LIVIVO - Search results -

Search results

Result 1 - 10 of total 13

Search options

Article ; Online: The Cyclin-dependent kinase 1: more than a cell cycle regulator.

Massacci, Giorgia / Perfetto, Livia / Sacco, Francesca

2023 Volume 129, Issue 11, Page(s) 1707–1716

Abstract: The Cyclin-dependent kinase 1, as a serine/threonine protein kinase, is more than a cell cycle regulator as it was originally identified. During the last decade, it has been shown to carry out versatile functions during the last decade. From cell cycle ... ...

Abstract	The Cyclin-dependent kinase 1, as a serine/threonine protein kinase, is more than a cell cycle regulator as it was originally identified. During the last decade, it has been shown to carry out versatile functions during the last decade. From cell cycle control to gene expression regulation and apoptosis, CDK1 is intimately involved in many cellular events that are vital for cell survival. Here, we provide a comprehensive catalogue of the CDK1 upstream regulators and substrates, describing how this kinase is implicated in the control of key 'cell cycle-unrelated' biological processes. Finally, we describe how deregulation of CDK1 expression and activation has been closely associated with cancer progression and drug resistance.
MeSH term(s)	Humans ; CDC2 Protein Kinase/genetics ; CDC2 Protein Kinase/metabolism ; Protein Serine-Threonine Kinases/genetics ; Genes, cdc ; Cell Cycle ; Cell Division
Chemical Substances	CDC2 Protein Kinase (EC 2.7.11.22) ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2023-10-28
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-023-02468-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.142: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Phosphoproteomics and Organelle Proteomics in Pancreatic Islets.

Caliskan, Özüm Sehnaz / Massacci, Giorgia / Krahmer, Natalie / Sacco, Francesca

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2456, Page(s) 123–140

Abstract: Over the recent years, mass spectrometry (MS)-based proteomics has undergone dramatic advances in sample preparation, instrumentation, and computational methods. Here, we describe in detail, how a workflow quantifies global protein phosphorylation in ... ...

Abstract	Over the recent years, mass spectrometry (MS)-based proteomics has undergone dramatic advances in sample preparation, instrumentation, and computational methods. Here, we describe in detail, how a workflow quantifies global protein phosphorylation in pancreatic islets and characterizes intracellular organelle composition on protein level by MS-based proteomics.
MeSH term(s)	Islets of Langerhans/metabolism ; Mass Spectrometry/methods ; Organelles/metabolism ; Phosphorylation ; Proteomics/methods
Language	English
Publishing date	2022-05-25
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2124-0_9
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- Full text online
- Order with fees

Article: Combining Mass Spectrometry-Based Phosphoproteomics with a Network-Based Approach to Reveal FLT3-Dependent Mechanisms of Chemoresistance.

Pugliese, Giusj Monia / Latini, Sara / Massacci, Giorgia / Perfetto, Livia / Sacco, Francesca

Proteomes

2021 Volume 9, Issue 2

Abstract: FLT3 mutations are the most frequently identified genetic alterations in acute myeloid leukemia (AML) and are associated with poor clinical outcome, relapse and chemotherapeutic resistance. Elucidating the molecular mechanisms underlying FLT3-dependent ... ...

Abstract	FLT3 mutations are the most frequently identified genetic alterations in acute myeloid leukemia (AML) and are associated with poor clinical outcome, relapse and chemotherapeutic resistance. Elucidating the molecular mechanisms underlying FLT3-dependent pathogenesis and drug resistance is a crucial goal of biomedical research. Given the complexity and intricacy of protein signaling networks, deciphering the molecular basis of FLT3-driven drug resistance requires a systems approach. Here we discuss how the recent advances in mass spectrometry (MS)-based (phospho) proteomics and multiparametric analysis accompanied by emerging computational approaches offer a platform to obtain and systematically analyze cell-specific signaling networks and to identify new potential therapeutic targets.
Language	English
Publishing date	2021-04-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720995-7
ISSN	2227-7382
ISSN	2227-7382
DOI	10.3390/proteomes9020019
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Transcription Factor Activation Profiles (TFAP) identify compounds promoting differentiation of Acute Myeloid Leukemia cell lines.

Riccio, Federica / Micarelli, Elisa / Secci, Riccardo / Giuliani, Giulio / Vumbaca, Simone / Massacci, Giorgia / Castagnoli, Luisa / Fuoco, Claudia / Cesareni, Gianni

Cell death discovery

2022 Volume 8, Issue 1, Page(s) 16

Abstract: Repurposing of drugs for new therapeutic use has received considerable attention for its potential to limit time and cost of drug development. Here we present a new strategy to identify chemicals that are likely to promote a desired phenotype. We used ... ...

