竹红菌素衍生物光动力作用诱导人胰腺癌细胞Capan-1凋亡机理的实验研究
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摘要
胰腺癌作为一种消化系统恶性肿瘤，具有恶性程度高，早期诊断困难，手术切除率低，预后差的特点，近年来，国内外报道胰腺癌发病率均有上升趋势，在西方国家胰腺癌居恶性肿瘤死亡原因的第4位，总的5年生存率不超过1％。在国内北京协和医院近年住院的胰腺癌病例比二十世纪五十年代增加了5倍，经过几十年的努力，虽然胰腺癌的手术方式大有改进，手术切除率有所提高，手术死亡率明显降低，但由于外科收治的病例多属中晚期，其5年生存率仍在5％左右，预后很差。因此胰腺癌被国际医学界列为“二十一世纪的顽固堡垒”。提高胰腺癌的早期诊断率和加强综合治疗是攻克这一堡垒的关键。因此探索除手术、化疗和放疗之外的新的治疗手段，施行综合治疗是提高胰腺癌疗效的重要策略，特别是中晚期胰腺癌。
恶性肿瘤的光动力治疗(Photodynamic therapy，PDT)是一种正在研究发展中的新型临床治疗技术，是指给人体施用光敏剂(Photosensitizer)，然后光照激活光敏剂产生活性氧从而达到治疗肿瘤的目的。光动力治疗于二十世纪七十年代末开始用于恶性肿瘤的临床诊断和治疗研究，早在二十世纪八十年代已有学者进行了胰腺癌细胞光动力损伤的研究，近年来又有许多新的光敏剂用于胰腺癌的实验研究，2002年英国已有学者报告了胰腺癌光动力治疗的Ⅰ期临床研究，标志着胰腺癌的光动力治疗正在从实验室走向临床。
光动力治疗的热点之一是寻找更理想的光敏剂，苝醌类光敏剂竹红菌素是一种来自真菌的天然色素，由我国学者首先发现，它的母体成分主要为竹红菌甲素和竹红菌乙素两类。与第一代光敏剂相比，由于竹红菌素具有在红光范围内有强吸收、很高的单线态氧产率和容易定点化学修饰等优点，我国科技工作者已经合成了一系列竹红菌甲素和乙素的衍生物，并对它们的生物物理特性和作用机制以及部分衍生物的生物学特性进行了研究。研究表明竹红菌素是具有很大潜力的新型光敏剂。
为进一步研究胰腺癌光动力治疗的机理，本文以新型光敏剂竹红菌素衍生物为
Pancreatic cancer is a malignant tumor of the digestive system with high malignancy and difficulty of early diagnosis, low rate of resection and poor prognosis. In recent studies, the incidence rate had risen in China and foreign countries. With only 1% overall survival of 5 years, pancreatic cancer currently rates forth in cancer-related deaths in western countries. The number of the patients in present each year is 5-fold contrast to the 1950s in PUMCH. In the past several decades, with advances in surgical technique and postoperative care, the rate of resection is steadily increasing and the mortality rate is decreasing as well. But the prognosis in pancreatic cancer remains pessimistic. So pancreatic cancer was dubbed as an "obstinate fortress in the 21st century". In order to improve survival or at least improve quality of life, initial primary diagnosis and adjunctive treatment is very important, especially in advanced tumors.
Photodynamic therapy has been described as a promising new modality for the treatment of cancer. In general, a photosensitizer is administrated to tumor, and stimulated upon light, the photosensitizer must be able to absorb the light and generates reactive oxygen species (ROS) through photosensitization resulting in tumor. Photodynamic therapy for cancer was first reported in 1970s and photodynamic therapy to pancreatic cancer was investigated from 1981. Many kinds of photosensitizers were used in pancreatic cancer experimental treatment for last two decades, in 2002, there is a phase I clinical trial for pancreatic cancer practiced in UK, which marked photodynamic therapy of pancreatic cancer from the lab to the clinical.
To quest new photosensitizers is one of the development tendency and current hot topics in the field of photodynamic therapy. The naturally occurring polycyclic quinines, including hypocrellin A and B, were isolated from the fungus Hypocrella bambuase sacc by Chinese scientists. Compared with the first generation photosensitizer they have the advantage of easy preparation, purification and chemical modification, high reactive
恶性肿瘤的光动力治疗(Photodynamic therapy，PDT)是一种正在研究发展中的新型临床治疗技术，是指给人体施用光敏剂(Photosensitizer)，然后光照激活光敏剂产生活性氧从而达到治疗肿瘤的目的。光动力治疗于二十世纪七十年代末开始用于恶性肿瘤的临床诊断和治疗研究，早在二十世纪八十年代已有学者进行了胰腺癌细胞光动力损伤的研究，近年来又有许多新的光敏剂用于胰腺癌的实验研究，2002年英国已有学者报告了胰腺癌光动力治疗的Ⅰ期临床研究，标志着胰腺癌的光动力治疗正在从实验室走向临床。
光动力治疗的热点之一是寻找更理想的光敏剂，苝醌类光敏剂竹红菌素是一种来自真菌的天然色素，由我国学者首先发现，它的母体成分主要为竹红菌甲素和竹红菌乙素两类。与第一代光敏剂相比，由于竹红菌素具有在红光范围内有强吸收、很高的单线态氧产率和容易定点化学修饰等优点，我国科技工作者已经合成了一系列竹红菌甲素和乙素的衍生物，并对它们的生物物理特性和作用机制以及部分衍生物的生物学特性进行了研究。研究表明竹红菌素是具有很大潜力的新型光敏剂。
为进一步研究胰腺癌光动力治疗的机理，本文以新型光敏剂竹红菌素衍生物为
Pancreatic cancer is a malignant tumor of the digestive system with high malignancy and difficulty of early diagnosis, low rate of resection and poor prognosis. In recent studies, the incidence rate had risen in China and foreign countries. With only 1% overall survival of 5 years, pancreatic cancer currently rates forth in cancer-related deaths in western countries. The number of the patients in present each year is 5-fold contrast to the 1950s in PUMCH. In the past several decades, with advances in surgical technique and postoperative care, the rate of resection is steadily increasing and the mortality rate is decreasing as well. But the prognosis in pancreatic cancer remains pessimistic. So pancreatic cancer was dubbed as an "obstinate fortress in the 21st century". In order to improve survival or at least improve quality of life, initial primary diagnosis and adjunctive treatment is very important, especially in advanced tumors.
Photodynamic therapy has been described as a promising new modality for the treatment of cancer. In general, a photosensitizer is administrated to tumor, and stimulated upon light, the photosensitizer must be able to absorb the light and generates reactive oxygen species (ROS) through photosensitization resulting in tumor. Photodynamic therapy for cancer was first reported in 1970s and photodynamic therapy to pancreatic cancer was investigated from 1981. Many kinds of photosensitizers were used in pancreatic cancer experimental treatment for last two decades, in 2002, there is a phase I clinical trial for pancreatic cancer practiced in UK, which marked photodynamic therapy of pancreatic cancer from the lab to the clinical.
To quest new photosensitizers is one of the development tendency and current hot topics in the field of photodynamic therapy. The naturally occurring polycyclic quinines, including hypocrellin A and B, were isolated from the fungus Hypocrella bambuase sacc by Chinese scientists. Compared with the first generation photosensitizer they have the advantage of easy preparation, purification and chemical modification, high reactive
引文
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