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Article: Corrigendum: Adherence to European society of gastrointestinal endoscopy quality performance measures for upper and lower gastrointestinal endoscopy: a nationwide survey from the Italian society of digestive endoscopy.

Zagari, Rocco Maurizio / Frazzoni, Leonardo / Fuccio, Lorenzo / Bertani, Helga / Crinò, Stefano Francesco / Magarotto, Andrea / Dajti, Elton / Tringali, Andrea / Da Massa Carrara, Paola / Cengia, Gianpaolo / Ciliberto, Enrico / Conigliaro, Rita / Germanà, Bastianello / Lamazza, Antonietta / Pisani, Antonio / Spinzi, Giancarlo / Capelli, Maurizio / Bazzoli, Franco / Pasquale, Luigi

Frontiers in medicine

2024 Volume 11, Page(s) 1406746

Abstract: This corrects the article DOI: 10.3389/fmed.2022.868449.]. ...

Abstract	[This corrects the article DOI: 10.3389/fmed.2022.868449.].
Language	English
Publishing date	2024-04-09
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2024.1406746
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Article ; Online: Malignant meningioma mTOR mutated and precision medicine.

Villani, Veronica / Tanzilli, Antonio / Vidiri, Antonello / Giangaspero, Felice / Ciliberto, Gennaro / Olivi, Alessandro / Pace, Andrea

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

2022 Volume 44, Issue 3, Page(s) 1073–1075

Abstract: Background: WHO grade II and III meningiomas are more invasive than grade I malignancies and determine patients' shorter overall survival. Their tendency to recur after treatment has represented an important therapeutic challenge because of the limited ... ...

Abstract	Background: WHO grade II and III meningiomas are more invasive than grade I malignancies and determine patients' shorter overall survival. Their tendency to recur after treatment has represented an important therapeutic challenge because of the limited treatment strategies at recurrence. Angiogenesis and mechanistic target of rapamycin (mTOR) activation are two of the main features of higher grade meningiomas, determining invasiveness and tendency to relapse. While these options prove promising, available clinical data on mTOR inhibitors' efficacy are somewhat limited. Case study: We report a case of a 25-year-old female patient diagnosed with a right parasagittal occipital anaplastic meningioma (grade III WHO) in 2013. The patient underwent multiple treatments and, in 2019, a further recurrence occurred. The patient reported an mTOR mutation, and it is for this reason that the MTB approved treatment with everolimus and bevacizumab. Therapy was administered in May 2019, and partial response and prolonged disease control was obtained in November 2021, when progression took place. The patient's death occurred in March 2022. Conclusions: This case report provides evidence on the efficacy of mTOR inhibitors as a treatment option in recurrent meningiomas. Furthermore, it highlights the importance of performing a molecular analysis as a preliminary step towards targeting the mTOR pathway.
MeSH term(s)	Female ; Humans ; Adult ; Meningioma/drug therapy ; Meningioma/genetics ; Meningioma/pathology ; Meningeal Neoplasms/drug therapy ; Meningeal Neoplasms/genetics ; Meningeal Neoplasms/pathology ; Precision Medicine ; MTOR Inhibitors ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/pathology ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/therapeutic use
Chemical Substances	MTOR Inhibitors ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; MTOR protein, human (EC 2.7.1.1)
Language	English
Publishing date	2022-12-26
Publishing country	Italy
Document type	Case Reports ; Journal Article
ZDB-ID	2016546-8
ISSN	1590-3478 ; 1590-1874
ISSN (online)	1590-3478
ISSN	1590-1874
DOI	10.1007/s10072-022-06575-x
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Article ; Online: Micromanaging checkpoint proteins.

Ciliberto, Andrea / Hauf, Silke

eLife

2017 Volume 6

Abstract: The kinase Mps1, long known to be the 'boss' in mitotic checkpoint signaling, phosphorylates multiple proteins in the checkpoint signaling cascade. ...

Abstract	The kinase Mps1, long known to be the 'boss' in mitotic checkpoint signaling, phosphorylates multiple proteins in the checkpoint signaling cascade.
MeSH term(s)	Cell Cycle Proteins/genetics ; Kinetochores ; Phosphorylation ; Protein-Serine-Threonine Kinases/genetics ; Signal Transduction
Chemical Substances	Cell Cycle Proteins ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2017-02-16
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.25001
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Article ; Online: Not all roads lead to Cdk1.

