蒋纪恺
研究方向为肿瘤发生与逆转,主要研究中药有效组分诱导白血病细胞分化与凋亡机理。
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- 姓名:蒋纪恺
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学术头衔:
博士生导师
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学科领域:
生物化学
- 研究兴趣:研究方向为肿瘤发生与逆转,主要研究中药有效组分诱导白血病细胞分化与凋亡机理。
蒋纪恺,1956年6月生,教授,博士研究生导师,1982年毕业于华东理工大学,1989年、1998年和2001年分别留学日本神户大学、日本関西医科大学和德国洪堡大学,现任汕头大学医学院生物化学与分子生物学教研室副主任,曾任中国抗癌协会肿瘤标志专业委员会委员,国外医学第三届临床生物化学与检验学分册编委会常务编委,国家自然科学基金生命科学部2000年度生物化学与分子生物学学科组项目二审特邀评委,曾参编卫生部临床生物化学(五年制,第二版)统编教材。研究方向为“肿瘤发生与逆转”,主要研究中药有效组分诱导白血病细胞分化与凋亡机理,主持过多项国家和省级科研课题,2003年以来,发表论文50余篇,SCI收录9篇,近5年来,指导培养硕士研究生8人、博士研究生2人。
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【期刊论文】Fractalkine gene therapy for neuroblastoma is more effective in combination with targeted IL-2
蒋纪恺, Yan Zeng a, Jikai Jiang a, Nicole Huebener a, Jens Wenkel a, Gerhard Gaedicke a, Rong Xiang b, Holger N. Lode a, *
Y. Zeng et al./Cancer Letters 228 (2005) 187-193,-0001,():
-1年11月30日
The induction of tumor protective immunity against neuroblastoma remains a major challenge for active immunotherapy. Fractalkine is a unique Th1 CX3C chemokine known to induce adhesion and migration of leukocytes mediated by both, membrane-bound and soluble form, respectively. Here, we tested the hypothesis that chemokine gene therapy with fractalkine (FKN) induces an effective anti-neuroblastoma immune response amplified by targeted IL-2 using the anti-GD2 antibody ch14.18 fused with IL-2 (ch14.18-IL-2). For this purpose, NXS2 cells were genetically engineered to stably produce murine FKN (NXS2-FKN). Transcription and expression of the mFKN gene in tumor tissue of mice inoculated with NXS2-FKN cells were demonstrated in vivo. Importantly, mFKN exhibited a reduction in primary tumor growth and spontaneous liver metastases in syngenic A/J mice. This effect was boosted by targeted IL-2 using small non-curative doses of ch14-18-IL-2. The amplification of the FKN induced immune response was specific, since a non-specific antibody-IL-2 fusion protein ch225-IL-2 was ineffective. In summary, we demonstrated for the first time that chemokine gene therapy is amplified by targeted IL-2 suggesting a combination of both strategies as an adjuvant therapy for neuroblastoma.
Fractalkine, GD2, Ch14., 18-IL-2, Neuroblastoma, Gene therapy, Immunotherapy
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蒋纪恺, J. Jikai a, M. Shamis b, N. Huebener a, U. Schroeder a, W. Wrasidlo a, J. Wenkel a, B. Lange a, G. Gaedicke a, D. Shabat b, , H.N. Lode a, *
J. Jikai et al./Cancer Letters 197 (2003) 219-224,-0001,():
-1年11月30日
Tumor directed cytotoxic therapy is one of the major challenges for the success of chemotherapy. In order to accomplish this goal in neuroblastoma, we rationally designed a prodrug of etoposide as substrate for tyrosine hydroxylase, a well established neuroblastoma associated enzyme. Here, we report synthesis and characterization of a 3,4 dihydroxy-phenyl carbamate derivative of etoposide. In order to demonstrate activation by tyrosine hydroxylase, the coding sequence of murine tyrosine hydroxylase was generated by reverse transcriptase-polymerase chain reaction from NXS2 neuroblastoma cells and cloned into the pRSET-A bacterial expression vector. The enzyme was expressed in Escherichia coli, characterized by Western blot and enzymatic activity was demonstrated by conversion of tyrosine into DOPA in the presence of cofactors using reversed phase high-performance liquid chromatography. Under these enzymatic conditions, we demonstrate conversion of 3,4 dihydroxyphenyl carbamate prodrug into free etoposide. This effect was clearly mediated by the enzyme since bacteria transformed with the empty vector were ineffective of prodrug activation. Furthermore, tyrosine hydroxylase positive cells exposed to the etoposide prodrug were effectively killed in contrast to tyrosine hydroxylase negative controls. These findings demonstrate that etoposide can be designed as a prodrug substrate for tyrosine hydroxylase and thereby establish proof of concept for neuroblastoma directed enzyme prodrug therapy.
Tyrosine hydroxylase, Etoposide, Prodrug, Neuroblastoma, Chemotherapy
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