姜黄素在光动力与声动力治疗恶性肿瘤中的研究进展

姜黄素作为一种中药在亚洲一些国家的使用已经有上千年。近年来发现姜黄素还是一种具有光敏活性的物质,可以用于光、声动力治疗恶性肿瘤。光动力疗法和声动力疗法作为无创的治疗手段,通过激活靶细胞内的增敏剂,与周围的氧反应产生活性氧,诱导细胞凋亡、坏死。本文就近年来姜黄素在光动力与声动力治疗恶性肿瘤中的研究进展进行综述。     

声动力疗法治疗疾病的研究进展

声动力疗法（sonodynamic therapy,SDT）是一种在光动力疗法（photodynamic therapy,PDT）基础上发展起来的非侵入性治疗方法,可以选择性、特异性地杀伤肿瘤细胞。最新的研究显示,声动力疗法在治疗实体肿瘤、白血病、动脉粥样硬化,消除增生性瘢痕以及抗病原微生物等方面显示出极大的潜力。本文将从以下四个方面对声动力疗法的研究进展予以综述:声动力疗法的机制,声动力疗法的应用,声动力疗法与其他治疗方法的联合应用,声动力疗法的现状和展望。     

声动力联合热疗抗肿瘤机制及其在肿瘤中的应用

声动力疗法(SDT)是一种利用声敏剂和低强度超声(US)结合治疗恶性肿瘤的新型无创治疗方法,SDT由光动力疗法(PDT)发展而来.由于超声波相对于光在组织中的传输深度更深,且声敏剂经过诱导而具有靶向性,同时还能利用超声波对声敏剂进行实时监测,所以SDT在肿瘤部位定位和激活深部组织内的敏化剂方面有着显著的优势.因此,与P...     

声动力疗法治疗肿瘤的发展与现状

对肿瘤细胞先给予声敏剂,再用超声照射肿瘤细胞,诱导一系列声化学反应,激活声敏剂分子,通过增效声动力效应杀伤肿瘤细胞、抑制肿瘤生长的方法,称SDT（sonody-namie therapy,声动力疗法）。     

5-氨基酮戊酸光动力疗法对CNE细胞迁移和侵袭的影响

 【摘要】　目的　观察5-氨基酮戊酸光动力疗法（5-ALA-PDT）作用于人类鼻咽癌细胞株CNE细胞后细胞生长抑制、迁移和侵袭性的改变。方法　通过MTT法检测5-ALA-PDT CNE细胞后,不同参数（5-ALA浓度及激光器能量密度）下的细胞生长抑制率变化。并观察不同参数下5-ALA-PDT后细胞划痕实验及Transwell侵袭小室试验。结果　5-ALA-PDT能明显抑制鼻咽癌高分化CNE细胞株的生长。5-ALA-PDT后,当药物浓度和能量密度达到一定水平时CNE细胞的迁移被抑制。并且药物浓度在饱和量1 mmol／L时,细胞迁移距离与光照时间呈线性负相关（P＜0.05）。光动力作用后,CNE细胞的侵袭能力也被抑制,与5-ALA浓度及激光的能量密度相关。在浓度相同的情况下,细胞侵袭数与照光时间呈线性负相关（r＞0.8,P＜0.0001）。结论　5-ALA-PDT作用于CNE细胞后,细胞的迁移和侵袭能力被抑制,抑制作用与能量密度和药物浓度相关。     

声动力疗法促肿瘤细胞凋亡的机制及研究进展

超声由于其安全性、无创性和低成本,如今被广泛应用。声动力疗法是指对肿瘤细胞给予声敏剂之后,再用超声照射肿瘤细胞,诱导一系列声-化学反应,激活声敏剂分子,通过增强声动力效应杀伤肿瘤细胞、抑制肿瘤生长的方法。它可以通过影响肿瘤血管的血液供应、凋亡相关基因以及凋亡信号通路等诱导肿瘤细胞的凋亡。此外,它能通过化疗药物,微泡等得到加强。本文就声动力疗法诱导肿瘤细胞凋亡的机制及其研究进展做一综述。     

