Biology subjects

Taraballi, F.

Publications and source records attributed to Taraballi, F..

3 recordsLinked to original sources

bioRxiv2025

Mechanical Fingerprints in Breast Cancer Research: A Multimodal Experimental Approach

Breast cancer remains the leading cause of cancer-related mortality among women worldwide. Tumor biomechanics are not merely a symptom: they represent a functional signature with translational relevance in diagnostic, prognostic, and therapeutic resistance. Despite this, few experimental models are engineered to systematically investigate these physical properties across biological systems. Here, this study presents a multimodal biomechanical platform combining engineered 3D breast cancer spheroids with ex vivo tissue analysis to profiling and compare viscoelastic behavior or of healthy and tumoral environments. Rheometry and compression testing revealed a consistent mechanical shift in tumor-derived samples marked by increased stiffness and force-dependent nonlinear behavior, mirroring the ECM remodeling typical of aggressive phenotypes. This increased rigidity may adversely affect chemotherapy effectiveness by hindering drug delivery and altering cellular mechanotransduction. These biomechanical fingerprints enable quantitative discrimination between healthy and cancerous tissues and can serve as a surrogate maker of malignancy. By supporting the development of mechanics-informed diagnostic tools, our platform offers a reproducible, clinically relevant framework to integrate biomechanical screening into translational breast cancer pipelines. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=166 SRC="FIGDIR/small/680332v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@2c87a3org.highwire.dtl.DTLVardef@17cecc8org.highwire.dtl.DTLVardef@9d56d3org.highwire.dtl.DTLVardef@1af509a_HPS_FORMAT_FIGEXP M_FIG C_FIG Translational Impact StatementWe propose a multimodal experimental approach that combines in vitro 3D breast-cancer models and ex vivo tissue analysis to measure and compare the viscoelastic properties of healthy and malignant breast tissues. By using mechanical behaviour as a fingerprint, this framework discriminates tumour tissue from its healthy counterpart. Revealing how tumour stiffness impacts drug delivery and therapy resistance, the approach provides a clinically relevant tool to inform diagnosis and optimise treatment strategies.

bioengineering↗

bioRxiv2023

Sex-dependent improvement in traumatic brain injury outcomes after liposomal delivery of dexamethasone in mice.

Traumatic Brain Injury (TBI) can have long-lasting physical, emotional, and cognitive consequences due to the neurodegeneration caused by its robust inflammatory response. Despite advances in rehabilitation care, effective neuroprotective treatments for TBI patients are lacking. Furthermore, current drug delivery methods for TBI treatment are inefficient in targeting inflamed brain areas. To address this issue, we have developed a liposomal nanocarrier (Lipo) encapsulating dexamethasone (Dex), an agonist for the glucocorticoid receptor utilized to alleviate inflammation and swelling in various conditions. In vitro studies show that Lipo-Dex were well tolerated in human and murine neural cells. Lipo-Dex showed significant suppression of inflammatory cytokines, IL-6 and TNF-, release after induction of neural inflammation with lipopolysaccharide. Further, the Lipo-Dex were administered to young adult male and female C57BL/6 mice immediately after a controlled cortical impact injury. Our findings demonstrate that Lipo-Dex can selectively target the injured brain, thereby reducing lesion volume, cell death, astrogliosis, the release of proinflammatory cytokines, and microglial activation compared to Lipo-treated mice in a sex-dependent manner, showing a major impact only in male mice. This highlights the importance of considering sex as a crucial variable in developing and evaluating new nano-therapies for brain injury. These results suggest that Lipo-Dex administration may effectively treat acute TBI.

neuroscience↗

bioRxiv2022

Microparticle-delivered Cxcl9 delays the relapse of Braf inhibitor-treated melanoma

Patients with BRAF-mutant melanoma show significant responses to combined BRAF and MEK inhibition, but most relapse within 2 years. A major reservoir for drug resistance is minimal residual disease (MRD), comprised of drug-tolerant tumor cells laying in a dormant state. Towards exploiting potential therapeutic vulnerabilities of MRD, we established a genetically engineered mouse model of BrafV600E-driven melanoma MRD wherein genetic BrafV600E extinction leads to strong but incomplete tumor regression. Transcriptional time-course analysis after BrafV600E extinction revealed that after an initial surge of immune activation, tumors later became immunologically "cold" after MRD establishment. Computational analysis identified candidate T-cell recruiting chemokines that may be central players in the process, being strongly upregulated initially and steeply decreasing as the immune response faded. Therefore, we hypothesized that sustaining the chemokine signaling could impair MRD maintenance through increased recruitment of effector T-cells. We show that intratumoral administration of recombinant Cxcl9, either naked or loaded in microparticles, significantly impaired MRD relapse in BRAF-inhibited tumors, including several complete responses after microparticle-delivered rCxcl9 combined with BRAF and MEK-inhibition. Our experiments constitute a proof of concept that chemokine-based microparticle delivery systems are a potential strategy to forestall tumor relapse and thus improve the clinical success of frontline treatment methods.

cancer biology↗