0000000000025363

AUTHOR

Federica Francescangeli

showing 5 related works from this author

Elimination of quiescent/slow-proliferating cancer stem cells by Bcl-XL inhibition in non-small cell lung cancer

2014

Lung cancer is the most common cause of cancer-related mortality worldwide, urging the discovery of novel molecular targets and therapeutic strategies. Stem cells have been recently isolated from non-small cell lung cancer (NSCLC), thus allowing the investigation of molecular pathways specifically active in the tumorigenic population. We have found that Bcl-XL is constantly expressed by lung cancer stem cells (LCSCs) and has a prominent role in regulating LCSC survival. Whereas chemotherapeutic agents were scarcely effective against LCSC, the small molecule Bcl-2/Bcl-XL inhibitor ABT-737, but not the selective Bcl-2 inhibitor ABT-199, induced LCSC death at nanomolar concentrations. Differen…

Lung NeoplasmsMice SCIDPharmacologyPiperazinesAntineoplastic AgentNitrophenolsMiceMice Inbred NODCarcinoma Non-Small-Cell LungCytotoxic T cellNon-Small-Cell Lungeducation.field_of_studySulfonamidesTumorAnimals; Antineoplastic Agents; Biphenyl Compounds; Carcinoma Non-Small-Cell Lung; Cell Line Tumor; Cell Proliferation; Cell Survival; Female; Humans; Lung Neoplasms; Mice Inbred NOD; Mice SCID; Neoplastic Stem Cells; Nitrophenols; Piperazines; Sulfonamides; Tumor Burden; Xenograft Model Antitumor Assays; bcl-X Protein; Molecular Biology; Cell BiologyTumor BurdenAnimals; Antineoplastic Agents; Biphenyl Compounds; Carcinoma Non-Small-Cell Lung; Cell Line Tumor; Cell Proliferation; Cell Survival; Female; Humans; Lung Neoplasms; Mice Inbred NOD; Mice SCID; Neoplastic Stem Cells; Nitrophenols; Piperazines; Sulfonamides; Tumor Burden; Xenograft Model Antitumor Assays; bcl-X ProteinNeoplastic Stem CellsFemaleStem cellHumanmedicine.drugXenograft Model Antitumor AssayCell SurvivalPopulationbcl-X ProteinAntineoplastic AgentsBiologySCIDSulfonamideCell LineCancer stem cellCell Line TumormedicineAnimalsHumanseducationLung cancerPiperazineMolecular BiologyCell ProliferationSettore MED/04 - Patologia GeneraleOriginal PaperNitrophenolAnimalCell growthCarcinomaBiphenyl CompoundsCell Biologymedicine.diseaseXenograft Model Antitumor AssaysGemcitabineLung NeoplasmCell cultureBiphenyl CompoundCancer researchInbred NODNeoplastic Stem Cell
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Aurora-A Is Essential for the Tumorigenic Capacity and Chemoresistance of Colorectal Cancer Stem Cells

2010

Abstract Colorectal cancer stem cells (CR-CSC) are responsible for the generation and maintenance of intestinal tumors and are highly resistant to conventional chemotherapeutic agents. Aurora-A, a serine-threonine kinase involved in mitosis regulation, plays multiple key functions in tumor initiation and progression. We found that Aurora-A is overexpressed in primary colorectal tumor cells, in the CR-CSC fraction, and in stem cell–derived differentiated cells, compared with normal colon tissue. Aurora-A expression was functionally linked to centrosome amplification in CR-CSC, as indicated by the decrease in cells with multiple centrosomes that followed Aurora-A silencing. Knockdown of Auror…

MaleOncologyCancer Researchmedicine.medical_specialtyColorectal cancerCellular differentiationcolorectal cancer stem cellsMice NudeCell Growth ProcessesTumor initiationProtein Serine-Threonine KinasesBiologyMiceAurora KinasesCell MovementCancer stem cellInternal medicinemedicineAnimalsHumansCytotoxic T cellGene silencingMitosisAgedAurora Kinase ACentrosomeCell CycleGene AmplificationMiddle Agedmedicine.diseaseOncologyDrug Resistance NeoplasmGene Knockdown TechniquesNeoplastic Stem CellsCancer researchFemalebiological phenomena cell phenomena and immunityStem cellColorectal NeoplasmsCancer Research
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Cancer stem cell-based models of colorectal cancer reveal molecular determinants of therapy resistance

2016

Abstract Colorectal cancer (CRC) therapy mainly relies on the use of conventional chemotherapeutic drugs combined, in a subset of patients, with epidermal growth factor receptor [EGFR]-targeting agents. Although CRC is considered a prototype of a cancer stem cell (CSC)-driven tumor, the effects of both conventional and targeted therapies on the CSC compartment are largely unknown. We have optimized a protocol for colorectal CSC isolation that allowed us to obtain CSC-enriched cultures from primary tumor specimens, with high efficiency. CSC isolation was followed by in vitro and in vivo validation, genetic characterization, and drug sensitivity analysis, thus generating panels of CSC lines w…