光动力疗法在食管癌治疗中的作用

光动力疗法（Photodynamic Therapy,PDT）是静脉注射光敏剂后,使用特定波长的激发光照射光敏剂聚集的肿瘤组织,在组织氧的参与下发生光化学反应,产生大量单态氧和自由基,进而对肿瘤组织引起选择性损伤。食管癌的光动力治疗是在内镜引导下进行,是一种微创性、高选择性治疗方法。本文将对PDT在食管癌及癌前病变治疗中的作用综述如下。     

浅表膀胱癌的光动力疗法

光动力疗法（PDT）是一种新兴的治疗方法，近年来被试用于浅表膀胱癌的治疗。综述光动力疗法治疗膀胱癌的原理、临床适证证、疗效、不良反应及发展前景。     

多发性基底细胞癌光动力疗法的临床观察

多发性基底细胞癌光动力疗法的临床观察邢汝东ＭｉｋｅＳｍｉｔｈ△关键词基底细胞癌光动力疗法中图号Ｒ７３０．２６１Ｒ７３０．５７光动力疗法（ｐｈｏｔｏｄｙｎａｍｉｃｔｈｅｒａｐｙ，ＰＤＴ）是近年开展的快速、无创伤治疗肿瘤的一种新方法，根据肿瘤组织吸收外源...     

5-氨基乙酰丙酸介导鼠脑C6胶质瘤荧光特性的研究

背景与目的：5．氨基乙酰丙酸（5-ALA）荧光引导手术切除神经胶质瘤的基础研究一直较为薄弱，本文旨在探讨5-AM诱导C6胶质瘤内生性卟啉荧光随时间的动力学变化及卟啉在C6胶质瘤和正常鼠脑中的分布。方法：将C6细胞与5-ALA共培养后，使用流式细胞仪检测细胞内原卟啉Ⅸ（Protoporphyrin Ⅸ，PpⅨ）含量。经股静脉向C6／Wistar大鼠脑胶质瘤模型体内注入5-ALA后，使用荧光显微镜和激光扫描共聚焦显微镜观察C6胶质瘤和正常鼠脑组织中卟啉荧光的分布。用鼠的冻伤皮质切片分析血脑屏障的破坏在卟啉产生中的影响。结果：体外C6细胞在加入5-ALA后1h检测到卟啉生成，主要集中在5～15h，11h达到高峰。C6胶质瘤切片荧光主要集中在注入5-ALA后2～10h，6h表现出最强荧光。肿瘤整体荧光呈斑片状分布，边界欠清楚。给药后对侧脑组织未检测到低水平荧光。给药后5h在皮质冻伤切片中检测到微量荧光。无瘤鼠脑组织在注入5-ALA后没有检测到荧光。结论：5-AM能诱导卟啉在C6细胞中积聚，其荧光表现是一个动态过程。5-ALA介导胶质瘤内生性卟啉蓄积与血脑屏障具有密切关系。肿瘤与正常脑组织具有不同荧光表现强度。可以为临床选择性应用5-ALA荧光引导胶质瘤切除术提供有益的指导作用。     

二甲亚砜促进5-氨基酮戊酸光动力疗法对A431细胞杀伤和小鼠皮肤鳞癌的抑制效应

目的:研究DMSO参与5-氨基酮戊酸介导的光动力疗法（ALA-based photodynamic therapy,ALA-PDT）对A431细胞杀伤和小鼠皮肤鳞癌的抑制效应,探讨治疗皮肤肿瘤的优化作用。方法:DMSO干预后,采用流式细胞仪检测A431细胞内PpⅨ水平和PDT后细胞凋亡率。激光共聚焦显微镜检测小鼠鳞癌瘤体组织的荧光强度,比较PDT后各组鳞癌小鼠的抑瘤率。结果:实验组A431细胞PpⅨ荧光强度率高于ALA组和空白对照组（P<0.01）,与DMSO含量呈浓度依赖性。PDT后实验组细胞凋亡率高于ALA组和空白对照组（P<0.01）。实验组瘤体组织PpⅨ荧光强度值高于10%ALA对照组和10%DMSO对照组（P<0.01）,与DMSO含量呈浓度依赖性。实验组鳞癌小鼠 PDT治疗后,抑瘤率高于对照组（P<0.05）,并有量效依从关系。结论:DMSO可促进ALA-PDT对A431细胞杀伤和小鼠皮肤鳞癌的抑制效应。     

Polymeric iron chelators for enhancing 5-aminolevulinic acid-induced photodynamic therapy

