• 대한핵의학회지
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• 제26권2호
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• pp.380-391
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• 1992

This study was designed to evaluate a direct method of $^{99m}Tc$ labeling using $\beta-mercaptoethanol$ as a reducing agent, and to investigate whether $^{99m}Tc$ labeled specific monoclonal antibody against carcinoembryonic antigen (CEA-92) can be used for the scintigraphic localization of human colon cancer xenograft. Purified CEA-92 IgG was fragmented into F $(ab')_2$ and then labeled with $^{99m}Tc$ by transchelation method using glucarate as a chelator. Labeling efficiency, immunological reactivity and in vitro stability of $^{99m}Tc$ CEA-92 F $(ab')_2$ were measured and then injected intravenously into nude mice bearing human colon cancer (SNU-C4). Scintigrams were obtained at 24 hour after injection. Then nude mice were sacrificed and the radioactivity was measured Labeling efficiency of injected $^{99m}Tc$ CEA-92 F $(ab')_2$, immunoreative fraction and in vitro stability at 24 hour of injected $^{99m}Tc$ CEA-92 F $(ab')_2$ was 45.2%, 32.8% and 57.4%, respectively. At 24 hour after injection, % ID/g in kidney (46.77) showed high uptake, but %ID/g in tumor (1.65) was significantly higher than spleen (0.69), muscle (0.16), intestine (0.45), stomach (0.75), heart (0.48) and blood (0.45). There was no significant difference between tumor and liver (1.81). Tumor contrast as quantitated by tumor to blood ratio of $^{99m}Tc$ CEA-92 F $(ab')_2$ was increased significantly (p<0.005) until 24 hours (3.70), and there was no statistical differece from tumor to blood ratio of I-131 CEA-92 F $(ab')_2$. The scintigram demonstrated localization of radioactivity over transplanted tumor, but significant background radioactivity was also noted over kidney and abdomen. It is concluded that CEA-92 F $(ab')_2$ can be labeled with $^{99m}Tc$ by a direct transchelation method using $\beta-mercaptoethanol$ as a reducing agent and $^{99m}Tc$ labeled CEA-92 F $(ab')_2$ can be used for the scintigraphic localization of human colon cancer xenograft in nude mice model.

• 대한세포병리학회지
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• 제8권2호
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• pp.164-169
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• 1997

A case of plasmacytoma of the ovary and breast, which developed in a patient with a solitary plasmacytoma in the lumbar vertebra for nine months, was diagnosed cytologically and histologically. Enlargement of the right ovary and multiple palpable masses in the right and left breast were already present at six months after the diagnosis of vertebral solitary plasmacytoma. At eight months, plasma cell leukemia developed, and nine months the enlarged both ovaries, replaced by yellowish-gray solid tumors showed infiltration of immature plasma cells. The cytologic features of the ovarian tumors were same with those of the breast tumor. The tumor cells were of predominantly immature plasma cells with one or more nuclei. Some mature plasma cell had an eccentric nucleus with single nucleolus and peripherally clumped chromatin. Binucleated or multinucleated giant cells were often present. Histologically, sheets of poorly differentiated plasmacytoid tumor cells were separated by strands of hyaline fibrous tissue. On immunohistochemical stains, the tumor cells showed strong reactivity for lambda-light chain but no reaction for kappa-light chain, cytokeratin, or leukocyte common antigen.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.695-700
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• 2013

Background: Mutations affecting the epidermal growth factor receptor (EGFR) are good predictors of clinical efficacy of EGFR tyrosine kinase inhibitors (TKI) in patients with non-small cell lung cancer. Serum carcinoembryonic antigen (CEA) levels are also regarded as predictive for the efficacy of EGFR-TKI and EGFR gene mutations. This study analyzed the association between EGFR gene mutations and clinical features, including serum tumor marker levels in lung adenocarcinomas patients. Patients and Methods: A total of 70 lung adenocarcinoma patients with complete clinical data and pathological specimens were investigated. EGFR gene mutations at exons 19 and 21 were assessed. Serum tumor markers were detected by protein chip-chemiluminescence at the corresponding time, and correlations were analyzed. Results: Mutations of the EGFR gene were detected in 27 of the 70 patients and the serum CEA and CA242 concentrations were found to be significantly associated with the incidence of EGFR gene mutations (P<0.05). The AUCs for CEA and CA242 were 0.724 (95% CI: 0.598~0.850, P<0.05) and 0.769 (95% CI: 0.523~0.800, P<0.05) respectively. Conclusions: Serum CEA and CA242 levels are associated with mutations of the EGFR gene in patients with lung adenocarcinomas.

