• 대한한방내과학회지
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• 제30권2호
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• pp.399-409
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• 2009

Objectives : The aim of this study was to experiment the antitumor activity of Agrimonia pilosa Ledebour (APL) in human stomach cancer (AGS) cell lines (in vitro) and male C57BL/6J mouse (in vivo). Methods : The effects of the ethanol extract from the plant on several transplantable rodent tumors were investigated in vitro by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. DNA content analysis and Western blot analysis. Agrimonia pilosa Ledebour (APL) was given to rats with Lewis Lung Carcinoma (LLC) cells. The experimental rats were divided into 3 groups in vivo. Saline was injected into the abdominal cavity in the first group, 50 mg/kg APL was injected into the abdominal cavity in the second group and 100 mg/kg was injected into the abdominal cavity in the third group. After that, we checked their tumor volume periodically. Results : At first, human gastric cancer (AGS) cell lines (in vitro) showed decreased cell viability, and increased $sub-G_1$ contents. When we experimented rat intestinal epithelial (RIE)l as same condition, this result didn't show. With this, compared to normal cells, Agrimonia pilosa Ledebour (APL) led selectively to the extinction of cells only in human gastric cancer. Moreover, we showed that the traditional herbal medicine APL induced caspase-dependent apoptosis in AGS cells. Next, APL inhibited the growth of LLC-bearing mouse tumor. However, we could not verify APL induced caspase-dependent apoptosis in LLC-bearing mouse tumor. Conclusions : The roots of Agrimonia pilosa Ledebour (APL) contain some antitumor constituents.

• 대한한방내과학회지
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• 제39권5호
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• pp.973-983
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• 2018

Objectives: We report a case of traditional Korean medicine (TKM) treatment for skin side effects after taking afatinib (Giotrif$^{(R)}$). Methods: A 62-year-old female who was diagnosed with non-small cell lung cancer stage 4 (T4N2M1b) and was on treatment with afatinib (29.56 mg/day for 4 months) complained of skin toxicity as a side effect. For 16 admission days, the patient was treated with acupuncture, moxibustion, and herbal medicine (oral decoction and external ointment). Results: Improvement of skin toxicity was measured by a numeric rating scale. In addition, Quality of life (QOL) was measured using EORTC Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) and EORTC Quality of Life Questionnaire, 13-item lung cancer-specific module (EORTC QLQ-LC13) Developed by the European Organization for Research and Treatment of Cancer (EORTC). Tumor size and carcinoembryonic antigen (CEA) were also examined during follow up. Conclusions: After a combined TKM treatment, skin toxicity symptoms and quality of life scales were significantly improved with no side effects. The tumor size was not changed on computed tomography during follow-up period. CEA levels were decreased.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2019년도 춘계학술대회
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• pp.112-112
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• 2019

Baicalein is one of the main flavonoids derived from roots of Scutellaria baicalensis Georgi, a traditional Oriental medicine. Although baicalein has high antitumor effect on several human carcinomas, the mechanism responsible for this property is not unclear. In this study, the data revealed that baicale-ininduced growth inhibition was associated with the induction of apoptosis connecting with cytochrome c release, down-regulation of anti-apoptotic Bcl-xl and increased the percentage of cells with a loss of mitochondria membrane permeabilization. Baicalein also induced the proteolytic activation of caspases and cleavage of PARP; however, blockage of caspases activation by z-VAD-fmk inhibited baicalein-induced apoptosis. In addition, baicalein enhanced the formation of autophagosomes and up-regulated LC3-II/LC3-I ratio. Interestingly, the pretreatment of bafilomycin A1 recovered baicalein-induced cell death suggesting that autophagy by baicalein roles as protective autophagy. Taken together, our results indicated that this flavonoid induces apoptosis and cell protective autophagy. These data means combination treatment with baicalein and autophagy inhibitor might be a promising anticancer drug.

• Journal of Chest Surgery
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• 제41권5호
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• pp.586-590
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• 2008

