A selective cyclin-dependent kinase 4, 6 dual inhibitor, Ribociclib (LEE011) inhibits cell proliferation and induces apoptosis in aggressive thyroid cancer

Lee, Hyun Joo,Lee, Woo Kyung,Kang, Chan Woo,Ku, Cheol Ryong,Cho, Yoon Hee,Lee, Eun Jig Elsevier 2018 Cancer letters Vol.417 No.-

<P><B>Abstract</B></P> <P>The RB-E2F1 pathway is an important mechanism of cell-cycle control, and deregulation of this pathway is one of the key factors contributing to tumorigenesis. Cyclin-dependent kinases (CDKs) and Cyclin D have been known to increase in aggressive thyroid cancer. However, there has been no study to investigate effects of a selective CDK 4/6 inhibitor, Ribociclib (LEE011), in thyroid cancer. Performing Western blotting, we found that RB phosphorylation and the expression of Cyclin D are significantly higher in papillary thyroid cancer (PTC) cell lines as well as anaplastic thyroid cancer (ATC) cell lines, compared with normal thyroid cell line and follicular thyroid cancer cell line. LEE011 dose-dependently inhibited RB phosphorylation and also decreased the expressions of its target genes such as <I>FOXM1, Cyclin A1,</I> and <I>Myc</I> in ATC. Furthermore, LEE011 induced cell cycle arrest in G0-G1 phase and cell apoptosis, and inhibited cell proliferation in ATC. Consistently, oral administration of LEE011 to ATC xenograft models strongly inhibited tumor growth with decreased expressions of pRB, pAKT and Ki-67, and also significantly increased tumor cell apoptosis. Taken together, our data support the rationale for clinical development of the CDK4/6 inhibitor as a therapy for patients with aggressive thyroid cancer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> pRB and Cyclin D were expressed high in aggressive thyroid cancer. </LI> <LI> LEE011 suppressed pRB and also decreased the expressions of its target genes in ATC. </LI> <LI> LEE011 induced cell cycle G1 arrest and apoptosis, and inhibited cell proliferation. </LI> <LI> LEE011 inhibited in vivo tumor growth with decreased expressions of pRB and Ki-67. </LI> <LI> We could explain the anticancer effects with the RB-E2F pathway. </LI> </UL> </P>

Safety of subtotal or total colectomy with primary anastomosis compared to Hartmann procedure for left-sided colon cancer obstruction or perforation

Eun-Do Kim,Jin-Kwon Lee,Jin-Kyu Cho,Jae-Myung Kim,Ji-Ho Park,Ju-Yeon Kim,Sang-Ho Jeong,Young-Tae Ju,Chi-Young Jeong,Eun-Jung Jung,Young-Joon Lee1,Soon-Chan Hong,곽승진 대한종양외과학회 2019 Korean Journal of Clinical Oncology Vol.15 No.2

Purpose: Whether subtotal or total colectomy with primary anastomosis (PA) is safer than Hartmann procedure (HP) for left-sided colon cancer obstruction or perforation remains controversial. The purpose of this study was to compare postoperative morbidity, mortality, and defecation frequency between PA and HP for left-sided colon cancer obstruction or perforation. Methods: This retrospective study enrolled 54 patients from January 2014 to February 2018 who underwent emergency surgery due to left-sided colon cancer obstruction or perforation. Results: PA was carried out in 20 patients while HP was performed for 34 patients. Thirty-day mortality did not show significant difference between the two groups (15.0% vs. 14.7%, P=1.000). No anastomotic leakage occurred in PA group while three (8.8%) cases of stump leakage occurred in HP group. Stoma repair was performed for 13 cases (44.8%) and stoma reformation was performed for one case in HP group (7.7%). Stoma related complications occurred in five cases (17.24%). For patients after stoma repair, defecation frequency at 3 months after operation was 2.91±2.88 times per day in PA group and 2.86±2.63 times per day in HP group. At 1 year after operation, defecation frequency was changed to 1.40±1.12 times per day in PA group and 1.17±0.39 times per day in HP group. Conclusion: Primary ileosigmoid or ileorectal anastomosis for left-sided colon cancer obstruction or perforation is safe, and shows similar outcome of defecation frequency compared to H

