氩激光改良法光动力治疗浅表性膀胱肿瘤

The killing effects of 514.5 nm argon laser and 630 nm dye laser radiation on the murine SP2/0 myeloma cells cultured in thin layer containing HPD were measured by clonogenic assay. It was found that the former was 3.34 fold higher than the latter. Improved argon laser photodynamic therapy was used in the treatment of 104 superficial bladder tumors in 40 patients. Firstly, high output (6-7 W/cm2) argon laser contact and interstitial radiation were used to eradicate visible tumors, and then cylindrical optic fiber was used to deliver argon laser (2.1-3.47 W/cm2) for whole bladder mucosal scattered irradiation to destroy small multi-focal tumors and reduce recurrence. In this series, the follow-up was 7-34 months. All patients achieved complete response and only 7 (17.5%) recurred.     

光动力疗法在肺癌治疗中的作用及其疗效评价

光动力疗法(photodynamic therapy，PDT)是一种微创的，以非产热方式引起局部组织坏死的治疗手段。早在4000多年前的古埃及时代，人们就发现植物中的补骨脂口服后会积聚在皮肤中，经日光照射后会导致皮肤色素沉着，并用此来治疗皮肤白斑。PDT应用于肿瘤治疗始于1903年，Jesionek和Tappeiner应用伊红作为光敏剂来致敏肿瘤细胞，引起肿瘤细     

浅谈肿瘤光动力治疗

上世纪的70年代,出现了一种肿瘤治疗的新技术--光动力疗法(photo.dynamictherapy),通称为PDT.它的基本原理是利用光辐射、光敏药物及氧之间发生的光动力反应,产生化学活性非常高的单态氧,可以用来杀灭肿瘤细胞,产生治疗效果.光动力疗法在体内杀伤肿瘤的作用机理很复杂,简而言之,是直接杀伤肿瘤细胞、损伤破坏肿瘤内的微血管、照光区内的急性炎症反应、以及可能刺激全身性的免疫功能等多种作用的综合效应.     

缺氧肿瘤光动力治疗的研究进展

光动力疗法(photodynamic therapy,PDT)是肿瘤治疗的补充疗法,但由于对氧气的依赖性,PDT的治疗效果严重受限于肿瘤缺氧微环境.PDT过程中产生的氧耗量和微血管损伤加剧肿瘤的缺氧也进一步阻碍其疗效.因此,如何在肿瘤缺氧微环境下增强PDT的疗效成为肿瘤治疗领域研究的热点之一,本文就肿瘤缺氧微环境下提高...     

光动力治疗肿瘤的生物学效应机制的研究进展

光动力疗法以其有效、安全、创伤小等特有的优势选择性地消灭局部的原发和复发肿瘤，可与放疗、化疗同时进行，发挥一定的协同作用。其生物学效应主要为：直接杀灭肿瘤细胞；诱导细胞调亡；局部血管闭塞导致继发性细胞死亡；参与免疫系统。本文就近年光动力疗法对肿瘤生物学效应的研究进行综述。     

光动力疗法治疗肿瘤的临床疗效观察

光动力疗法(photodynamic Therapy简称PDT),是指利用某些可被恶性肿瘤细胞特异性摄入,或可在恶性肿瘤细胞中选择性潴留的光敏物质经一定波长光的激发后产生一系列化学变化,从而造成肿瘤细胞坏死,达到选择性的杀伤肿瘤目的,是一种肿瘤辅助性治疗方法.我院引进该项技术自1993年4月至1994年3月期间对31例肿瘤患者进行治疗,取得了一定效果和经验,现总结如下:1 材料与方法1.1 一般资料 本组31例中,男性21例,女性10例;年龄23～70岁,平均53.3岁.所有病例都经病理组织学诊断确诊.其中食道癌6例,胃癌8例,直肠癌6例,左颌下腺癌1例,舌癌1例,纤维肉瘤2     

光动力治疗早期喉癌

一个世纪以来,喉癌的治疗主要是手术切除,术后病人丧失了喉功能,致使正常的发音、呼吸、吞咽等遭到不同程度破坏,影响到正常社交、工作及生活,病人十分痛苦。本世纪六十年代起,国内外喉科专家为喉术后重建功能作了大量研究、先后采用人工喉、电子喉、喉移植及发音重建手术等各种方法,谋求代偿部份喉功能、但都距生理要求十分遥远。 1988年我院摆脱常规手术治疗喉癌方法,应用光动力疗法(photodynamic therapy)治疗早期喉癌,保全了正常喉功能,取得初步效果。     

光动力学治疗肿瘤的简史和现状

光动力学治疗经历了经验应用，实验室研究和临床应用研究三个阶段。目前已有多国政府批准光动力学治疗应用于肿瘤的治疗，临床适应证也由体表肿瘤和腔内肿瘤，扩大到肝癌，胰腺癌等实质性脏器的肿瘤。光敏剂已发展到第三代，第一代已被多国政府批准临床应用，第二代多在临床研究阶段，第三代处在实验室研究阶段。     

食管癌光动力治疗进展

随着光敏剂及激光发生系统的发展,光动力疗法在各期食管癌治疗上成为一种新的有效手段。目前已应用于临床并取得较好疗效。本文回顾了光敏剂及激光发生系统的最新研究成果,以及目前最新关于PDT的作用机制,并对国内外应用PDT治疗各期食管癌取得的疗效及应用前景进行总结。     

Efficacy of antitumoral photodynamic therapy with hypericin: relationship between biodistribution and photodynamic effects in the RIF-1 mouse tumor model.

