,최종투여 24시간 후 랫드의 간을 적출하였다. 간 대사에 미치는 영향을 살펴보기 위한 모질약뿔인 7-etliokycournarin을 적출간에 과관류하면서 2시간동안 일정시간 간격으로 관류액을 채취하여 생성된 7-ethoxycoumarin의 대사체인 7-hydroxycoin, glucuronide 포합체, sulfate포합체를 대조군과 배교 관찰하였다. 또한 긴독성 지표로서 혈청 ALT, AST를 측정하였으며 적출관류간에 대해 lipid peronidation 정도를 살펴보고 ÷t직병리검사를 실시하였다. 대촹 투여군에서는 7-ethoxycoumarin의 gulcuronidation이 갛소하였고fP<0.01), 마황투여군에서는 7-ethoxycoumarin의 o-deethylation이 증가하였다(P<0.01). 이러한 7-ethoxycoumariu 대사의 변화가 대황, 마황에 의한 관련 효소의 생합성 증가/감소에 의한 것인지 여부를 살펴보고자 일착로 CYPIAI, Ct'P2Bl CDHA primer를 사용하여 적출관류간 소포체에서 mRNA level을 측정하였다.마황투옥군에서 CVPIAI mRNA level의 증가가 관찰되었지만 통계적으로 유의한 차이를 나타내지는 않았다. 또한 이들 천연물에 의한 간독성 유발여부를 비교 평가한 결과 혈청 ALT 및 AST는 대조군에 비하여 유의한 차이가 없었다. 그러나 만성 간염정도를 나타내는 지표인 ALT/AST ratio는 마황 투여군에ㅓ 대조군에 비하여 유으한 차이를 나타내었고 대황투여군에서 간소포체내 lipid Peroxidation(MDA production)이 대조군에 비해 증가하였다.반면 조직학적 관찰결과는 대조군에 비하여 유의한 차이를 나타내지 않았다. 이상의 결과를 요약하면 랫드에서 대황 투여에 의해 7-ethoxycoumarin gtucuronidation이 감소되었으며, 마황 투여에 의해서 7-ethoxycoumarin의 o-deethylation은 증가되었고 마창 투여군의 경우 이러한 효소의 활성증가는 CYPIA1 induction에 의한 것일 수도 있다는 가능성을 제시하고 있다. In recent 3rears, hepatotoxicity concerned with Ephedrae herba or Scutellariae radixadmiBistration was case reported and Rhei rhizoma is commonly used with them. Tn order to study theeffect of Rhei rhizoma, Ep]ledrae herba and Scutellariae radix on hepatic metabolism, we exalnined theeffect of those pretreatment on the metabolism of 7-ethoxycoumarin(EC). Water extracts(Ig/fg) ofRhei rhiaoma, Ephedrae tterba and Scutetlariae radix were admi3tistered orally to rats for T days,respectively. Livers were t:ten isolated and perfused with 100uM EC for 2 hours. The metabolites of EC,7-hydroxycoernarin, sulfate conjugate and glucuronide conjugate, were measured in the perfusates dur-ing perfusion. The amount of glucuronide conjvgates was decreased iB ahei rhizoma pretreated rats (p <0.01) and 7-bfdroxycournarin was increased in Ephedrae herba pretreated rats(p < 0.01). To examineTrhether the change of enByme activity is related to the induction ,or inhibition of enzymes concerned,we measured the change oif CYPIAt and CYPaBl mRNA level in the perfused rat liver, which are con-sidered to be EC specifie. However, CYPIAI and CYPEBI rnRNA ilevel were not found to be changedwith Rhei rhizoma nor I]3hedrae herba pretreatmen·t. We also assessed the hepatic toxicity of Rheirhizoma,.:phedrae herba and Scutellariae radix. The activity of ALT and AST was assayed at 34hrsafter 7 dfyt ndrninistratiofl and it was not found to be changed- Only the ratio of ALT over AST was in-creased in Epedrae herbs. pretreated rats(p < 0.05), which implies possible chronic hepatitis. Lipidperoxidation was increased in Rhei rhizoma treatment(p <0.05) , while histopathological examinationperformed after liver perfusion did not show any difference compared with vehicle treatmeut. Theseresutts suggest that Ephedrae herba pretreatment increases the o-deethylation of 7- ethoxrcoumariB inrats, which Inay be mediated by CYPIAI mRNA induction.

