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GU 16-257: Neoadjuvant gemcitabine, cisplatin, plus nivolumab in patients with muscle- invasive bladder cancer with selective bladder sparing: CIMACC-CIDC (Cohort 1)

ABSTRACT: GU 16-257: Neoadjuvant gemcitabine, cisplatin, plus nivolumab in patients with muscle- invasive bladder cancer with selective bladder sparing: CIMACC-CIDC (Cohort 1)

PROVIDER: PRJNA1001525 | ENA |

REPOSITORIES: ENA

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GU 16-257: Neoadjuvant gemcitabine, cisplatin, plus nivolumab in patients with muscle- invasive bladder cancer with selective bladder sparing: CIMACC-CIDC (Cohort 1)

Project description:GU 16-257: Neoadjuvant gemcitabine, cisplatin, plus nivolumab in patients with muscle- invasive bladder cancer with selective bladder sparing: CIMACC-CIDC (Cohort 1)

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Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer

Project description:Background: Bladder-sparing trimodality therapy (TMT) is an alternative to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC), and biomarkers to inform therapy selection are needed. Objective: To evaluate immune and stromal signatures in MIBC treated with TMT.

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Human - murine concordance of molecular signatures in nerve-sparing murine partial bladder outlet obstruction (NeMO)

Project description:Recently, we described a nerve-sparing mid-urethra model of partial outlet obstruction (NeMO) that has high consistency and minimal mortalities, unlike the traditional model of obstruction proximal to the bladder neck. To uncover pathogenic pathways in PBO, we performed NeMO and examined the transcriptional responses in the bladder. NeMO increased bladder mass, relative bladder mass, hyperactivity and decreased voiding efficiency. In NeMO vs. sham bladders, there were 831 differentially expressed genes, which correlated significantly with physiologic parameters. Of the 796 genes mapped to human orthologues, upregulated genes were enriched for functions related to extracellular matrix, and cytokine activation, and downregulated genes were enriched for functions relating to muscle contraction and metabolism. To identify candidate drug targets for the treatment of PBO, we analysed the conserved transcriptional response to PBO in human and mouse. Gene sets related to cytokine activation, including the TNF pathway, were consistently upregulated in both human and mouse bladders affected by obstruction, revealing a potential therapeutic target. Accordingly, we depleted macrophages, which are an important source of TNF, with clodronate (CL). In NeMO, CL significantly decreased hyperactive voiding, residual volumes and improved voiding efficiency (p<0.05). Moreover, the expression levels of cytokines/chemokines correlated with several bladder functional parameters. Thus, genes that control progression of pathology in bladder obstruction are consistently dysregulated in NeMO and human bladders affected by PBO, supporting the use of the nerve-sparing mouse obstruction model for therapeutic exploration.

2022-07-27 | GSE209625 | GEO

Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer

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