Biology subjects

Tirinato, L.

Publications and source records attributed to Tirinato, L..

4 recordsLinked to original sources

bioRxiv2026

Correlation of OCT-Based Radiomic Signatures With Dose-Associated Radiation Response in Tumor Spheroids

BackgroundThree-dimensional tumor spheroids are an established radiobiology model, but scalable, reproducible readouts of dose-dependent radiation response are lacking. We evaluated whether optical coherence tomography (OCT) radiomics can quantify dose-associated response in spheroids, and how it compares with conventional brightfield morphology. MethodsThis in vitro, cross-sectional study used SAS oral squamous cell carcinoma spheroids seeded at two densities (5000 and 10000 cells), irradiated at 0 to 12 Gy, and imaged on days 1 to 11 post-irradiation. Each OCT acquisition yielded co-registered structural-intensity and speckle-variance volumes. Radiomic features (shape, first-order, texture) were extracted with Radiomics.jl, filtered for repeatability, correlation-pruned, and ensemble-ranked. Dose correlation was assessed by repeated 5-fold cross-validation across five regressors, comparing brightfield-only (BF), OCT-only, and combined OCT+BF feature sets with paired Wilcoxon tests. ResultsOCT-only models consistently outperformed the BF baseline (median R2 0.77 to 0.85 versus 0.61 to 0.69; p < 0.001 for all regressors). Adding brightfield to OCT gave no consistent benefit, reaching significance only for Random Forest (p = 0.026, power 0.62). A compact shared feature subset combined brightfield area dynamics with OCT texture, shape, and speckle-variance descriptors, all showing low repeat-scan variability relative to cohort variability. ConclusionsOCT radiomics provides a sensitive, reproducible, label-free high-throughput readout of spheroid radiation dose response that outperforms the current brightfield-based approach, without requiring concurrent brightfield acquisition. Key pointsO_LIOCT radiomics quantifies dose-dependent radiation response in 3D tumor spheroids. C_LIO_LIOCT-only models outperformed brightfield imaging in radiation dose prediction. C_LIO_LISelected radiomic features showed high repeatability across repeated acquisitions. C_LIO_LIAdding brightfield to OCT gave no consistent performance benefit. C_LIO_LILabel-free OCT enables reproducible, high-throughput spheroid radiation-response assessment. C_LI

cancer biology↗

bioRxiv2024

A post-mitotic in vitro murine as a model of muscle damage and repair

Sarcopenia is a degenerative condition characterized by the atrophy and functional decline of myofibers, resulting in disability. While the clinical risk factors are known, there is no validated in vitro model to understand the molecular mechanisms and identify therapeutics. To tackle this challenge, we generated an in vitro post-mitotic muscular system by differentiating mouse myoblast cells, namely C2C12. After 12 days of differentiation, cells were expressing physiological markers of myotubes and became self-contracting. Importantly, transcriptomic analyses demonstrated high similarity (r=0.70) when compared to primary human myotubes (HSkMC) providing evidence of resemblance to human cells. Next, we starved and incubated cells with dexamethasone and observed myotube shrinkage, oxidative stress, modification of anabolic, inflammatory, and catabolic markers recapitulating sarcopenia. Conversely, cell refeeding resulted in a recovery in the model with nutrient deprivation but not when incubated also with dexamethasone. In conclusion, we present a model of sarcopenia due to nutrient deprivation and corticosteroids. This model may allow more efficient and effective future research to identify therapeutics against sarcopenia in humans.

cell biology↗

bioRxiv2022

Lipid Droplets Fuel Small Extracellular Vesicle Biogenesis

Despite an increasing gain of knowledge regarding small extracellular vesicle (sEV) composition and functions in cell-cell communication, the mechanism behind their biogenesis remains unclear. Here, we revealed for the first time that the sEV biogenesis and release into the microenvironment are tightly connected with another important organelle: Lipid Droplets (LD). We have observed this correlation using different human cancer cell lines as well as patient-derived colorectal cancer stem cells (CR-CSCs). Our results showed that the use of external stimuli such as radiation, pH, hypoxia, or lipid interfering drugs, known to affect the LD content, had a similar effect in terms of sEV secretion. Additional validations were brought using multiple omics data, at the mRNA and protein levels. Altogether, the possibility to fine-tune sEV biogenesis by targeting LDs, could have a massive impact on the amount, the cargos and the properties of those sEVs, paving the way for new clinical perspectives. Significance Statement

cancer biology↗

bioRxiv2021

Lipid Droplets and Ferritin Heavy Chain: a Devilish Liaison in Cancer Radioresistance

Although much progress has been made in cancer treatment, the molecular mechanisms underlying cancer radioresistance (RR) as well as the biological characteristic of radioresistant cancer cells still need to be clarified. In this regard, we discovered that breast, bladder, lung, neuroglioma and prostate 6 Gy X-ray resistant cells were characterized by an increase of Lipid Droplet (LD) number and that the cells containing highest LDs showed the highest clonogenic potential after irradiation. Moreover, we observed that LD content was tightly connected with the iron metabolism and in particular with the presence of the ferritin heavy chain (FTH1). In fact, breast and lung cancer cells silenced for the FTH1 gene showed a reduction in the LD numbers and, by consequence, became radiosensitive. FTH1 restoration as well as iron-chelating treatment by Deferoxamine were able to restore the LD amount and RR. Overall, these results provide evidence of a novel molecular mechanism behind RR in which LDs and FTH1 are tightly connected to each other, a synergistic effect which might be worth deeply investigating in order to make cancer cells more radiosensitive and improve the efficacy of radiation treatments.

cancer biology↗