췌담관 질환 환자에서 담즙내 carcinoembryonic antigen의 진단적 역할

추연익 ( Chu Yeon Ig ),주광로 ( Ju Gwang Lo ),박종호 ( Park Jong Ho ),방성조 ( Bang Seong Jo ),김도하 ( Kim Do Ha ),신정우 ( Sin Jeong U ),박능화 ( Park Neung Hwa ),박재후 ( Park Jae Hu ),이지호 ( Lee Ji Ho ) 대한내과학회 2003 대한내과학회지 Vol.65 No.5

Background : Recently there has been notion that fluids bathing tumors might contain higher levels of carcinoembryonic antigen (CEA) than those found in the blood. Thus, we evaluated the diagnostic role of biliary CEA in patients with pancreatobiliary dis

자궁선암 및 자궁내막증식증의 조직 내 Carcinoembryonic Antigen에 관한 연구

홍성란 인제대학교 1987 仁濟醫學 Vol.8 No.1

Goldman과 Freedman(1965)이 대장선암 환자의 혈청에서 CEA를 처음 기술한 이래, CEA 가위장관 선암 이외에도 폐암 유방암, 두경부암 비뇨기과 종양 및 부인과 질환 등 다양한 악성 종양의 표식자로 알려져 왔다. 본 연구는 immunoperoxidase 방법으로 자궁내막증식과 자궁선암에서의 조직학적 유형에 따른 CEA 양성율 및 분포 양상을 관찰한에 목적이 있고, 그 결과는 다음과 같다. 1.CEA에 대한 양성율은 자궁경부선암이 84.2%였고, 자궁내막선암이 66.7%였다. 낭포성 및 선종성 자궁내막증식중에서는 모두 음성 반응이었으나, 이형성 증식증에서는 6례 중 1례가 양성 반응을 보였다. 2.CEA 양성 반응의 강도를 보면, 자궁경부선암에는 중등도 이상의 양성 반응이 많았으나, 자궁내막선암에는 중등도 이하의 양성 반응이 많았다. 3.CEA양성 반응의 분포 양상을 볼 때, 자궁경부선암에서는 개개 암 세포의 세포질 전체에 미만성으로 나타내는 경우가 많았고, 자궁내막선암에서는 개개 암 세포의 표면에 국소적으로 나타나는 경우가 많았다. Carcinoembryonic antigen (CEA) first described by Gold and Freedman(1965) has new become one of the best known tumor markers. Although CEA was originally described as a tumor associated antigen of the colon, it is demonstrated in serum of patients with various kinds of neoplasm. In patients with gynecological malignancies, CEA is edsmonstrated in the serum by radioimmunoassay and in the tissue by immunohistochemistry. The histological difference of adenocarcinoma of the uterus and endometrial hyperplasia has been a diagnostic problems and it is very important for subsequent treatment and prognosis. The aim of the present study is to clarify the difference in degree and distribution of CEA between endocervical and endometrial adenocarcinoma and to distinguish between endometrial hyperplasia and adenocarcinoma, using immunoperoxidase technique for CEA. The 19 endocervical adenocarcinoma, 18 endometrial adenocarcinoma and 44 endometrial hyperplasia (20 cystic, 18 adenomatous and 6 atypical) were studied by peroxidase antiperoxidase method (PAP) for CEA. The following results were obtained; 1.Sexteen cases (84.2%) of 19 endocervical adenocarcinoma and 12(6.7%) of 18 endometrial adenocarcinoma revealed positive CEA immunostain. Only 1 case of the 6 endometrial hyperplasia contained CEA with moderately focal positive immunostain. All 20 cystic and 18 adenomatous hyperplasia revealed negative CEA immunostain. 2.In degree of CEA immunostain, 12(63.1%) of endocervical adenocarcinoma and 5(27.8%) endometrial adenocarcinoma contained CEA with moderately and strongly positive immunostain. 3.Indistribution,CEA was present in entire cytoplasm in 15(78.9%) and diffuse patern in 12(63.1%) of endocervical adenocarcinoma. In contrast, CEA was focally stained in 10(55.6%) and on cell surface in 10(55.6%). 4.Both endocervical and endometrioid types of endocervical adenocarcinoma revealed positive CEA over whole cytoplasm more frequently than on cell surface. In summary, the majority of endocervical adenocarcinoma showed abundant diffusely distributed intracellular CEA in degree of moderate and strong positivity, while endometrial adenocarcinomas contained focal small amounts of cell surface CEA. Only 1 case of the 6 atypical endometrial endometrial hyperplasia contained CEA with moderately focal immunostain. In contrast, 12(66.7%) endometrial adenocarcinoma revealed positive CEA immunostain.

