自血光化学疗法对放疗肿瘤患者细胞免疫功能的影响

本文通过对肿瘤患者Ｅ玫瑰花环及淋巴细胞转化率的检测,探讨自血光化学放射敏疗法对机体免疫功能的影响。结果表明：单纯放疗组Ｅ玫瑰花环形成及淋巴细胞转化率较放职前明显下降,而自血光化学放疗增敏组治疗前后上述免疫功能无明显改变,表明自血光化学疗法对肿瘤放疗患者的细胞免疫功能具有保护作用。     

自血光化学（光动力）疗法放疗增敏治疗中晚期恶性肿瘤200例的研究

利用光量子疗法（ＵＢＩ）的氧效应及促进机体免疫功能、改善微循环的作用,同时借助血卟啉衍生物（ＨＰＤ）的放疗增敏的效应,二者结合与放射治疗综合应用治疗中晚期恶性肿瘤患者２００例。方法是从患者静脉采血２００～３００ｍｌ加入ＨＰＤ１００～１５０ｍｇ（ＨＰＤ...     

辐射增敏剂增敏活性的分子连接性研究

计算４２个辐射增敏剂的各阶分子连接性指数ｍＸｔ及△ｍＸｔ,并对其中３８个非对称性化合物的分子连接性指数与其增敏活性进行定量构效关系（ＱｕａｎｔｉｔａｔｉｒｅＳｔｒｕｃｔｕｒｅＡｃｔｉｖｉｔｙＲｅｌａｔｉｏｎｓｈｉｐ,ＱＳＡＲ）的研究,得到相关方程。并分析了影响增敏活性的１ｇＰ、ＥＳ及σ在一定程度上都可通过分子连接性指数表达出来。对这些增敏剂进行分子对称性的研究,发现对称性会降低分子的极性,进而降低其增敏活性。另外,还发现在这些增敏剂中存在亚类现象,并对各亚类的反应机理进行了探讨。     

RAF-1与辐射增敏

RAF-1在调控细胞增殖和凋亡的信号转导途径中起着关键作用。近期研究发现,阻断RAF-1或其介导的信号通路中其他信号分子位点,可以显著提高部分辐射抵抗肿瘤的辐射敏感性。     

PVCL-MnO2纳米探针用于多形性胶质母细胞瘤的放疗增敏及MRI成像的实验研究

摘要 目的：探讨PVCL-MnO₂对多形性胶质母细胞瘤的放疗增敏作用,并进行体内MRI成像研究。方法：制备PVCL-MnO₂纳米探针,利用透射电子显微镜(Transmission Electron Microscope, TEM)对其形态进行表征,并使用Image J分析其尺寸分布。采用细胞增殖-毒性实验 (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT),测定PVCL-MnO₂协同放疗处理肿瘤细胞48 h后的细胞活性。将多形性胶质母瘤细胞瘤细胞进行PVCL-MnO₂共孵育后,协同放疗处理,分别使用免疫荧光,蛋白质印迹法等实验技术检测H2AX 组蛋白异型的磷酸化形式 (phosphorylated form of the histone protein H2AX, γ-H2AX),活性氧自由基(reactive oxygen species, ROS) 的产生及Bax,Bcl-2凋亡相关蛋白的表达。PVCL-MnO₂尾静脉注射至原位多形性胶质母细胞瘤小鼠中,在不同的时间点进行MRI扫描,观察成像效果。结果：PVCL-MnO₂颗粒粒径分布均匀,结构规整, 表现出良好的单分散性。PVCL-MnO₂联合放疗可有效增强DNA双链的断裂,ROS及促凋亡蛋白Bax的产生,同时下调了抗凋亡蛋白Bcl-2。MRI成像显示,PVCL-MnO₂具有较好的T1-加权MRI成像效果,在尾静脉注射PVCL-MnO₂ 后4 h,肿瘤部位的信号增强最明显, 随后信号开始下降。结论：PVCL-MnO₂可实现多形性胶质母细胞瘤的放疗增敏及MRI成像。     

脂多糖结合蛋白及其对内毒素增敏机制的研究进展

脂多糖结合蛋白（ＬＢＰ）是近年来发现的一种能够与脂多糖（ＰＬＳ）特异性结合,并倡导机体细胞对ＬＰＳ识别、应答的调节蛋白。研究表明它可在多方面增敏内毒素刺激细胞的作用。抗ＬＢＰ的抗体可有效地减弱内毒素的毒性作用,在脓毒症的防治中可能具有一定意义。     

