A5050048181- Lung Cancer Treatments and Mutations
- Lymphoma Diagnosis and Treatment
- Cancer therapeutics and mechanisms
- Lung Cancer Research Studies
- Colorectal Cancer Treatments and Studies
- Chronic Lymphocytic Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Acute Myeloid Leukemia Research
- Cancer-related gene regulation
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Cancer-related Molecular Pathways
- Neuroblastoma Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Advanced biosensing and bioanalysis techniques
- Retinoids in leukemia and cellular processes
- PI3K/AKT/mTOR signaling in cancer
- Ubiquitin and proteasome pathways
- RNA Interference and Gene Delivery
- DNA and Nucleic Acid Chemistry
- Cancer Mechanisms and Therapy
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Eosinophilic Disorders and Syndromes
- Thyroid Cancer Diagnosis and Treatment
- interferon and immune responses
University of Milano-Bicocca
2016-2025
LUCA School of Arts
2017
Creative Research Enterprises (United States)
2015
University Hospital Regensburg
2014
University of Geneva
2006-2012
Génétique Moléculaire Génomique Microbiologie
2010
McGill University
2006-2010
Technische Universität Braunschweig
2010
University of Helsinki
1999-2006
Fondazione IRCCS Istituto Nazionale dei Tumori
1996-2006
Abstract Activated ALK and ROS1 tyrosine kinases, resulting from chromosomal rearrangements, occur in a subset of non–small cell lung cancers (NSCLC) as well other tumor types their oncogenic relevance actionable targets has been demonstrated by the efficacy selective kinase inhibitors such crizotinib, ceritinib, alectinib. More recently, low-frequency rearrangements TRK kinases have described NSCLC, colorectal carcinoma, glioblastoma, Spitzoid melanoma. Entrectinib, whose discovery...
Anaplastic lymphoma kinase (ALK)-positive lymphomas respond to chemotherapy, but relapses, which bear a poor prognosis, occur. Crizotinib inhibits ALK in vitro and vivo was administered as monotherapy 11 ALK+ patients who were resistant/refractory cytotoxic therapy. The overall response rate 10 of (90.9%; 95% confidence interval [CI] = 58.7% 99.8%). Disease status at the latest follow-up is follows: four are complete (CR) (months >21, >30, >35, >40) under continuous crizotinib...
BACKGROUND: The leukemia cells of approximately 95% patients with chronic myeloid and 30%-50% adult acute lymphoblastic express the Bcr/Abl oncoprotein, which is product a fusion gene created by chromosomal translocation [(9:22) (q34;q11)]. This oncoprotein expresses constitutive tyrosine kinase activity that crucial for its cellular transforming activity. In this study, we evaluated antineoplastic CGP57148B, competitive inhibitor kinase. METHODS: Nude mice were given an injection...
BRAF-activating mutations have been reported in several types of cancer, including melanoma ( approximately 70% cases), thyroid (30-70%), ovarian (15-30%), and colorectal cancer (5-20%). Mutant BRAF has constitutive kinase activity causes hyperactivation the mitogen-activated protein pathway. silencing induces regression xenografts, indicating essential role for cell survival. We set up an inducible short hairpin RNA system to compare oncogenic carcinoma versus cells. Although knockdown led...
BCR/ABL (Breakpoint Cluster Region protein/Abelson tyrosine-protein kinase 1) domain (KD) mutations represent the most frequently described mechanism of resistance to treatment with tyrosine inhibitors (TKI) in patients chronic myeloid leukemia (CML). Mutations may impair TKI activity by directly or indirectly impairing drug binding protein. We report discovery three new mutations, L248R, T315V, and F317R identified two CML (L248R T315V) one patient Ph+ acute lymphoblastic (ALL) (F317R)....
Abstract Anaplastic lymphoma kinase ( ALK ) is a tyrosine receptor involved in both solid and hematological tumors. About 80% of ‐positive anaplastic large‐cell ALCL cases are characterized by the t(2;5)(p23;q35) translocation, encoding for aberrant fusion protein nucleophosmin NPM )‐ , whereas 5% non‐small‐cell lung cancer NSCLC patients carry inv(2)(p21;p23) rearrangement, echinoderm microtubule‐associated protein‐like 4 EML 4)‐ fusion. The /c‐ MET / ROS inhibitor crizotinib successfully...
Abstract The dual ALK/MET inhibitor crizotinib was recently approved for the treatment of metastatic and late-stage ALK+ NSCLC, is currently in clinical trial other ALK-related diseases. As predicted after tyrosine kinase inhibitors' experience, first mutations that confer resistance to have been described patients with non–small cell lung cancer (NSCLC) one patient inflammatory myofibroblastic tumor (IMT). Here, we focused our attention on anaplastic large lymphoma (ALCL), where oncogenic...
Abstract Targeted therapy changed the standard of care in ALK-dependent tumors. However, resistance remains a major challenge. Lorlatinib is third-generation ALK inhibitor that inhibits most mutants resistant to current inhibitors. In this study, we utilize lorlatinib-resistant anaplastic large cell lymphoma (ALCL), non–small lung cancer (NSCLC), and neuroblastoma lines vitro vivo investigate acquisition its underlying mechanisms. ALCL cells acquired compound mutations G1202R/G1269A...
Patients diagnosed with Anaplastic Large Cell Lymphoma (ALCL) are still treated toxic multi-agent chemotherapy and as many 25-50% of patients relapse. To understand disease pathology to uncover novel targets for therapy, Whole-Exome Sequencing (WES) Kinase (ALK)+ ALCL was performed well Gene-Set Enrichment Analysis. This revealed that the T-cell receptor (TCR) Notch pathways were most enriched in mutations. In particular, variant T349P NOTCH1, which confers a growth advantage cells it is...
Ulcerative colitis (UC) is a chronic inflammatory disorder of unknown aetiology. Gut virome dysbiosis fundamental in UC progression, although its role the early phases disease far from fully understood. Therefore, we sought to investigate virome-associated protein encoded by
ALK is a tyrosine kinase receptor involved in broad range of solid and hematologic tumors. Among 70% to 80% ALK(+) anaplastic large cell lymphomas (ALCL) are caused by the aberrant oncogenic fusion protein NPM-ALK. Crizotinib was first clinically relevant inhibitor, now approved for treatment late-stage metastatic cases lung cancer. However, patients frequently develop drug resistance Crizotinib, mainly due appearance point mutations located domain. Fortunately, other inhibitors available...
Abstract The investigation of genetic forms juvenile neurodegeneration could shed light on the causative mechanisms neuronal loss. Schinzel-Giedion syndrome (SGS) is a fatal developmental caused by mutations in SETBP1 gene, inducing accumulation its protein product. SGS features multi-organ involvement with severe intellectual and physical deficits due, at least part, to early neurodegeneration. Here we introduce human model that displays disease-relevant phenotypes. We show neural...
Anaplastic lymphoma kinase (ALK) tyrosine inhibitors (TKIs) show potent efficacy in several ALK-driven tumors, but the development of resistance limits their long-term clinical impact. Although mechanisms have been studied extensively non–small cell lung cancer, they are poorly understood anaplastic large (ALCL). Here, we identify a survival pathway supported by tumor microenvironment that activates phosphatidylinositol 3-kinase γ (PI3K-γ) signaling through C-C motif chemokine receptor 7...