A5054302048- Bladder and Urothelial Cancer Treatments
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- FOXO transcription factor regulation
- Urinary and Genital Oncology Studies
- Cancer, Hypoxia, and Metabolism
- Ferroptosis and cancer prognosis
- Immune Cell Function and Interaction
- Genetics and Neurodevelopmental Disorders
- Protein Degradation and Inhibitors
- Immune cells in cancer
Segeberger Kliniken
2021
UNC Lineberger Comprehensive Cancer Center
2021
University of North Carolina at Chapel Hill
2018-2020
Abstract High-grade urothelial cancer contains intrinsic molecular subtypes that exhibit differences in underlying tumor biology and can be divided into luminal-like basal-like subtypes. We describe here the first subtype-specific murine models of bladder show Upk3a-CreERT2; Trp53L/L; PtenL/L; Rosa26LSL-Luc (UPPL, luminal-like) BBN (basal-like) tumors are more faithful to human than widely used MB49 cells. Following engraftment immunocompetent C57BL/6 mice, were responsive PD-1 inhibition...
The transcription factor FOXM1 contributes to cell cycle progression and is significantly upregulated in basal-like breast cancer (BLBC). Despite its importance normal cycles, we lack a complete understanding of mechanisms that regulate FOXM1. We identified USP21 an RNAi-based screen for deubiquitinases control abundance. increases the stability FOXM1, binds deubiquitinates vivo vitro, indicating direct enzyme-substrate relationship. Depleting downregulates transcriptional network causes...
Although immune-checkpoint inhibitors (ICIs) have been a remarkable advancement in bladder cancer treatment, the response rate to single-agent ICIs remains suboptimal. There has substantial interest use of epigenetic agents enhance ICI efficacy, although precisely how these potentiate not fully elucidated. We identified entinostat, selective HDAC1/3 inhibitor, as potent antitumor agent our immune-competent mouse models (BBN963 and BBN966). demonstrate that entinostat selectively promoted...
<div>Abstract<p>High-grade urothelial cancer contains intrinsic molecular subtypes that exhibit differences in underlying tumor biology and can be divided into luminal-like basal-like subtypes. We describe here the first subtype-specific murine models of bladder show Upk3a-Cre<sup>ERT2</sup>; Trp53<sup>L/L</sup>; Pten<sup>L/L</sup>; Rosa26<sup>LSL-Luc</sup> (UPPL, luminal-like) BBN (basal-like) tumors are more faithful to human than...
<p>Supplemental Figure Legends</p>
<p>Supplemental Figure 1: Inactivation of Pten and Trp53 in Keratin 5 expressing cells does not result bladder cancer. Supplemental 2: Histologic features BBN induced tumors. 3: Generation KT normal urothelial comparison to MB49 3T3 cells. 4: Hierarchical clustering MB49, BBN963, UPPL1541 cell lines line derived 5: IPA Pathways enriched BBN963 versus 6: tumors are more mesenchymal than 7: Immune Gene Signatures correlation between tumor-infiltrating lymphocyte phenotype tumor size. 8:...
<p>Supplemental Figure Legends</p>
<p>Supplemental Figure 1: Inactivation of Pten and Trp53 in Keratin 5 expressing cells does not result bladder cancer. Supplemental 2: Histologic features BBN induced tumors. 3: Generation KT normal urothelial comparison to MB49 3T3 cells. 4: Hierarchical clustering MB49, BBN963, UPPL1541 cell lines line derived 5: IPA Pathways enriched BBN963 versus 6: tumors are more mesenchymal than 7: Immune Gene Signatures correlation between tumor-infiltrating lymphocyte phenotype tumor size. 8:...
<div>Abstract<p>High-grade urothelial cancer contains intrinsic molecular subtypes that exhibit differences in underlying tumor biology and can be divided into luminal-like basal-like subtypes. We describe here the first subtype-specific murine models of bladder show Upk3a-Cre<sup>ERT2</sup>; Trp53<sup>L/L</sup>; Pten<sup>L/L</sup>; Rosa26<sup>LSL-Luc</sup> (UPPL, luminal-like) BBN (basal-like) tumors are more faithful to human than...
Abstract In patients with bladder cancer, programmed death-ligand-1 (PD-L1) and death-1 (PD-1) inhibitors have been shown to be effective in around twenty percent of patients, there is evidence indicating that the level immune infiltration suppression within tumor microenvironment correlates response these treatments. We previously are intrinsic subtypes basal subtype characterized by high levels infiltration, luminal exclusion. Here we show treatment current standard care chemotherapeutic...
Abstract Aberrant chromatin remodeling by epigenetic modifier proteins such as histone deacetylases (HDACs) is common within many types of cancer, including muscle-invasive bladder cancer (MIBC). The removal acetyl groups from the lysine residues histones leads to transcriptional silencing that promotes tumor growth and potentially enhances cells' ability evade host immune response. Therefore, HDACs present themselves attractive targets for therapy. Histone deacetylase inhibitors (HDACi)...
Abstract Bladder cancer harbors a high frequency of somatic mutations that occur randomly across the genome. A fraction these can be expressed and processed into peptides called neoantigens. When presented on surface tumor cells by major histocompatibility complexes (MHC), neoantigens invoke an adaptive immune response. In general, neoantigen burden is associated with significant increase in overall survival. However, avoid detection silencing expression The post-translational acetylation...