췌장 선방세포암 1예

이화정,지준호,박승찬,박정철,최은정,서혜진,이원식,이정림,배병조,손경락,이경희 영남대학교 의과대학 2008 Yeungnam University Journal of Medicine Vol.25 No.2

Acinar cell carcinoma is a rare tumor that represents 1~2% of al1 pancreatic cancers. Clinical and radiologic findings are inconclusive in this disease Acinar cell carcinoma is characterized by rapid progression and early metastasis, which lead to its poor prognosis. A 41-year-o1d man was admitted to our hospital for abdominal pain. Abdominal computed tomography (CT) and positron emission tomography-computed tomography (PET-CT) showed a splenic mass, which was being invaded by a pancreatic tail mass and which had increased ^(18)F-fluorodeoxyglucose (FDG) uptake Primary radical distal pancreatectomy and splenectomy were performed. Pathologic findings revealed an acinar cell carcinoma of the Pancreas The patient underwent a total gastrectomy three months later because of gastric recurrence Four months later, multiple hepatic metastases were discovered, and the patient underwent a left hepatectomy During treatment with capecitabine, there was no evidence of tumor progression for 14 months. We report a case of metastatic pancreatic acinar cell carcinoma, which did not progress for an extended period while the patient was being treated with capecitabme.

교대로 운전되는 두 개의 UV/광촉매반응기로 구성된 폐가스 처리시스템에서의 광촉매의 비활성화 및 재생 특성

이은주 ( Eun Ju Lee ),정찬홍 ( Chan Hong Chung ),임광희 ( Kwang-hee Lim ) 한국화학공학회 2021 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.59 No.4