We investigated the hypericin-mediated PDT effects on the tumor and normal skin and in correlation with its biodistribution. These studies were carried out on C3H mice bearing RIF-1 tumors. The hypericin distribution and PDT effects were recorded at different intervals (0.5-24 hr) after intravenous injection of a 5-mg/kg dose of hypericin. After administration, rapid biphasic exponential decay was observed in the plasma drug concentration. It was found that hypericin was preferentially bound to the plasma lipoproteins. The tumor drug levels increased rapidly over the first few hours and reached a maximum around 6 hr after injection. In contrast, PDT efficacy was maximal when irradiation was performed at 0.5 hr after hypericin administration, which led to 100% cure. The PDT efficacy decreased rapidly as the administration-irradiation interval was prolonged. No tumor cure was obtained at the 6-hr interval, even though it was at this time that the tumor drug level peaked. Fluorescence microscopic studies showed that hypericin was mainly confined within the tumor vasculature at 0.5 hr after injection, whereupon it rapidly diffused to the surrounding tumor tissue. At 6 hr, a strong hypericin fluorescence was observed in the tumor tissue with only faint fluorescence within the vasculature, whereas at 24 hr the fluorescence in the tumor also decreased and became more diffused, and no fluorescence could be seen in the tumor vasculature. Like the tumor response, skin reactions were also found to be much more dramatic at short administration-irradiation intervals. Hypericin distribution and PDT response studies revealed a close correlation between the plasma drug level and the PDT effects, which suggests that vascular damage is the primary effect of hypericin-mediated PDT in this tumor model.     

上转换纳米材料在光动力疗法中的研究进展

光动力疗法(photodynamic therapy,PDT)是一种新型的肿瘤治疗方法,它与传统的手术治疗、放疗、化疗和免疫治疗等方法相比具有选择性高、创伤小和不良反应小等优点.随着对PDT的深入研究,研究人员发现传统的光敏剂水溶性差,且激发光的能量低,这些缺陷限制了PDT的发展.而近年来纳米技术和纳米材料的发展为研究人员带来了希望,上转换纳米材料(upconversion nanomaterials,UCNs)独特的性质可以克服传统光敏剂的缺点,为PDT带来新的进展.本综述主要集中于UCNs在PDT中的研究进展,并对其在PDT领域的未来发展趋势进行展望.     

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。     

空腔脏器肿瘤的光动力治疗进展

光动力治疗是一种有前景的治疗肿瘤的方法,光敏剂注入肿瘤患者体内很快富集于肿瘤组织,采用特定波长可见光照射肿瘤组织,光敏剂会产生致死性细胞毒剂,杀死肿瘤细胞,引起肿瘤组织的微血管完全封闭,营养枯竭,进而肿瘤组织坏死。近年来多种肿瘤的光动力治疗体现出良好的临床疗效,并取得了很大的进步。随着新型光敏剂及光源的开发应用,PDT将会成为治疗多种肿瘤更加切实可行的方法。由于空腔脏器的解剖学特点,光动力治疗在该类肿瘤的治疗中具有独特的优势。光动力正逐渐整合到空腔脏器肿瘤的治疗中,以提高治疗效果,现就空腔脏器的光动力治疗做一综述。     

Targeting tumour energy metabolism potentiates the cytotoxicity of 5-aminolevulinic acid photodynamic therapy

Background:

Cancerous cells usually exhibit increased aerobic glycolysis, compared with normal tissue (the Warburg effect), making this pathway an attractive therapeutic target.

Methods:

Cell viability, cell number, clonogenic assay, reactive oxygen (ROS), ATP, and apoptosis were assayed in MCF-7 tumour cells and corresponding primary human mammary epithelial cells (HMEC).

Results:

Combining the glycolysis inhibitors 2-deoxyglucose (2DG; 180 mM) or lonidamine (300 μM) with 10 J cm⁻² 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) increases MCF-7 cytotoxicity (by 3.5-fold to 70% death after 24 h, and by 10-fold in 9-day clonogenic assays). However, glycolysis inhibition only slightly increases HMEC PDT cytotoxicity (between two-fold and three-fold to a maximum of 9% death after 24 h). The potentiation of PDT cytotoxicity only occurred if the glycolysis inhibitors were added after ALA incubation, as they inhibited intracellular accumulation of photosensitiser if coincubated with ALA.

