A5018841312- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Cancer Cells and Metastasis
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Single-cell and spatial transcriptomics
- Phagocytosis and Immune Regulation
- Ovarian cancer diagnosis and treatment
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Circular RNAs in diseases
- Ubiquitin and proteasome pathways
- DNA Repair Mechanisms
- Chromatin Remodeling and Cancer
- Cancer Mechanisms and Therapy
- Kruppel-like factors research
- Galectins and Cancer Biology
- Cancer-related gene regulation
- Immune responses and vaccinations
- Proteoglycans and glycosaminoglycans research
- interferon and immune responses
Centro di Riferimento Oncologico
2016-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2018-2025
The University of Texas MD Anderson Cancer Center
2020-2025
Scripps MD Anderson Cancer Center
2024
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...
While pancreatic ductal adenocarcinomas (PDACs) are addicted to KRAS-activating mutations, inhibitors of downstream KRAS effectors, such as the MEK1/2 kinase inhibitor trametinib, devoid therapeutic effects. However, extensive rewiring regulatory circuits driven by attenuation pathway may induce vulnerabilities relevance. An in-depth molecular analysis transcriptional and epigenomic alterations occurring in PDAC cells initial hours after inhibition trametinib unveiled induction endogenous...
miR-223 is an anti-inflammatory miRNA that in cancer acts either as oncosuppressor or oncopromoter, a context-dependent manner. In breast cancer, we demonstrated it dampens the activation of EGF pathway. However, little known on role during onset and progression. expression was decreased luminal HER2 subtypes inversely correlated with patients' prognosis. normal mammary epithelial cells, acted cell autonomously control their growth morphology three-dimensional context. MMTV-Δ16HER2...
Abstract Molecular routes to metastatic dissemination are critical determinants of aggressive cancers. Through in vivo CRISPR–Cas9 genome editing, we generated somatic mosaic genetically engineered models that faithfully recapitulate renal tumors. Disruption 9p21 locus is an evolutionary driver systemic disease through the rapid acquisition complex karyotypes cancer cells. Cross-species analysis revealed recurrent patterns copy number variations, including 21q loss and dysregulation...
In breast cancer (BC) patients, local recurrences often arise in proximity of the surgical scar, suggesting that response to surgery may have a causative role. Radiotherapy (RT) after lumpectomy significantly reduces risk recurrence. We investigated direct effects and RT delivered intraoperatively (IORT), by collecting irradiated non-irradiated tissues from BC tumor removal. These tissue specimens been profiled for their microRNA (miR) expression, search differentially expressed miR among...
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...
Purpose: Head and neck squamous cell carcinomas (HNSCCs) cause more than 300,000 deaths worldwide each year. Locoregional distant recurrences represent worse prognostic events accepted surrogate markers of patients' overall survival. No valid biomarker salvage therapy exist to identify treat patients at high-risk recurrence. We aimed verify if selected miRNAs could be used as biomarkers recurrence in HNSCC.Experimental Design: A NanoString array was associated with locoregional 44 HNSCC....
Breast cancer ranks as the most prevalent form of globally. Currently, advanced screening methods have significantly improved early detection rates. These achievements led to more non-invasive diagnoses and underscored clinical relevance precursor lesions like flat epithelial atypia (FEA), a histological condition characterized by mild atypical changes in normal epithelium lining mammary ducts. Despite increasing FEA biopsy, our understanding biological behavior this entity remains limited...
DNA replication stress responses are key genomic stability guardians critical during development, aging, hematopoiesis, disease suppression and cancer therapy response. Reversed forks (RF) form at stalled as a distinct four-way structure to protect against formation exposure toxic lesions. So far, prevailing methods measure RFs involve specialized electron microscopy precluding studies within their cellular context. Here we describe an in-situ method quantitatively by harnessing intrinsic...
Epithelial Ovarian Cancer (EOC) is the most lethal gynecological cancer in developed countries, and development of new strategies to overcome chemoresistance an awaited clinical need. Angiogenesis, blood vessels from pre-existing vasculature, has been validated as a therapeutic target this tumor type. The aim study verify if EOC cells with acquired resistance platinum (PT) treatment display altered angiogenic potential. Using proteomic approach, we identified tissue inhibitor...