自血光量子疗法对放射治疗鼠肿瘤增敏作用的研究

本文应用多功能图像分析仪,检测了鼠Ｗ２５６移植性肿瘤细胞ＤＮＡ含量,探讨自血池子量子疗法（ＵＢＩ）对放射治疗的增敏作用,结果表明,经ＵＢＩ后放疗与单纯放疗的肿瘤相比,肿瘤细胞ＤＮＡ含量显著降低,而且肿瘤体积减小,细胞变性坏死显著,间质淋巴细胞数量明显增多,表明ＵＢＩ对肿瘤放射治疗有明显的增敏作用。     

胶束增敏荧光法测定丹参中丹参酮ⅡA的含量研究

本文以十二烷基磺酸钠为胶束增敏试剂,在优化的实验条件下,对丹参中的丹参酮Ⅱ_A进行了定量测定,其线性范围在2×10~(-8)～8×10~(-7)g/ml,检测下限达1.2×10~(-9)g/ml,平均回收率为94.9％,测定市售丹参中丹参酮Ⅱ_A为0.539％,效果良好。     

核黄素体外辐射增敏机理研究

采用MTT方法和荧光显微镜技术, 以小鼠胸腺细胞和人肝L02细胞株为研究对象, 对核黄素的体外辐射增敏作用进行研究. 在5 Gy ⁶⁰Co γ 射线辐照条件下, 低浓度(5~50 μmol/L)和高浓度(100~400 μmol/L)核黄素作用下的小鼠胸腺细胞存活率的时间依赖关系表现出明显的差异, 其规律为: 低浓度下, 细胞受g射线辐照后并不立刻大量死亡, 但随着时间的推移存活率迅速下降, 4 h后存活水平降低到较低的水平; 而高浓度下, 细胞立刻大量的死亡, 且随时间的变化, 细胞存活仅有微弱的下降. 荧光显微镜研究结果显示, 核黄素在细胞中的分布因高浓度和低浓度而有所不同, 低浓度时核黄素集中于细胞核区, 高浓度时细胞膜区也有较高的分布. 由此得到结论: 低浓度时(<50 μmol/L), 核黄素作用的位点在细胞核, 对DNA辐射损伤增敏; 高浓度时(>100 μmol/L), 核黄素辐射增敏的主要靶位点为细胞膜, 两者均显示出核黄素对细胞辐射损伤具有显著的增敏效应.     

二烯丙基二硫对荷S180肉瘤小鼠的辐射增敏效应

研究大蒜素重要活性成分二烯丙基二硫(Diallyl disulfide,DADS)对荷S180肉瘤小鼠的辐射增敏效应。利用X射线对荷瘤小鼠全身辐照。测量肿瘤体积、重量;检测肿瘤组织中细胞凋亡及Bcl-2、Bax、caspase-3等凋亡因子的表达。同时测定了DADS对S180细胞增殖及细胞内活性氧(reactive oxygen species,ROS)的影响。结果显示:与对照组、单纯药物组及单纯辐照组相比,DADS联合辐照组小鼠的肿瘤体变小、重量减轻(P<0.01);肿瘤组织中TUNEL阳性细胞增多(P<0.01);Bax、caspase-3表达增强,而Bcl-2表达减弱。此外,DADS引起了S180细胞内大量ROS的产生。结果提示DADS对荷S180肉瘤小鼠具有辐射增敏效应,其机制与上调Bax、Caspase-3、下调Bcl-2表达及诱导肿瘤细胞产生ROS有关。     

Time Modulation Effect of Diethyldithiocarbamate (DDC) on Radiosensitization by Superoxide Dismutase (SOD) Inhibition

Superoxide dismutase (SOD) is known to protect cells from the lethal effects of ionizing radiation by the dismutation of oxygen radicals. Diethyldithiocarbamate (DDC) is known inhibitor of SOD and may therefore be useful as a radiosensitizer. DDC however, is also a thinly radio protector due to its ability to scavenge radiation induced free radicals. We have shown that DDC. if administered to turnours 1 hour prior to x-irradiation exerts a protective effect, whereas if administered 4 hours prior to irradiation, it radiosensitizes. This time modulation effect is not apparent after neutron irradiation where DDC protects in both situations. We have also examined the effect of DPC on the LD_50/30 in mice after total body irradiation.     