본 연구에서는 교대로 운전되는 두 개의 UV/광촉매 반응기로 구성된 폐가스 처리시스템의 운전단계와 단계별 광촉매의 비활성화의 상관관계를 사용된 광촉매에 대한 기기분석을 통하여 규명하였다. 선행연구[Lee와 Lim, Korean Chem. Eng. Research, 59(4), 574-583 (2021)]의 광촉매 반응기 시스템 운전에 사용되지 않은 광촉매를 담지한 다공성 SiO₂ 담체(A4), 1회 운전하는 동안 사용되고 재생을 경험하지 않은 광촉매를 담지한 다공성 SiO₂ 담체(A1), 2회 운전에 사용되고 1회 재생된 광촉매를 담지한 다공성 SiO₂ 담체(A2) 및 3회 운전에 사용되고 2회 재생된 광촉매를 담지한 다공성SiO₂ 담체(A3)와, 1차 재생(AD1) 또는 3차 재생(AD3)된 광촉매를 담지한 다공성 SiO₂ 담체에 대한 BET 분석, SEM, XPS, SEM-EDS 및 FTIR 분석 등을 수행하여, 광촉매를 담지한 다공성 SiO₂ 담체의 비활성화 및 재생 특성을 포함하는 특성 분석을 수행하였다. 그 결과로서, 3회 이상의 여러 번 재생을 수행하는 광촉매의 적정 재생 온도를 200℃ 미만으로 도출하였다. 이러한 광촉매의 적정 재생 온도는 BET 분석결과에서 도출된 기공에 흡착된 에탄올 산화분해 중간생성물의 대부분이 완전 분해가 되어 기공이 재생되는 재생 온도와 거의 일치하였다. 특히, XPS 분석 결과는, 선행 연구[Lee와 Lim, Korean Chem. Eng. Research, 59(4), 574-583 (2021)]에서 광촉매 반응기의 첫 번째 운전 후에 광촉매의 미세한 비활성화가 발생하였음을 나타내었다. 또한, XPS 분석 결과는, 선행연구[Lee와 Lim, Korean Chem. Eng. Research, 59(4), 574-583 (2021)]에서 광촉매 반응기의 두 번째 운전에서 비교적 큰 광촉매의 비활성화가 발생하여 첫번째 운전성능보다 약 5%만큼 못 미치는 에탄올과 황화수소 각각의 제거효율을 초래하였으나, 세 번째 운전에서의 에탄올과 황화수소의 제거효율은 두 번째 운전에서의 에탄올과 황화수소의 제거효율 실험 결과와 거의 비슷하였다는 연구 결과와 일치하였다. 한편, AD3를 사용하여 선행연구[Lee와 Lim, Korean Chem. Eng. Research, 59(4), 574-583 (2021)]에서와 같은 광촉매 반응기의 네 번째 운전을 수행할 것을 가정하면, 두 번째 운전에서보다 더 큰 광촉매의 비가역적 비활성화의 발생으로 인하여 에탄올과 황화수소 제거효율이 가장 크게 저하되리라 예상되었다. In this study, the correlation between operating stages of waste air-treating system composed of two alternatively-operating UV/photocatalytic reactors, and the deactivation of photocatalyst used in each operating stage, was investigated by instrumental analysis thereon. The repeated deactivation and subsequent re-generation of photocatalyst used in the waste air treating system of previous investigation performed by Lee and Lim (Korean Chem. Eng. Research, 59(4), 574-583(2021)), were characterized on virgin photocatalyst-carrying porous SiO₂ media (A4), used photocatalystcarrying porous SiO₂ media (A1, A2 and A3) collected from the corresponding photocatalytic reactor upon 1^st, 2^nd, and 3^rd run, respectively, regenerated photocatalyst-carrying porous SiO₂ media upon 1 time-run (AD1) and 3 times regenerated photocatalyst-carrying porous SiO₂ media upon 3 time-runs (AD3) by instrumental analysis including BET analysis, SEM, XPS, SEM-EDS and FT-IR. As a result, the proper regeneration-temperature for deactivated photocatalyst to be regenerated several times (more than 3 times), was suggested below 200℃. Such temperature of deactivated photocatalystregeneration was almost consistent to the one, according to BET analysis, at which tiny nano-pores blocked by adsorbed ethanol-oxidative and degraded intermediates (AEODI), were regenerated to be reopened through almost complete mineralization of AEODI. In particular, the results of XPS analysis indicated an incurrence of insignificant deactivation of photocatalysis upon 1^st run of UV/photocatalytic reactor (A or C) of the previous investigation. In addition, the results of XPS analysis were consistent with the experimental results of the previous investigation in that 1) deactivation of photocatalyst incurred during 2^nd run of the UV/photocatalytic reactor (A or C) resulted in decreased removal efficiency, by ca. 5% and 5%, of ethanol and hydrogen sulfide, respectively, compared with its 1^st run; 2) there was insignificant difference between the removal efficiencies of its 2^nd run and 3^rd run. Furthermore, the removal efficiencies of ethanol and hydrogen sulfide for hypothetical 4^th run of photocatalytic reactor in the previous investigation, using AD3, were expected to decrease, compared with its 3^rd run, by much more than those for 2^nd run in the previous investigation did, compared with its 1^st run.

