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: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) 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: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: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: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:Retinoblastoma (RB) is an intraocular childhood tumor which, if left untreated, leads to blindness and mortality. Nucleolin (NCL) protein which is differentially expressed on the tumor cell surface, binds ligands and regulates carcinogenesis and angiogenesis. We found that NCL is over expressed in RB tumor tissues and cell lines compared to normal retina. We studied the effect of nucleolin-aptamer (NCL-APT) to reduce proliferation in RB tumor cells. Aptamer treatment on the RB cell lines (Y79 and WERI-Rb1) led to significant inhibition of cell proliferation. Locked nucleic acid (LNA) modified NCL-APT administered subcutaneously (s.c.) near tumor or intraperitoneally (i.p.) in Y79 xenografted nude mice resulted in 26 and 65% of tumor growth inhibition, respectively. Downregulation of inhibitor of apoptosis proteins, tumor miRNA-18a, altered serum cytokines, and serum miRNA-18a levels were observed upon NCL-APT treatment. Desorption electrospray ionization mass spectrometry (DESI MS)-based imaging of cell lines and tumor tissues revealed changes in phosphatidylcholines levels upon treatment. Thus, our study provides proof of concept illustrating NCL-APT-based targeted therapeutic strategy and use of DESI MS-based lipid imaging in monitoring therapeutic responses in RB.
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.