Branzei, Dana / Ciliberto, Andrea

Cell cycle (Georgetown, Tex.)

2017 Volume 16, Issue 5, Page(s) 395–396

MeSH term(s)	Adenosine Triphosphatases ; CDC2 Protein Kinase/genetics ; Chromatin ; DNA Damage ; DNA-Binding Proteins ; Multiprotein Complexes
Chemical Substances	Chromatin ; DNA-Binding Proteins ; Multiprotein Complexes ; condensin complexes ; CDC2 Protein Kinase (EC 2.7.11.22) ; Adenosine Triphosphatases (EC 3.6.1.-)
Language	English
Publishing date	2017-02-06
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.1080/15384101.2016.1274585
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Zs.A 5881: Show issues

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Article ; Online: The MITF/mir-579-3p regulatory axis dictates BRAF-mutated melanoma cell fate in response to MAPK inhibitors.

Liguoro, Domenico / Frigerio, Rachele / Ortolano, Arianna / Sacconi, Andrea / Acunzo, Mario / Romano, Giulia / Nigita, Giovanni / Bellei, Barbara / Madonna, Gabriele / Capone, Mariaelena / Ascierto, Paolo Antonio / Mancini, Rita / Ciliberto, Gennaro / Fattore, Luigi

Cell death & disease

2024 Volume 15, Issue 3, Page(s) 208

Abstract: Therapy of melanoma has improved dramatically over the last years thanks to the development of targeted therapies (MAPKi) and immunotherapies. However, drug resistance continues to limit the efficacy of these therapies. Our research group has provided ... ...

Abstract	Therapy of melanoma has improved dramatically over the last years thanks to the development of targeted therapies (MAPKi) and immunotherapies. However, drug resistance continues to limit the efficacy of these therapies. Our research group has provided robust evidence as to the involvement of a set of microRNAs in the development of resistance to target therapy in BRAF-mutated melanomas. Among them, a pivotal role is played by the oncosuppressor miR-579-3p. Here we show that miR-579-3p and the microphthalmia-associated transcription factor (MITF) influence reciprocally their expression through positive feedback regulatory loops. In particular we show that miR-579-3p is specifically deregulated in BRAF-mutant melanomas and that its expression levels mirror those of MITF. Luciferase and ChIP studies show that MITF is a positive regulator of miR-579-3p, which is located in the intron 11 of the human gene ZFR (Zink-finger recombinase) and is co-transcribed with its host gene. Moreover, miR-579-3p, by targeting BRAF, is able to stabilize MITF protein thus inducing its own transcription. From biological points of view, early exposure to MAPKi or, alternatively miR-579-3p transfection, induce block of proliferation and trigger senescence programs in BRAF-mutant melanoma cells. Finally, the long-term development of resistance to MAPKi is able to select cells characterized by the loss of both miR-579-3p and MITF and the same down-regulation is also present in patients relapsing after treatments. Altogether these findings suggest that miR-579-3p/MITF interplay potentially governs the balance between proliferation, senescence and resistance to therapies in BRAF-mutant melanomas.
MeSH term(s)	Humans ; Melanoma/genetics ; Proto-Oncogene Proteins B-raf/metabolism ; Microphthalmia-Associated Transcription Factor/genetics ; Neoplasm Recurrence, Local/genetics ; MicroRNAs/genetics ; Protein Kinase Inhibitors/pharmacology ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic
Chemical Substances	Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Microphthalmia-Associated Transcription Factor ; MicroRNAs ; Protein Kinase Inhibitors ; MITF protein, human ; BRAF protein, human (EC 2.7.11.1) ; MIRN579 microRNA, human
Language	English
Publishing date	2024-03-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-024-06580-2
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Article ; Online: Chlorpromazine affects glioblastoma bioenergetics by interfering with pyruvate kinase M2.

Abbruzzese, Claudia / Matteoni, Silvia / Matarrese, Paola / Signore, Michele / Ascione, Barbara / Iessi, Elisabetta / Gurtner, Aymone / Sacconi, Andrea / Ricci-Vitiani, Lucia / Pallini, Roberto / Pace, Andrea / Villani, Veronica / Polo, Andrea / Costantini, Susan / Budillon, Alfredo / Ciliberto, Gennaro / Paggi, Marco G

Cell death & disease

2023 Volume 14, Issue 12, Page(s) 821

Abstract: Glioblastoma (GBM) is the most frequent and lethal brain tumor, whose therapeutic outcome - only partially effective with current schemes - places this disease among the unmet medical needs, and effective therapeutic approaches are urgently required. In ... ...