Time Modulation Effect of Diethyldithiocarbamate (DDC) on Radiosensitization by Superoxide Dismutase (SOD) Inhibition

Superoxide dismutase (SOD) is known to protect cells from the lethal effects of ionizing radiation by the dismutation of oxygen radicals. Diethyldithiocarbamate (DDC) is known inhibitor of SOD and may therefore be useful as a radiosensitizer. DDC however, is also a thinly radio protector due to its ability to scavenge radiation induced free radicals. We have shown that DDC. if administered to turnours 1 hour prior to x-irradiation exerts a protective effect, whereas if administered 4 hours prior to irradiation, it radiosensitizes. This time modulation effect is not apparent after neutron irradiation where DDC protects in both situations. We have also examined the effect of DPC on the LD_50/30 in mice after total body irradiation.     

Radiosensitization by celastrol is mediated by modification of antioxidant thiol molecules

The radiosensitizing effects of naturally occurring triterpenes were investigated in human lung cancer cells. Several quinone methide-containing triterpenes (QMTs) enhanced the cytotoxic effect of ionizing radiation (IR) and of these QMTs, celastrol (CE) had the greatest enhancing effect on IR-induced cell death in vitro. Additionally, the quinone methide moiety of CE was shown to be essential for CE-mediated radiosensitization; in contrast, dihydrocelastrol (DHCE), does not contain this moiety. Reactive oxygen species (ROS) production by IR was augmented in combination with CE, which was responsible for CE-mediated radiosensitization. CE induced the thiol reactivity and inhibited the activities of antioxidant molecules, such as thioredoxin reductase and glutathione. In vivo, nude mouse xenografting data also revealed that tumor growth delay was greater in mice treated with CE plus IR, compared with those treated with CE or IR alone. When DHCE, instead of CE, was combined with IR, tumor growth delay was similar to that in IR alone-treated mice. These results demonstrate that CE synergistically enhances the effects of IR and suggest the novel anticancer therapeutic use of CE in combination with radiation therapy.     

Radiosensitization of wildtype p53 cancer cells by the MDM2-inhibitor PXN727 is associated with altered heat shock protein 70 (Hsp70) levels

The oncoprotein MDM2 (murine double minute 2) is often overexpressed in human tumors and thereby attenuates the function of the tumor suppressor p53. In this study, we investigated the effects of the novel MDM2-inhibitor PXN727 on p53 activation, cell proliferation, cell cycle distribution and radiosensitivity. Since the localization of heat shock protein 70 (Hsp70) exerts different effects on radioresistance of tumor cells, we investigated the impact of PXN727 on intracellular, membrane, and secreted Hsp70 levels. We could show that PXN727 exerts its effects on wildtype p53 (HCT116 p53^+/+, A549) but not p53 depleted (HCT116 p53^−/−) or mutated (FaDu) tumor cells. PXN727 activates p53, induces the expression of p21, reduces the proportion of cells in the radioresistant S-phase and induces senescence. Radiosensitivity was significantly increased by PXN727 in HCT116 p53^+/+ tumor cells. Furthermore, PXN727 causes a downregulation of Hsp70 membrane expression and an upregulated secretion of Hsp70 in wildtype p53 tumor cells. Our data suggest that re-activation of p53 by MDM2-inhibition modulates Hsp70 membrane expression and secretion which might contribute to the radiosensitizing effect of the MDM2-inhibitor PXN727.     

Liquid crystal precursor system as a vehicle for curcumin-mediated photodynamic inactivation of oral biofilms

Curcumin has great potential as a photosensitizer, but it has low solubility in aqueous solutions. This study reports the antimicrobial efficacy of photodynamic inactivation (PDI) mediated by a curcumin-loaded liquid crystal precursor (LCP) on in situ dental biofilms. Thirty volunteers used intraoral devices containing enamel samples for 48 hours for biofilm formation. The samples were then removed from the device and treated either with LCP with 160 μM of curcumin plus illumination at 18 J/cm² (C + L+ group) or with LCP without curcumin in the dark (C – L − group). Following this, the biofilm from the samples was plated for quantifying the viable colonies at 37°C for 48 hours. Specific and nonspecific media were used for the presumptive isolation of Streptococcus mutans, Lactobacillus species/aciduric microorganisms, Candida species, and total microbiota. The C + L+ group showed a highly significant (P < .001) reduction in the log₁₀ (colony forming units/mL) values as compared to the C − L − group for all culture media. Hierarchical linear regression indicated that there may be predictors at individual volunteer level explaining the difference in the PDI efficacy among different individuals (P = .001). The LCP system retained curcumin and released it slowly and continuously, thus protecting the drug from photodegradation. LCP with curcumin is considered effective for the photoinactivation of dental biofilms, but the PDI efficacy may differ based on the host's individual characteristics.     

