A5000422869- Ovarian cancer diagnosis and treatment
- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- Cancer Genomics and Diagnostics
- Cancer-related Molecular Pathways
- Cancer Research and Treatments
- CRISPR and Genetic Engineering
- Cancer Cells and Metastasis
- Renal cell carcinoma treatment
- Cancer Treatment and Pharmacology
- Microtubule and mitosis dynamics
- Fibroblast Growth Factor Research
- Angiogenesis and VEGF in Cancer
- Renal and related cancers
- Lung Cancer Treatments and Mutations
- HER2/EGFR in Cancer Research
- PI3K/AKT/mTOR signaling in cancer
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Cancer Mechanisms and Therapy
- Metal complexes synthesis and properties
- Cancer, Hypoxia, and Metabolism
- Drug Transport and Resistance Mechanisms
- BRCA gene mutations in cancer
- Nanoparticle-Based Drug Delivery
Mario Negri Institute for Pharmacological Research
2015-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2015-2024
University College Dublin
2012
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. On basis of its histopathology and molecular-genomic changes, has been divided into subtypes, each with distinct biology outcome. The aim this study was to develop a panel patient-derived EOC xenografts that recapitulate molecular biologic heterogeneity human cancer. Thirty-four were successfully established, either subcutaneously or intraperitoneally, in nude mice. histologically similar corresponding patient tumor...
// Rosaria Chilà 1 , Alessandra Basana Monica Lupi Federica Guffanti Eugenio Gaudio 2 Andrea Rinaldi Luciano Cascione 2, 3 Valentina Restelli Chiara Tarantelli Francesco Bertoni Giovanna Damia Laura Carrassa Laboratory of Molecular Pharmacology and Cancer Pharmacology, Department Oncology, IRCCS- Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy Lymphoma Genomics Research Program, IOR Institute Oncology Research, Bellinzona, Switzerland Unit, IOSI Southern Switzerland,...
Abstract Occurrence of resistance to olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) approved in ovarian carcinoma, has already been shown clinical settings. Identifying combination treatments sensitize tumor cells and/or overcome olaparib is critical. Polo-like kinase 1 (PLK1), master regulator mitosis, also involved the DNA damage response promoting homologous recombination (HR)-mediated repair and recovery from G2/M checkpoint. We hypothesized that PLK1 inhibition could...
The fibroblast growth factor receptor (FGFR) pathway has been implicated both as an escape mechanism from anti-angiogenic therapy and a driver oncogene in different tumor types. Lucitanib is small molecule inhibitor of vascular endothelial (VEGF) receptors 1 to 3 (VEGFR1 3), platelet derived α/β (PDGFRα/β) FGFR1-3 tyrosine kinases demonstrated activity phase I/II clinical study, with objective RECIST responses breast cancer patients FGFR1 or FGF3/4/19 gene amplification, well anticipated...
Poly(ADP-ribose) polymerases inhibitor (PARPi) have shown clinical efficacy in ovarian carcinoma, especially those harboring defects homologous recombination (HR) repair, including BRCA1 and BRCA2 mutated tumors. There is increasing evidence however that PARPi resistance common develops through multiple mechanisms. ID8 F3 (HR proficient) Brca1-/- deficient) murine cells resistant to olaparib, a PARPi, were generated stepwise drug concentrations vitro. Both sensitive lines pharmacologically...
Even if ovarian cancer patients are very responsive to a cisplatinum-based therapy, most will relapse with resistant disease. New experimental animal models needed explore the mechanisms of resistance, better tailor treatment and improve patient prognosis. To address these aims, seven patient-derived high-grade serous/endometrioid xenografts were characterized for antitumor response after one two cycles cisplatinum classified as Very Responsive, Low Responsive drug treatment. Xenografts...
Platinum compounds are very active in first-line treatments of ovarian carcinoma. In fact, high rates complete remission achieved, but most patients eventually relapse with resistant disease. Many mechanisms underlying the platinum-resistant phenotype have been reported. However, there no data same isogenic cell system proficient and deficient homologous recombination (HR) on platinum-acquired resistance that might unequivocally clarify important mechanism associated resistance. We generated...
