Effects of Photodynamic Therapy on Tumor Stroma

Photodynamic therapy (PDT) is a treatment that combines a photosensitizer with light to generate oxygen-dependent photochemical destruction of diseased tissue. This modality has been approved worldwide since 1993 for the treatment of several oncological and nononcological disorders. PDT continues to be interested in both preclinical and clinical research, with more than 500 publications each year during the past 5 years. This minireview focuses on the effects of PDT on tumor stroma. A tumor consists of two fundamental elements: parenchyma (neoplastic cells) and stroma. The stroma is composed of vasculature, cellular components, and intercellular matrix and is necessary for tumor growth. All the stromal components can be targeted by PDT. Although the exact mechanism of PDT is unknown, emerging evidence has indicated that effective PDT of tumor requires destruction of both parenchyma and stroma. Further, damage to subendothelial zone of vasculature, in addition to endothelium, also appears to be a crucial factor. The PDT-generated immune response as a way of vaccination for treatment and prevention of metastatic tumors remains to be exploited.     

光动力学疗法和声动力学疗法

目的:通过对肿瘤治疗中光动力学疗法和声动力学疗法的研究现状及研究进展的综述,以期对临床应用或实验研究起到一定的借鉴作用。方法:本文具体阐述了光动力学疗法和声动力学疗法杀伤肿瘤细胞的分子机制以及光敏剂与声敏剂的分类,介绍了两种方法在肿瘤方面的应用及对新的治疗模式的探索,展望了光动力学疗法和声动力学疗法临床应用的巨大潜力。结果:光动力学疗法和声动力学疗法的研究已取得了一定的成果,但在组织内氧含量、新型光敏剂与声敏剂的开发、药物剂量的把握及对声动力学疗法作用机理的研究方面仍存在问题。结论:光动力学疗法和声动力学疗法作为两种新的肿瘤治疗手段,在肿瘤的防治中已展现出良好的应用前景,但在临床实际应用中光动力学疗法还未普及,而声动力学疗法起步较晚,尚处于研究阶段,未应用于临床。     

Correlation of Subcellular and Intratumoral Photosensitizer Localization with Ultrastructural Features After Photodynamic Therapy

Photodynamic therapy (PDT) of cancer typically involves systemic administration of tumor-localizing photosensitizers followed 48-72 h later by exposure to light of appropriate wavelengths. Knowledge about the distribution of photosensitizers in tissues is still fragmentary. In particular, little is known as to the detailed localization patterns of photosensitizers in neoplastic and normal tissues as well as the relationship between such patterns and the actual targets for the photosensitizing effect. This review focuses on ultrastructural features seen in treated cells and tumors. An attempt is made to correlate these findings with the subcellular/intratumoral localization pattern of the photosensitizers in tumor cell lines in vitro and in tumor models in vivo. Several subcellular sites are main targets of PDT with different sulfonated aluminum phthalocyanines (AIPcS_n) in the human tumor cell line LOX. Nuclei are not among the primary targets. Overall, the ultrastructural changes correlate well with the data about the subcellular localization patterns for each analogue of AIPcS_n in the same cell line. Similar findings are also obtained for the family of sulfonated mesotetraphenylporphines (TPPS_n) in the NHIK 3025 cell line. The mechanisms involved in the killing of tumors by PDT seem to be a complex interplay between direct and indirect (via vascular damage) effects on neoplastic cells according to the intratumoral localization pattern of the applied dye. Several factors can affect the localization pattern of a drug, such as its chemical character, the mode of drug delivery, the time interval between drug administration and light exposure, and tumor type. Furthermore, whether local immune reactions (such as macrophages) and apoptosis (programmed cell death) are involved in the destruction of neoplastic cells by PDT in vivo is still an enigma. A general model for PDT-induced tumor destruction is suggested.     