배경: 본 연구는 술전 종격동 내시경 혹은 흉강경을 통한 종격동 림프절 생검을 통해 병리조직학적으로 N2 진단을 받고 신보조 항암방사선치료를 받은 환자에 있어서 신보조 항암방사선치료 후 N병기의 변화에 따른 생존률 및 재발률에 미치는 영향에 대해 알아보고자 하였다. 대상 및 방법: 1998년 1월에서 2005년 12월 사이에 조직학적 N2로 확진된 환자 69명을 대상으로 후향적 연구를 진행하였다. 이들을 3그룹으로 나누어 신보조 항암방사선치료 후 병기가 낮아진 환자들을 그룹 A, 변화 없는 환자들을 그룹 B, 그리고 신보조 항암방사선 치료중 병기가 악화되어 수술을 진행하지 못한 환자들을 그룹 C로 구분하여 각 그룹간 평균생존기간, 3년 생존률 및 평균무병생존기간, 3년 무병생존률을 조사하였고 이들을 비교 분석해 보았다. 결과: 연령, 성별, 폐암의 조직형 및 수술명은 그룹별 유의한 차이는 없었다. 평균 생존기간은 그룹 A, B, C에서 각각 58, 47, 21개월로 그룹A가 가장 높았으나 A-B 및 B-C 사이에는 통계적으로 유이한 차이는 없었고 그룹 A와 C 사이에만 통계적으로 유의한 차이(p : 0.01)를 보였다. 3년 생존률 역시 그룹 A, B, C에서 67%, 41%, 21.6%로 평균생존기간과 비슷한 차이를 보였다. 평균무병생존기간은 그룹 A, B에서 44, 45개월로 통계적으로 유의한 차이는 보이지 않았고 3년 무병생존률도 55.1%, 46.8%로 통계적으로 유의한 차이는 보이지 않았다. 결론: IIIa기 폐암 환자에서 술전 항암방사선 치료 후 N병기가 감소된 그룹A에서 감소되지 않은 그룹 B보다 Mean survival, 3-Yr survival rate 및 3-Yr disease-free survival rate가 더 높은 경향을 볼 수 있었다. 그러나 통계학적 유의성은 없었으므로 더 명확한 결론을 위해서는 향후 더 많은 case 및 오랜 기간의 추적관찰이 필요할 것으로 생각된다.

• Radiation Oncology Journal
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• 제6권1호
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• pp.41-47
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• 1988

가톨릭의대 강남성모병원 방사선치료실에서는 1983년 5월부터 1987년 5월 사이 수술 후 재발되거나 국소적으로 진행되어 절제 불가능한 위암환자 35예에 대하여 외부방사선치료를 실시하였다. 방사선치료는 6MV선형가속기를 사용하여 매일 $160\~180cGy$씩, 주 5회 분할 조사하여 총 $4500\~5500cGy$를 시도하였으며, 전예에서 Box Technique을 이용하였다. 방사선치료만을 실시하였다. 3예를 제외한 전예에서 5-FU 또는 FAM 화학요법을 병행하였다. 1. 총 35예는 남자 25명 여자 10명이었으며 연령은 38세에서 80세사이에(평균 56세)분포하였다. 조직학적으로는 전 예가 선세포암이었다. 2. 수술후 재발되어 방사선치료하기까지의 기간은 수술후 1년이내에 $18(51\%)$명, $1\~2$년내 $8(23\%)$명, 그리고 $2\~3$년내에 $5(14\%)$명이었다. 3. 방사선치료를 하게된 주된 증상으로는 통증 30명$(86\%)$, 종괴 29명$(85\%)$, 위장관폐쇄 11$(31\%)$명 및 폐쇄성 황달이 9$(26\%)$명이었다. 4. 이증상들의 방사선치료 후 반응은 총 치료선량에 따라 $40\~50Gy$에서 14/16$(88\%)$, 50Gy이상에서 8/10$(80\%)$, $30\~40 Gy$에서 6/8$(75\%)$, 및 $20\~30Gy$에서 8/15$(53\%)$의 호전율을 관찰할 수 있었다. 5. 국소 진행된 위암환자의 방사선치료 후 평균 생존율은 3.6개월이었으며 방사선치료에 의한 부작용으로서는 오심, 구토$(46\%)$, 설사$(20\%)$, 백혈구 감소증$(27\%)$, 그리고 빈철 및 폐염$(9\%)$등의 순을 보였다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7179-7188
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• 2015