CEA 발현 마우스 종양모델에서 Cyclophosphamide와 수지상세포 백신의 병합치료에 의한 상승적인 항종양 효과

박미영 ( Mi-young Park ) 대한임상검사과학회 2022 대한임상검사과학회지(KJCLS) Vol.54 No.1

Carcinoembryonic antigen (CEA)는 다양한 종양에서 발현되는 자가 항원으로 면역치료에서 강력한 표지 인자이며 면역치료를 위한 표적 종양항원으로 널리 알려져 있다. 그러나 수지상세포 단독 치료는 동물모델에서 종양의 발생을 억제하는 데 효과가 있지만 이미 확립된 종양을 제거하는 데는 한계가 있다. 본 연구에서는 항종양 면역 효과를 증가시키기 위하여 화학치료제인 cyclophosphamide (CYP)와 종양 특이 면역치료법인 수지상세포 백신의 병합치료 효과를 CEA를 발현하는 마우스 종양 모델에서 검증하였다. 종양세포 주입 후 2일 소종양군과 10일 대종양군에서 CYP의 항종양 효과를 비교한 결과, 소종양군에서는 100 mg/kg에서 뚜렷한 종양 성장의 억제 효과가 관찰되었지만 대종양군에서는 약한 억제 효과가 관찰되어 본 연구에서는 대종양군을 병합치료의 적합한 모델로 설정하였다. CYP 와 수지상세포 백신의 병합치료(화학면역치료) 시 종양항원 특이 면역반응이 증가되었을 뿐만 아니라 상승적인 항종양 효과가 나타났다. 또한 CYP 치료에서 나타나는 체중 감소 및 조절 T세포와 골수유래 억제세포의 증가에 의한 면역억제는 화학면역치료에 의해 개선되었다. 항원 특이 면역치료를 병합한 화학면역치료가 화학치료의 부작용을 감소시키고 항종양 효과를 증가시킬 수 있는 치료 전략이 될 수 있을 것이다. Carcinoembryonic antigen (CEA) is an oncofetal antigen primarily detected in the peripheral blood of cancer patients, particularly in those with colorectal cancer. CEA is considered a valuable target for antigen-specific immunotherapy. In this study, we induced the anti-tumor immunity for CEA through the administration of a dendritic cell (DC) vaccine. However, there was a limitation in inducing tumor regression in the DC vaccinated mice. To enhance the efficacy of anti-tumor immunity in MC38/CEA2 tumor-bearing mice, we evaluated the effects of DC vaccine in combination with cyclophosphamide (CYP). Administration of CYP 100 mg/kg in mice resulted in significant inhibition of tumor growth in the 2-day tumor model, whereas a lower inhibition of tumor growth was seen in the 10-day tumor model. Therefore, the 10-day tumor model was selected for testing chemo-immunotherapy. The combined CYP and DC vaccine not only increased tumor antigen-specific immune responses but also induced synergistic anti-tumor immunity. Furthermore, the adverse effects of CYP such as weight loss and immunosuppression by regulatory T cells and myeloid-derived suppressor cells showed a significant reduction in the combined chemo-immunotherapy treatment compared with CYP alone. Our data suggest that chemoimmunotherapy with the DC vaccine may offer a new therapeutic strategy to induce a potent anti-tumor effect and reduce the adverse effects of chemotherapy.

CEA와 Tat 융합 단백질을 이용한 CEA 특이 항종양 면역능의 유도 증가

안창혁,강원경,오승택,조현일,김태규 대한대장항문학회 2003 Annals of Coloproctolgy Vol.19 No.3

결핵성 흉막염에서 Interferon - gamma , Adenosine Deaminase 와 Carcinoembryonic Antigen 의 진단적 가치

김현태(Hyeon Tae Kim),김효석(Hyo Seok Kim),박준영(Jun Young Park),안영수(Young Soo Ahn),이상무(Sang Moo Lee),어수택(Soo Taek Uh),김용훈(Yong Hoon Kim),박춘식(Choon Sik Park) 대한내과학회 1994 대한내과학회지 Vol.46 No.2