5-Aminolevulinic acid (5-ALA) is an amino acid that can be metabolized into a photosensitizer, protoporphyrin IX (PpIX) selectively in a tumor cell, permitting minimally invasive photodynamic diagnosis/therapy. However, some malignant tumor cells have excess intracellular labile iron and facilitate the conversion of PpIX into heme, which compromises the therapeutic potency of 5-ALA. Here, we examined the potential of chelation of such unfavorable intratumoral labile iron in photodynamic therapy (PDT) with 5-ALA hydrochloride, using polymeric iron chelators that we recently developed. The polymeric iron chelator efficiently inactivated the intracellular labile iron in cultured cancer cells and importantly enhanced the accumulation of PpIX, thereby improving the cytotoxicity upon photoirradiation. Even in in vivo study with subcutaneous tumor models, the polymeric iron chelator augmented the intratumoral accumulation of PpIX and the PDT effect. This study suggests that our polymeric iron chelator could be a tool for boosting the effect of 5-ALA-induced PDT by modulating tumor microenvironment.     

Optimization of differential photodynamic effectiveness between normal and tumor urothelial cells using 5-aminolevulinic acid-induced protoporphyrin IX as sensitizer

Photodynamic therapy using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX is a promising tool in bladder-cancer therapy. However, little is known about the cellular mechanisms of phototoxicity. Our aim was to characterize the cellular damage and to optimize differential photodynamic effectiveness between tumor and normal urothelial cells. RT4 tumor and UROtsa normal urothelial cells were used to simulate a papillary bladder tumor in contrast to normal urothelium. Photodynamically induced damage in plasma membrane and mitochondria was monitored by flow cytometry with propidium iodide exclusion and analysis of aggregate formation of the dye JC-1. Cell morphology was investigated by phase-contrast and fluorescence microscopy following acridine orange staining. Long incubation times (3 hr) led to complete RT4 tumor cell kill accompanied by a marked fraction of damaged normal UROtsa cells. Shorter incubation intervals (1 hr) also resulted in complete RT4 tumor cell kill; however, most UROtsa cells retained their cell properties, including intact plasma membrane and active mitochondria as well as intact cellular morphology. Phototoxicity depends not only on cellular sensitizer accumulation but also on intracellular localization. Analysis of phototoxic mechanisms is an important step for planning combination therapy regimens with, e.g., DNA-damaging agents. Further, data indicate that differential phototoxicity in normal and tumorous urothelium can be enhanced using differences in cellular protoporphyrin IX distribution following short 5-ALA incubation times. These data are encouraging for the in vivo situation since short incubation times are a more practical approach for local photodynamic therapy of early tumor stages not only in the bladder but also, e.g., in the gastro-intestinal tract or bronchial mucosa.     

负载５-ＡＬＡ纳米微球对膀胱癌光动力学作用的初步研究

目的　探讨负载５-盐酸乙酰氨基丙酸（５-ａｍｉｎｏｌｅｖｕｌｉｎｉｃａｃｉｄ,５-ＡＬＡ）的光敏感纳米微球的制备方法,并初步研究其在体外对膀胱癌Ｔ２４细胞的光动力学效应。方法　以纳米沉淀法制备光敏感纳米微球,紫外分光光度法检测载药率,动态光散射的方法检测纳米粒径,原子力显微镜观察纳米微球形貌。将膀胱癌Ｔ２４细胞分别与不同浓度的光敏感纳米微球共同孵育,以能量密度为６Ｊ／ｃｍ２,波长为６５０ｎｍ半导体激光照射。另设空白对照组、空载体组、５-ＡＬＡ组。以ＭＴＴ比色法测定Ｔ２４细胞的生长抑制率。结果　光敏感纳米微球载药量为７％,负载效率８５％。处理组５、１０、２５和５０μｇ／ｍｌ光敏感纳米微球的细胞生长抑制率分别为７３.１９％、７９.９５％、８３.８６％和８９.７４％,与空白对照组、空载体组、５-ＡＬＡ组比较差异有统计学意义（Ｐ＜０.０５）。结论　纳米微球负载５-ＡＬＡ具有理想的载药率,光敏感纳米微球能显著提高光动力学杀伤效应。     

声动力疗法诱导肿瘤细胞内源性凋亡

声动力疗法现已被广泛学者关注,其具有损伤小,选择性高的特点在治疗肿瘤方面备受青睐,声动力疗法诱导肿瘤细胞凋亡机制有多种理论,而内源性细胞凋亡在声动力疗法诱导肿瘤细胞凋亡中占主要作用,线粒体在细胞凋亡中起决定性作用,通过声动力疗法处理肿瘤细胞后可使细胞内源性凋亡相关因子Bax、caspase-9、caspase-3 表达均有所增加,细胞膜电位改变,从而导致细胞凋亡.     