韓ㆍ中 鬼神觀에 나타난 문화적 다양성 연구

李澯旭(Chan-wook, Lee),金芝恩(Ji-eun, Kim) 중앙대학교 문화콘텐츠기술연구원 2012 다문화콘텐츠연구 Vol.0 No.13

동양 문화권에서 죽음과 鬼神에 대한 담론은 동양의 死生觀을 이해하는 하나의 중요한 단초가 된다. 인간은 누구나 살아가는 과정에서 겪게 되는 불가항력적이며 불가피한 죽음을 공포와 경외감으로 인식하고 있다. 삶과 죽음의 문제는 단선적으로 설명할 수 없고, 접근 방식이나 바라보는 관점에 따라 다양한 해석이 가능하다. 그리고 그러한 해석은 민족성과 전통, 종교와 사상에 따라서 의식과 인식체계의 차이가 드러나게 되는데 특히나 동양에 있어서 죽음과 사후세계, 그리고 거기서 비롯되는 귀신의 존재는 현세의 삶에 영향을 미칠 만큼 깊이 자리매김 해 온 것이 사실이다. 바로 그러한 형성과정 속에서 고착된 것이 바로 동양의 귀신관이다. 관념적이며 추상적인 귀신에 대한 화두에 접근하는 방식은 다면적일 수밖에 없다. 따라서 한국과 중국 두 나라에 형성되어 온 귀신관은 어떠했는지, 또 어떻게 일상의 삶 속에 반영되었는지를 파악하기 위해서는 문학적 텍스트를 살펴보는 것도 의미 있는 작업이라고 생각된다. 왜냐하면 귀신 이야기에는 풍부한 문화사적 함의가 내포되어 있기 때문이다. 물론 한국과 중국의 귀신관을 하나로 정리하는 것은 사실 대단히 지난한 문제이다. 귀신이란 존재자체가 형이상학적이고 실제 존재여부조차 증명되지 않은 초월적인 성격을 지니기에 더욱 그렇다. 본 논의는 한국의 任?(1640~1724)과 중국의 蒲松齡(1640~1715)의 대표적인 작품인 〈天倪錄〉과 〈聊齋志異〉를 통해 귀신을 통해 드러나는 문화의 다양성의 실체를 단편적이나마 구명하고자 했다. 그리하여 두 작품은 모두 기본적으로는 유교적 귀신관을 전제로 하지만 그 안에는 불교나 무속, 도교의 신선사상까지도 아우르고 있음을 확인할 수 있었다. 그러나 귀신에 대한 관념이 한국보다 중국에서는 한층 더 자유롭고 다채롭게 다루어 왔음을 확인할 수 있다. 〈천예록〉에서는 祭祀를 통해 祖靈을 경외심의 대상으로 인식하는 부분이 있지만 〈요재지이〉에서는 귀신과의 만남과 사랑이 훨씬 자유롭고 거리낌이 없이 형상화되는 이유에서다. 이는 포송령이 인간과 귀신사이에는 명확한 구분이 없다는 일차원적 시각으로 본 결과이다. 즉, 만물은 다 영혼이 있다고 믿고 영혼과 음양의 기가 서로 연결되어 있어서 인간과 귀신 그리고 동식물의 영혼은 본질적으로 차이가 없다는 것이다. 그러므로 인간과 귀신이 함께 존재할 수 있고 사랑을 위해 인간이 귀신으로, 귀신이 인간으로 변화할 수 있다는 것이다. 그리하여 상황에 따라서 귀신이 사람보다 더 인간적일 수도 있고 사람이 귀신보다 더 사악할 수도 있다고 보았다. 그래서 인간세상과 저승세계가 별 차이가 없다고 본 〈요재지이〉는 〈천예록〉보다 더 환상적이며 흥미롭고 기이한 작품이다. 이상으로 〈天倪錄〉과 〈聊齋志異〉의 두 작품을 통해 나타난 귀신에 대한 다층성과 복합성은 한국과 중국 문화의 다양성으로 인정할 수 있을 것이다. Understanding the discourse between death and phantoms in the Asian culture can be an important clue into understanding the oriental world view. Death is an inevitable part of life and sudden death is often meet with fear and awe. Life and death cannot be explained in simple terms. As such, approaching the subject from different directions and angles can lead to a variety of explanations and viewpoints. Through these viewpoints, the different understanding and paradigm regarding ethnicity and tradition can be revealed. Moreover, understanding of death and afterlife in Asia and the resulting current real world influence of the existence of phantoms cannot be ignored for its place in daily life. Through this process is where the Asian phantom theory exists. The following paper attempts to uncover the true cultural diversity expressed through the examination of Asian phantom theories. The ideal and abstract nature of phantoms can lead of a variety ways in which the issue can be approached. As such, it is important to narrow the understanding through examining how phantom theory was created in Korea and through Chinese people, and how the historical works have expressed its understanding on phantoms. The paper looks at the cultural diversity expressed through phantoms examined in parts of the famous works of Leem Bang (임방) and Po Sung Ryong (포송령), 〈Chun Yeo Rok〉 (天倪錄) and 〈Ryo Jae Ji Lee〉 (聊齋志異). It is an extremely difficult task to define the theory of phantoms in words. As such, even Confucius and other saints, as well as many academics in Korea, could not give a clear guidance to the subject. Thus, even though the two works mentioned above includes the doctrines of Confucius as its base, one can find parts of Buddhism, shamanism, and theory of eternal life in Taoism embedded within. Therefore, understanding the microcosm and complexity of phantoms expressed through the two works, 〈Chun Yeo Rok〉 (天倪錄) and 〈Ryo Jae Ji Lee〉 (聊齋志異) can be brought together to accept the cultural paradigm that it attempts to explain.