GH_3 세포(rat somatomammotropic tumor cell)에서 TRH가 Phospholipase D 활성에 미치는 효과

김동선,김태화,이창범,안유헌,윤미섭,한중수 대한내분비학회 2002 Endocrinology and metabolism Vol.17 No.4

연구배경: GH_3 세포는 TRH에 반응하여 세포막의 수용체와 G 단백, PI-PLC, PKC를 활성시켜 성장호르몬 및 프로락틴을 분비한다고 알려져 있다. PLD는 phosphatidylcholine을 phosphatidic acid(PA)와 choline으로 가수분해하는 효소로서 세포의 증식과 호르몬 분비에 관여한다. 본 연구는 GH_3 세포에서 아직 알려지지 않은 TRH의 PLD 활성에 대한 영향을 규명하고자 하였다. 방법: GH_3 세포를 1.5×10^6씩 분주하고 [^3H] myristate로 표지한 다음에 0.3% 알코올로 전 처치하였다. TRH 등의 시험제를 처치한 후에 메탄올로 반응을 종결하고 세포에서 총 지질을 추출하였다. PLD 활성은 박층크로마토그래피를 이용하여 총 [^3H] phospholipid에서 [^3H] phosphatidylethanol의 비율로 구하였다. 결과: TRH (1μM)의 처치 시에 PLC 활성은 44배 증가하였다. PLD 활성은 TRH (1μM), mastoparan (5μM), PMA(500nM)를 30분간 처치 시에 각각 1.9, 1.5, 2.2배 증가하였다. TRH(1μM)의 시간에 따른 PLD 활성 변동은 15, 30, 60, 120, 240분에 각각 142%, 170%, 172%, 160%, 115%의 증가를 보였다. 결론: GH_3 세포에서 TRH의 호르몬 분비와 세포증식의 신호전달 기전으로서는 PLC 활성뿐 아니라 PLD의 활성도 관여함을 시사한다. Backgroud: GH_3 cells are a well characterized and widely used model used for the in vitro study of growth hormone (GH) secretion. Thyrotropin releasing hormone (TRH) binds to receptors belonging to the family of G protein-coupled receptors, and secrets both GH & prolactin. Phospholipase D (PLD) is and enzyme that hydrolyses phosphatidylcholine to yield phosphatidic acid and choline, and plays important roles in cellular proliferation and hormonal secretion. To elucidate the pathway of the action of TRH in GH_3 cells, we investigated the activities of PLC and PLD in GH_3 cells treated with TRH or phorbor 12-myristate 13-acetate (PMA). Methos : GH_3 cells were labeled with [^3H] myristate, followed by incubation of with 0.3% ethanol, prior to before the addition of the agonists. The total lipids were extracted from the harvested cells following treatment with the agonists. The PLD activity was assessed by measuring [^3H] phosphatidylethanol from the [^3H] phospholipid using thin layer chromatography. Results : TRH (1μM) stimulated the PLD activity by 44-fold over that of the control values. TRH (1μM), mastoparan (5μM), and PMA (500μM) for 30 minutes increased PLD activity by 1.9, 1.5 and 2.2 fold, respectively, in comparison to the controls, The PLD activities after 15, 30, 60, 120 and 240 min treatments of TRH (1μM) were 142%, 170%, 172%, 160% and 115%, respectively. Conclusion : These results suggest that TRH stimulates not only PLC activity, but also the PLD activity in GH_3 cells (J Kor Soc Endocrinol 17:465∼472, 2002).