Comparison between sonodynamic effect with protoporphyrin IX and hematoporphyrin on sarcoma 180

Purpose The comparison between sonodynamic antitumor effect with protoporphyrin IX (PPIX) and hematoporphyrin (Hp) at a concentration of 5 mg/kg on Sarcoma 180 (S180) cells was studied in vivo, and the potential cell damage mechanism was also investigated. Methods The sonodynamically induced anti-tumor effect of PPIX was studied in mice bearing S180 solid tumors. In order to determine the optimum timing of ultrasound exposure after administration of PPIX, the PPIX concentrations in plasma, skin, muscle and tumor were determined by the fluorescence intensity of tissue extractions with a fluorescence spectrophotometer based on the standard curve. Anti-tumor effects were estimated by measuring the tumor size and the tumor weight. Additionally, the morphological changes of S180 cells were evaluated by transmission electron microscope (TEM) observation immediately after sonodynamic therapy (SDT) treatment. Results A time of 24 h after the intravenous administration of PPIX was chosen as the best time for ultrasound exposure. The antitumor effect induced by PPIX mediated sonodynamic therapy (PPIX-SDT) was in a dose dependent manner when ultrasound intensity was at or above the inertial cavitation threshold (5 W/cm²). A significant tumor growth delay was observed both in PPIX mediated sonodynamic therapy and in Hp mediated sonodynamic therapy treatments (Hp-SDT), and the tumor weight inhibition ratios after the synergistic treatments were 42.82 ± 0.03 and 35.22 ± 0.03%, respectively, this difference was significant at P < 0.05. While ultrasound alone (5 W/cm²) showed a slight tumor growth inhibitory effect compared with the control group, and PPIX or Hp alone showed almost no significant effect. Furthermore, TEM observation indicated cell damage was more serious in PPIX-SDT treatment group than in Hp-SDT treatment group. After sonication, the cell ultra-structure such as cell membrane destruction, mitochondria swelling, chromatin condensation might be important factors that inhibited the tumor growth and even induced cell death. Conclusions The comparative results suggested that PPIX as a sonosensitizer might have more potential cytotoxicity than Hp when irradiated with ultrasound, and the ultra-structural changes may account for cell destruction induced by sonodynamic therapy in our experiment mode.     

Enhancement of photodynamic therapy by use of aminolevulinic acid/glycolic acid drug mixture

5-aminolevulinic acid (5-ALA) is a precursor in synthesis of endogenous porphyrins used to sensitize tumor tissues in photodynamic therapy (PDT). It is administered topically into a tumor which after the certain time, required for porphyrins to accumulate, is irradiated with visible light from the proper source at established wavelength. Our main aim in the present study was to increase the penetration of 5-ALA through the skin and other tissues by addition of glycolic acid (GA) to 5-ALA on cell lines in vitro and on animals. We also applied 5-ALA ointment with glycolic acid to patients suffering from squamous cell carcinoma (SCC). In our study, we used 5-ALA, dimethyl sulfoxide (DMSO), ethylenediaminetetraacetic acid, disodium salt (EDTA) and GA together in one formulation (5-ALA-GA) on eucerin support. We compared both therapeutic and cosmetic effects in 5-ALA-GA-PDT and in control group of patients. Our results showed that modification of 5-ALA ointment by addition of 5% GA caused that the treated lesions responded with rapid regression. In 12 patients with single lesions of SCC type subjected to 5-ALA-GA-PDT, we observed 100% regression of tumors following single or repeated two-three times PDT. In vitro and in vivo in animals total porphyrin levels after addition of 5% GA increased significantly (P<0.01). These results provide evidence that addition of glycolic acid should be considered as the agent which enhances 5-ALA penetration in tissues and thus increases the effectiveness of photodynamic therapy.