Genomic instability represents a typical feature of aggressive cancers. Normal cells have evolved intricate responses to preserve genomic integrity in response stress, such as DNA damage induced by γ-irradiation. Cyclin-dependent kinases (CDKs) take crucial part these safeguard mechanisms, but involvement CDK-inhibitors, p27Kip1, is less clear. We generated immortalized fibroblasts from p27kip1 knock-out (KO) mouse embryos and re-expressed WT, or its mutant forms, identify the function...
Postnatal development of the mammary gland relies on maintenance oriented cell division and apicobasal polarity, both which are often deregulated in cancer. The microtubule (MT) network contributes to control these processes; however, very little is known about impact altered MT dynamics a complex organ role played by MT-interacting proteins such as stathmin. In this study, we report that female stathmin knock-out (STM KO) mice unable nurse their litters due frank impairment development....
Repositioning of clinically approved drugs that may reduce the severity, hospitalization events, and time recovery from SARS-CoV2 infection is a global health priority. Clinical reports drug effects lung pathology are providing insight into pathogenesis Covid-19, comparison these findings with our knowledge severe acute respiratory syndrome (SARS) Middle East (MERS) can be used to develop rational hypotheses prioritize clinical studies available therapeutics. Recently, Cao colleagues [[1]Cao...
Abstract It is unclear how cells counteract the potentially harmful effects of uncoordinated DNA replication in context oncogenic stress. Here, we identify WRAD (WDR5/RBBP5/ASH2L/DPY30) core as a modulator pancreatic ductal adenocarcinoma (PDAC) models. Molecular analyses demonstrated that interacts with replisome complex, disruption DPY30 resulting re-replication, damage, and chromosomal instability (CIN) without affecting cancer cell proliferation. Consequently, immunocompetent models,...
Abstract The CDKN1B gene, encoding for the CDK inhibitor p27 kip1 , is mutated in defined human cancer subtypes, including breast, prostate carcinomas and small intestine neuroendocrine tumors. Lessons learned from tumors suggest that mutations could be subclonal, raising question of whether a deeper sequencing approach lead to identification higher numbers patients with mutations. Here, we addressed this analyzed biopsies breast ( n = 396), ovarian 110) head neck squamous carcinoma 202)...
The p27kip1 protein, mainly known as a negative regulator of cell proliferation, has also been involved in the control other cellular processes, including regulation cytoskeleton dynamics. Notably, these two functions involve distinct protein domains, residing N- and C-terminal halves, respectively. In last decades, reported to interact with microtubule acto-myosin cytoskeletons, both direct indirect ways, overall drawing picture which several factors play their role either synergy or...
Epithelial ovarian cancer (EOC) is a rare, highly lethal disease. In subset of high grade EOC patients, maintenance therapy with the antiangiogenic drug Bevacizumab (BEV) valuable option. To date, no validated predictive or prognostic biomarkers exist for selecting patients that might benefit from BEV treatment.Immunohistochemistry and RT-qPCR evaluated expression seven angiogenesis-related proteins twelve microRNAs angio-signature in treated first line chemotherapy plus (MITO16A/ManGO OV-2...
Abstract Mesenchymal plasticity has been extensively described in advanced and metastatic epithelial cancers; however, its functional role malignant progression, dissemination therapy response is controversial. More importantly, the of mesenchymal transition (EMT) cell tumor heterogeneity, clonal selection evolution poorly understood. Functionally, our work clarifies contribution EMT to progression metastasis pancreatic cancer. We leveraged ad hoc somatic mosaic genome engineering, lineage...
The tumor suppressor protein p27Kip1 plays a pivotal role in the control of cell growth and metastasis formation.Several studies pointed to different roles for Ras induced transformation, although no explanation has been provided elucidate these differences. We recently demonstrated that p27kip1 regulates H-Ras activity via its interaction with stathmin.Here, using vitro vivo models, we show is an important regulator transformation. In H-RasV12 transformed cells, suppressed proliferation two...
Abstract DNA replication is a tightly regulated, multi-step process orchestrated by licensing and factors that ensure the faithful duplication of entire genome exclusively during S phase cell cycle. Although mechanisms preventing uncoordinated are well characterized, it remains unclear how cells counteract its potentially harmful effects when does occur, especially in context oncogenic stress. Here, we identify DPY30, an understudied component all COMPASS-like complexes, as modulator...
Abstract 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...