위저선 폴립의 임상 및 병리학적 분석 : 가족성 선종성 폴립증에 동반된 다발성 위저선 폴립과 산발적으로 발생된 위저선 폴립의 비교 A Clinical and Pathologic Analysis with Special Reference to Familial Adenomatous Polyposis

김나영,이동호,송인성,김용일,김우호,최규완,이국래,최기영,장미수 대한소화기내시경학회 1997 Clinical Endoscopy Vol.17 No.2

Background/Aims: The aims of this study are to clarify the morphology of fundic gland polyp (FGP) and to compare the features of FGP between familial adenomatous polyposis-associated group and sporadic development group. Methods: A total of 15 endo- scopic biopsy specimens of FGP from 13 patients were divided into three groups; Group A(3 cases; familial adenomatous polyposis family, multiple FGPs), Group B(3 cases; sporadic development, multiple FGPs) and Group C(7 cases; sporadic development, single FGP), and their endoseopic /microscopic features including mucin histochemistry and immunohistoc- hemistty(for PCNA) were compared. Results: FGPs were confined to the gastric body and fundus in all 3 groups, and measured 2-8 mm. Their numbers varied even in Group A and Group B, The difference was observed in their median age: 26 years in Group A and 55 years in Group B, respectively, but there were no differences in endoscopic, histologic, mucin histochemical and immunohistochemical(for PCNA) features. Micro-scopically, all FGPs were composed of fundic glands and scattered microcysts with a spectrum of disordered glandular architecture which ranged from convoluted gland to Y-shaped gland, to stellateshaped gland, and to irregular tortuous glancl with dilated lumen. Conclusions: We assume that diversity af morphologic features of FGP may develop from progression of hyperplastic/hamartomatous fundic glandular proliferation which may end up with microcyst formation as an evolutional change. Familial adenomatous polyosis-associated FGPs were not endoscopically and histologically distingishable from sporadic deveoped FGPs.

직장의 원발성 Linitis Plastica형 암종 -5예에 대한 병리학적 분석 및 위암 Borrmann제 4형과의 비교 관찰-

장미수,김용일,김우호,박인애,장미수,김용일,김우호,박인애 대한병리학회 1991 Journal of Pathology and Translational Medicine Vol.25 No.2

Binding of Toxic Shock Syndrome Toxin-1 to HLA-DR and HLA-DQ Molecules by L-cell Transfectants

Chang, Mee Soo,Ryu, Jiso,Lee, Mi Sook,Woo, Jun Hee 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.4