0301 basic medicineProteomicscancer stem cellsColorectal cancerDrug ResistanceMice SCIDAnti-EGFR therapy; Cancer stem cells; Cetuximab; Colorectal cancer; Proteomic arrays; Animals; Cells Cultured; Colorectal Neoplasms; Drug Resistance Neoplasm; Female; Gene Expression Profiling; Humans; Mice Inbred NOD; Mice SCID; Mice Transgenic; Microarray Analysis; Models Biological; Neoplastic Stem Cells; Protein Kinase Inhibitors; Proteomics; Signal Transduction; Developmental Biology; Cell BiologyTransgenicMiceMice Inbred NODModelsproteomic arrayscetuximabcell biologyEpidermal growth factor receptorCells CulturedCulturedCetuximabbiologyGeneral MedicinePrimary tumorNeoplastic Stem CellsFemaleSettore MED/46 - Scienze Tecniche Di Medicina Di LaboratorioStem cellColorectal Neoplasmsmedicine.drugSignal TransductionCellsMice Transgeniccolorectal cancerSCIDModels Biological03 medical and health sciencesdevelopmental biologyProteomic arrayCancer stem cellIn vivoSettore MED/04 - PATOLOGIA GENERALEmedicineAnimalsHumansProtein Kinase InhibitorsSettore MED/06 - ONCOLOGIA MEDICAMicroarray analysis techniquesbusiness.industryCancer stem cellGene Expression Profilingmedicine.diseaseMicroarray AnalysisBiological030104 developmental biologyanti-EGFR therapyDrug Resistance Neoplasmanti-EGFR therapy; cancer stem cells; cetuximab; colorectal cancer; proteomic arrays; cell biology; developmental biologyImmunologyCancer researchbiology.proteinNeoplasmInbred NODbusiness
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Proliferation state and polo-like kinase1 dependence of tumorigenic colon cancer cells.

2012

Abstract Tumor-initiating cells are responsible for tumor maintenance and relapse in solid and hematologic cancers. Although tumor-initiating cells were initially believed to be mainly quiescent, rapidly proliferating tumorigenic cells were found in breast cancer. In colon cancer, the proliferative activity of the tumorigenic population has not been defined, although it represents an essential parameter for the development of more effective therapeutic strategies. Here, we show that tumorigenic colon cancer cells can be found in a rapidly proliferating state in vitro and in vivo, both in human tumors and mouse xenografts. Inhibitors of polo-like kinase1 (Plk1), a mitotic kinase essential fo…

Colorectal cancerCancer stem cellscolorectal cancercell proliferationcell cycle.Cell Cycle ProteinsMice0302 clinical medicineMice Inbred NODAC133 AntigenRNA Small Interfering0303 health scienceseducation.field_of_studyPteridinesCell CycleCell cycleImmunohistochemistry3. Good healthMitochondriaGene Expression Regulation Neoplastic030220 oncology & carcinogenesisColonic NeoplasmsMolecular MedicineFemaleStem cellPopulationTransplantation HeterologousCell Growth ProcessesBiologyProtein Serine-Threonine KinasesPLK103 medical and health sciencesCancer stem cellAntigens CDCell Line TumorProto-Oncogene ProteinsmedicineAnimalsHumanseducationProtein Kinase Inhibitors030304 developmental biologyGlycoproteinsSettore MED/04 - Patologia GeneraleCell growthCell Biologymedicine.diseaseTumor progressionImmunologyCancer researchPeptidesDevelopmental BiologyStem cells (Dayton, Ohio)
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Dynamic regulation of the cancer stem cell compartment by Cripto-1 in colorectal cancer.

2015

Stemness was recently depicted as a dynamic condition in normal and tumor cells. We found that the embryonic protein Cripto-1 (CR1) was expressed by normal stem cells at the bottom of colonic crypts and by cancer stem cells (CSCs) in colorectal tumor tissues. CR1-positive populations isolated from patient-derived tumor spheroids exhibited increased clonogenic capacity and expression of stem-cell-related genes. CR1 expression in tumor spheroids was variable over time, being subject to a complex regulation of the intracellular, surface and secreted protein, which was related to changes of the clonogenic capacity at the population level. CR1 silencing induced CSC growth arrest in vitro with a …

Colorectal cancerColorectal NeoplasmCriptoMiceIntercellular Signaling Peptides and ProteinTumor Cells CulturedRegulation of gene expressionCulturedstem cell; CRIPTO 1GPI-Linked ProteinCell biologyNeoplasm ProteinsTumor CellsGene Expression Regulation NeoplasticGenes srcNeoplastic Stem CellsIntercellular Signaling Peptides and ProteinsFemaleStem cellColorectal NeoplasmsHumanSignal Transductioncolorectal cancerBiologyGPI-Linked ProteinsAnimals; Colorectal Neoplasms; Female; GPI-Linked Proteins; Gene Expression Regulation Neoplastic; Genes src; Humans; Intercellular Signaling Peptides and Proteins; Mice; Neoplasm Proteins; Neoplastic Stem Cells; Proto-Oncogene Proteins c-akt; Signal Transduction; Spheroids Cellular; Tumor Cells Cultured; Cell Biology; Molecular BiologyNeoplasm ProteinCancer stem cellSettore MED/04 - PATOLOGIA GENERALESpheroids CellularmedicineGene silencingAnimalsHumansClonogenic assayProtein kinase BMolecular BiologysrcOriginal PaperNeoplasticAnimalCell Biologymedicine.diseaseGene Expression RegulationGenesNeoplastic Stem CellCellularSpheroidsanimals; colorectal neoplasms; female; GPI-linked proteins; gene expression regulation; neoplastic; genes src; humans; intercellular signaling peptides and proteins; mice; neoplasm proteins; neoplastic stem cells; proto-oncogene proteins c-akt; signal transduction; spheroids; cellular; tumor cells; culturedAnimals; Colorectal Neoplasms; Female; GPI-Linked Proteins; Gene Expression Regulation Neoplastic; Genes src; Humans; Intercellular Signaling Peptides and Proteins; Mice; Neoplasm Proteins; Neoplastic Stem Cells; Proto-Oncogene Proteins c-akt; Signal Transduction; Spheroids Cellular; Tumor Cells Cultured; Molecular Biology; Cell BiologyProto-Oncogene Proteins c-akt
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