Expression of ATP-binding cassette (ABC) transporters has long been implicated in cancer chemotherapy resistance. Increased expression the ABCC subfamily reported prostate cancer, especially androgen-resistant cases. are known to efflux drugs but, recently, we have demonstrated that they can also a more direct role progression. The pharmacological potential targeting ABCC1, however, remained be assessed. In this study, investigated whether blockade ABCC1 affects cell proliferation using both...
Abstract Background Alteration of signalling pathways regulating cell cycle progression is a common feature cancer cells. Several drugs targeting distinct phases the have been developed but inability many them to discriminate between normal and cells has strongly limited their clinical potential because reduced efficacy at concentrations used limit adverse side effects. Mechanisms resistance also described, further affecting efficacy. Identification novel targets that can potentiate effect...
A xenobank of patient-derived (PDX) ovarian tumor samples has been established consisting tumors with different sensitivity to cisplatin (DDP), from very responsive resistant. As the DNA repair pathway is an important driver in response DDP, we analyzed mRNA expression 20 genes involved nucleotide excision repair, fanconi anemia, homologous recombination, base mismatch and translesion pathways methylation patterns some these genes. We also investigated correlation platinum-based therapy. The...
Abstract Late stage epithelial ovarian cancer has a dismal prognosis. Identification of pharmacogenomic markers (i.e. polymorphisms) to stratify patients optimize individual therapy is paramount importance. We here report the retrospective analysis polymorphisms in 5 genes ( ATM , ATR Chk1 Chk2 and CDK12) involved cellular response platinum cohort 240 with late cancer. The aim present study was evaluate associations between above mentioned SNPs patients’ clinical outcomes: overall survival...
Adult skin fibroblasts represent the most common starting cell type used to generate human induced pluripotent stem cells (F-hiPSC) for clinical studies. Yet, a foetal source would offer unique advantages, primarily absence of accumulated somatic mutations. Herein, we generated hiPSC from cord blood multipotent mesenchymal stromal (MSC-hiPSC) and compared them with F-hiPSC. Assessment full activation pluripotency gene regulatory network (PGRN) focused on circular RNA (circRNA), recently...
Abstract Ultrasmall nanoparticles of 10 nm or less in size have been shown to great potential the biomedical field due their high surface area and strong tissue penetration. Their easy functionalization unique behavior at nanoscale, such as reduced corona formation lower liver retention allow them be a tool for precision targeting. In this study, PEGylated ultrasmall gold (GNPs) with 4 core are developed. They functionalized cyclic RGD (cRGD) targeting peptide, which provides binding...
Purpose: Thrombospondin-1 (TSP-1), a major regulator of cell interaction with the environment, is often deregulated in cancers, including ovarian carcinoma. Both tumor and host cells can release TSP-1 microenvironment. The relative contribution two sources determining levels cancer remains to be elucidated. This study was designed investigate expression panel 29 patient-derived adenocarcinoma xenografts (PDX), using analytical tools specific for human (tumor-derived) rather than murine...
Platinum resistance is an unmet medical need in ovarian carcinoma. Molecular biomarkers to predict the response platinum-based therapy could allow patient stratification and alternative therapeutic strategies early clinical management. Sensitivity platinum are partially determined by tumor’s intrinsic DNA repair activities, including nucleotide excision (NER) base (BER). We investigated role of NER proteins—ERCC1, XPF, ERCC1/XPF complex—and BER protein polymerase β, as possible cisplatin...
Cyclin-dependent kinase 12 (CDK12) is a serine/threonine involved in the regulation of RNA polymerase II and transcription subset genes DNA damage response. CDK12 one most mutated ovarian carcinoma. These mutations result loss-of-function can predict responses to PARP1/2 inhibitor platinum. To investigate role cancer, CRISPR/Cas9 technology was used generate stable knockout (KO) clone A2780 carcinoma cells. This first report on null cell line. The had slower growth less clonogenic than...