苦瓜蛋白MAP30的HLA—A2／A3限制性CTL表位预测

目的：预测苦瓜蛋白MAP30的HLA—A2／A3限制性CTL表位。方法：应用lasergene7．0和NetCTL-1．2Server对MAP30进行HLA—A2／A3限制性CTL表位预测。结果：MAP30的二级结构含有8个d-螺旋和9个B-折叠股;柔韧性良好氨基酸区域为19—40、99—146、166—273;亲水性指数较高区域为22—45、97—114、117～148、180—198、224—257、265—275;抗原性指数较高区域为19—28、63—71、98-114、118—123、224—246、248—260、262—274;有30个可能CTL表位,综合分析后获得2个HIJA—A2和5个HLA—A3限制性CTL表位。结论：MAP30具有潜在的7个HLA—A2／A3限制性CTL表位。     

肝癌相关肿瘤抗原AFP新的HLA—A2／A24限制性CTL表位的预测及分析

目的：预测肝癌肿瘤抗原AFP新的HLA—A2／A24限制性CTL表位,为肝癌CTL表位肽的筛选及鉴定提供依据。方法：选择与肝癌密切相关的肿瘤抗原AFP为研究目标,采用NetCTL1．2Server远程预测系统进行HLA—A2／A24限制性CTL表位预测。结果：共预测出与肝癌相关的肿瘤相关抗原AFP的8个HLA—A2限制性CTL表位,13个HLA—A24限制性CTL表位。结论：应用NetCTL1．2Server法预测CTL表位是一种高效准确的预测方法。所预测的肿瘤抗原AFP的HLA—A2／24限制性CTL表位经实验筛选、鉴定后,可为肝癌治疗性疫苗的制备选择合适的CTL表位提供依据。     

癌-睾丸抗原SSX-3的HLA-A2/A3限制性CTL广谱表位的预测

目的:预测基于癌-睾丸抗原SSX-3的HLA-A2/A3限制性CTL广谱表位.方法: 采用MULTIPRED在线预测系统分别针对HLA-A2超型和HLA-A3超型对SSX-3序列进行CTL表位预测,其中对两种超型分值均较高的表位被初步认定为广谱表位;然后,运用NetCTL 1.2在线预测系统对初步认定的广谱表位进行蛋白酶体裂解和TAP转运效率预测进一步筛选.结果: 共预测出9个SSX-3抗原的HLA-A2/A3限制性广谱表位.结论: MULTIPRED与NetCTL 1.2在线预测系统相结合可以高效的预测广谱CTL表位;本报道为SSX-3的广谱CTL表位的实验研究提供了重要的理论依据.     

肿瘤相关抗原CT45的HLA-A2/A3限制性CTL表位的预测

目的:预测肿瘤相关抗原CT45的HLA-A2/A3限制性CTL表位,为CTL表位肽的合成和活性筛选提供依据。方法:基于新近发现的CT45抗原的氨基酸序列,用NetCTL 1.2 Server人工神经网络法远程预测系统进行HLA-A2/A3限制性CTL表位预测打分,挑选出分值较高的作为候选表位。结果:共预测出了5个潜在的HLA-A2限制性CTL表位九肽,15个潜在的HLA-A3限制性CTL表位九肽,所有这些表位均为首次报道。结论:NetCTL 1.2 Server人工神经网络法能高效的预测CTL表位肽,基于新近发现的CT45抗原,我们通过该系统成功预测出了5个潜在的HLA-A2限制性CTL表位,15个潜在的HLA-A3限制性CTL表位,可以对其进行进一步的研究。     

肿瘤抗原MAGE-12新的HLA-A2限制性细胞毒性T细胞表位的预测

目的预测黑色素瘤抗原MAGE-12的HLA—A2限制性CTL表位。方法采用SYFPEITHI超基序远程预测系统与量化基序多项式法、延展基序联合应用，筛选MAGE-12抗原HLA—A0201限制性CTL表位。结果共预测出5个MAGE-12抗原HLA—A2限制性CTL表位。结论超基序法与量化基序，延展基序联合应用可以提高预测效率，为实验方法探索MAGE-12的表位提供有用线索。     

肝癌相关肿瘤抗原AFP新的HLA-A2/A24 限制性CTL表位的预测及分析

目的:预测肝癌肿瘤抗原AFP新的HLA-A2/A24限制性CTL表位,为肝癌CTL表位肽的筛选及鉴定提供依据.方法:选择与肝癌密切相关的肿瘤抗原AFP为研究目标,采用NetCTL 1.2 Server远程预测系统进行HLA-A2/A24限制性CTL表位预测.结果:共预测出与肝癌相关的肿瘤相关抗原AFP的8个HLA-A2 限制性CTL表位,13个HLA-A24限制性CTL 表位.结论:应用NetCTL 1.2 Server法预测CTL表位是一种高效准确的预测方法.所预测的肿瘤抗原AFP的HLA-A2/24 限制性CTL表位经实验筛选、鉴定后,可为肝癌治疗性疫苗的制备选择合适的CTL表位提供依据.     