Open carpal tunnel release using a 1-centimeter incision: technique and outcomes for 104 patients

The advantages of endoscopic carpal tunnel release, compared with traditional open techniques, include smaller incisions, less scar tenderness, and faster recoveries. However, endoscopic carpal tunnel release has also been associated with higher complication rates. The goal of this study was to evaluate the safety and functional outcomes of minimal-incision open carpal tunnel release. In this prospective study involving a 2-year period, 104 patients (149 hands) underwent open carpal tunnel release with a 1-cm incision. Prospective data on complications among 104 patients were recorded, and functional outcomes among 20 patients were assessed by using the Michigan Hand Outcomes Questionnaire, the Jebsen-Taylor Hand Function Test, and pinch/grip strength testing. Data were collected before the operation and 3 weeks and 6 months after the operation. Complications included three wound infections and one carpal tunnel syndrome recurrence, 18 months after the initial release procedure. Michigan Hand Outcomes Questionnaire scores improved significantly between the preoperative and postoperative periods. There were no significant changes in Jebsen-Taylor Hand Function Test results or pinch/grip strength. Minimal-incision open carpal tunnel release can be performed safely and is associated with good functional outcomes.     

Radiosensitization by the 2,4-dinitro-5-aziridinyl benzamide CB 1954: a structure/activity study

CB 1954 (2,4-dinitro-5-aziridinyl benzamide) is a radiosensitizer which is up to 10 times more efficient in vitro than would be predicted on the basis of its electron affinity. In order to determine the contribution of the various functional groups comprising the molecule to overall sensitizing efficiency, nine structural analogues have been studied. The redox potential, E7(1), and sensitizing efficiency, C1.6, were obtained for each compound. The value of C1.6 depends on both redox potential and the magnitude of an additional component defined by C1.6/C1.6, where C1.6 is derived from a structure/activity relationship (Adams et al. 1979 b, Wardman 1982) described by the equation: log (C1.6/mol dm-3) = (6.96 +/- 0.22) + (9.54 +/- 0.56)E7(1)V. The magnitude of C1.6/C1.6 for CB 1954 and its analogues depends on alkyl substitution of the amide, the presence/absence and position of the nitro groups and is independent of the presence of the aziridine group. Holding cells in the presence of the drug post-irradiation marginally enhanced sensitization by CB 1954, CB 10-107 and by CB 10-092 but the largest effect was seen with the mononitro compound CB 7060 which also has a value of 26 for C1.6/C1.6. This compound was also interesting in that when combined with 2-phenyl-4(5)amino-5(4)-imidazole carboxamide (phenyl AIC) an enhancement of sensitization was obtained. In contrast, phenyl AIC protected against radiosensitization by CB 1954. Taken together, the data suggest that multiple mechanisms of radiosensitization may contribute to the abnormal radiosensitizing efficiency of CB 1954 and its analogues. This has implications for the further design and development of novel radiosensitizing drugs.     

Radiosensitization of a mouse melanoma by withaferin A: in vivo studies

The radiosensitizing effect of a plant withanolide, withaferin A, on the B16F1 mouse melanoma was studied in vivo. Treatment of 100 mm3 tumours with 10 to 60 mg/kg withaferin A intraperitoneally produced a dose dependent increase in growth delay and volume doubling time. Injection of 30-50 mg/kg withaferin A, followed by 30 Gy local gamma irradiation, significantly enhanced the tumour response. No systemic or local adverse reactions were noted in these groups. The drug was most effective when injected intraperitoneally 1 h before irradiation. However, neither the individual agents nor their combination could produce any complete response (tumour cure). Melanoma is a relatively radioresistant tumour. The present results indicate that the radiation response of this tumour can be significantly enhanced by pretreatment with withaferin A.