Project description:Photodynamic therapy (PDT) is a tumor treatment strategy that relies on the production of reactive oxygen species (ROS) in the tumor following local illumination. Although PDT has shown promising results in the treatment of non-resectable perihilar cholangiocarcinoma, it is still employed palliatively. In this study, tumor-comprising cells (i.e., cancer cells, endothelial cells, macrophages) were treated with the photosensitizer zinc phthalocyanine that was encapsulated in cationic liposomes (ZPCLs). Post-PDT survival pathways were studied following sublethal (50% lethal concentration (LC50)) and supralethal (LC90) PDT using a multi-omics approach. ZPCLs did not exhibit toxicity in any of the cells as assessed by toxicogenomics. Sublethal PDT induced survival signaling in perihilar cholangiocarcinoma (SK-ChA-1) cells via mainly hypoxia-inducible factor 1 (HIF-1)-, nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-кB)-, activator protein 1 (AP-1)-, and heat shock factor (HSF)-mediated pathways. In contrast, supralethal PDT damage was associated with a dampened survival response. (Phospho)proteomic and metabolomic analysis showed that PDT-subjected SK-ChA-1 cells downregulated proteins associated with epidermal growth factor receptor (EGFR) signaling, particularly at LC50. PDT also affected various components of glycolysis and the tricarboxylic acid cycle as well as metabolites involved in redox signaling. In conclusion, sublethal PDT activates multiple pathways in tumor parenchymal and non-parenchymal cells that, in tumor cells, transcriptionally regulate cell survival, proliferation, energy metabolism, detoxification, inflammation/angiogenesis, and metastasis. Accordingly, sublethally afflicted tumor cells are a major therapeutic culprit. Our multi-omics analysis unveiled multiple druggable targets for pharmacological intervention.
Project description:Photodynamic therapy (PDT) is a tumor treatment strategy that relies on the production of reactive oxygen species (ROS) in the tumor following local illumination. Although PDT has shown promising results in the treatment of non-resectable perihilar cholangiocarcinoma, it is still employed palliatively. In this study, tumor-comprising cells (i.e., cancer cells, endothelial cells, macrophages) were treated with the photosensitizer zinc phthalocyanine that was encapsulated in cationic liposomes (ZPCLs). Post-PDT survival pathways were studied following sublethal (50% lethal concentration (LC50)) and supralethal (LC90) PDT using a multi-omics approach. ZPCLs did not exhibit toxicity in any of the cells as assessed by toxicogenomics. Sublethal PDT induced survival signaling in perihilar cholangiocarcinoma (SK-ChA-1) cells via mainly hypoxia-inducible factor 1 (HIF-1)-, nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-кB)-, activator protein 1 (AP-1)-, and heat shock factor (HSF)-mediated pathways. In contrast, supralethal PDT damage was associated with a dampened survival response. (Phospho)proteomic and metabolomic analysis showed that PDT-subjected SK-ChA-1 cells downregulated proteins associated with epidermal growth factor receptor (EGFR) signaling, particularly at LC50. PDT also affected various components of glycolysis and the tricarboxylic acid cycle as well as metabolites involved in redox signaling. In conclusion, sublethal PDT activates multiple pathways in tumor parenchymal and non-parenchymal cells that, in tumor cells, transcriptionally regulate cell survival, proliferation, energy metabolism, detoxification, inflammation/angiogenesis, and metastasis. Accordingly, sublethally afflicted tumor cells are a major therapeutic culprit. Our multi-omics analysis unveiled multiple druggable targets for pharmacological intervention.
Project description:We report the application of 5-ALA ( 5-Aminolevulinic acid)-mediated photodynamic therapy on mouse brain tissue, and further explored the impact of PDT on nervous system.
Project description:We report the application of Porfimer sodium-mediated photodynamic therapy on mouse brain endothelial cells, and further identified the impact of PDT on the normal vessel cells.
Project description:This study looked for signals produced in UV-B irradiated leaves, and possibly induced in shielded leaves, that modulate physiological responses in maize. Transcriptome and proteomics profiling tracked changes in exposed and shielded organs. Metabolic profiling was examined for signaling molecules. Exposure of just the top leaf substantially alters the transcriptome of both irradiated and shielded organs, with greater changes as an additional 1-2 leaves are irradiated. Transcriptome, proteome and metabolome changes are UV-B regulated in shielded organs. Early steps in signal transduction and possible signal molecules are identified utilizing a time course experiment. Keywords: UVB, maize, leaves, ears Compared irradiated leaves in a time course, irradiated leaves versus shielded leaves, and shielded ears on plants with irradiated leaves. Also compared different number of leaves being irradiated. Spike-in controls were included.
Project description:This study looked for signals produced in UV-B irradiated leaves, and possibly induced in shielded leaves, that modulate physiological responses in maize. Transcriptome and proteomics profiling tracked changes in exposed and shielded organs. Metabolic profiling was examined for signaling molecules. Exposure of just the top leaf substantially alters the transcriptome of both irradiated and shielded organs, with greater changes as an additional 1-2 leaves are irradiated. Transcriptome, proteome and metabolome changes are UV-B regulated in shielded organs. Early steps in signal transduction and possible signal molecules are identified utilizing a time course experiment. Keywords: UVB, maize, leaves, ears