光动力法制备抗小鼠H22肝癌肿瘤疫苗的实验和理论研究
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摘要
用疫苗来预防疾病是人类追求的目标,更是肿瘤防治的方向。关于肿瘤疫苗的制备,当前大多数的研究主要集中在应用基因工程技术或者肿瘤相关抗原诱导DC(Dendritic Cells)制备肿瘤疫苗。但是这些方法大部分仍处于实验研究阶段。光动力法(PDT)是一种治疗肿瘤的新方法,PDT法能否应用于制备肿瘤疫苗,其制备的肿瘤疫苗对肿瘤是否具有预防和治疗作用,正在成为肿瘤预防和治疗领域一个新的研究热点。
论文首先介绍了本研究的选题背景,接着对国内外光动力现状和肿瘤疫苗技术做了详细的介绍,在此基础上,将PDT法应用于肿瘤疫苗制备技术。论文主要从以下几个方面展开。
1、分别采用532nm和630nm激光器作为光源,光敏剂采用HMME(Hematoporphyrin Monomethyl Ether,血卟啉单甲醚),瘤株选用H22小鼠肝癌体外培养细胞株,制备相应的肿瘤疫苗,并且对所制备肿瘤疫苗的效果进行了检测。实验结果表明PDT法制备的抗小鼠H22肝癌肿瘤疫苗对小鼠肝癌肿瘤具有一定的抑制作用,提示该方法制备的肿瘤疫苗有可能成为一种辅助预防肿瘤的手段。
2、主要讨论了氧含量对PDT所制备疫苗效果的影响。由于PDT对氧含量的要求比较高。为了观察氧含量的不同对所制备抗肿瘤疫苗效果的影响。我们针对同一种肿瘤细胞选择不同的功率密度来制备相对应的疫苗,并用所制备的疫苗免疫小鼠,然后再接种同种肿瘤细胞,观察其抗肿瘤效果,优化制备肿瘤疫苗的光学参数。
3、对PDT法所制备疫苗的治疗效果和安全性做了初步的研究。指出对于PDT方法制备的肿瘤疫苗的使用,同样存在把握时机的问题。实验结果表明,在肿瘤生长早期,PDT法制备的肿瘤疫苗还是具有一定的治疗作用,但是当在肿瘤生长中晚期的时候,采用该疫苗不但没有治疗作用,反而会加快肿瘤生长。
4、我们对光动力疗法制备疫苗过程中,与氧有关的问题进行了理论研究。探索氧含量与光动力疗法所制备肿瘤疫苗的无效或效果轻微是否有所关联以及关联的机制;是否存在氧含量的阈值,使得光动力效果产生质的区别;有无方法可以改善疫苗的抗肿瘤效果等等。由于光动力疗法中的氧的消耗涉及代谢耗氧、反应耗氧、氧扩散等一系列问题,在分析中最合理的方法是建立数学模型,通过解析这个数学模型,争取能够解答以上问题。改变光照射条件,降低光功率密度,将这种改变用数学方式代入模型,验证是否能够对所制备的疫苗的抗瘤效果产生优化,将理论研究与实验结果对比。
论文最后总结了本论文创新性的工作,同时提出了一些将继续深入开展的研究问题。PDT之所以能够在世界范围内形成热潮,是源于现代社会对它的需要。因此作者有理由相信基于PDT法制备肿瘤疫苗的技术将开辟肿瘤疫苗研究的一片新天地。
For human, vaccines can not only be used to defend against diseases but also to be a good prevention and cure for different kinds of tumor. Now most research is mainly focused on the application of gene technology or tumor vaccines prepared from tumor-related antigen inducing dendritic cells (DCs), but most of them are all under laboratory experimental stage, Photodynamic therapy is a new technique for tumor therapy, whether it can be used for tumor vaccines generation, and whether tumor vaccines generated by PDT can be used for cancer defence and cure, which now is becoming a new hot research topic in the field of tumor therapy.
In this dissertation, the background of this topic is introduced, and then the study and developments of PDT and tumor vaccines at home and abroad have been reviewed in detail. Based on above statement, the author applied PDT to the generation of tumor vaccines.
1、We adopted the PDT method with 532nm and 630nm laser system where HMME was used as a photosensitizer to prepare the tumor vaccine on H22 tumor. Our studies suggest that PDT-generated vaccines could effectively inhibit tumor growth, improve survival rate of mice in experimental group, and enhance antitumor immune response significantly. PDT-generated vaccines may have well clinical potential as an adjuvant therapy.
2、The influences of Oxygen content on PDT-generated vaccines are discussed. Oxygen content has great influences on PDT effect. In order to research the influences of different level of oxygen content on antitumor effects of PDT-generated vaccines, the same tumor cells are treated with different power density under the same energy, after immunity with PDT-generated vaccines, mice are challenged with the same cell line, antitumor effects were observed to optimize the optical parameter during process of PDT-generated vaccines.
3、Pilot study about the security and therapy effect of tumor vaccines were carried out. We draw a conclusion that for the use of PDT-vaccines should also grasps at right time. The experimental results indicated that PDT-generated vaccines are of some good curative effect at the early stage of tumor development, but at the medium and late stage of tumor development, PDT-generated vaccines have no any curative effects, on the contrary, it can accelerate the tumor growth.
4、The theoretical studies with different oxygen content during the progress of PDT-generated vaccines were carried out. We explore whether there are relations between oxygen content and the effect of PDT-generated vaccines, and mechanism of these relations also is studied. Is there a threshold value which can decide the effects of PDT? And are there methods which can improve the antitumor effects of PDT-generated vaccines? Oxygen deplete during PDT is related to many progress such as metabolism, reaction, diffusion and so on. We designed mathematical model and parsed it to solve the problems which were put forward above. We compared the experimental results with the results which are deduced from mathematical model, and found the results from mathematical model are consistent with experimental results.