光动力治疗大鼠大面积创伤感染的实验研究

探讨新型卟啉类光敏剂PA1介导的光动力抗菌疗法治疗大鼠大面积创伤感染的效果。体外培养创面易感染的3种菌株,有抗药性金黄色葡萄球菌(MRSA)、大肠杆菌(E.coli)和铜绿假单胞菌(P.aeruginosa),探讨3种细菌对PA1的吸收量、光照PA1的最小抑菌浓度和最低杀菌浓度; 取清洁级雄性Wistar大白鼠40只,建立皮肤大面积创伤感染模型,创面滴加光敏剂PA1,用650 nm激光照射治疗,检测各实验组的创面愈合率、不同时相点创面下的菌落数。结果表明,上述3种细菌对PA1的最大吸收量都发生于前30 min,以后趋于平稳。光照PA1对3种细菌均有灭活作用,对MRSA和E.coli的最低杀菌浓度为31 μM,对P.aeruginosa的最低杀菌浓度为62.5 μM。体内实验结果显示,治疗组的各项指标优于模型对照组(P<0.05或P<0.01),高剂量治疗组的各项指标优于中、低量治疗组(P<0.01),为临床治疗大面积创伤感染积累一定的实验经验。     

Hydroxyaluminium Tetra-3-Phenylthiophthalocyanine is a New Effective Photosensitizer for Photodynamic Therapy and Fluorescent Diagnosis

We studied the possibility of using liposomal forms of hydroxyaluminium tetra-3-phenylthiophthalocyanine as a near infrared band photosensitizer. Experiments on mice with solid Ehrlich tumor and subcutaneously transplanted P-388 leukemia revealed high selectivity of accumulation of the photosensitizer in tumors in comparison with normal tissues and high photodynamic activity of the preparation. This photosensitizer can be used as the basis for creating an effective preparation for photodynamic therapy and fluorescent diagnosis.__________Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 139, No. 4, pp. 420–423, April, 2005     

苯并卟啉衍生物单环酸A光动力作用对血管平滑肌细胞增殖的影响

目的：探讨苯并卟啉衍生物单酸环A（BPD—MA）光动力作用对血管平滑肌细胞增殖的影响。方法：用不同浓度的光敏剂BPD-MA作用于体外培养的兔血管平滑肌细胞，经波长650nm半导体激光以能量密度1．2J／cm^2、2．4J／cm^2、4．8J／cm^2。照射，MTT法检测细胞增殖抑制率，用PCNA观察细胞增殖。结果：在1．2J／cm^2．2．4J／cm^2,4．8J／cm^2激光照射下，与空白对照组比较，BPD-MA光动力对平滑肌细胞有显著地抑制作用（P〈0．01），单纯激光组照射对平滑肌细胞的增殖无明显抑制作用（P〉0．05）。PCNA检测显示光动力作用抑制细胞增殖。结论：：BPD—MA光动力作用对血管平滑肌细胞增殖有明显抑制作用。     

中晚期食管癌光动力治疗联合化疗的回顾性研究

目的比较中晚期食管癌的单纯光动力治疗与光动力＋化疗联合治疗的短期疗效，探讨中晚期食管癌光动力＋化疗的治疗模式的优势。方法回顾性分析我院自2002年至2005年期间光动力治疗及光动力＋化疗治疗的食管癌患者60例（Ⅲ～Ⅳ期），其中单纯光动力治疗27例，光动力＋化疗治疗33例。光动力治疗使用光敏剂Photofrin 2mg／kg，48h后内镜引导下使用波长为630nm的激光照射，综合治疗组化疗方案为5-FU＋DDP，动力治疗后1周开始化疗，共化疗4周期。结果60例病人随访时间全部满2年，综合治疗组和单纯光动力治疗组症状缓解率分别为85．2％、93．9％，内镜评价有效率分别为85．2％、90．9％，无明显差异；2年生存率分别为54．5％、29．6％，综合治疗组中位生存期明显延长（Ⅲ期为22m、13m；Ⅳ期为7m、5m），差异有统计学意义（P=0．046）。结论光动力＋化疗治疗中晚期食管癌优于单纯光动力治疗，短期疗效相当，2年生存期有优势。     