Abstract	Repurposing of drugs for new therapeutic use has received considerable attention for its potential to limit time and cost of drug development. Here we present a new strategy to identify chemicals that are likely to promote a desired phenotype. We used data from the Connectivity Map (CMap) to produce a ranked list of drugs according to their potential to activate transcription factors that mediate myeloid differentiation of leukemic progenitor cells. To validate our strategy, we tested the in vitro differentiation potential of candidate compounds using the HL-60 human cell line as a myeloid differentiation model. Ten out of 22 compounds, which were ranked high in the inferred list, were confirmed to promote significant differentiation of HL-60. These compounds may be considered candidate for differentiation therapy. The method that we have developed is versatile and it can be adapted to different drug repurposing projects.
Language	English
Publishing date	2022-01-10
Publishing country	United States
Document type	Journal Article
ISSN	2058-7716
ISSN	2058-7716
DOI	10.1038/s41420-021-00811-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Unveiling the signaling network of FLT3-ITD AML improves drug sensitivity prediction.

Latini, Sara / Venafra, Veronica / Massacci, Giorgia / Bica, Valeria / Graziosi, Simone / Pugliese, Giusj Monia / Iannuccelli, Marta / Frioni, Filippo / Minnella, Gessica / Marra, John Donald / Chiusolo, Patrizia / Pepe, Gerardo / Helmer Citterich, Manuela / Mougiakakos, Dimitros / Böttcher, Martin / Fischer, Thomas / Perfetto, Livia / Sacco, Francesca

eLife

2024 Volume 12

Abstract: Currently, the identification of patient-specific therapies in cancer is mainly informed by personalized genomic analysis. In the setting of acute myeloid leukemia (AML), patient-drug treatment matching fails in a subset of patients harboring atypical ... ...

Abstract	Currently, the identification of patient-specific therapies in cancer is mainly informed by personalized genomic analysis. In the setting of acute myeloid leukemia (AML), patient-drug treatment matching fails in a subset of patients harboring atypical internal tandem duplications (ITDs) in the tyrosine kinase domain of the FLT3 gene. To address this unmet medical need, here we develop a systems-based strategy that integrates multiparametric analysis of crucial signaling pathways, and patient-specific genomic and transcriptomic data with a prior knowledge signaling network using a Boolean-based formalism. By this approach, we derive personalized predictive models describing the signaling landscape of AML FLT3-ITD positive cell lines and patients. These models enable us to derive mechanistic insight into drug resistance mechanisms and suggest novel opportunities for combinatorial treatments. Interestingly, our analysis reveals that the JNK kinase pathway plays a crucial role in the tyrosine kinase inhibitor response of FLT3-ITD cells through cell cycle regulation. Finally, our work shows that patient-specific logic models have the potential to inform precision medicine approaches.
MeSH term(s)	Humans ; Signal Transduction ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; MAP Kinase Signaling System ; Cell Line ; Drug Resistance ; fms-Like Tyrosine Kinase 3/genetics
Chemical Substances	FLT3 protein, human (EC 2.7.10.1) ; fms-Like Tyrosine Kinase 3 (EC 2.7.10.1)
Language	English
Publishing date	2024-04-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.90532
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Impact of FLT3-ITD location on cytarabine sensitivity in AML: a network-based approach.

Pugliese, Giusj Monia / Venafra, Veronica / Bica, Valeria / Massacci, Giorgia / Latini, Sara / Graziosi, Simone / Fischer, Thomas / Mougiakakos, Dimitrios / Boettcher, Martin / Perfetto, Livia / Sacco, Francesca

Leukemia

2023 Volume 37, Issue 5, Page(s) 1151–1155

MeSH term(s)	Humans ; Cytarabine/pharmacology ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Cell Line, Tumor ; fms-Like Tyrosine Kinase 3/genetics ; Mutation
Chemical Substances	Cytarabine (04079A1RDZ) ; fms-Like Tyrosine Kinase 3 (EC 2.7.10.1) ; FLT3 protein, human (EC 2.7.10.1)
Language	English
Publishing date	2023-03-25
Publishing country	England
Document type	Research Support, Non-U.S. Gov't ; Letter
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-023-01881-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2295: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Integrating Patient-Specific Information into Logic Models of Complex Diseases: Application to Acute Myeloid Leukemia.

Palma, Alessandro / Iannuccelli, Marta / Rozzo, Ilaria / Licata, Luana / Perfetto, Livia / Massacci, Giorgia / Castagnoli, Luisa / Cesareni, Gianni / Sacco, Francesca

Journal of personalized medicine

2021 Volume 11, Issue 2

Abstract: High throughput technologies such as deep sequencing and proteomics are increasingly becoming mainstream in clinical practice and support diagnosis and patient stratification. Developing computational models that recapitulate cell physiology and its ... ...