Cancer is a major health obstacle around the world, with hepatocellular carcinoma (HCC) and colorectal cancer (CRC) as major causes of morbidity and mortality. Nowadays, there isgrowing interest in the therapeutic use of natural products for HCC and CRC, owing to the anticancer activity of their bioactive constituents. Boswellia serrata oleo gum resin has long been used in Ayurvedic and traditional Chinese medicine to alleviate a variety of health problems such as inflammatory and arthritic diseases. The current study aimed to identify and explore the in vitro anticancer effect of B. Serrata bioactive constituents on HepG2 and HCT 116 cell lines. Phytochemical analysis of volatile oils of B. Serrata oleo gum resin was carried out using gas chromatography-mass spectrometry (GC/MS). Oleo-gum-resin of B. Serrata was then successively extracted with petroleum ether (extract 1) and methanol (extract 2). Gas-liquid chromatography (GLC) analysis of the lipoidal matter was also performed. In addition, a methanol extract of B. Serrata oleo gum resin was phytochemically studied using column chromatography (CC) and thin layer chromatography (TLC) to obtain four fractions (I, II, III and IV). Sephadex columns were used to isolate ${\beta}$-boswellic acid and identification of the pure compound was done using UV, mass spectra, $^1H$ NMR and $^{13}C$ NMR analysis. Total extracts, fractions and volatile oils of B. Serrata oleo-gum resin were subsequently applied to HCC cells (HepG2 cell line) and CRC cells (HCT 116 cell line) to assess their cytotoxic effects. GLC analysis of the lipoidal matter resulted in identification of tricosane (75.32%) as a major compound with the presence of cholesterol, stigmasterol and ${\beta}$-sitosterol. Twenty two fatty acids were identified of which saturated fatty acids represented 25.6% and unsaturated fatty acids 74.4% of the total saponifiable fraction. GC/MS analysis of three chromatographic fractions (I,II and III) of B. Serrata oleo gum resin revealed the presence of pent-2-ene-1,4-dione, 2-methyl- levulinic acid methyl ester, 3,5- dimethyl- 1-hexane, methyl-1-methylpentadecanoate, 1,1- dimethoxy cyclohexane, 1-methoxy-4-(1-propenyl)benzene and 17a-hydroxy-17a-cyano, preg-4-en-3-one. GC/MS analysis of volatile oils of B. Serrata oleo gum resin revealed the presence of sabinene (19.11%), terpinen-4-ol (14.64%) and terpinyl acetate (13.01%) as major constituents. The anti-cancer effect of two extracts (1 and 2) and four fractions (I, II, III and IV) as well as volatile oils of B. Serrata oleo gum resin on HepG2 and HCT 116 cell lines was investigated using SRB assay. Regarding HepG2 cell line, extracts 1 and 2 elicited the most pronounced cytotoxic activity with $IC_{50}$ values equal 1.58 and $5.82{\mu}g/mL$ at 48 h, respectively which were comparable to doxorubicin with an $IC_{50}$ equal $4.68{\mu}g/mL$ at 48 h. With respect to HCT 116 cells, extracts 1 and 2 exhibited the most obvious cytotoxic effect; with $IC_{50}$ values equal 0.12 and $6.59{\mu}g/mL$ at 48 h, respectively which were comparable to 5-fluorouracil with an $IC_{50}$ equal $3.43{\mu}g/mL$ at 48 h. In conclusion, total extracts, fractions and volatile oils of B. Serrata oleo gum resin proved their usefulness as cytotoxic mediators against HepG2 and HCT 116 cell lines with different potentiality (extracts > fractions > volatile oil). In the two studied cell lines the cytotoxic acivity of each of extract 1 and 2 was comparable to doxorubicin and 5-fluorouracil, respectively. Extensive in vivo research is warranted to explore the precise molecular mechanisms of these bioactive natural products in cytotoxicity against HCC and CRC cells.

• Molecules and Cells
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• 제43권5호
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• pp.469-478
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• 2020

Hepatitis C virus (HCV) propagation is highly dependent on cellular proteins. To identify the host factors involved in HCV propagation, we previously performed protein microarray assays and identified the LIM and SH3 domain protein 1 (LASP-1) as an HCV NS5A-interacting partner. LASP-1 plays an important role in the regulation of cell proliferation, migration, and protein-protein interactions. Alteration of LASP-1 expression has been implicated in hepatocellular carcinoma. However, the functional involvement of LASP-1 in HCV propagation and HCV-induced pathogenesis has not been elucidated. Here, we first verified the protein interaction of NS5A and LASP-1 by both in vitro pulldown and coimmunoprecipitation assays. We further showed that NS5A and LASP-1 were colocalized in the cytoplasm of HCV infected cells. NS5A interacted with LASP-1 through the proline motif in domain I of NS5A and the tryptophan residue in the SH3 domain of LASP-1. Knockdown of LASP1 increased HCV replication in both HCV-infected cells and HCV subgenomic replicon cells. LASP-1 negatively regulated viral propagation and thereby overexpression of LASP-1 decreased HCV replication. Moreover, HCV propagation was decreased by wild-type LASP-1 but not by an NS5A binding-defective mutant of LASP-1. We further demonstrated that LASP-1 was involved in the replication stage of the HCV life cycle. Importantly, LASP-1 expression levels were increased in persistently infected cells with HCV. These data suggest that HCV modulates LASP-1 via NS5A in order to regulate virion levels and maintain a persistent infection.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7905-7909
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• 2015