• Preventive Nutrition and Food Science
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• 제12권1호
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• pp.11-15
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• 2007

This study was conducted to evaluate the influence of diets containing genistein and soy extract on the growth of MDA-MB-231 cells implanted into female Balb/c mice. Four-week-old female athymic nude mice (Balb/c) were acclimated to an AIN-93G control diet for 1 week and then injected MDA-MB-231 cells ($1{\times}10^6$/site) and were continued on the on AIN-93G control diet. Five weeks after injecting the MDA-MB-231 cells ($1{\times}10^6$/site), two experimental groups were assigned to diets containing genistein (750 ${\mu}g/g$ AIN-93G diet) or 0.6% soy extract (containing genistein at 750 ${\mu}g/g$ AIN-93G diet) until they were sacrificed. Tumor growth was significantly reduced in the groups treated with genistein and soy extract compared to the control group. The results of the proliferating cell nuclear antigen (PCNA) assay also revealed that genistein and soy extract treatment reduced the proliferation of MDA-MB-231 cells in vivo. In the present study, dietary isoflavone was provided just before solid tumor formation, and thus the timing of dietary isoflavone administration may be critical to the suppression of tumor growth.

• Biomolecules & Therapeutics
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• 제27권1호
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• pp.63-70
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• 2019

Myeloid-derived suppressor cells (MDSCs) that are able to suppress T cell function are a heterogeneous cell population frequently observed in cancer, infection, and autoimmune disease. Immune checkpoint molecules, such as programmed death 1 (PD-1) expressed on T cells and its ligand (PD-L1) expressed on tumor cells or antigen-presenting cells, have received extensive attention in the past decade due to the dramatic effects of their inhibitors in patients with various types of cancer. In the present study, we investigated the expression of PD-1 on MDSCs in bone marrow, spleen, and tumor tissue derived from breast tumor-bearing mice. Our studies demonstrate that PD-1 expression is markedly increased in tumor-infiltrating MDSCs compared to expression in bone marrow and spleens and that it can be induced by LPS that is able to mediate $NF-{\kappa}B$ signaling. Moreover, expression of PD-L1 and CD80 on $PD-1^+$ MDSCs was higher than on $PD-1^-$ MDSCs and proliferation of MDSCs in a tumor microenvironment was more strongly induced in $PD-1^+$ MDSCs than in $PD-1^-$ MDSCs. Although we could not characterize the inducer of PD-1 expression derived from cancer cells, our findings indicate that the study on the mechanism of PD-1 induction in MDSCs is important and necessary for the control of MDSC activity; our results suggest that $PD-1^+$ MDSCs in a tumor microenvironment may induce tumor development and relapse through the modulation of their proliferation and suppressive molecules.

• KSBB Journal
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• 제24권1호
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• pp.80-88
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• 2009

glandular kallikrein에 광범위한 상동성을 가지는 인간 전립성 산성 인산 가수분해 효소는, 전립선암의 대표적인 혈청 biomarkers이다. 수지상세포는 유력한 항원 제시 세포이며, 바이러스, 미생물 병원체 및 종양에 대하여 면역 계통에서 강력한 T 세포 응답을 유도할 수 있다. 따라서, 종양 특이적인 항원으로 감작된 수지상세포를 이용한 면역요법은 anti-tumor 면역 유도를 위한 강력한 방법중의 하나이다. 크레아젠(주)에서 개발된 CTP (세포막 투과성 펩티드) 기술은 세포 내로의 높은 침투 효율성을 가지며 핵산이나 단백질과 같은 생체 고분자 물질을 접합하여 세포내로 수송할 수 있는 기술이다(36). 하지만 활성형의 인간 전립성 산성 인산 가수분해 효소는 세포사멸을 매개할 수 있기 때문에, 본 연구진은 항암 치료용 백신으로의 수지상세포 감작을 위해 비활성형 형태의 다중체 (multimer) 항원을 개발하였다. 본 연구에서, 수지상 세포의 감작과 활성화에 안전하고 효율적인 다중체 형태 (multimeric form)의 세포막 투과성 펩티드가 융합된 인간 전립성 산성 인산 가수분해 효소를 얻기 위한 정제공정을 기법을 개발하였고 젤 여과 크로마토그래피, western blot과 Dynamic Light Scattering을 이용하여 확인하였다. 아울러, 정제된 다중체 형태 (multimeric form)의 세포막 투과성 펩티드가 융합된 인간 전립성 산성 인산 가수분해 효소는 수지상 세포의 감작시 세포질 내로 효과적으로 침투되었다. 결과적으로 세포의 사멸의 부작용이 없이 MHC class I 분자를 통해 수지상세포의 표면으로 효과적으로 제시되었다.