Background: The cell-mediated immunity in tuberculosis is enhanced by the activated T lymphocyte, Tuberculous antigen is phagocyted by antigen-presenting macrophages, and T lymphocytes are stimulated by these macrophages, and then activated T lymphocytes release cytokines such as interferon- gamma (IFN-γ), and interleukin 2. In turn protective functions of macrophages and other T lymphocytes are amplified by released cytokines, In tuberculous pleural effusion, these immunologic phenomena are localized in pleural space according to the compartmentalization theory. This study was designed to evaluate the diagnostic significance of IFN-γ in the tuberculous pleural effusion. Methods: Carcinoembryonic antigen, adenosine deaminase (ADA) activity, and IFN-γ level as well as cell counts and differential count, and biochemical assay such as protein content, glucose concentration, and lactic dehydrogenase was performed in 27 cases of tuberclous pleural effusions, 17 cases of malignant pleural effusion, and 14 cases of empyemas. Results: In tuberculous pleural effusions, IFN-γ levels were significantly elevated than those in malignant effusions and empyemas. The correlation between IFN-γ level and percentage of lymphocyte was not significant in tuberculous pleural effusions, but IFN-γ levels were proportionally increased as percentage of lymphocytes in malignant pleural effusions and empymas. ADA activities were also elevated significantly in tuberculous pleural effusions. Correlation between IFN-γ level and ADA was statistically significant. Conclusion: In tuberculous pleural effusion, elevated INF-γ level and ADA activity can display markedly enhanced cell-mediated immunity and IFN-γ level in pleural fluid is decisive role in the diagnosis of tuberculous pleural effusion.

CEA 발현 수지상 세포를 이용한 CEA 특이 살해 T 세포의 유도

원은하,김창현,박미영,조현일,오승택,홍용길,김태규,Won, Eun-Ha,Kim, Chang-Hyun,Park, Mi-Young,Cho, Hyun-Il,Oh, Seong-Taek,Hong, Yong-Kil,Kim, Tai-Gyu 대한면역학회 2003 Immune Network Vol.3 No.4

Background: Carcinoembryonic antigen (CEA) is well-known soluble tumor marker frequently detectable in peripheral blood of carcinoma patients and considered as good target for antigen-specific immunotherapy. In this study, we used a replication-deficient adenovirus containing CEA to study CTL induction in vitro after adenovirus-mediated gene transfer into DC. Methods: DC were obtained from mouse bone marrow and cultured with IL-4 and GM-CSF. For measuring CTL activity, splenocytes were harvested from the mice, which were immunized with DC that had been infected AdV-CEA or pulsed with CEA peptide. Untreated DC was used as a control. Splenocytes were re-stimulated in vitro with DC pulsed with CEA peptide for 7 days and CTL activity with CEA peptide-pulsed EL-4 cells were assessed in a standard $^{51}Cr$-release assay. The frequencies of antigen-specific cytokine-secreting T cell were determined with $mIFN-{\gamma}$ELISPOT. Results: DC infected with recombinant adenovirus expressing CEA induced CEA-specific CTL responses in vivo. Splenocyte induced from mice immunized with AdV-CEA-infected DC increase in the number of $IFN-{\gamma}$ secreting T cells compared with those from mice immunized with CEA peptide-pulsed DC. Conclusion: These results suggested that DC infected with recombinant adenovirus has advantages over other forms of vaccination and could provide an alternative approach vaccination therapies.

MicroRNA-29a suppresses the growth, migration, and invasion of lung adenocarcinoma cells by targeting carcinoembryonic antigen-related cell adhesion molecule 6

Han, H.S.,Son, S.M.,Yun, J.,Jo, Y.N.,Lee, O.J. North-Holland Pub ; Elsevier Science Ltd 2014 FEBS letters Vol.588 No.20

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is an important regulator of cell adhesion, invasion, and metastasis. The aim of this study was to evaluate the functional roles of CEACAM6 in lung adenocarcinoma and to identify miRNAs that inhibit the growth, migration, and invasion of lung adenocarcinoma cells by targeting CEACAM6. CEACAM6 expression is associated with poor prognosis of patients with lung adenocarcinoma, and CEACAM6 has important functional roles in controlling the growth, migration, and invasion of lung adenocarcinoma cells in vitro and in vivo. Furthermore, miR-29a can suppress the growth, migration, and invasion of lung adenocarcinoma cells by targeting CEACAM6. Therefore, miR-29a/CEACAM6 axis represents a potential therapeutic target for treatment of lung adenocarcinoma.

