癌胚抗原及粘液组织化学在胃癌中表达的研究

对60例胃癌进行了粘液组织化学和癌胚抗原免疫组织化学研究。结果表明:胃癌发病率肠型和胃肠混合型占多数。60例胃癌中含大肠型粘液者占50例,而单纯含胃型粘液为极少数。癌胚抗原分布方式,肠型胃癌与胃肠混合型胃癌比较无显著差异性(P>0.05)。癌胚抗原的阳性率,胃肠混合型胃癌高于肠型胃癌,两者之间有非常显著差别(P<0.01)。认为选用能显示硫粘蛋白和氧乙酰基唾液酸粘蛋白的粘液组织化学方法,作为胃癌组织分型和确定胃粘膜肠化性质,对癌前病变诊断有一定价值。     

人肝癌及癌周组织中γ-谷氨酰转肽酶、甲胎蛋白癌胚抗原的表达

用丫-谷氨酞转肽酶-甲胎蛋白(GGT-AFP)双染色法研究了人肝癌及癌周组织中GGT,AFP的表达,同时观察了癌胚抗原(CEA)的分布.20例肝癌组织中,11例GGT阳性,10例AFP阳性.13例CEA阳性.在癌周组织中,6例GGT阳性,2例AFP阳性,20例CEA阳性.证实肝细胞癌可表达GGT,AFP,增生结节属癌前期病变,与肝癌的发生有关,GGT,AFP的增高与肝癌密切相关,CEA无特异性.     

结肠腺癌CEA的超微结构定位

用辣根过氧化物酶标记的癌胚抗原（ＣＥＡ）抗体，对结肠腺癌患者的手术标本进行了免疫组织化学染色，观察了ＣＥＡ在肿瘤组织及正常组织细胞中的分布。结果显示，正常结肠组织中，ＣＥＡ沿粘膜上皮细胞的游离面分布；结肠腺癌细胞则失去极性，ＣＥＡ除见于细胞游离面，在细胞侧面和基底面也呈阳性反应。提示ＣＥＡ在结肠细胞表面的分布失去极性可能是腺癌细胞的特点。     

Carcinoembryonic antigen like antigen in granular cell myoblastomas

Summary A series of granular cell myoblastomas (GCM) and other benign and malignant tumours of soft tissue were examined for cytoplasmic content of carcinoembryonic antigen (CEA) by the two-layer conjugated immunoperoxidase technique. Using a commercial rabbit anti-CEA serum only granular cell myoblastomas showed positive cytoplasmic reaction. Pretreatment with periodic acid made this reaction less intense, but when the commercial rabbit anti-CEA serum was absorbed with tissue powder from normal human spleen the positive reaction was totally abolished. It is concluded that the positivity of GCM for CEA using commercial rabbit anti-CEA serum is due to the content of non-specific cross-reacting antigen (NCA) and maybe other cross-reacting glycoproteins in this tumour, and not to CEA as claimed in a previous study.     

人癌胚抗原重组痘苗病毒转染树突状细胞体外诱导的抗肿瘤免疫

目的：研究人癌胚抗原重组痘苗病毒（rV-CEA)转染外周血树突状细胞（DC）后在外体诱导的抗CEA分泌性肿瘤免疫。方法：分离晚期结肠癌患者的外周血单核细胞，在体外用人重组粒－巨噬细胞集落刺激因子（GM－CSF）及白细胞介素4（IL－4）培养成DC，再用rV-CEA转染DC后激发自体T细胞，观察其体外激发自体T细胞的增殖能力及其诱导的细胞毒性T淋巴细胞（CTL）对自体CEA分泌性肿瘤细胞的杀伤活性，并与野生型痘苗病毒（W－VV）及无病毒转染的DC所激发的T细胞进行比较。结果：经rV-CEA转染的DC能显著刺激自体T细胞的增殖，其激活的T细胞对CEA分泌性自体肿瘤细胞具有特异性杀伤作用。结论：rV-CEA转染的DC可以诱导体CEA分泌性肿瘤免疫。     

Combined use of positive and negative immunomagnetic isolation followed by real-time RT-PCR for detection of the circulating tumor cells in patients with colorectal cancers