Several studies reported there was a polymorphism (rs531564 C > G) in miR-124 gene. To investigate the MiR-124 rs531564 polymorphism and cancer risk. We conducted a literature search of the Medline, Embase and Wangfang Medicine databases to identify all relevant studies for this meta-analysis. We determined that the miR-124 rs531564 polymorphism was significantly associated with decreased risks of cancers in the allelic model (G vs C, OR=0.71, 95% CI=0.53-0.94, P=0.02), homozygote model (GG vs CC, OR=0.42, 95% CI=0.26-0.66, P=0.0002), dominant model (GG/GC vs CC, OR=0.71, 95% CI=0.51-0.98, P=0.04) and recessive model (GG vs GC/CC, OR=0.43, 95% CI=0.27-0.69, P=0.0004). In an analysis stratified by cervical cancer group, significant associations were observed in the allelic model (G vs C, OR=0.46, 95% CI=0.32-0.66, P<0.0001), and dominant model (GG/GC vs CC, OR=0.45, 95% CI=0.3-0.66, P<0.0001). Subgroup analysis also revealed a decreased risk for esophageal squamous cell carcinoma in the homozygote model (GG vs CC, OR=0.45, 95% CI=0.27-0.75, P=0.002) and recessive model (GG vs GC/CC, OR=0.46, 95% CI=0.28-0.75, P=0.002). This meta-analysis suggests that the miR-124 rs531564 C > G polymorphism is an important risk factor for cancers among the Chinese population.

• IMMUNE NETWORK
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• 제4권1호
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• pp.31-37
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• 2004

Background: 1-8D gene is a member of human 1-8 interferon inducible gene family and is shown to be overexpressed in fresh colon cancer tissues. Three peptides 1-6, 3-5 and 3-7 derived from 1-8D gene were shown to have immunogenicity against colon cancer. Methods: To study tumor immunotherapy of these peptides we established an adoptive transfer model. $D^{b-/-}{\times}{\beta}2$ microglobulin (${\beta}2m$) null mice transgenic for a chimeric HLA-A2.1/$D^b-{\beta}2m$ single chain (HHD mice) were immunized with irradiated peptide-loaded RMA-S/HHD/B7.1 transfectants. Spleens were removed after last immunization, and splenocytes were re-stimulated in vitro. Lymphocytes from vaccinated HHD mice were transferred together with IL-2 to the tumor bearing nude mice that were challenged S.C. with the HCT/HHD/B7 colon carcinoma cell line that was found to grow in these mice. Results: Peptide 3-5 was found to be highly effective in CTL activity. Adoptively transferred anti-peptide 3-5 cytolytic T lymphocytes caused significant retardation in tumor growth. Conclusion: This study shows that peptide 3-5 can be the most effective candidate for the vaccine of adoptive immunotherapy against colon cancer.

• 대한세포병리학회지
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• 제9권1호
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• pp.21-28
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• 1998

Cytologic evaluation of cerebrospinal fluid(CSF) is an effective tool in diagnosing many disorders involving the central nervous system(CNS). CSF examination has been found to be of particular value in the diagnosis of metastatic carcinoma, lymphomatous or leukemic involvement of CNS and certain primary CNS tumors. As a survey of metastatic tumors to CSF and an evaluation of the preparation techniques increasing cellular yield in our laboratory, 713 CSF specimens examined between July 1995 and April 1997(1 year 10 months), were reviewed. There were 75 positive and 5 suspicious cases, the latter have had no evidence of tumors clinically. Primary tumors of 75 positive cases were classified as follows; 4(5.3%) as primary brain tumors, 40(53.3%) as secondary carcinomas, 13(17.3%) as leukemias, and 18 (24.0%) as lymphomas. The most common primary site of metastatic carcinomas was the lung in 17 cases(42.5%) followed by the stomach in 13(32.5%), breast in 8 (20.0%), and unknown primary in 2(5.0%). Four primary brain tumors were 3 cerebellar medulloblastomas and a supratentorial primitive neuroectodermal tumor (PNET). All 40 metastatic carcinomas were adenocarcinoma presented as single cells or cell clusters. Although signet ring cells were frequent in the cases of gastric primary cancers, no significant cytologic differences according to the primary site were observed. The cytologic features of leukemia and lymphoma were characterized by hypercellular smears presenting as individual atypical cells with increased N/C ratio, presence of nucleoli, and nuclear protrusions. In medulloblastomas and PNET, the principal cytologic findings were small undifferentiated cells arranged singly or in loose clusters with occasional rosettoid features. This study suggests that the CSF cytology is useful in the diagnosis of malignancy, especially metastatic extracranial tumors and the diagnostic accuracy can be improved by increasing cellular yield using cytocentrifuge.