Bremachlorin®, also known as “Radachlorin®” and Photochlorin, a composition of 3 chlorophyll a derivatives in an aqueous solution [1], was initially introduced into the Russian and South Korean Pharmac...Bremachlorin®, also known as “Radachlorin®” and Photochlorin, a composition of 3 chlorophyll a derivatives in an aqueous solution [1], was initially introduced into the Russian and South Korean Pharmacopoeias with the corresponding marketing authorizations received in 2006 and 2008, on the basal cell skin carcinoma PDT protocol. Phase I-II clinical trials led in 2002-2005 showed no side effects, a good tolerability by patients and a high clinical anti-tumor efficacy. Further studies described in the present paper were fulfilled in accordance with a skin melanoma PDT + surgery combined technique protocol in 2006-2016. Resulting from the present trial, up to the 100% complete responses were achieved after resection and plastic surgery following PDT, with no melanoma regrowth or metastases during 5 and 10-year observation periods. Conducting PDT one day prior to tumor dissection can guarantee to meet the ablastics principles at the subsequent surgery. At the same time, the PDT + surgery protocol can allow for dissecting the tumor with less distance from its edge, which seems to be important for the face localizations of tumors.展开更多
This paper presents a multimodal approach that combines time-resolved fluorescence microscopy and spatial light interference microscopy into a single complex allowing for a concurrent comprehensive analysis of cell sa...This paper presents a multimodal approach that combines time-resolved fluorescence microscopy and spatial light interference microscopy into a single complex allowing for a concurrent comprehensive analysis of cell samples in vitro.The combined application of quantitative phase imaging using partially coherent radiation with timeresolved fluorescence imaging of endogenic coenzymes NADH and FAD,as well as Radachlorin photosensitizer,allowed for evaluation of a set of morphological and physiological parameters of cells of the two lines,HeLa and A549,in the course of photodynamic treatment.Besides comparison of cells of the two lines in terms of volume,height,dry mass,projected area,and redox ratio,we analysed the mechanisms and rate of Radachlorin accumulation.Using the developed multimodal approach,we demonstrated that in both the cell lines,Radachlorin was taken up in complexes with serum albumin,transported by endocytosis,and accumulated primarily in lysosomes.The Radachlorin transportation through the cellular membrane to lysosomes was accompanied by a decrease in its fluorescence lifetime,which was apparently owing to a gradual increase in endosome acidity.The different contributions of the fast and slow components of time-resolved fluorescence signals of nicotinamide adenine dinucleotide(NADH)and flavin adenine dinucleotide(FAD)enabled us to demonstrate the difference in the redox ratios of cells of the two lines.The average concentration of the accumulated Radachlorin photosensitizer in cells of the two lines and their resistivity to photodynamic treatment also differed:HeLa cells tended to accumulate more Radachlorin and demonstrated lower resistivity to photodynamic treatment.展开更多
文摘Bremachlorin®, also known as “Radachlorin®” and Photochlorin, a composition of 3 chlorophyll a derivatives in an aqueous solution [1], was initially introduced into the Russian and South Korean Pharmacopoeias with the corresponding marketing authorizations received in 2006 and 2008, on the basal cell skin carcinoma PDT protocol. Phase I-II clinical trials led in 2002-2005 showed no side effects, a good tolerability by patients and a high clinical anti-tumor efficacy. Further studies described in the present paper were fulfilled in accordance with a skin melanoma PDT + surgery combined technique protocol in 2006-2016. Resulting from the present trial, up to the 100% complete responses were achieved after resection and plastic surgery following PDT, with no melanoma regrowth or metastases during 5 and 10-year observation periods. Conducting PDT one day prior to tumor dissection can guarantee to meet the ablastics principles at the subsequent surgery. At the same time, the PDT + surgery protocol can allow for dissecting the tumor with less distance from its edge, which seems to be important for the face localizations of tumors.
基金financial support provided by the Russian Science Foundation under grant No.21–72-10044.
文摘This paper presents a multimodal approach that combines time-resolved fluorescence microscopy and spatial light interference microscopy into a single complex allowing for a concurrent comprehensive analysis of cell samples in vitro.The combined application of quantitative phase imaging using partially coherent radiation with timeresolved fluorescence imaging of endogenic coenzymes NADH and FAD,as well as Radachlorin photosensitizer,allowed for evaluation of a set of morphological and physiological parameters of cells of the two lines,HeLa and A549,in the course of photodynamic treatment.Besides comparison of cells of the two lines in terms of volume,height,dry mass,projected area,and redox ratio,we analysed the mechanisms and rate of Radachlorin accumulation.Using the developed multimodal approach,we demonstrated that in both the cell lines,Radachlorin was taken up in complexes with serum albumin,transported by endocytosis,and accumulated primarily in lysosomes.The Radachlorin transportation through the cellular membrane to lysosomes was accompanied by a decrease in its fluorescence lifetime,which was apparently owing to a gradual increase in endosome acidity.The different contributions of the fast and slow components of time-resolved fluorescence signals of nicotinamide adenine dinucleotide(NADH)and flavin adenine dinucleotide(FAD)enabled us to demonstrate the difference in the redox ratios of cells of the two lines.The average concentration of the accumulated Radachlorin photosensitizer in cells of the two lines and their resistivity to photodynamic treatment also differed:HeLa cells tended to accumulate more Radachlorin and demonstrated lower resistivity to photodynamic treatment.