Conclusion:

As 2DG and lonidamine are already used as cancer chemotherapeutic agents, our results are directly translatable to combination therapies with existing topical PDT.     

Interaction of acid ceramidase inhibitor LCL521 with tumor response to photodynamic therapy and photodynamic therapy‐generated vaccine

Acid ceramidase has been identified as a promising target for cancer therapy. One of its most effective inhibitors, LCL521, was examined as adjuvant to photodynamic therapy (PDT) using mouse squamous cell carcinoma SCCVII model of head and neck cancer. Lethal effects of PDT, assessed by colony forming ability of in vitro treated SCCVII cells, were greatly enhanced when combined with 10 µM LCL521 treatment particularly when preceding PDT. When PDT‐treated SCCVII cells are used to vaccinate SCCVII tumor‐bearing mice (PDT vaccine protocol), adjuvant LCL521 treatment (75 mg/kg) resulted in a marked retardation of tumor growth. This effect can be attributed to the capacity of LCL521 to effectively restrict the activity of two main immunoregulatory cell populations (Tregs and myeloid‐derived suppressor cells, MDSCs) that are known to hinder the efficacy of PDT vaccines. The therapeutic benefit with adjuvant LCL521 was also achieved with SCCVII tumors treated with standard PDT when using immunocompetent mice but not with immunodeficient hosts. The interaction of LCL521 with PDT‐based antitumor mechanisms is dominated by immune system contribution that includes overriding the effects of immunoregulatory cells, but could also include a tacit contribution from boosting direct tumor cell kill.     

mTHPC-mediated photodynamic therapy for early oral squamous cell carcinoma

Surgery and radiotherapy are standard treatments for early oral squamous cell carcinoma, both resulting in good tumour control. However, neither of these modalities is without consequent functional or cosmetic impairment, and there are patients in whom both are contraindicated. Furthermore, there is a significant risk of metachronous tumours developing in the oral cavity, and salvage or retreatment with either surgery or radiotherapy poses difficulties. Photodynamic therapy (PDT) offers the potential for improved functional and cosmetic outcomes, while achieving comparable tumour control. We conducted an open-label, multicentre study to assess the efficacy and safety of meta-tetrahydroxyphenylchlorin (mTHPC) in patients with early oral cancer. One hundred twenty-one patients received intravenously administered mTHPC, followed 96 hr later by illumination of the tumour surface with 652 nm laser light. Of these patients, 114 were protocol compliant. A complete tumour response was achieved in 85% of protocol-compliant patients (97 of 114 patients). A complete response was maintained in 85% of responders at 1 year and in 77% at 2 years. One- and 2-year actuarial survival rates were 89% and 75%, respectively. In the opinion of the investigators, tumour clearance was accompanied by excellent cosmetic and functional results, without impact on the patients' performance status. Mild-to-moderate pain at the treatment site, a recognised side effect of PDT in the oral cavity, was reported by 82% of patients but was manageable with appropriate analgesia. Mild-to-moderate skin photosensitivity reactions were reported for 13% of patients. mTHPC offers an effective alternative treatment for early oral squamous cell carcinoma. It is associated with excellent functional and cosmetic results and can be used in conjunction with other standard therapies.     

ALA- and ALA-ester-mediated photodynamic therapy of human glioma spheroids

The effects of photodynamic therapy (PDT) in human glioma spheroids incubated in 5-aminolevulinic acid (ALA), or ALA esters, are investigated. Spheroid survival and growth are monitored following PDT at representative drug concentrations, light doses, and dose rates. The primary finding of this study is that the response of human glioma spheroids to PDT with lipophilic ester derivatives, such as benzyl-ALA and hexyl-ALA, is equivalent to that observed with ALA, however, this equivalency is obtained for ester concentrations 10–20 times lower than the parent compound. The enhanced efficiency of the esters is likely due to their increased membrane penetrance. Potential clinical advantages of using lipophilic esters in PDT of gliomas are discussed.     

Repetitive 5-aminolevulinic acid-mediated photodynamic therapy on human glioma spheroids

The response of human glioma spheroids to repetitive 5-aminolevulinic acid-mediated photodynamic therapy (PDT) was investigated. In all cases, light fluences were kept below toxic thresholds to simulate conditions typically found at 1–2cm depths in brain adjacent to tumor. Significant inhibition of spheroid growth was observed following multiple PDT treatments at sub-threshold light fluences. The effect appears to be insensitive to the treatment intervals investigated (weekly or bi-monthly). In all cases, suppression of growth was observed for the duration of treatment. Low fluence rates (5mWcm^–2) appear to be more effective than high fluence rates (25mWcm^–2). No evidence of PDT resistance was found in this investigation.