• Clinical and Experimental Reproductive Medicine
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• 제30권4호
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• pp.317-324
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• 2003

목 적: 본 실험의 목적은 자궁내막세포를 분리 및 배양법 확립과 함께 불멸화 시키는 것이다. 방 법: 자궁내막에서 상피세포(epithelial cells)와 기질세포(stromal cells)의 분리는 Satyawaroop 등(1979)의 방법에 기초를 두었다. 자궁내막에서 상피세포와 기질세포의 순수 분리도를 확인하고, 불멸화된 기질세포에서 SV40 large T antigen을 확인하기 위하여 면역형광 염색(immunocytochemistry)과 Western blot 기법을 이용하였다. 정상 기질세포의 경우 subconfluence (60%) 상태에서 transfection을 진행하였다. 순수 분리된 plasmid DNA와 Qiagen 사의 superfect를 이용하여 transfection을 실시하였다. 결 과: 본 연구에서 우리는 두 가지 형태의 자궁내막 세포의 분리 및 배양에 성공하였다. 상피세포는 다면체의 형태를 띠며, 선(grandular)조직의 조각으로부터 나선형으로 자란다.기질 세포는 길쭉한 형태를 띠며, 상피세포에 비해 오래 살고, 빠르게 증식하여 나란한 형태로 배열된 세포 다발(cell bundle)을 형성한다. 이렇게 분리된 세포들은 95%의 균질성을 보였으며, 면역형광염색과 western blot을 통해 확인 하였다. 한편 SV40(Simian Virus 40) large T 항원을 암호화 하고 있는 염기 서열을 포함한 플라스미드 벡터로 안정적인 트랜스펙션을 시킴으로써 불멸화 된 자궁내막의 기질 세포주를 확립하였다. 불멸화 된 세포는 그 세포가 유래한 정상의 세포와 동일한 표현형을 가지고 있었다. 결 론: 본 연구에서, 우리는 자궁내막에서 상피세포(epithelial cells)과 기질세포(stromal cells)를 분리하여 배양법을 확립하였다. 동시에 SV40 large T antigen을 이용하여 불멸화된 세포주를 확립하였다. 이렇게 확립된 세포주는 자궁의 생리작용 연구 및 자궁내막증(Endometriosis)과 자궁암(Endometrial cancer) 등과 같은 여러 자궁관련 질병 연구에 많은 도움이 될 것으로 사료된다.

• Journal of Korean Neurosurgical Society
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• 제29권4호
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• pp.477-484
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• 2000

Objective : Despite advances in the understanding of tumor biology and the tumor immunology, there has been no effective treatment. The Intercellular adhesion molecule-1(ICAM-1) has been shown to be important in interaction involving cells of the immune system and to be upregulated in a number of cell culture systems by cytokines, including immune interferon($IFN-{\gamma}$) and tumor necrosis $factor-{\alpha}$($TNF-{\alpha}$). ICAM-1 has been identified as one of the ligands for lymphocyte function-associated antigen-1(LFA-1). The effectiveness of various cytokines to ICAM-1 induction on cultured human glioblastoma cell lines and potential efficacy of immunotherapy were studied. Method : Human glioblastoma cell lines, U-251 MG, U-373 MG were trypsinized and suspended at $1{\times}10^5cells/ml$ and grown on 8 well chamber slide, the cells were incubated in 0.3ml medium alone or medium containing $IFN-{\gamma}$(1000U/ml) or $TNF-{\alpha}$(250U/ml) or $IFN-{\gamma}$ plus $TNF-{\alpha}$ for 6, 12, 24, 48 and 72 hours. The coverslip were then removed and stained with a 1/30 dilution of anti-ICAM-1 antibody. Result : Surface antigen expression of ICAM-1 was increased by incubating glioblastoma cell lines with $IFN-{\gamma}$ and $TNF-{\alpha}$. Combined effect of $IFN-{\gamma}$ and $TNF-{\alpha}$ has induced more ICAM-1 expression on glioblastoma cell lines. Upregulation of ICAM-1 expression in an established glioblastoma cell line was of greater magnitude and more rapid following incubation with $IFN-{\gamma}$ plus $TNF-{\alpha}$. Surface antigen expression of ICAM-1 was increased for up to 48 hours after cytokine treatment on both cell lines(p<0.05). There was no difference on both cell lines(p>0.05). Conclusion : The results of the present study indicate that ICAM-1 expression in glioblastoma cell lines, U-251 MG and U-373 MG, are induced and enhanced after treatment with $IFN-{\gamma}$ and $TNF-{\alpha}$. Combined effect of $IFN-{\alpha}$ and $TNF-{\gamma}$ is stronger and more rapid than $IFN-{\gamma}$ or $TNF-{\alpha}$ alone.

