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:The efficacy of photodynamic therapy for treating premalignant and malignant tumors is often limited by the emerging resistant tumor cells. We have developed experimental model systems to study the mechanisms associated with resistance to photodynamic therapy induced by structurally similar photosensitizers (two novel porphyrin-based photosensitizers and temoporfin) in mouse mammary carcinoma cell line 4T1. Photodynamic therapy resistant clones were obtained in vitro by exposure to constant photosensitizer concentration and irradiation with increasing light doses.
Project description:Tumor microenvironmental cellular components like bone marrow cells stromal cells macrophages changes due to sunitinib resistance may affect their efficacy in advanced stage renal cell carcinomas. Immune checkpoint inhibitors (ICIs) have been approved as 2nd line therapy over acquired resistance. Each ICI uniquely affected different cellular components. Better understanding of transcriptomic, metabolomic or proteomic changes due to ICI treatment is necessary to development proper immunotherapy.
Project description:Tumor microenvironmental cellular components like bone marrow cells stromal cells macrophages changes due to sunitinib resistance may affect their efficacy in advanced stage renal cell carcinomas. Immune checkpoint inhibitors (ICIs) have been approved as 2nd line therapy over acquired resistance. Each ICI uniquely affected different cellular components. Better understanding of transcriptomic, metabolomic or proteomic changes due to ICI treatment is necessary to development proper immunotherapy.
Project description:Tumor microenvironmental cellular components like bone marrow cells stromal cells macrophages changes due to sunitinib resistance may affect their efficacy in advanced stage renal cell carcinomas. Immune checkpoint inhibitors (ICIs) have been approved as 2nd line therapy over acquired resistance. Each ICI uniquely affected different cellular components. Better understanding of transcriptomic, metabolomic or proteomic changes due to ICI treatment is necessary to development proper immunotherapy.
Project description:The goal of the study was to determine whether photodynamic oncolytic virus therapy of glioblastoma and malignant meningioma xenografts in mice alters transciptomics associated with efficacy. RNA sequencing was used from tumors treated with PBS, laser, G47delta-KillerRed, and G47delta-KillerRed and laser, which is photodynamic oncolytic virus therapy.
Project description:We used selenium as a photodynamic anti-tumor synergist of phycocyanin to explore its inhibitory effect on lung cancer and its molecular mechanism in vitro. First of all, we used LLC-luc mouse lung cancer cells to establish a tumor-bearing model. Selenium-enriched phycocyanin was injected next to the tumor. When it was absorbed by the tumor tissue, the tumor site was irradiated by a 620nm wavelength laser. The changes in tumor size were monitored in real-time and the physiological indexes of mice were measured. It was found that selenium phycocyanin photodynamic therapy could enhance the inhibitory effect of tumors and improve the level of antioxidation in tumor-bearing mice. In addition, the pathological section observation and electron microscope microstructure analysis of the tumor tissue showed that the effect of the selenium-enriched phycocyanin photodynamic treatment group was more significant. At the same time, the tumor tissue transcriptional group sequencing analysis and qRT-PCR verification analysis showed that selenium-enriched phycocyanin photodynamic treatment group could reduce the expression of Mmp13, Serpine1, Vegfa, and Ppbp genes inhibit tumor cell metastasis and proliferation, up-regulate the expression of Ccl2, Ccl3, Cxcl2 and down-regulate the expression of Ccl24 chemokine, and promote tumor local immunity. Our results show that selenium phycocyanin photodynamic therapy plays an anti-tumor effect by promoting tumor cell apoptosis, reducing inflammation, and promoting tumor immunity.