B16 멜라닌 세포에서 해양소재 추출물의 멜라닌 생성 저해 효과

이찬 ( Chan Lee1 ),장정희 ( Jung Hee Jang ),안은미 ( Eun Mi Ahn ),박찬익 ( Chan Ik Park ) 대한본초학회 2012 大韓本草學會誌 Vol.27 No.4

Objectives : Under normal condition melanin protects the skin from extracellular stimuli including ultraviolet (UV)-induced oxidative skin damages, but excess production and accumulation of melanin can induce hyperpigmentation causing esthetic problems. Therefore, in this study we tried to search for natural skin whitening materials from marine natural resources. Methods : Water and ethanol extracts of marine natural resources were prepared from Porphyra thalli (PT), Laminariae thallus (LT), Ostreae concha (OC), Sargassum thallus (ST), Undaria thallus (UT), Codium thalli (CT), Enteromorpha thalli (ET), Syngnathoides biaculeatus (SB), and Hippocampus coronatus (Hc). Their effects against UVB and α-melanocyte stimulating hormone (α-MSH)-induced melanogenesis were investigated based on melanin formation in B16 mouse melanoma cells. The mRNA and protein expression of enzymes involved in the melanogenic process were further examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. Results : Water extract of Ostreae concha (OCW/E) effectively inhibited UVB and α-MSH-induced melanin production in B16 melanocytes, which seemed to be mediated by inhibition of mRNA expression of tyrosinase and tyrosinase-related protein 1 (TRP-1). In another experiment, ethanol extracts from Porphyra thalli (PTE/E), Laminariae thallus (LTE/E), Sargassum thallus (STE/E), Undaria thallus (UTE/E), Codium thalli (CTE/E), Syngnathoides biaculeatus (SBE/E), and Hippocampus coronatus (HcE/E) significantly suppressed UVB and α-MSH-induced melanin formation. Furthermore, ethylacetate fraction isolated form LTE/E (LTE/EEt) decreased UVB and α-MSH-elevated extracellular melanin levels via inhibition of tyrosinase protein expression. Conclutions : These results suggest that marine natural resources such as Porphyra thalli, Laminariae thallus, Ostreae concha, Sargassum thallus, Undaria thallus, Codium thalli, Syngnathoides biaculeatus and Hippocampus coronatus have anti-melanogenic effects, thereby exhibiting high potentials to be utilized as one of the ingredients for the development of new whitening functional cosmetics.

원발성 후복막 점액낭샘암종 1예

지준호,이화정,박승찬,박정철,최은정,서혜진,이원식,이정림,배병조,손경락,이경희 영남대학교 의과대학 2008 Yeungnam University Journal of Medicine Vol.25 No.2

Primary retroperitoneal mucinous cystadenocarcinoma is a very rare malignancy, and little is known concerning its Pathogenesis, optimal treatment, and prognosis. A 29-year-o1d pregnant woman (21 weeks) Presented with abdominal discomfort CA 19-9, CA 125, and CEA were normal Abdominal CT scanning revealed a 19x15x13 cm retropentoneal tumor Exploratory laparotomy and tumor excision were performed. Mucinous retropentoneal implants were removed as completely as possible Histologically, the tumor showed focal areas of capsular invasion, but free resection margins The uterus and both ovaries were normal in appearance No adjuvant therapy was pursued. Six months later, Peritoneal and bilateral ovarian metastases were discovered. Hence, we report the details of this case of primary retroperitoneal mucinous Cystadeno-carcinoma and present a review of the literature.

고요산혈증의 위험인자 : 아산시 지역 주민을 대상으로

김용배,장원기,황보영,김화성,안규동,이병국,이용진,이종은,이준숙,이찬구,이한정,이성수 순천향대학교 2006 Journal of Soonchunhyang Medical Science Vol.12 No.1

Objective : Serum uric acid has now been identified as a marker for a number of metabolic and hemodynamic abnormalities. The aim of this study is to evaluate risk factors which influence hyperuricemia in the citizens of Asan. Method : The study design was cross-sectional and research subjects were 1086 citizens of Asan. General characteristics, cigarette smoking, alcohol consumption, and past history were obtained by interview using a structural questionnaire. Also, we measured height, weight and blood pressure, and serum uric acid of the subjects. Results : The mean serum uric acid level was 5.27 ㎎/㎗ in men and 4.01 ㎎/㎗, in women, In the multiple logistic regression analysis, statically significant risk factors of hyperuhcemia were gender, body mass index, blood lead concentration, and serum creatinine. Conclusion : Our results suggest that gender, body mass index, blood lead concentration, and serum creatinine might be the most important risk factors of hyperurcemia. Education program as well as routine check-up for serum uric acid was highly recommended for the effective prevention of hyperuricemia.

