Investigating the photodynamic efficacy of chlorin e6 by millisecond pulses in metastatic melanoma cells.
- 作者列表："Kulbacka J","Chodaczek G","Rossowska J","Szewczyk A","Saczko J","Bazylińska U
:Melanoma is considered the most aggressive type of skin cancer, still without effective treatment. Thus, alternative therapeutic methods are still in demand, and electroporation-supported photodynamic therapy (EP-PDT) of cancer cells seems a promising approach. New developments in EP-PDT aim at enhanced tumor selectivity and biocompatibility by applying a second-generation photosensitizer, i.e., Chlorin e6 (Ce6). We have verified the improved photodynamic effect of Ce6 on skin cancer melanoma (Me45) cells and control (CHO-K1) cells. In this study, we applied 1 or 5 pulses of 10 ms duration and assessed the EP-PDT effect with a variety of tests, such as singlet oxygen scavenger (ABMDMA) photooxidation, oxidoreductive potential measurements, kinetic measurements with fluorescent microscopy, photosensitizer uptake studies, lipid peroxidation level, and actin fibers organization. The optimization of photosensitizer uptake as a function of temperature was also performed. Our results indicated efficient Ce6 delivery into Me45 cells and good photodynamic efficiency enhanced by the electroporation of cancer cells.
: 黑色素瘤被认为是最具侵袭性的皮肤癌类型，仍然没有有效的治疗。因此，仍然需要替代的治疗方法，并且癌细胞的电穿孔支持的光动力疗法 (ep-pdt) 似乎是有希望的方法。Ep-pdt的新发展旨在通过应用第二代光敏剂 (即，Chlorin e6 (Ce6)。我们已经验证了Ce6对皮肤癌黑素瘤 (Me45) 细胞和对照 (CHO-K1) 细胞的改善的光动力作用。在这项研究中，我们应用了1或5个10毫秒持续时间的脉冲，并通过各种测试评估了EP-PDT效应，如单线态氧清除剂 (ABMDMA) 光氧化、氧化还原电位测量、荧光显微镜动力学测量、光敏剂摄取研究、脂质过氧化水平和肌动蛋白纤维组织。还进行了作为温度的函数的光敏剂吸收的优化。我们的结果表明，Ce6有效地递送到Me45细胞中，并且癌细胞的电穿孔增强了良好的光动力效率。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.