A5017944414- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Phagocytosis and Immune Regulation
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- Cell Image Analysis Techniques
- Cancer Cells and Metastasis
- Microtubule and mitosis dynamics
- Single-cell and spatial transcriptomics
- Ferroptosis and cancer prognosis
- Pancreatitis Pathology and Treatment
- Cancer-related Molecular Pathways
- Supramolecular Self-Assembly in Materials
- Nanoparticle-Based Drug Delivery
- Nanoplatforms for cancer theranostics
- Enzyme function and inhibition
- Mathematical Biology Tumor Growth
- Neuroendocrine Tumor Research Advances
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Pancreatic function and diabetes
- Chemical Reactions and Isotopes
- Immune cells in cancer
- 3D Printing in Biomedical Research
- Endoplasmic Reticulum Stress and Disease
The University of Texas MD Anderson Cancer Center
2015-2024
University of Florence
2013-2016
Istituto Nazionale di Fisica Nucleare, Sezione di Firenze
2016
Inflammation is a major risk factor for pancreatic ductal adenocarcinoma (PDAC). When occurring in the context of pancreatitis, KRAS mutations accelerate tumor development mouse models. We report that long after its complete resolution, transient inflammatory event primes epithelial cells to subsequent transformation by oncogenic KRAS. Upon recovery from acute inflammation, display an enduring adaptive response associated with sustained transcriptional and epigenetic reprogramming. Such...
// Corti Denise 1, 2, * , Paolo Paoli Maura Calvani 1 Maria Letizia Taddei Elisa Giannoni Scott Kopetz 2 Syed Mohammad Ali Kazmi Morelli Pia Piergiorgio Pettazzoni Elena Sacco 3 Anna Caselli Marco Vanoni Matteo Landriscina 4 Cirri Paola Chiarugi Department of Experimental and Clinical Biomedical Sciences, University Florence, Italy Genomic Medicine, The Texas MD Anderson Cancer Center, Houston, Texas, USA SYSBIO Centre for Systems Biology, Biotechnology Biosciences, Milano-Bicocca, Milano,...
Current treatment regimens for pancreatic ductal adenocarcinoma (PDAC) yield poor 5-year survival, emphasizing the critical need to identify druggable targets essential PDAC maintenance. We developed an unbiased and in vivo target discovery approach molecular vulnerabilities low-passage patient-derived xenografts or genetically engineered mouse model-derived allografts. Focusing on epigenetic regulators, we identified WDR5, a core member of COMPASS histone H3 Lys4 (H3K4) MLL (1-4)...
Adaptive drug-resistance mechanisms allow human tumors to evade treatment through selection and expansion of treatment-resistant clones. Here, studying clonal evolution tumor cells derived from pancreatic tumors, we demonstrate that in vitro cultures vivo are maintained by a common set tumorigenic can be used establish replica (CRTs), large cohorts animals bearing with identical composition. Using CRTs conduct quantitative assessments adaptive responses therapeutics, uncovered multitude...
Abstract Mutated KRAS (KRAS*) is a fundamental driver in the majority of pancreatic ductal adenocarcinomas (PDAC). Using an inducible mouse model KRAS*-driven PDAC, we compared KRAS* genetic extinction with pharmacologic inhibition MEK1 tumor spheres and vivo. ablation blocked proliferation induced apoptosis, whereas exerted cytostatic effects. Proteomic analysis evidenced that was accompanied by sustained activation PI3K–AKT–MTOR pathway AXL, PDGFRa, HER1–2 receptor tyrosine kinases (RTK)...
Tumors represent ecosystems where subclones compete during tumor growth. While extensively investigated, a comprehensive picture of the interplay clonal lineages dissemination is still lacking. Using patient-derived pancreatic cancer cells, we created orthotopically implanted replica tumors to trace dynamics unperturbed expansion and dissemination. This model revealed multifaceted nature growth, with rapid changes in fitness leading continuous reshuffling architecture alternating dominance...
An efficient drug delivery system through a straightforward approach to multi-walled carbon nanotube decoration.
Solid tumors are composed of both cancer cells and various types accessory cells, mainly fibroblasts, that collectively compose the so called tumor-microenvironment. Cancer-associated fibroblasts have been described to actively participate in progression by establishing a cytokine-mediated as well metabolic crosstalk with cells. In present paper we show activated human able boost tumor proliferation this effect is greatly dependent on stromal carbonic anhydrase IX (CA IX) activity. fact...
