Biology subjects

Catucci, M.

Publications and source records attributed to Catucci, M..

3 recordsLinked to original sources

bioRxiv2025

Establishing a Canine Urothelial Organoid Repository: A Platform for Comparative and Translational Carcinoma Studies

Despite the increasing number of treatment options for patients with muscle-invasive bladder Cancer (MIBC), many of these patients ultimately have a poor prognosis. Drug responses vary considerably among patients and in many who respond initially, drug resistance may ultimately develop leading to tumor progression. Scope for improvement has been limited by the phenotypic and molecular diversity of MIBC, which impacts the selection pressures of therapy. To address this translational gap, we describe the largest known canine urothelial carcinoma organoid bioarchive, with in-depth phenotypical and molecular characterization. Immunohistochemistry confirmed the expression of key biomarkers including UPKIII, E-cadherin, Vimentin, and Ki-67 in organoids. Single-nucleus RNA sequencing revealed cellular heterogeneity, while bulk RNA sequencing showed canine patient-to-patient variability in transcriptomic profiling. Bulk RNA sequencing also displayed highly similar expression profiles between tissue- and urine-derived organoids, as well as similarity to previously published human MIBC transcriptome data. Whole genome sequencing in a subset of patients further supported the overall genomic fidelity of the organoids with their tissue of origin. Finally, for proof-of-concept of usefulness for drug testing studies, organoid cytotoxicity to vinblastine was investigated in several organoid lines. These canine bladder cancer organoid lines can be thawed, expanded, and screened for response to potential novel therapeutics to expand personalized medicine approaches. In addition, the organoid lines can serve as a valuable resource for comparative bladder cancer research, and as a pre-clinical screening tool to identify efficacious drugs before taking them into canine clinical trials to support future human clinical trials.

cancer biology↗

bioRxiv2025

Frequency and Characterization of Rare Histologic Subtypes in Canine Invasive Urothelial Carcinoma

The histologic and molecular heterogeneity of human muscle-invasive bladder cancer (MIBC) is a major contributor to poor treatment outcomes. While most cases of MIBC are diagnosed as conventional urothelial carcinoma (UC), there is growing recognition of histologic subtypes and divergent differentiation within conventional UC. This is clinically significant, as some require modification of therapy and some are associated with more aggressive behavior. Spontaneously occurring UC in dogs has been shown to exhibit histologic and molecular features that closely resemble those of human MIBC. In this study, we evaluated 31 canine UC tumor samples for histologic subtypes and divergent differentiation. Slides were reviewed by a human uropathologist and three board-certified veterinary pathologists and assessed for expression of uroplakin III and E-cadherin. All tumors were classified as high-grade UC. Fifteen cases were identified as conventional UC. Among the remainder, eight displayed glandular differentiation, four were classified as sarcomatoid UC, two showed squamous differentiation, and one case each was classified as large nested and tubular and microcystic subtypes. In summary, this study found a higher frequency of certain histologic subtypes and divergent differentiation in canine UC--particularly sarcomatoid UC and UC with glandular differentiation--compared to previous reports in both canine UC and human MIBC. ConclusionThe relatively high prevalence of the sarcomatoid UC subtype in dogs observed in this study suggests that canine UC may serve as a valuable translational model for evaluating novel therapeutic agents, particularly for this rare and aggressive variant in humans.

pathology↗

bioRxiv2025

Development and Characterization of Chicken Lung Organoids for Future In Vitro Modeling of Avian Influenza Virus-Host Cell Interaction

High pathogenicity avian influenza viruses pose a growing threat to poultry, livestock, wildlife, and humans as they undergo accelerated expansion of host and geographical ranges. Since 2020, these viruses have driven a panzootic characterized by extensive viral diversification and spillover into species previously considered to be resistant to the disease. There is currently a lack of physiologically relevant in vitro models that can be used to screen the rapidly changing viral landscape. To address this need, we describe the first chicken lung organoids derived from adult stem cells of specific pathogen free White Leghorns. We analyze their gene expression with bulk RNA sequencing, confirm their cellular heterogeneity via single-nuclei RNA sequencing, and provide basic morphological characterization using hematoxylin and eosin staining, immunohistochemistry, immunofluorescence, and transmission electron microscopy. The results indicate that the organoids contained several cell types, including non-ciliated columnar, cuboidal, squamous, and mucin-producing cells, representative of different regions of the avian respiratory system. Furthermore, expression of genes relevant to influenza A virus infection and replication appeared to be conserved across different sample types. These organoids have the potential to effectively and efficiently model viral infection of the chicken lung, enabling the investigation of viral pathogenesis and evolutionary potential, virus-host interactions, and discovery of targets for antiviral treatments.

cell biology↗