2 甲胎蛋白的临床研究进展
临床研究表明, 甲胎蛋白不仅具有临床诊断价值, 而且具有临床治疗价值。1)AFP 临床诊断价值自六十年代发现甲胎蛋白(AFP) 与肝癌的高度相关性以来, AFP 作为肝细胞癌(HCC) 的标志已广泛用于肝癌的筛检、诊断、早期诊断、鉴别诊断、疗效评价、提示预后等多方面。近年, 国内外通过许多方法发现AFP具有不同的糖化形式与凝聚素结合特性检测这些不同形式的AFP 有助于相关疾病间的鉴别诊断[23]。2)AFP 的临床治疗价值AFP 可作为肝癌免疫治疗的靶抗原。早在70 年代初期针对AFP 的肝癌体液免疫治疗就已兴起, 但由于时代的限制有关研究虽也取得了一些结果,但其疗效始终未能得到临床的确证, 到八十年代中期后已鲜有报道。针对AFP的肝癌细胞免疫治疗研究始于90 年代末。实验研究表明, 个体发育中T 细胞库内针对AFP 的特异性CTL 克隆却并未清除, 适当条件或方法可使之激活; 以AFP 为靶抗原的DNA 疫苗或多肽疫苗能诱导特异性细胞毒性T 细胞免疫应答, 并杀灭产生APP 的肝癌细胞[24- 26]。综上所述, 基础与临床研究表明, 甲胎蛋白具有免疫抑制、促进肿瘤细胞生长及调节细胞凋亡的作用; 对于肝癌不仅具有很好的临床诊断价值, 而且在肝癌免疫治疗中也极具应用前景。
参考文献
1 urgita RA, Tomasi TB. Suppression of the immuneresponse by α- fetoprotdin. J Exp Med,1975,141(2):269- 282.
2 Murgita RA, Tomasi TB. Suppression of the immuneresponse by α- fetoprotdin II. Jexp, Med,1975,141(2):440- 452.
3 Dattwyler RJ, Murgita RA. Tomasi TB. <inding ofα- fetoprotdin ti marine T cells. Nature, 1975,256(5512):656- 657.
4 Alpert E, Dienstag JL, Sepersly S, et al. Immunosuppressivecharacteristics of human AFP: effect ontests of cell mediated immunity and induction ofhuman suppressor cells. Immunol Commun, 1978,7(2):163- 185.
5 Sheppard HW, Sell S, Trefts P, et al. Effects of α-fetoprotdin on murime immune responses Isrudieson mice. J Immunol, 1977,119(1):91- 97.
6 Sell S, Sheppard HW, Poler M, et al. Effects ofα- fetoprotdin on murime immune responsesⅡ Studieson rats. J Ommunol, 1977, 119(1):98- 103.
7 Littman BH, Alpert E, Rocklin RE. The effect ofpurified alpha - fetoprotein on in vitro assays ofcell - mediated immunity. Cell Immunol, 1977,30(1):35- 42.
8 Lu CY, Changellan PS, Unanue ER.α- fetoprotdininhibits macrophage expression of Ia antigens. JImmunol, 1984,132(4):1722- 1727.
9 中国科学院上海生物化学研究所. 甲种胎儿蛋白(AFP)对免疫功能的影响.肿瘤防治研究,1978,(3):9～11.
10 王兴旺,胥彬.甲胎蛋白对荷H- 22 肝癌小鼠脾淋巴细胞增殖的影响.上海免疫学杂志,1995,15(6):327-329.
11 王兴旺,胥彬.人甲胎蛋白对H- 22 肝癌小鼠免疫功能的影响.上海免疫学杂志,1997,17(4):224- 226.
12 Semenkova LN, Dudich EI, Dudich Ⅳ.Induction ofapoptosis in human hepatona cells by alopha- fetoprotein.Tumour Biol, 1997,18(5):261- 273.
13 udich E,Semenkova L, Gorbatova E, et al.Growth- regulative activity of human alpha- fetoproteinfor different types of tumor and normal cells.Tumour Biol, 1998,19(1):30- 40.
14 Wang XW, XU B.Stimulation of tumor- cell growghby alpha- fetoprotein.Int J Cancer, 1998,75(4):596-599.
15 Wang XW, Xie H.Alpha- fetoprotein enhances theproliferation of human hepatoma cells in vitro.Life, Sci, 1999,64(1):17- 23.
16 Mizejewski GJ, Allen RP. Alpha- Fetopotein: studiesof tumor - associated antigen cytotozicity inmouse hepatoma BW7756.Clin Immunol Immunopathol,1978,11(3):307- 317.
17 Villacampa MJ, Moro R, Naval J, et al. Alpha- fetoproteinreceptors in a human breast cancer cellline. Biochem Biophys Res Commun, 1984,122(3):1322- 1327.
18 Uriel J, Failly CC, Villacampa MJ, et L. Incorporationof alphafetoprotein by the MCF- 7human breastcancer cell line. Tumour Biol 1984,5(1):41- 51.
19 Esteban C, Geuskens M, Uriel J. Activation of analpha - fetoprotein (AFP)/receptor autocrine loop inHT- 29human colon carcinoma cells. Int J Cancer,1991,49(3):425- 430.
20 Laderoute MP, Pilarski LM. The imhibition ofapoptosis by alpha- fetoprotein (AFP) and the roleof AFP receptors in anti- cellular cenescence. AnticancerRes, 1994,14(6B);2429- 2438.
21 Semenkova LN, Dudich EI, Dudich IV, er al. Alpha-fetoprotein as a TNF resistance factor for thehuman hepatocarcinoma cll line hepG2. TumourBiol 1997,18(1):30- 40.
22 Dudich E, Semenkva LN, Dudich I, et al. alphafetoproteincanses apoptosis in tumor cells via apathway independent of CD95,TNFRI and TNFR2through activation of caspase- 3- like proteases. EurJ Biochem, 1999,266(3):750- 761.
23 Taketa K. α- fetoprotein: reevaluation in hepatology.Hepatology, 1990,12(6):1420- 1432.
24 Voller CM, Eliba JFC, Butterfield LH, et al. α-fetoprotein- specific genetic immunotherapy for hepatocllularcarcinoma. Cancer Res 1999,59(13):364-3067.
25 Butterfield LH, Koh A Meng W, et al. Generationof human T- cell responses to an HLA- A2.1 - restrictdepeptide epitope derived from alpha - fetoprotein.Cancer Res, 1999,59(13):3134- 3142.
26 Butterfield LH, Meng WS, Koh A, et al. T cellresponses to HLA- A*0201- restrictde peptides derivedfrom human alpha - fetoprotein. J Immunol,2001,(8):5300- 5308.
