Project description:A subset of T-ALL/T-LBL patients is characterized by overexpression of the oncogenic Serine/Threonine kinase PIM1. Mechanisms for PIM1 overexpression are translocations involving the TCRb and PIM1 loci, JAK/STAT activating mutations and responsiveness to cytokinens in the tumor microenvironment, such as IL7. In this study, we generated a TLX3+ JAKwt/STATwt IL7 responsive T-ALL PDX model using NSG mice. Splenocytes were ex vivo treated with the PIM inhibitor PIM447 and QuantSeq 3’ mRNA sequencing was performed, in order to elucidate the transcriptional effects and molecular mechanisms by which PIM447 induces apoptosis in T-ALL PDX cells.
Project description:We have previously shown that fed-batch processes with the longest uncoupling phase (ethanol adapted) were characterized by induction of storage carbohydrates, a metabolic event typical of yeast cells experiencing nutrient limitation, at the onset of this phase, whereas this metabolic event was not seen in processes with a short uncoupling phase (ethanol non adapted culture). Taken together, our results suggested that reproducible high bioethanol performance in aerated fed-batch process may be linked to the ability of yeast cells to impede ethanol toxicity by triggering a metabolic remodelling reminiscent to that of cells entering a quiescent G0/G1 state. The aim of this study was to search for genes implicated in the induction an ethanol adapted culture vs ethanol non-adapted culture. We measure the changes in the gene expression of Ethanol adapted culture (Test : fermentation I in ref 17005001[PMID]) and Ethanol non-adapted (reference : Fermentation II in ref 17005001[PMID]) at the same ethanol concentration of 60 g/l and the same growth rate of the cells (0,14 h-1 :Test) and (0,13 h-1 : reference) to reduce the risk of observing secondary effects due to growth and ethanol stress. For each sample, total RNAs from one yeast culture (no biological replicate) were extracted four times (technical replicates -extract). For labelling, we employed a dye-switch (dCTP-Cy3 and dCTP-Cy5) repeated 2 times and hybridized cDNA on four independent microarrays, given rise to eight data value per gene (each gene is duplicate on the slide).
Project description:Muscle pre-injury is commonly used prior to cell transplantation to enhance engraftment and to further promote homing of injected cells to diseased muscles. To better understand the changes that occurred in the diaphragm upon swimming (1hour/day for 2 weeks), we analyzed global changes using RNA-Seq in dystrophic FKRPP448L-NSG mice as well as in NSG control mice.
Project description:The BCBC Promoter Chip 5B was used to identify genomic targets of Pdx-1 binding. Genomic DNA from mouse NIT-1 insulinoma cells was immunoprecipitated with a Pdx-1 Antibody, PCR amplified, and labeled to the chip. All hybridizations were versus a common reference sample which was a labeled IgG IP. Additionally a Pdx1 SACO library for NIT-1 cells was generated.
Project description:To induce leukemia in NOD/SCID/γc−/− (NSG) mice, we injected 10^5 human B-ALL cells, into the tail vein of non-irradiated mice. Two different PDX mice models were studied (PDX-1; #1 and PDX-2; #2). The InVivoMAb anti-human CD40 antibody (BE0189, clone G28.5, BioXCell) was i.v. administrated (CD40) at the dose of 1 mg/kg, the same was done with the recommended isotype (Ig) (BE0083, MOPC-21, BioXCell). We administrated antibodies, at days 15 and 25. At day 35, when mice developed leukemia, B-ALL cells were purified from the BM of PDX-mice, with magnetic beads-conjugated to human CD45 antibodies. Three mice per condition were tested (replicat 1 to 3; mice m1 to m3).
Project description:Testicular cancer (TC) is the most common solid tumour in young men. While cisplatin-based chemotherapy is highly effective in TC patients, chemoresistance still accounts for 10% of disease-related deaths. Pre-clinical models that faithfully reflect patient tumours are needed to assist in target discovery and drug development. Tumour pieces from eight TC patients were subcutaneously implanted in NOD scid gamma (NSG) mice. Three patient-derived xenograft (PDX) models of TC, including one chemoresistant model, were established containing yolk sac tumour and teratoma components. Whole-exome sequencing, copy number variation analysis and RNA-sequencing was performed on these TP53 wild type PDX tumours to assess the effects of passaging, showing high concordance of molecular features between passages.
Project description:Testicular cancer (TC) is the most common solid tumour in young men. While cisplatin-based chemotherapy is highly effective in TC patients, chemoresistance still accounts for 10% of disease-related deaths. Pre-clinical models that faithfully reflect patient tumours are needed to assist in target discovery and drug development. Tumour pieces from eight TC patients were subcutaneously implanted in NOD scid gamma (NSG) mice. Three patient-derived xenograft (PDX) models of TC, including one chemoresistant model, were established containing yolk sac tumour and teratoma components. Whole-exome sequencing, copy number variation analysis and RNA-sequencing was performed on these TP53 wild type PDX tumours to assess the effects of passaging, showing high concordance of molecular features between passages.