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Biology subjects

Girmatsion, H.

Publications and source records attributed to Girmatsion, H..

2 recordsLinked to original sources

Longitudinally cultured precision cut lung slices as a predictive ex vivo model for lung cancer

Exploring alternatives to in vivo models, this study validates Precision Cut Lung Slices (PCLS) as a viable ex vivo platform for lung cancer research. We established the prolonged viability and structural preservation of PCLS, essential for accurate drug response studies. Using Paclitaxel as a benchmark drug and a therapeutically promising silver nanoparticles in combination with immunotherapy, we conducted a pioneering comparative analysis of its therapeutic effects on PCLS against traditional in vivo models. Results revealed that PCLS closely mimics in vivo responses, demonstrating comparable drug efficacy in tumor growth inhibition. This direct comparison not only confirms the utility of PCLS in simulating real-world outcomes but also emphasizes its potential in reducing animal testing. By providing a reliable, ethical, and efficient alternative for lung cancer studies, PCLS could significantly enhance preclinical research and drug development, marking a critical step towards more humane and representative scientific investigations.

cancer biology↗

Silver nanoparticle induced immunogenic cell death can improve immunotherapy

Cancer immunotherapy is often hindered by an immunosuppressive tumor microenvironment (TME). Various strategies are being evaluated to shift the TME from an immunologically cold to hot tumor and hereby improve current immune checkpoint blockades (ICB). One particular hot topic is the use of combination therapies. Here, we set out to screen a variety of metallic nanoparticles and explored their in-vitro toxicity against a series of tumor and non-tumor cell lines. For silver nanoparticles, we also explored the effects of core size and surface chemistry on cytotoxicity. Ag-citrate-5nm nanoparticles were found to induce high cytotoxicity in Renca cells through excessive generation of reactive oxygen species (ROS) and significantly increased cytokine production. The induced toxicity resulted in a shift of the immunogenic cell death (ICD) marker calreticulin to the cell surface in-vitro and in-vivo. Subcutaneous Renca tumors were treated with anti-PD1 or in combination with Ag-citrate-5nm. The combination group resulted in significant reduction in tumor size, increased necrosis, and immune cell infiltration at the tumor site. Inhibition of cytotoxic CD8+ T cells confirmed the involvement of these cells in the observed therapeutic effects. Our results suggest that Ag-citrate-5nm is able to promote immune cell influx and increase tumor responsiveness to ICB therapies.

cancer biology↗