Combined anti-C1-INH and Radiotherapy against Glioblastoma
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ABSTRACT: Animals with intracranial glioblastoma of the NS1 cells line were treated with anti-C1-INH +/- radiotherapy or were untreated control animals.
Project description:Gliomas are mostly incurable secondary to their diffuse infiltrative nature. Thus, specific therapeutic targeting of invasive glioma cells is an attractive concept. As cells exit the tumor mass and infiltrate brain parenchyma, they closely interact with a changing micro-environmental landscape that sustains tumor cell invasion. In this study, we used a unique microarray profiling approach on a human glioma stem cell (GSC) xenograft model to explore gene expression changes in situ in invading glioma cells compared to tumor core, as well as changes in host cells residing within the infiltrated microenvironment relative to the unaffected cortex. Replicate sets of mice (n=4) were inoculated with either of two different GSC's derived from from human glioma, and each mouse had samples taken from the tumor mass, the infiltrating area and the mouse brain parenchyma, resulting in 3 samples per animal. The tumor mass and infiltrating samples were hybridized on human U133Plus2 Arrays, whereas the infiltrating samples and mouse brain parenchyma were hybridized on mouse
Project description:Neuroblastoma (NB) is a pediatric cancer characterized by significant heterogeneity and poor prognosis, particularly in high-risk cases with MYCN amplification. Understanding the molecular response of neuroblastoma to different treatments can provide valuable insights into potential therapeutic strategies. This experiment assessed the in vivo response to treatment with BAY390 and A967079. A neuroblastoma in vivo model was established via subcutaneous injection of human high-risk, MYCN-amplified neuroblastoma organoids into female NSG mice (PDX, LU-NB-3R). Once tumors reached 150 mm³, mice were randomized into treatment groups: control (n=8), A967079 (n=6), and BAY390 (n=7). All drugs were administered via oral gavage at the following concentrations: A967079 (300 mg/kg, once daily) or BAY390 (90 mg/kg, once daily), with a vehicle control group. Treatment was administered for 21 days, after which mice were euthanized. Tumor samples were collected in RNA later and frozen at -80 °C until RNA extraction. RNA was extracted from tumor tissue, and RNA sequencing was performed.
Project description:The experiment was designed to achieve Cre recombinase mediated deletion of Id1, Id2 and Id3 in a temporally controlled fashion in tumor cells of Id1, Id2, Id3 floxed mice with the aim of comparing the gene expression profiles of Id expressing versus Id deleted tumors.
Project description:In hemochorial placentation, trophoblast stem cells differentiate into multiple lineages to aquire specific functions, such as invasive and endocrine phenotype. FOSL1 has been identified as a key regulator for trophoblast differentiation. We used microarray to detail mechanisms underlying FOSL1 signaling pathway in trophoblast differentiation. 3 replicates of differentiated Rcho1 TS cells expressing control shRNA; 3 replicates of differentiated Rcho1 TS cells expressing Fosl1 shRNA
Project description:T cells (all CD4 or Treg) measured by RNA-seq, infected or not-infected by N.brasiliensis, across different tissues, with or without CD4-Cre RORA KO. Several different cohorts were analyzed, either as a time course (TC), two rounds of analyzing WT vs RORA KO differences (oldko and newko), and a comparison of CD4+Foxp3+ Tregs specifically (tregkovswt)
Project description:To determine the roles of oncogenic EGFR signaling in gliomagenesis and tumor maintenance, we generated a novel glioma mouse model driven by inducible expression of a mutant EGFR (EGFR*). Genetic suppression of EGFR* induction led to significant tumor regression and prolonged survival. But in spite of the initial response, the tumors relapsed invariably and propagated independent of EGFR*. We used microarrys to directly compare geen expression of control and relapse tumors and identified gene sets specifically activated in relapse tumors. Control and relasped glioma samples upon mutant EGFR extinction were selected for RNA extraction and hybridization on Affymetrix microarrays.
Project description:Understanding MoA of ceralasertib (AZD6738) in driving efficacy through immune regulation via T-cells and tumour intrinsic pathways (STING/IFN) for AZD6738 driven efficacy.
Project description:We found the reality that each Coomassie blue-stained 2D gel spot contained lots of protein species in analysis of in tissue proteome.
Project description:KRAS mutations frequently co-occur with alterations in STK11/LKB1 and/or KEAP1, defining an aggressive subset of tumors associated with resistance to immuno- and chemotherapy. While LKB1 loss is associated with vulnerability to DNA-damage response (DDR)-based therapies, the impact of KEAP1 alterations remains unknown. Here we demonstrate that KEAP1/NRF2 pathway drives a compensatory modulation of ATR-CHK1 signaling, enhancing vulnerability to ATR inhibitors (ATRi) particularly in the setting of increased replication stress associated with LKB1 loss. ATRis show enhanced anti-tumor activity in LKB1 and/or KEAP1-deficient NSCLC models and synergy combined with gemcitabine. ATRi also enhances antitumor immunity and helps mitigate the immunosuppressed phenotype of LKB1 and/or KEAP1-deficient tumors. Finally, in the HUDSON trial, LKB1/KEAP1-deficient NSCLC patients demonstrate enhanced benefits to the ATRi ceralasertib plus durvalumab. These findings suggest that alterations in the KEAP1/NRF2 pathway and/or LKB1 are associated with enhanced sensitivity to ATRi and could serve as useful biomarkers for predicting response to ATRi combination regimens.