Abstract	Glioblastoma (GBM) is the most frequent and lethal brain tumor, whose therapeutic outcome - only partially effective with current schemes - places this disease among the unmet medical needs, and effective therapeutic approaches are urgently required. In our attempts to identify repositionable drugs in glioblastoma therapy, we identified the neuroleptic drug chlorpromazine (CPZ) as a very promising compound. Here we aimed to further unveil the mode of action of this drug. We performed a supervised recognition of the signal transduction pathways potentially influenced by CPZ via Reverse-Phase Protein microArrays (RPPA) and carried out an Activity-Based Protein Profiling (ABPP) followed by Mass Spectrometry (MS) analysis to possibly identify cellular factors targeted by the drug. Indeed, the glycolytic enzyme PKM2 was identified as one of the major targets of CPZ. Furthermore, using the Seahorse platform, we analyzed the bioenergetics changes induced by the drug. Consistent with the ability of CPZ to target PKM2, we detected relevant changes in GBM energy metabolism, possibly attributable to the drug's ability to inhibit the oncogenic properties of PKM2. RPE-1 non-cancer neuroepithelial cells appeared less responsive to the drug. PKM2 silencing reduced the effects of CPZ. 3D modeling showed that CPZ interacts with PKM2 tetramer in the same region involved in binding other known activators. The effect of CPZ can be epitomized as an inhibition of the Warburg effect and thus malignancy in GBM cells, while sparing RPE-1 cells. These preclinical data enforce the rationale that allowed us to investigate the role of CPZ in GBM treatment in a recent multicenter Phase II clinical trial.
MeSH term(s)	Humans ; Glioblastoma/pathology ; Chlorpromazine/pharmacology ; Chlorpromazine/therapeutic use ; Pyruvate Kinase/metabolism ; Cell Line, Tumor ; Energy Metabolism
Chemical Substances	Chlorpromazine (U42B7VYA4P) ; Pyruvate Kinase (EC 2.7.1.40)
Language	English
Publishing date	2023-12-13
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/s41419-023-06353-3
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Article ; Online: Missing Value Monitoring Enhances the Robustness in Proteomics Quantitation.

Matafora, Vittoria / Corno, Andrea / Ciliberto, Andrea / Bachi, Angela

Journal of proteome research

2017 Volume 16, Issue 4, Page(s) 1719–1727

Abstract: In global proteomic analysis, it is estimated that proteins span from millions to less than 100 copies per cell. The challenge of protein quantitation by classic shotgun proteomic techniques relies on the presence of missing values in peptides belonging ... ...

Abstract	In global proteomic analysis, it is estimated that proteins span from millions to less than 100 copies per cell. The challenge of protein quantitation by classic shotgun proteomic techniques relies on the presence of missing values in peptides belonging to low-abundance proteins that lowers intraruns reproducibility affecting postdata statistical analysis. Here, we present a new analytical workflow MvM (missing value monitoring) able to recover quantitation of missing values generated by shotgun analysis. In particular, we used confident data-dependent acquisition (DDA) quantitation only for proteins measured in all the runs, while we filled the missing values with data-independent acquisition analysis using the library previously generated in DDA. We analyzed cell cycle regulated proteins, as they are low abundance proteins with highly dynamic expression levels. Indeed, we found that cell cycle related proteins are the major components of the missing values-rich proteome. Using the MvM workflow, we doubled the number of robustly quantified cell cycle related proteins, and we reduced the number of missing values achieving robust quantitation for proteins over ∼50 molecules per cell. MvM allows lower quantification variance among replicates for low abundance proteins with respect to DDA analysis, which demonstrates the potential of this novel workflow to measure low abundance, dynamically regulated proteins.
MeSH term(s)	Cell Cycle Proteins/genetics ; Cell Cycle Proteins/isolation & purification ; Peptides/genetics ; Peptides/isolation & purification ; Proteome/genetics ; Proteomics ; Tandem Mass Spectrometry
Chemical Substances	Cell Cycle Proteins ; Peptides ; Proteome
Language	English
Publishing date	2017-04-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2078618-9
ISSN	1535-3907 ; 1535-3893
ISSN (online)	1535-3907
ISSN	1535-3893
DOI	10.1021/acs.jproteome.6b01056
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Article ; Online: Micromanaging checkpoint proteins

Andrea Ciliberto / Silke Hauf

eLife, Vol

2017 Volume 6

Abstract: The kinase Mps1, long known to be the ‘boss’ in mitotic checkpoint signaling, phosphorylates multiple proteins in the checkpoint signaling cascade. ...