Abstract	High throughput technologies such as deep sequencing and proteomics are increasingly becoming mainstream in clinical practice and support diagnosis and patient stratification. Developing computational models that recapitulate cell physiology and its perturbations in disease is a required step to help with the interpretation of results of high content experiments and to devise personalized treatments. As complete cell-models are difficult to achieve, given limited experimental information and insurmountable computational problems, approximate approaches should be considered. We present here a general approach to modeling complex diseases by embedding patient-specific genomics data into actionable logic models that take into account prior knowledge. We apply the strategy to acute myeloid leukemia (AML) and assemble a network of logical relationships linking most of the genes that are found frequently mutated in AML patients. We derive Boolean models from this network and we show that by priming the model with genomic data we can infer relevant patient-specific clinical features. Here we propose that the integration of literature-derived causal networks with patient-specific data should be explored to help bedside decisions.
Language	English
Publishing date	2021-02-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm11020117
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Details ▾
- Full text online
- Order with fees

Article ; Online: A key role of the WEE1-CDK1 axis in mediating TKI-therapy resistance in FLT3-ITD positive acute myeloid leukemia patients.

Massacci, Giorgia / Venafra, Veronica / Latini, Sara / Bica, Valeria / Pugliese, Giusj Monia / Graziosi, Simone / Klingelhuber, Felix / Krahmer, Natalie / Fischer, Thomas / Mougiakakos, Dimitrios / Boettcher, Martin / Perfetto, Livia / Sacco, Francesca

Leukemia

2022 Volume 37, Issue 2, Page(s) 288–297

Abstract: The insertion site of the internal tandem duplications (ITDs) in the FLT3 gene affects the sensitivity to tyrosine kinase inhibitors (TKIs) therapy in acute myeloid leukemia (AML). Patients with the ITD in the tyrosine kinase domain lack effective ... ...

Abstract	The insertion site of the internal tandem duplications (ITDs) in the FLT3 gene affects the sensitivity to tyrosine kinase inhibitors (TKIs) therapy in acute myeloid leukemia (AML). Patients with the ITD in the tyrosine kinase domain lack effective therapeutic options. Here, to identify genotype-driven strategies increasing the TKI therapy efficacy, we developed SignalingProfiler, a strategy supporting the integration of high-sensitive mass spectrometry-based (phospho)proteomics, RNA sequencing datasets with literature-derived signaling networks. The approach generated FLT3-ITD genotype-specific predictive models and revealed a conserved role of the WEE1-CDK1 axis in TKIs resistance. Remarkably, pharmacological inhibition of the WEE1 kinase synergizes and strengthens the pro-apoptotic effect of TKIs therapy in cell lines and patient-derived primary blasts. Finally, we propose a new molecular mechanism of TKIs resistance in AML and suggest the combination of WEE1 inhibitor and TKI as a therapeutic option to improve patients clinical outcome.
MeSH term(s)	Humans ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Drug Resistance, Neoplasm/genetics ; Cell Line ; Signal Transduction ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; fms-Like Tyrosine Kinase 3/genetics ; fms-Like Tyrosine Kinase 3/metabolism ; Mutation ; Protein-Tyrosine Kinases/genetics ; Protein-Tyrosine Kinases/metabolism ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; CDC2 Protein Kinase/genetics ; CDC2 Protein Kinase/metabolism ; CDC2 Protein Kinase/pharmacology
Chemical Substances	Protein Kinase Inhibitors ; fms-Like Tyrosine Kinase 3 (EC 2.7.10.1) ; FLT3 protein, human (EC 2.7.10.1) ; WEE1 protein, human (EC 2.7.10.2) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Cell Cycle Proteins ; CDK1 protein, human (EC 2.7.11.22) ; CDC2 Protein Kinase (EC 2.7.11.22)
Language	English
Publishing date	2022-12-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-022-01785-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2295: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: SCA-1 micro-heterogeneity in the fate decision of dystrophic fibro/adipogenic progenitors.

Giuliani, Giulio / Vumbaca, Simone / Fuoco, Claudia / Gargioli, Cesare / Giorda, Ezio / Massacci, Giorgia / Palma, Alessandro / Reggio, Alessio / Riccio, Federica / Rosina, Marco / Vinci, Maria / Castagnoli, Luisa / Cesareni, Gianni

Cell death & disease

2021 Volume 12, Issue 1, Page(s) 122

Abstract: The term micro-heterogeneity refers to non-genetic cell to cell variability observed in a bell-shaped distribution of the expression of a trait within a population. The contribution of micro-heterogeneity to physiology and pathology remains largely ... ...