Abstract Pancreatic ductal adenocarcinoma (PDAC) continues to have a poor prognosis despite new drugs advancing the clinic. We recently characterized population of cells able survive genetic and pharmacologic extinction oncogenic pathways demonstrated that surviving (SC) are tumor stem (CSC) remain in quiescent state for months before relapsing. In-depth transcriptomics metabolomics analyses revealed SCs exhibit different metabolic features compared bulk cells. Specifically, SC relied on...
<div>Abstract<p>Mutated KRAS (KRAS*) is a fundamental driver in the majority of pancreatic ductal adenocarcinomas (PDAC). Using an inducible mouse model KRAS*-driven PDAC, we compared KRAS* genetic extinction with pharmacologic inhibition MEK1 tumor spheres and <i>in vivo</i>. ablation blocked proliferation induced apoptosis, whereas exerted cytostatic effects. Proteomic analysis evidenced that was accompanied by sustained activation PI3K–AKT–MTOR pathway AXL, PDGFRa,...
<div>Abstract<p>Mutated KRAS (KRAS*) is a fundamental driver in the majority of pancreatic ductal adenocarcinomas (PDAC). Using an inducible mouse model KRAS*-driven PDAC, we compared KRAS* genetic extinction with pharmacologic inhibition MEK1 tumor spheres and <i>in vivo</i>. ablation blocked proliferation induced apoptosis, whereas exerted cytostatic effects. Proteomic analysis evidenced that was accompanied by sustained activation PI3K–AKT–MTOR pathway AXL, PDGFRa,...
<p>supplementary Figures S1-S10. S1 growth and regression of iKRAS tumors. S2 culture comparison. S3 immunohistochemistry p-erk p-s6 S4 Phospho rtk array S5 Validation anti AXL antibodies S6 validationn the inhibitor in vitro S7 vivo S8 efficacy targeting S9 RTK cells treated with multiple inhibitors S10 P-ERK levels</p>
<p>supplementary material and method</p>
<p>supplementary Figures S1-S10. S1 growth and regression of iKRAS tumors. S2 culture comparison. S3 immunohistochemistry p-erk p-s6 S4 Phospho rtk array S5 Validation anti AXL antibodies S6 validationn the inhibitor in vitro S7 vivo S8 efficacy targeting S9 RTK cells treated with multiple inhibitors S10 P-ERK levels</p>
<p>supplementary material and method</p>
Abstract Tumor evolution and adaptation, especially in response to therapy, are well-established concepts clinical oncology a major causes of treatment failure. The inability current experimental models, including genetically engineered mouse inform on the breadth functional heterogeneity within human tumors has substantially limited our understanding tumor architecture under perturbations such as pharmacologic treatments with profound negative impact cancer drug discovery research, where...
Abstract Tumors are comprised of heterogenous populations tumor cells that rely on both glycolysis and oxidative phosphorylation (OXPHOS) for bioenergy synthetic processes in support cell proliferation. Over the past few years, we others have reported there is a subpopulation tumors resistant to standard care treatment or targeted therapies, these so-called persistent possess stem like properties. Of note, elevated levels mitochondria dependent OXPHOS survival. We previously disclosed...
Abstract Intrinsic and adaptive drug-resistance mechanisms allow human tumors to evade treatment through the demonstrated expansion of treatment-resistant clones. Thus, are complex, dynamic ecosystems wherein populations cells harboring both founder clones unique, subclonal mutations coexist progressively evolve. Modeling this functional heterogeneity can uncover critical contributions distinct tumor cell sub-populations toward identifying rational drug combinations. Here, studying clonal...
Abstract A major barrier to achieving durable remission and definitive cure in oncology patients is the emergence of tumor resistance, a common outcome different disease types independent from therapeutic approach undertaken. Patients with pancreatic ductal adenocarcinoma (PDAC) continue have poor prognosis despite concerted efforts advance new drugs clinic. One reason for this, PDAC other tumors, that tumors are constantly adapting evolving response external perturbations. To better...
Adaptive drug-resistance mechanisms allow human tumors to evade treatment through selection and expansion of treatment-resistant clones. Modeling the functional heterogeneity can unmask critical contributions distinct tumor cell sub-populations toward identifying rational drug combinations. Here, studying clonal evolution cells derived from pancreatic tumors, we demonstrate that in vitro adherent cultures vivo are maintained by a common set long term self-renewing tumorigenic be used...
Abstract Adaptive drug-resistance mechanisms allow human tumors to evade treatment through selection and expansion of treatment-resistant clones. Modeling the functional heterogeneity can unmask critical contributions distinct tumor cell sub-populations toward identifying rational drug combinations. Here, studying clonal evolution cells derived from pancreatic tumors, we demonstrate that in vitro adherent cultures vivo are maintained by a common set long term self-renewing tumorigenic be...