• Journal of Gastric Cancer
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• 제14권2호
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• pp.123-128
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• 2014

Purpose: Since there are no proven tumor markers that reflect the course of gastric cancer, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are commonly used alternatives. However, the degree of progression that corresponds to an increase in these markers, and the values of these markers at different cancer stages, remains unclear. Materials and Methods: This study enrolled 1,733 gastric cancer patients who underwent surgery and whose pre-operative CEA and CA19-9 levels were known. Survival curves and mean values of the two markers were compared according to the degree of cancer progression: serosa-unexposed (SU), serosa-exposed (SE), direct invasion (DI), localized seeding (P1), and extensive seeding (P2). Results: The 5-year overall survival rates at each stage differed significantly, except between DI and P1 patients (17.1% vs. 10.5%, P=0.344). The mean CEA values in SU, SE, DI, P1, and P2 patients were 5.80, 5.48, 13.36, 8.06, and 22.82, respectively. The CA19-9 values for these patients were 49.40, 38.97, 101.67, 73.77, and 98.57, respectively. The increase in CEA in P2 patients was statistically significant (P=0.002), and the increases in CA19-9 in DI and P2 patients were significant (P=0.025, 0.007, respectively). There was a fair correlation between the two markers in P2 patients (r=0.494, P<0.001). Conclusions: CA19-9 can be used to assess DI of gastric cancer into adjacent organs. Both markers are useful for predicting the presence of extensive peritoneal seeding.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10299-10306
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• 2015

The esophageal squamous cell carcinoma (ESCC) is thought to develop through a multi-stage process. Epigenetic gene silencing constitutes an alternative or complementary mechanism to mutational events in tumorigenesis. Posttranscriptional regulation of human leukocyte antigen class I (HLA-I) and antigen processing machinery (APM) proteins expression may be associated with novel epigenetic modifications in cancer development. In the present study, we determined the expression levels of HLA-I antigen and APM components by immunohistochemistry. Then by a bisulfite-sequencing PCR (BSP) approach, we identified target CpG islands methylated at the gene promoter region of APM family genes in a ESCC cell line (ECa109), and further quantitative analysis of CpG site specific methylation of these genes in cases of Kazakh primary ESCCs with corresponding non-cancerous esophageal tissues using the Sequenom MassARRAY platform. Here we showed that the development of ESCCs was accompanied by partial or total loss of protein expression of HLA-B, TAP2, LMP7, tapasin and ERp57. The results demonstrated that although no statistical significance was found of global target CpG fragment methylation level sof HLA-B, TAP2, tapasin and ERp57 genes between ESCC and corresponding non-cancerous esophageal tissues, there was significant differences in the methylation level of several single sites between the two groups. Of thesse only the global methylation level of LMP7 gene target fragments was statistically higher ($0.0517{\pm}0.0357$) in Kazakh esophageal cancer than in neighboring normal tissues ($0.0380{\pm}0.0214$, p<0.05). Our results suggest that multiple CpG sites, but not methylation of every site leads to down regulation or deletion of gene expression. Only some of them result in genetic transcription, and silencing of HLA-B, ERp57, and LMP7 expression through hypermethylation of the promoters or other mechanisms may contribute to mechanisms of tumor escape from immune surveillance in Kazakh esophageal carcinogenesis.