Finally, the creationary points of the dissertation are summarized. Some further research proposals are given.The reason why PDT can be popular all over the world is the need of modern society. Therefore, we believe that PDT will exploit a new field for tumor vaccine study.
论文首先介绍了本研究的选题背景,接着对国内外光动力现状和肿瘤疫苗技术做了详细的介绍,在此基础上,将PDT法应用于肿瘤疫苗制备技术。论文主要从以下几个方面展开。
1、分别采用532nm和630nm激光器作为光源,光敏剂采用HMME(Hematoporphyrin Monomethyl Ether,血卟啉单甲醚),瘤株选用H22小鼠肝癌体外培养细胞株,制备相应的肿瘤疫苗,并且对所制备肿瘤疫苗的效果进行了检测。实验结果表明PDT法制备的抗小鼠H22肝癌肿瘤疫苗对小鼠肝癌肿瘤具有一定的抑制作用,提示该方法制备的肿瘤疫苗有可能成为一种辅助预防肿瘤的手段。
2、主要讨论了氧含量对PDT所制备疫苗效果的影响。由于PDT对氧含量的要求比较高。为了观察氧含量的不同对所制备抗肿瘤疫苗效果的影响。我们针对同一种肿瘤细胞选择不同的功率密度来制备相对应的疫苗,并用所制备的疫苗免疫小鼠,然后再接种同种肿瘤细胞,观察其抗肿瘤效果,优化制备肿瘤疫苗的光学参数。
3、对PDT法所制备疫苗的治疗效果和安全性做了初步的研究。指出对于PDT方法制备的肿瘤疫苗的使用,同样存在把握时机的问题。实验结果表明,在肿瘤生长早期,PDT法制备的肿瘤疫苗还是具有一定的治疗作用,但是当在肿瘤生长中晚期的时候,采用该疫苗不但没有治疗作用,反而会加快肿瘤生长。
4、我们对光动力疗法制备疫苗过程中,与氧有关的问题进行了理论研究。探索氧含量与光动力疗法所制备肿瘤疫苗的无效或效果轻微是否有所关联以及关联的机制;是否存在氧含量的阈值,使得光动力效果产生质的区别;有无方法可以改善疫苗的抗肿瘤效果等等。由于光动力疗法中的氧的消耗涉及代谢耗氧、反应耗氧、氧扩散等一系列问题,在分析中最合理的方法是建立数学模型,通过解析这个数学模型,争取能够解答以上问题。改变光照射条件,降低光功率密度,将这种改变用数学方式代入模型,验证是否能够对所制备的疫苗的抗瘤效果产生优化,将理论研究与实验结果对比。
论文最后总结了本论文创新性的工作,同时提出了一些将继续深入开展的研究问题。PDT之所以能够在世界范围内形成热潮,是源于现代社会对它的需要。因此作者有理由相信基于PDT法制备肿瘤疫苗的技术将开辟肿瘤疫苗研究的一片新天地。
For human, vaccines can not only be used to defend against diseases but also to be a good prevention and cure for different kinds of tumor. Now most research is mainly focused on the application of gene technology or tumor vaccines prepared from tumor-related antigen inducing dendritic cells (DCs), but most of them are all under laboratory experimental stage, Photodynamic therapy is a new technique for tumor therapy, whether it can be used for tumor vaccines generation, and whether tumor vaccines generated by PDT can be used for cancer defence and cure, which now is becoming a new hot research topic in the field of tumor therapy.
In this dissertation, the background of this topic is introduced, and then the study and developments of PDT and tumor vaccines at home and abroad have been reviewed in detail. Based on above statement, the author applied PDT to the generation of tumor vaccines.
1、We adopted the PDT method with 532nm and 630nm laser system where HMME was used as a photosensitizer to prepare the tumor vaccine on H22 tumor. Our studies suggest that PDT-generated vaccines could effectively inhibit tumor growth, improve survival rate of mice in experimental group, and enhance antitumor immune response significantly. PDT-generated vaccines may have well clinical potential as an adjuvant therapy.
2、The influences of Oxygen content on PDT-generated vaccines are discussed. Oxygen content has great influences on PDT effect. In order to research the influences of different level of oxygen content on antitumor effects of PDT-generated vaccines, the same tumor cells are treated with different power density under the same energy, after immunity with PDT-generated vaccines, mice are challenged with the same cell line, antitumor effects were observed to optimize the optical parameter during process of PDT-generated vaccines.
3、Pilot study about the security and therapy effect of tumor vaccines were carried out. We draw a conclusion that for the use of PDT-vaccines should also grasps at right time. The experimental results indicated that PDT-generated vaccines are of some good curative effect at the early stage of tumor development, but at the medium and late stage of tumor development, PDT-generated vaccines have no any curative effects, on the contrary, it can accelerate the tumor growth.
4、The theoretical studies with different oxygen content during the progress of PDT-generated vaccines were carried out. We explore whether there are relations between oxygen content and the effect of PDT-generated vaccines, and mechanism of these relations also is studied. Is there a threshold value which can decide the effects of PDT? And are there methods which can improve the antitumor effects of PDT-generated vaccines? Oxygen deplete during PDT is related to many progress such as metabolism, reaction, diffusion and so on. We designed mathematical model and parsed it to solve the problems which were put forward above. We compared the experimental results with the results which are deduced from mathematical model, and found the results from mathematical model are consistent with experimental results.
Finally, the creationary points of the dissertation are summarized. Some further research proposals are given.The reason why PDT can be popular all over the world is the need of modern society. Therefore, we believe that PDT will exploit a new field for tumor vaccine study.
引文
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