To establish a novel molecular diagnostic method of detecting circulating tumor cells (CTCs) LS174T colon cancer cells were serially diluted with normal blood. Additional peripheral blood samples were collected from 25 patients with colorectal carcinoma. Mononuclear cells (MNCs) were collected, equally divided into four parts, and then cancer cells were enriched by four methods: method A, nonimmunobead method; method B, negative immunobead method: CD45 immunomagnetic beads were used to deplete the leukocytes; method C, positive immunobead method: Ber-EP4 immunomagnetic beads were used to enrich cancer cells; method D, negative-and-positive immunobead method: CD45 immunomagnetic beads were first used to deplete the leukocytes from MNC and then Ber-EP4 immunomagnetic beads were used to enrich cancer cells. Finally, real-time quantitative RT-PCR was used to monitor mRNA expression of ₂-mircoglobulin (2M) and carcinoembryonic antigen (CEA). The relative CEA mRNA values were corrected with reference to 2M mRNA, to CEA mRNA/2M mRNA ratios according to a CEA mRNA external standards prepared with tenfold serial dilutions (1–10⁴ IS174T cells) of cDNA and 2M mRNA external standards prepared with tenfold serial dilutions (10²–10⁷ leukocytes) of cDNA. In recovery experiments a significant correlation between the number of cancer cells and CEA mRNA expression was found when CD45 or Ber-EP4 immunomagnetic beads were used alone. A highly significant correlation was found when CD45 and Ber-EP4 immunomagnetic beads were used successively. The sensitivity of method D was one cancer cell per milliliter of blood. Circulating cancer cells were detected in 19 of 25 patients with colorectal cancers. The relative CEA mRNA value obtained by method D was the smallest. The positive detection rate of circulating cancer cells in patients at Dukes B, C, and D stages were 25.0% (1/4), 83.3% (10/12), and 88.9% (8/9). Combinative use of immunomagnetic isolation followed by real-time RT-PCR is a useful technique to detect circulating tumor cells in patients with colorectal carcinomas. Applying negative and positive immunomagnetic beads successively yields the highest correlation with amount of tumor cells.     

Growth suppression of human colorectal carcinoma in nude mice by monoclonal antibody C27-abrin A chain conjugate

PURPOSE: The aim of this study was to assess an immunotoxin, monoclonal antibody C27-abrin A chain conjugate (MAAC), that might be effective in the treatment of colorectal carcinoma. METHODS: The immunotoxin was prepared by a specific monoclonal antibody against carcinoembryonic antigen (CEA), monoclonal antibody C27, linked toN-succinimidyl-3-(2-pyridyldithio)propionate and then coupled covalently to the toxic abrin-A chain to synthesize MAAC. The therapeutic role of this immunotoxin in suppressing thein vitro andin vivo growth of CEA-secreting human colorectal cancer cells (LS174T) was assayed by methods of protein biosynthesis inhibition, cell colony proliferation, and treatment of tumor cells before and after inoculation in nude mice. RESULTS: We found that MAAC effectively suppressed the growth of LS174T in culture medium and completely eradicated cells in inoculated nude mice. In contrast, irrelevant immunotoxin antiferritin-abrin A chain conjugate and isotype-matched monoclonal immunoglobin (MOPC21IgG1)-abrin A chain conjugate did not cause such effects. Thein vitro toxicity was highly specific because the conjugate (MAAC) inhibitedde novo protein biosynthesis, impeded growth, and caused death of cells possessing surface CEA determinants. The 50 percent inhibition dose values of the conjugate for colonogenic survival and for protein biosynthesis in LS174T cells were 0.09 g/ml and 0.06 g/ml, respectively. Colony survival was inhibited 96.3 percent after prolonged MAAC treatment. MAAC showed selective cytotoxicity; the inhibitory effect of MAAC to the CEA-secreting LS174T cells over the CEA-nonsecreting human embryonic kidney cells was 16-fold. CONCLUSION: These results indicate that MAAC may be of benefit in therapy during or soon after resection of colorectal carcinoma or in patients who have micrometastasis.Supported by a grant from the National Science Council and the Veterans General Hospital-Taipei, Taipei, Taiwan.     

大肠癌组织中端粒酶活性的研究

目的研究大肠癌组织及相应癌旁组织中的端粒酶活性,探讨其作为肠癌肿瘤标记物的可能性。方法采用ＴＲＡＰ方法研究了４０例大肠组织（包括３７例大肠癌,３例良性大肠疾病）和２０例相应癌旁上皮组织中的端粒酶活性表达。结果２０例癌旁上皮和３例良性疾病组织中,端粒酶活性表达均为阴性;而３７例大肠癌组织中,３５例显示端粒酶活性表达为阳性,阳性率为９４．６％。结论端粒酶是特异性较强的恶性肿瘤基因标志,有可能成为大肠癌早期诊断和治疗的理想标志物     

食管癌患者手术切除前后SA、CEA和SCP检测的临床意义

目的　探讨食管癌患者手术切除前后血清 SA、CEA、SCP水平的变化。方法　应用放免法测定 4 3例食管癌患者血清 CEA含量 ,化学法测定 SA和 SCP含量 ,并以 35名正常健康人作对照。结果　食管癌患者在手术切除前血清 SA、CEA、SCP水平非常显著地高于正常人组 (P<0 .0 1) ,手术切除后 6个月转移者血清 SA、CEA、SCP水平持续异常 ,未转移者血清 SA、CEA、SCP在正常水平。结论　血清 SA、CEA、SCP含量测定的变化与食管癌患者的病情和预后密切相关 ,有一定的临床应用价值