纯氧及LED阵列光动力复合治疗设备的研制

基于变压吸附制氧原理产生纯氧,并采用微透镜阵列多光谱LED发光器件与二次透镜阵列相结合构成光动力治疗辐照器,研制一种纯氧及LED阵列光动力复合治疗设备。其辐照器输出纯氧浓度大于90%,照射光包括波长625 nm红光、465 nm蓝光和520 nm绿光,应用光排序辐照技术实现纯氧及多光谱光动力复合治疗。通过辐照器上纯氧和照射光同步输出等多种外源性给氧保持光动力治疗区域的富氧状态,解决由于乏氧影响光动力疗效的问题。辐照器光学系统解决现有技术采用LED阵列排布替代激光器作为光动力治疗光源时存在的光能利用率低、光功率密度分布不均匀、不同波长光束在目标靶面光功率密度分布曲面差异大等缺陷。     

Modification of Hemostatic Status Improves Antitumor Efficiency of Photodynamic Therapy

Complex treatment with acetylsalicylic acid, heparin, and dexamethasone improves the efficiency of photodynamic therapy in rats with myosarcoma-I.     

Role of Laser Energy Density for Photodynamic Therapy of Radiation Injuries of the Skin

The role of different laser energy densities used in photodynamic therapy in the reparation of radiation ulcers caused by X-ray exposure in a dose of 80 Gy was studied. Tissue reparation manifested differently at different laser energy densities. After photodynamic therapy at energy density of 0.1 J/cm² the rate of healing was notably higher during early periods. After exposure at 5 and 40 J/cm² acceleration of ulcer healing was observed 14 and more days after the treatment, indicating the emergence of another mechanism of photodynamic therapy effect. Laser energy density of 5 J/cm² was the most effective for maximally complete healing of radiation ulcers. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 11, pp. 570–573, November, 2005     

光动力疗法对慢性牙周炎治疗效果的Meta分析

目的：比较并评价在慢性牙周炎治疗中,光动力疗法辅助龈下刮治和根面平整术（scaling and root planing,SRP）的临床效果是否优于单纯龈下刮治和根面平整术。方法：主要检索OVID、springerlink、ScienceDirect、Pubmed数据库等,收集自建库到2011年11月公开发表的关于光动力疗法辅助龈下刮治和根面平整术治疗慢性牙周炎随机对照试验的英文文献,随访时间不得少于一个月,测量结果包括术后牙周探诊深度（probing depth,PD）的减少、临床附着水平（clinical attach-ment level,CAL）的增加等。采用Jadad法对文章质量进行评价,并使用Revman5.2对实验数据进行Meta分析。结果：共有5篇文献符合纳入条件,Meta分析结果显示光动力学疗法辅助SRP和单纯SRP相比,三个月及六个月后两组之间牙周探诊深度差异无统计学意义,附着丧失也无统计学意义。结论：在慢性牙周炎的治疗过程中,光动力疗法辅助SRP并不能明显降低牙周探针深度和附着丧失。     

生物组织内三维光动力学传输过程的Monte Carlo模拟方法

目的探讨激光在组织中的传输规律，为光动力学治疗计划的制定打下基础。方法建立可同时求解生物组织内三维激光场、光敏剂浓度场及温度场发展过程的Monte Carlo计算方法，以临床上常见的甲状腺癌的治疗过程为例进行模拟。结果两种典型激光照射方式即从光纤端面或侧面出射所引起的光动力学反应和热效应分布存在明显不同，在临床上有不同价值。结论计算结果有助于更好地理解光动力学治疗中组织内的基础光热质传输机制，本文方法为光动力学治疗计划的拟定建立了相对完整的理论基础。     

