Publications by authors named "J E Guidotti"

Benign prostate hyperplasia (BPH) is caused by the nonmalignant enlargement of the transition zone of the prostate gland, leading to lower urinary tract symptoms. Although current medical treatments are unsatisfactory in many patients, the limited understanding of the mechanisms driving disease progression prevents the development of alternative therapeutic strategies. The probasin-prolactin (Pb-PRL) transgenic mouse recapitulates many histopathological features of human BPH.

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Inhibition of androgen signaling is the gold standard treatment of benign prostate hyperplasia and prostate cancer. Despite the initial response to these treatments, therapeutic resistance is ultimately observed in most patients. Single cell RNAseq studies have shown that castration-tolerant luminal cells share several molecular and functional features with cells identified as luminal progenitor in physiological conditions.

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The molecular and cellular mechanisms that drive castration-resistant prostate cancer (CRPC) remain poorly understood. LSC cells defines an FACS-enriched population of castration-tolerant luminal progenitor cells that has been proposed to promote tumorigenesis and CRPC in -deficient mice. The goals of this study were to assess the relevance of LSC cells through the analysis of their molecular proximity with luminal progenitor-like cell clusters identified by single-cell (sc)RNA-seq analyses of mouse and human prostates, and to investigate their regulation by in silico-predicted growth factors present in the prostatic microenvironment.

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Article Synopsis
  • New predictive biomarkers, like Keratin-7 (KRT7), are important for assessing metastasis-free survival (MFS) and cancer-specific survival (CSS) in localized prostate cancer (PC).
  • KRT7 was evaluated using various methods on prostatic cell lines and human tissue samples, revealing its presence in healthy and benign tissues but loss in tumor cells.
  • High KRT7 expression in benign glands is linked to improved MFS and CSS, suggesting its potential as a prognostic marker, although further validation is needed with larger patient groups.
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Stem and progenitor cells of the adult prostate epithelium have historically been believed to reside mainly or exclusively within the basal cell compartment and to possess basal-like phenotypic characteristics. Within the past decade, evidence of the existence of luminal epithelial cells exhibiting stem/progenitor properties has been obtained by lineage tracing and by functional characterization of sorted luminal-like cells. In 2020, the boom of single-cell transcriptomics led to increasingly exhaustive profiling of putative mouse luminal progenitor cells and, importantly, to the identification of cognate cells in the human prostate.

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