경화성 한관 선암 - 1예 보고 -

박광화,조남훈,이광길 대한병리학회 1989 Journal of Pathology and Translational Medicine Vol.23 No.3

위암 환자에서 Anti-CEA Antibody의 임상적 의의

김종익,김운원,홍관희 인제대학교 1999 仁濟醫學 Vol.20 No.1S

태아성 암항원은 종양 표지자로 소화기 암의 수술후 예후 판정 및 추적 조사 등에 널리 사용되고 있다. 태아성 암항원에 대한 체성 면역의 작용으로 항 태아성 암항원 항체가 나타나고 이 항태아성 암항원 항체는 radioimmunoscintigraphy를 이용하여 암진단과 면역 치료에 사용될 수 있다. 이에 저자들은 위암에서 항 태아성 암항원 항체에 대한 상관 관계를 조사 확인하여 체성면역에 대한 이해를 높여 면역진단과 면역치료에 도움을 주고자 연구를 시행하였으며 연구 대상은 부산백병원에 입원하여 수술받은 위암 환자 42명이었다. 이들 42예의 임상병기는 1기 16예, 2기 5예, 3기 16예, 4기 5예였으며 위암의 항 태아성 암항원 항체를 ELISA 및 Western blot 방법으로 분석하여 다음과 같은 결과를 얻었다. 1) 42예의 ELISA 검사 결과 정상인과 위암 환자간의 항체 역가는 0.221과 0.217로서 유의한 차이가 없었다(P>0.05). 2) 각 병기의 항체가는 1기 0.205, 2기 0.254, 3기 0.224, 4기 0.186로서 유 의한 차이가 없었다(P>0.05). 3) IgG, IgM, IgGAM의 항체가도 각 병기간 유의한 차이가 없었다(P>0.05) 4) 항체가가 비교적 높은 암환자 5명과 정상인 5명의 혈청을 Western blot방법으로 비교한 결과 95KDa, 200KDa에서 두 그룹 모두 항원과 반응하였다. 이상의 결과, 정상인과 암환자 간의 항 태아성 암항원 항체에 대한 역가의 차이를 볼 수 없었으며, 각 병기 간의 역가도 통계적 유의성이 관련되지 않았다(P>0.05). 또한 각 병기간의 IgM, IgG, IgGAM의 차이가 없었고, 비교적 높은 항 태아성 암항원 항체를 보인 암환자 그룹의 태아성 암항원에 대한 항체의 특이성도 유의하지 않았다(P>0.05). 이와 같은 결과의 의미는 위암에서는 항 태아성 암항원 항체의 면역원성이 상대적으로 낮거나, 전반적인 체성 면역 반응력의 감소 혹은 항 태아성 암항원 항체 유발 epitope의 masking현상을 고려해야 할 것으로 사료된다. Carcinoembryonic antigen has been widely used as tumor masker to predict the prognosis after operation of colorectal or stomach cancer and its follow up. Anti-carcinoembryonic antigen antibodies against CEA as humoral immunity was thought to be used for radioim-munoscintigraphy and immunotheraphy. Using an enzyme-linked immunoassay(ELISA) and Western blot, we measured the serum concentration of anti-carcinoembryonic antigen antibodies in 42 patients who underwent operation for stomach cancer at the Department of General Surgery, Pusan Paik Hospital. Among 42 cases, 16 cases were stage I, 5 cases were stage II, 16 cases were stage III, 5 cases were stage IV. The results were as follows : 1) The average serum concentration of anti-carcinoembryonic antigen antibodies in patients with stomach cancer was 0.217 and that was no significance(P>0.05) in comparing with normal person's level of 0.221. 2) The average serum concentration of anti-carcinoembryonic antigen antibodies according to the stage showed 0.205 in stage I, 0.254 in stage II, 0.224 in stage III, 0.186 in stage IV. 3) In the immunoglobulin analysis, there was no significance (P>0.05) in serum concentracions of IgM, IgG, IgGAM according to the stage of stomach cancer. 4) Five patients wish stomach cancer and five normal persons with relatively higher concentration of anti-carcinoembryonic antigen antibodies showed positive reaction to the antigens at 95KDa, 200KDa by Western blot method. According to the above results, it can be considered that in stomach cancer, immunogenicity of anti-CEA antibody and humoral immunity are relatively low or there may be masking effect of antibody-inducing epitope.

위암 환자엥서 Anti-CEA Antibody의 임상적 의의

김종익,김운원,홍관희 인제대학교 1999 仁濟醫學 Vol.20 No.1