BPD-MA光动力作用诱导兔血管平滑肌细胞凋亡的初步研究

目的：探讨新型光敏剂苯并卟啉衍生物单环酸A（BPD-MA）光动力作用诱导血管平滑肌细胞凋亡及机制。方法：用体外培养的兔血管平滑肌细胞，加浓度0．25mg／ml的光敏剂BPD-MA，经能量密度4．8J／cm^2波长650nm半导体激光照射。免疫组化染色鉴定平滑肌细胞，HE染色观察细胞形态，MTT法测定细胞增殖活性，TUNEL法观察细胞凋亡。结果：在4．8J／cm^2激光能量密度照射下，与空白对照组比较，光动力作用对平滑肌细胞增殖活性有显著地抑制作用（P〈0．01），单纯激光组照射埘平滑肌细胞的增殖则无明显抑制作用（P〉0．05）。BPD-MA光动力作用使光动力组的大多数细胞出现凋亡。结论：凋亡可能是苯并卟啉衍生物单环酸A光动力抑制兔血管平滑肌细胞增殖的关键因素。     

肿瘤靶向治疗精确靶向定位认知系统的研究

肿瘤靶向治疗可实现最大限度消灭肿瘤的同时,使周围正常组织损伤最小.本肿瘤靶向定位认知系统将肿瘤图像、温度场分布信息集成,并结合图像识别技术、力场模拟及气泡填充技术处理后,得到氩氦刀探针的最佳路径方案,用于治疗过程中实时手术引导.实验表明,在氩氦刀靶向治疗中应用靶向定位认知系统提高了探针的定位精度,确保了手术质量.     

细胞凋亡抑制蛋白:肿瘤治疗的障碍与靶点

细胞凋亡抑制蛋白(inhibitor of apoptosis protein,IAP)主要通过结合并抑制细胞凋亡执行分子caspase蛋白家族而抑制细胞凋亡。肿瘤细胞高表达IAP是其获得抗凋亡特性的原因之一,成为肿瘤传统治疗(放疗,化疗等)的障碍。但特异的在肿瘤细胞内高表达而在正常细胞特别是高分化细胞中低表达或无表达也为肿瘤治疗提供了新靶点。干涉IAP分子在肿瘤细胞内的表达或功能已被作为肿瘤传统治疗方法的辅助治疗方法来研究。     

减毒的沙门氏菌在肿瘤基因治疗中的研究进展

减毒的沙门氏菌是一种非病原性细菌,能靶向肿瘤并产生局部抗肿瘤的效应。减毒的沙门氏菌能选择性地在肿瘤组织中复制,表达编码治疗性蛋白的效应基因是肿瘤基因治疗有应用前景的一种途径,这种方式也将成为目前实体瘤放疗、化疗的一种辅助的治疗方法。     

ALA-PDT对K562、HL60细胞株破坏的实验研究

探讨基于氨乙酰丙酸介导的光动力作用(ALA-PDT)对白血病细胞株HL60和K562细胞的杀伤模式及其可能机制。在ALA-PDT处理细胞的优化条件下,用透射电镜对处理细胞进行超微结构观察,选择AnnexinV-FITC/PI双标法明确ALA-PDT对两种白血病细胞的杀伤模式,PI染色流式细胞仪分析ALA-PDT后细胞周期的变化,以Fluo-3/AM为钙离子指示剂采用激光共聚焦显微镜检测细胞内钙离子浓度的变化。透射电镜观察发现PDT后即刻的细胞呈现典型的凋亡小体,24h后大部分发生坏死;双标法检测显示PDT后即刻及24h后细胞的死亡模式分别以凋亡和凋亡后坏死为主。光动力作用后即刻和作用后2h,K562细胞S期所占的比例分别为57.67%±1.13%和84.77%±6.20%,HL60细胞S期所占的比例分别为74.6%±7.27%和84.60%±1.74%;两种细胞内钙离子浓度的均明显升高。在最佳试验条件下,凋亡是ALA-PDT杀伤白血病细胞K562和HL60细胞的最初模式,而凋亡后坏死为其主要模式,ALA-PDT使白血病细胞株阻滞于S期,在白血病细胞株死亡的过程中,细胞内钙离子浓度的增加可能起着重要的作用。     

Comparative Characteristics of the Methods of Treatment of Chronic Periodontitis Using Antibacterial Photodynamic Therapy (Per One Visit) and Calasept Preparation

Background

The article describes the results of research on efficiency of using antimicrobial photodynamic therapy in treatment of chronic periodontitis.