肝癌MAGE-n抗原HLA-A2限制性细胞毒性T细胞表位的预测

目的 预测肝癌MAGE—n抗原HLA—A2限制性细胞毒性T淋巴细胞(CTL)表位。方法 应用SYFPEITHI超基序多项式法远程预测系统和量化基序多项式法结合的预测方法，筛选MAGE—n抗原HLA—A2限制性CTL表位。结果 筛选到MAGE—n抗原5个HLA—A2限制性CTL表位(九肽)。结论 SYFPEITHI超基序法和量化基序多项式法结合的预测方法是一种高效和准确的表位预测方法。     

原癌基因Bmi-1 B细胞抗原表位及 HLA I类限制性CTL表位的生物信息学分析

目的:预测原癌基因Bmi-1(B-cell-specific Moloney murine leukemia virus insertion site 1)的B细胞抗原表位及HLA I类限制性细胞毒性T细胞（cytotoxic T cell）表位。方法:采用Ellipro(http://tools.immuneepitope.org/ellipro/)预测Bmi-1蛋白中可能存在的线性B细胞表位和构象B细胞表位；采用ProtParam、NetCTL等软件和方法预测Bmi-1中可能存在的HLA I类限制性CTL表位。结果:Bmi-1蛋白中含有6个线性B细胞表位和8个构象B细胞表位；结合HLA结合力、蛋白酶体切割效率和TAP转运效率，经过NetCTL程序预测表明:针对不同的HLA I类分子，原癌基因Bmi-1中都存在多个HLA I类分子的限制性CTL表位。结论:综合运用多个程序预测了原癌基因Bmi-1中的B细胞抗原表位及HLA I类分子的限制性CTL表位，为下一步开展针对Bmi-1的免疫靶向治疗等研究打下了基础。     

食管癌高表达抗原HLA-A2/A3 限制性细胞毒性T 淋巴细胞表位预测

 目的 预测食管癌普遍高表达蛋白COX-2和MAGE-4的HLA-A2/A3限制性CTL表位。方法运用生物信息学的方法,SYFPEITHI初步预测,结合三维构效定量关系和蛋白酶体酶切位点分析。结果 对SYFPEITHI预测〉20的九肽用MHCPred和NetChop3.0作进一步分析,并与已报道抗原肽进行比对,初步筛选出了42个潜在的CTL表位。结论 这42个九肽均未见文献报道,进一步鉴定将为CTL表位疫苗的研究提供更多的线索。其中,MAGE-422-30、202-210、286-294及COX-2479-4874个九肽具有与HLA-A2和HLA-A3超型潜在的交叉免疫活性,将为研制简约的高效广谱食管癌疫苗提供候选肽。     

慢性粒细胞白血病相关抗原HLA-A2.1限制性CTL表位的生物信息学分析

目的:预测慢性粒细胞白血病BCR/ABL融合基因HLA-A2.1限制性细胞毒性T细胞表位.方法:运用BIMAS、SYFPEITHI、Predep、Immune Epitope Database和Analysis Resource(IEDB)软件预测BCR/ABL融合基因可能的HLA-A2.1限制性CTL表位.结果:结合BIMAS、SYFPEITHI、Predep和IEDB预测BCR/ABL融合基因的HLA-A2.1限制性CTL表位,共6条.结论:综合运用多个预测软件可提高预测效率获得目的表位肽,为下一步基础实验打下基础.     

Aurora A激酶研究进展

Aurora A激酶是进化上保守的有丝分裂丝/苏氨酸激酶Aurora激酶家族成员之一,在细胞内随细胞周期的变化呈动态分布,它广泛的参与了细胞周期不同阶段的各种事件,并在人类多种恶性肿瘤的发生发展过程中起到了至关重要的作用,因而很有可能成为一个极具前途的恶性肿瘤的分子治疗靶点。     

A phase I trial of CGS 16949A. A new aromatase inhibitor

CGS 16949A is a new, nonsteroidal competitive inhibitor of the aromatase enzyme. In this Phase I trial, 16 heavily pretreated postmenopausal patients with metastatic breast cancer were treated with escalating doses of CGS 16949A from 0.6 to 16 mg total daily oral dose. No hematologic, biochemical, or significant clinical toxicity was encountered. Endocrinologic and pharmacologic data were available from 12 of these patients. Maximum inhibition of estrogen biosynthesis was observed at a dose of 2 mg CGS 16949A daily. At this dose, the inhibition of estrogen biosynthesis was equivalent to 1000 mg aminoglutethimide (AG). The fall in plasma and urinary estrogens without a concomitant drop in androgens confirmed the specific blockade of aromatase activity. At doses of 4 to 16 mg daily, CGS 16949A appeared to inhibit the C21-hydroxylase enzyme as well. The t1/2 of CGS 16949A in the circulation was 10.5 hours. Of 16 evaluable patients there were two partial responses and seven patients with stable disease.     

A gist of gastrointestinal stromal tumors: A review

Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract (GIT). They constitute the majority of gastrointestinal mesenchymal tumors of the GIT and are known to be refractory to conventional chemotherapy or radiation. They are defined and diagnosed by the expression of a proto-oncogene protein detected by immunohistochemistry which serves as a crucial diagnostic and therapeutic target. The identification of these mutations has resulted in a better understanding of their oncogenic mechanisms. The remarkable antitumor effects of the molecular inhibitor imatinib have necessitated accurate diagnosis of GIST and their distinction from other gastrointestinal mes-enchymal tumors. Both traditional and minimally invasive surgery are used to remove these tumors with minimal morbidity and excellent perioperative outcomes. The revolutionary use of specific, molecularlytargeted therapies, such as imatinib mesylate, reduces the frequency of disease recurrence when used as an adjuvant following complete resection. Neoadjuvant treatment with these agents appears to stabilize disease in the majority of patients and may reduce the extent of surgical resection required for subsequent complete tumor removal. The important interplay between the molecular genetics of GIST and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumors. This review summarizes our current knowledge and recent advances regarding the histogenesis, pathology, molecular biology, the basis for the novel targeted cancer therapy and current evidence based management of these unique tumors.