자궁암세포(HeLa)에 대한 사군자탕과 수종 항암제의 병용투여 효과

은재순,김현욱,소준노,오찬호,이송재 又石大學校 1993 論文集 Vol.15 No.-

The studies were conducted to investigate the combined effects of Sa Kunja Tang(SKT) and several anti-cancer drugs. The effects of SKT and several anti-cancer drugs on the proliferation of HeLa cells, human cervical cell line, was estimated by MTT colorimetric assays. The SKT extract inhibited the proliferation of HeLa cell at 10^-4g/ml. The inhibitory action of the mitomycin C(MMC), mercaptopurine(MCP) and 5-fluorouracil(5-Fu) treated group, respectively, on the proliferation of HeLa cell was increased by the SKT. When the mice were treated by the MMC, the number of leukocyte was decreased significantly at the 1st and 3rd day, but recovered at the 7th day. In the groups of the MMC treated with the SKT, the number of leukocytes was increased significantly than the group of the MMC treated only at the 3rd day. The SKT extract decreased the thymus weight of mice. The SKT extract increased the number of plaque forming cells(PFC), but the MMC treated group decreased the number of PFC. The combined treatment of MMC and the SKT increased the number of PFC significantly than the MMC treated group. The SKT extract increased the proliferation of T cells, but the MMC treated group decreased the proliferation of T cells. The combined treatment of MMC and the SKT increased T cell proliferation significantly than the MMC treated group. In conclusion, the results presented in this paper suggest that the SKT extract can decrease the dose of anti-cancer drugs on HeLa cell, and recover the side dffects of the MMC, such as leukopenia and immunosuppresion, without any intercalating the anti-proliferative action of the MMC in vivo.

정상 초기 임신에서 갑상선 기능과 입덧의 심한 정도와의 상관관계에 관한 연구

이은찬,이임순,조태호 순천향의학연구소 1997 Journal of Soonchunhyang Medical Science Vol.3 No.1

Nausea and vomiting are extremely common symptoms in first trimester of the pregnancy. The reported frequency is ranging from 50-75% of all pregnancy. Hyperemesis gravidarum is clinically characterized by profuse vomiting which may some time be so severe as to cause electrolytes imbalance especially hypokalemia which can be like threatening or even fatal requiring hospitalization and intravenous therapy. Pregnant women with severe emesis might have a similar condition of non-thyroidal illness. However, little is known about the relation between morning sickness and thyroid function. Mori(1988) reported that increased free T₄and hCG and decreased TSH correlated with the severity of morning sickness, and these changes were especially marked in subject with nausea and vomiting. Thyroid gland is physiologically activated in early pregnancy, possibly by hCG or related substance, which may be gestational emesis. The purpose of this study was to determine thyroid function in early pregnancy with reference to morning sickness, using a highly sensitive immunoradiometric assay for TSH and a newly developed free T₄RIA that is not influenced by changes in thyroxine-binding globulin or albumin. The results were as follows: 1. Among groups in early pregnancy, the severity of morning sickness correlated significantly with changes of free T₄(p<0.05), TSH(p<0.01) and hCG(p<0.05) 2. The serum levels of free T₄in all 100 pregnant women correlated negatively with their TSH level (r=-0.451, p<0.001) and positively with their hCG levels (r=0.292, p<0.05). More their serum TSH levels correlated negatively with hCG levels(r=-0.279, p<0.05) 3. The increased free T₄and decreased TSH in subjects with emesis returned to the normal ranges of nonpregnant controls after improvement of emesis in five normal pregnant women. 4. An increased level of free T₄and a reduced level of TSH in early normal pregnancy are not indication of thyrotoxicosis and may not necessitate antithyroid drug treatment.