Abstract	The term micro-heterogeneity refers to non-genetic cell to cell variability observed in a bell-shaped distribution of the expression of a trait within a population. The contribution of micro-heterogeneity to physiology and pathology remains largely uncharacterised. To address such an issue, we investigated the impact of heterogeneity in skeletal muscle fibro/adipogenic progenitors (FAPs) isolated from an animal model of Duchenne muscular dystrophy (DMD), the mdx mouse. FAPs play an essential role in muscle homoeostasis. However, in pathological conditions or ageing, they are the source of intramuscular infiltrations of fibrotic or adipose tissue. By applying a multiplex flow cytometry assay, we characterised and purified from mdx muscles two FAP cell states expressing different levels of SCA-1. The two cell states are morphologically identical and repopulate each other after several growth cycles. However, they differ in their in vitro behaviour. Cells expressing higher levels of SCA-1 (SCA1-High-FAPs) differentiate more readily into adipocytes while, when exposed to a fibrogenic stimulation, increase the expression of Col1a1 and Timp1 mRNA. A transcriptomic analysis confirmed the adipogenic propensity of SCA1-High-FAPs. In addition, SCA1-High-FAPs proliferate more extensively ex vivo and display more proliferating cells in dystrophic muscles in comparison to SCA1-Low-FAPs. Adipogenesis of both FAP cell states is inhibited in vitro by leucocytes from young dystrophic mice, while leucocytes isolated from aged dystrophic mice are less effective in limiting the adipogenesis of SCA1-High-FAPs suggesting a differential regulatory effect of the microenvironment on micro-heterogeneity. Our data suggest that FAP micro-heterogeneity is modulated in pathological conditions and that this heterogeneity in turn may impact on the behaviour of interstitial mesenchymal cells in genetic diseases.
MeSH term(s)	Adipogenesis/physiology ; Animals ; Antigens, Ly/metabolism ; Cell Differentiation ; Membrane Proteins/metabolism ; Mesenchymal Stem Cells/metabolism ; Mice
Chemical Substances	Antigens, Ly ; Ly6a protein, mouse ; Membrane Proteins
Language	English
Publishing date	2021-01-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-021-03408-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: The immunosuppressant drug azathioprine restrains adipogenesis of muscle Fibro/Adipogenic Progenitors from dystrophic mice by affecting AKT signaling.

Reggio, Alessio / Spada, Filomena / Rosina, Marco / Massacci, Giorgia / Zuccotti, Alessandro / Fuoco, Claudia / Gargioli, Cesare / Castagnoli, Luisa / Cesareni, Gianni

Scientific reports

2019 Volume 9, Issue 1, Page(s) 4360

Abstract: Fibro/Adipogenic Progenitors (FAPs) define a stem cell population playing a pro-regenerative role after muscle damage. When removed from their natural niche, FAPs readily differentiate into adipocytes or fibroblasts. This digressive differentiation ... ...

Abstract	Fibro/Adipogenic Progenitors (FAPs) define a stem cell population playing a pro-regenerative role after muscle damage. When removed from their natural niche, FAPs readily differentiate into adipocytes or fibroblasts. This digressive differentiation potential, which is kept under tight control in the healthy muscle niche, contributes to fat and scar infiltrations in degenerative myopathies, such as in Duchenne Muscular Dystrophy (DMD). Controlling FAP differentiation by means of small molecules may contribute to delay the adverse consequences of the progressive pathological degeneration while offering, at the same time, a wider temporal window for gene therapy and cell-based strategies. In a high content phenotypic screening, we identified the immunosuppressant, azathioprine (AZA) as a negative modulator of FAP adipogenesis. We show here that AZA negatively affects the adipogenic propensity of FAPs purified from wild type and mdx mice by impairing the expression of the master adipogenic regulator, peroxisome proliferator-activated receptor γ (PPARγ). We show that this inhibition correlates with a decline in the activation of the AKT-mTOR axis, the main pathway that transduces the pro-adipogenic stimulus triggered by insulin. In addition, AZA exerts a cytostatic effect that has a negative impact on the mitotic clonal process that is required for the terminal differentiation of the preadipocyte-committed cells.
MeSH term(s)	Adipogenesis/drug effects ; Animals ; Azathioprine/pharmacology ; Cell Differentiation/drug effects ; Cells, Cultured ; Disease Models, Animal ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Immunosuppressive Agents/pharmacology ; Mice ; Mice, Inbred mdx ; Models, Biological ; Muscular Dystrophy, Duchenne ; Myoblasts, Skeletal/drug effects ; Myoblasts, Skeletal/metabolism ; PPAR gamma ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/drug effects ; Stem Cells/drug effects ; Stem Cells/metabolism ; TOR Serine-Threonine Kinases/metabolism
Chemical Substances	Immunosuppressive Agents ; PPAR gamma ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Azathioprine (MRK240IY2L)
Language	English
Publishing date	2019-03-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-39538-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito