Project description:To explore the effect of IDO-APT on T cell function, we conducted RNA transcriptome profiling of NPs, named as NP-Scr-APT in article, and NP-IDO-APT treated lymphocytes.
Project description:aCGH of control cells not subjected to PDT (Parental) and cells subjected to 5 or 10 sequential PDT treatments (5ºG and 10ºG, respectively).
Project description:aCGH of control cells not subjected to PDT (Parental) and cells subjected to 5 or 10 sequential PDT treatments (5M-BM-:G and 10M-BM-:G, respectively). Three-condition experiment, cultures of SCC-13 cells not subjected to PDT (Parental) vs 5M-BM-:G and 10M-BM-:G generations of resistant cells.
Project description:The 3′-ends of eukaryotic pre-mRNAs are processed in the nucleus by a large multiprotein complex, the cleavage and polyadenylation factor (CPF). CPF cleaves RNA, adds a poly(A) tail and signals transcription termination. CPF harbors four enzymatic activities essential for these processes but how these are coordinated remains poorly understood. Several subunits of the CPF including two protein phosphatases are also found in a related complex, the ‘associated with Pta1’ (APT) complex, but the relationship between CPF and APT is unclear. Here, we show that the APT complex is physically distinct from CPF. The 21 kDa Syc1 protein is associated only with APT, and not with CPF, and is therefore the defining subunit of APT. Using ChIP-seq, PAR-CLIP and RNA-seq, we show that Syc1 has functions separable from those of CPF. Syc1 plays a role in sn/snoRNA production whereas CPF processes the 3ʹ-ends of protein-coding pre-mRNAs. These results define distinct protein machineries for synthesis of mature eukaryotic protein-coding and non-coding RNAs.
Project description:aCGH of control cells not subjected to PDT (Parental), cells subjected to 10 sequential PDT treatments (10G) and 10G cells inoculated in immunosuppressed mice; the induced tumors were subcultured by explants to obtain a cell resistant population called 10GT
Project description:The response of tumors to PDT treatment is expected to provide information on effects of oxygen depletion, induced apoptosis, induction of an inflammatory response and induction of an ani-tumor immune response. Experiment Overall Design: NCI-H69 human SCLC xenografts were induced in SCID mice. Three pairs of xenograft tumors, PDT treated and untreated controls, were harvested four hours after PDT treatment. RNA was isolated and prepared for hybridization to human Affymetrix GeneChip arrays.
Project description:Drosophila tdf, another name apontic (apt), encodes a bZIP transcription factor that is required for the development of trachea, heart, head and neural system. However, little is known about the target of TDF/Apt. To identify theTDF/ Apt regulated genes, we compared expression profiles of mRNA purified from wild-type and tdf mutant embryos. Summary file is emtdf-yw.CHP.
Project description:Despite decades of research, brain tumours remain among the deadliest of all forms of cancer. As recurrence in glioblastoma is locally generated around the resection cavity, the ability of these tumours to resist almost all conventional and novel treatments relates, in part, to the unique cell-intrinsic and microenvironmental properties of neural tissues. Photodynamic therapy (PDT) relies on photo-toxic effects induced by specific molecules (photosensitisers) upon absorption of photons from a light source. Such toxic effects are not specific to a particular molecular fingerprint of GBM, but rather depend on selective accumulation of the photosensitiser inside tumour cells and their sensitivity to the effects, triggered by light. Here we report four new GICs obtained in Hospital Clinic Barcelona, HCB-GICs, to optimize preclinical studies of PDT, and to explore neoadjuvant protocols for a more effective PDT and photodiagnostic visualization. HCB-GIC cells express the known “stemness” markers Nestin and SOX2, Vimentin and CD44, contributing to invasiveness and to infiltrative ability within brain organoids, properties associated also to mesenchymal phenotype. HCB-GICs are susceptible to be treated with PDT, since the burden of cells into organoids decreased while increased cell death after irradiation. Moreover, we optimize an experimental in vivo model, able to assess the antitumoral effect of 5-ALA mediated PDT in engraftments of HCB-GICs co-cultures on the kidneys of high immunosupressed mice. In conclusion, we suggest that PDT might be an effective therapy to kill GICs with heterogeneous molecular fingerprint that achieve high levels of PPIX accumulation in tumor niche.
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.