배경 : 포도구균에 의해 생산되는 TSST-1이 원인인 독성쇽증후군은 재래의 세균독소와는 달리 초항원으로 작용하는 기전에 의해 여러 장기에 병변이 합병되어 기능 부전을 초래한다. TSST-1이 초항원으로 작용하는 기전 중 TSST-1이 MHC와 결합하는 수용체를 밝히기 위하여 실험을 하였다. 방법 건강성인에서 말초혈액을 채취하여 말초혈액단핵구를 그리고 피부생검조직에서 정상 피부섬유원세포를 분리하였다. TSST-1이 결합하는 분자수용체를 동정하기 위한 방법으로 분자융합방법, 단클론항체, 결합능측정(binding assay), T cell proliferation assay을 이용하여 실험을 진행하였다. HLA-DRα, HLA-β1, HLA-DPw4β, HLA-DQ7α, HLA-DQw3β의 cDNA 클론을 expression vector에 selection amrker를 가진 plasmid pSV-neo를 Murine L-cell fibroblast에 transfection 시켜서 L-cell transfectants를 만들었고, Chloramine T를 이용한 iodination 한 TSST-1과 HLA-DR, DQ, DP의 결합능을 측정하였고 HLA-DR, DQ, DP에 대한 단클론항체로 억제한 뒤에 결합능과 비교하였다. 결과 TSST-1가 HLA-DR, DQ, DP의 결합능을 측정하고, 뒤이어 HLA-DR, DQ, DP에 대한 단클론항체로 TSST-1과의 결합을 억제시킬 수 있는지 보조세포 존재하에 증식능을 측정한 결과 HLA-DR에 대한 단클론항체는 TSST-1결합을 강력히 억제하는데 비하여 HLA-DP, HLA-DQ에 대한 단클론항체는 강하게 억제하지 못하였다. 결론 TSST-1은 HLA-DR L-cell transfectants와 결합하고, HLA-DQ L-cell transfectants에도 약간 결합하는 것으로 판단하여 TSST-1은 HLA-DR, HLA-DQ 분자의 특이부위에 결합하는 것이 관찰되었다. 초항원의 작용기전을 이해하는데 기초적인 설명을 가능하게 하는 것이다. Background : Expressible HLA class Ⅱa and cDNA were used for DNA-mediated gene transfer to produce L cell transfectants expressing single types of human class Ⅱ molecules. Cells with the highest degree of MHG class Ⅱ expression exhibited the highest number of TSST-l-binding sites. In contrast, cells with low or undetectable MHC class Ⅱ expression (resting T cells, and fibroblasts) exhibited very low or undetectable numbers of TSST-1-binding sites. Methods' The relationship between surface MHC class Ⅱ molecules and TSST-1 binding sites was assessed by examining the effect of antibodies to MHC class Ⅱ molecules on TSST-I binding. We examined TSST-I binding to mouse L-cell transfectants that expressed HLA-DR. DQ, DP gene products. Results : Immunofluorescence staining with anti-HLA-DR, -DP. and -DQ mAbs revealed comparable surface expression of the respective MHC class Ⅱ antigens by each of the three transfectants. TSST-1 bound to the HLA-DR transfectant and to the HLA-DQ transfectant but not to the HLA-DP transfectant and not to untransfected L cells. Conclusion : In summary, monoclonal antibodies to HLA-DR. but not to HLA-DP or HLA-DQ. strongly inhibited TSST-1 binding. Binding of TSST-1 was shown to HLA-DR and HLA-DQ L cell transfectants. These resu Its indicate that TSST-1 bind to distinct sites on HLA-DR and HLA-DQ molecules.

Leptin, MUC2 and mTOR in Appendiceal Mucinous Neoplasms

Chang, Mee Soo,Byeon, Sun-ju,Yoon, Sun Och,Kim, Baek-hui,Lee, Hye Seung,Kang, Gyeong Hoon,Kim, Woo Ho,Park, Kyu Joo S. Karger AG 2012 Pathobiology Vol.79 No.1

<P><I>Objective:</I> Leptin contributes to mucin production in colonic epithelium and regulates carcinogenesis via various signalling pathways. We evaluated the proteins involved in mucin-producing carcinogenesis and putative targets for molecular therapy in appendiceal mucinous neoplasms. <I>Methods:</I> Immunohistochemistry and fluorescence in situ hybridization were performed in 22 cases of appendiceal mucinous adenoma, 20 mucinous neoplasms of uncertain malignant potential and 14 mucinous adenocarcinomas. <I>Results:</I> Leptin, MUC2, MUC5AC, mTOR and ERK were more frequently immunopositive in mucinous adenocarcinomas compared with mucinous adenomas or mucinous neoplasms of uncertain malignant potential (p < 0.05). STAT3 revealed immunopositivity in 82% of tumours, regardless of tumour category. MUC2 immunopositivity was associated with pseudomyxoma peritonei (p < 0.05). None of the tumours exhibited c-kitimmunoexpression, amplification of <I>Her2</I> or <I>EGFR,</I> or translocation of <I>ALK</I>. The mTOR-immunopositive group of patients had a lower rate of disease-free survival compared with the mTOR-immunonegative group (p < 0.05). <I>Conclusions:</I> Leptin may collaborate with MUC2 and MUC5AC in mucin-producing carcinogenesis in an mTOR-, STAT3- and ERK-dependent manner. STAT3 may be activated early during tumorigenesis. <I>MUC2</I> and <I>mTOR</I> (but not c<I>-kit</I>, <I>Her2</I>, <I>EGFR </I>and <I>ALK</I>) may represent targets for molecular therapy in pseudomyxoma peritonei and appendiceal mucinous adenocarcinoma, respectively.</P><P>Copyright © 2012 S. Karger AG, Basel</P>

위 신경초종 보고 - 병리학적 , 면역조직화학적 및 초미세구조적 관찰

장미수(Mee Soo Chang),김용일(Yong Il Kim) 대한소화기학회 1996 대한소화기학회지 Vol.28 No.4

Neurilemmoma of the stomach is a rare controversial neoplasm which requires extensive studies to clarify its nature from stromal tumor or leiornyoma. This paper describes the pathologic, immunohistochemical and ultrastructural characteristics of neurilemmoma of the stomach from a 52-year-old woman. The tumor was a 2.2cm, well circumscribed submucosal mass located in the anterior wall of midbody. Microscopically, the cells were made up of fasciculating bundles of spindle cells featured with benign nuclear atypia and peripheral lymphoid cell cuffing. The tumor cells revealed a diffuse strong immunoreactivity to S-100 protein and vimentin, but were negative to desmin and smooth muscle actin, and focal positive reaction to glial fibrillary acidic protein. Peripheral lymphoid cuffing was suggested an immune reaction against the tumor tissue. Ultrastructurally, rnany tumor cells showed a number of thin e]ongated and interdigitating dendritic- like cell processes, distinct uniform basal laminae, frequent cellular attachments and microfila- ments. The findings supported the schwannian nature of the tumor, and the focal positive immunoreactivity for GFAP indicates the possibility of focally modified schwann cell. (Korean J Gastroenterol 1996;28:556 - 560)

Immunohistochemical Staining to Identify Concomitant Systemic Mastocytosis in Acute Myeloid Leukemia with RUNX1::RUNX1T1

Hwang Sang Mee,Kim Beom Joon,Lee Jee-Soo,Seong Moon-Woo,Seo Soo Hyun,Paik Jin Ho,Kim Sang-A,Lee Ji Yun,Lee Jeong-Ok,Chang Yoon Hwan,Bang Soo Mee 대한진단검사의학회 2022 Annals of Laboratory Medicine Vol.42 No.6

Systemic mastocytosis with associated hematological neoplasm (SM-AHN) poses diagnostic challenges because of the coexistence of atypical mast cell proliferation and hematological neoplasms. We assessed the presence of SM-AHN in patients with acute myeloid leukemia (AML) with RUNX1::RUNX1T1 from 2014 to 2020. Bone marrow (BM) samples were evaluated for mast cell aggregates using CD117 and CD25 immunohistochemical (IHC) staining. The KIT D816V variant burden at diagnosis and post induction was assessed using droplet digital PCR. Among 23 patients diagnosed as having AML with RUNX1::RUNX1T1, four (17.4%) were also diagnosed as having SM-AHN. No significant differences in clinical characteristics or overall survival (P=0.565) were observed between patients with or without SM-AHN, except for the presence of KIT variants (P=0.040). After induction therapy, IHC staining revealed the presence of mast cell aggregates in the BM, and the KIT D816V variant burden decreased with decreasing blast count and was similar in BM aspirates, smear slides, and sections. Concomitant SM-AHN was not infrequent in AML patients with RUNX1::RUNX1T1. This study showed the importance of CD117 and CD25 IHC staining after induction chemotherapy for SM-AHN screening, especially in patients with KIT variants.

횡문근육종성 증식을 동반한 신세포 암종 1예

장미수,지미경,이교영,심상인,김선무 대한병리학회 1987 Journal of Pathology and Translational Medicine Vol.21 No.1