Abstract	The kinase Mps1, long known to be the ‘boss’ in mitotic checkpoint signaling, phosphorylates multiple proteins in the checkpoint signaling cascade.
Keywords	spindle checkpoint ; kinetochore ; protein kinase ; cell cycle ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2017-02-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
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Article ; Online: COV-BT Ire study: safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with brain tumors.

Tanzilli, Antonio / Pace, Andrea / Ciliberto, Gennaro / La Malfa, Antonia Marina / Buonomo, Valentina / Benincasa, Dario / Biscu, Annamaria / Galiè, Edvina / Villani, Veronica

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

2022 Volume 43, Issue 6, Page(s) 3519–3522

Abstract: Background: The BNT162b2 vaccine conferred 95% protection against COVID-19 in people aged 16 years or older.: Objective: The aim of this observational study was to evaluate safety and efficacy of vaccine in patients affected by primary brain tumor ( ... ...

Abstract	Background: The BNT162b2 vaccine conferred 95% protection against COVID-19 in people aged 16 years or older. Objective: The aim of this observational study was to evaluate safety and efficacy of vaccine in patients affected by primary brain tumor (PBT). Methods: We proposed COVID-19 vaccine to all patients affected by PBT followed by Neuroncology Unit of National Cancer Institute Regina Elena. Results: 102 patients received the first dose, 100 the second, and 73 patients received the booster dose. After first dose, we observed one patient with fever and severe fatigue, while after the second one, we recorded adverse events in ten patients. No correlation was observed between adverse events and comorbidities. Conclusions: The COVID-19 vaccine is safe and well tolerated in PBT patients.
MeSH term(s)	BNT162 Vaccine ; Brain Neoplasms/complications ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Humans ; RNA, Messenger ; SARS-CoV-2
Chemical Substances	COVID-19 Vaccines ; RNA, Messenger ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2022-04-09
Publishing country	Italy
Document type	Journal Article ; Observational Study
ZDB-ID	2016546-8
ISSN	1590-3478 ; 1590-1874
ISSN (online)	1590-3478
ISSN	1590-1874
DOI	10.1007/s10072-022-06054-3
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Article ; Online: Implications of alternative routes to APC/C inhibition by the mitotic checkpoint complex.

Gross, Fridolin / Bonaiuti, Paolo / Hauf, Silke / Ciliberto, Andrea

PLoS computational biology

2018 Volume 14, Issue 9, Page(s) e1006449

Abstract: The mitotic checkpoint (also called spindle assembly checkpoint) is a signaling pathway that ensures faithful chromosome segregation. Mitotic checkpoint proteins inhibit the anaphase-promoting complex (APC/C) and its activator Cdc20 to prevent precocious ...

Abstract	The mitotic checkpoint (also called spindle assembly checkpoint) is a signaling pathway that ensures faithful chromosome segregation. Mitotic checkpoint proteins inhibit the anaphase-promoting complex (APC/C) and its activator Cdc20 to prevent precocious anaphase. Checkpoint signaling leads to a complex of APC/C, Cdc20, and checkpoint proteins, in which the APC/C is inactive. In principle, this final product of the mitotic checkpoint can be obtained via different pathways, whose relevance still needs to be fully ascertained experimentally. Here, we use mathematical models to compare the implications on checkpoint response of the possible pathways leading to APC/C inhibition. We identify a previously unrecognized funneling effect for Cdc20, which favors Cdc20 incorporation into the inhibitory complex and therefore promotes checkpoint activity. Furthermore, we find that the presence or absence of one specific assembly reaction determines whether the checkpoint remains functional at elevated levels of Cdc20, which can occur in cancer cells. Our results reveal the inhibitory logics behind checkpoint activity, predict checkpoint efficiency in perturbed situations, and could inform molecular strategies to treat malignancies that exhibit Cdc20 overexpression.
MeSH term(s)	Anaphase ; Anaphase-Promoting Complex-Cyclosome ; Cdc20 Proteins/metabolism ; Cell Cycle Proteins/antagonists & inhibitors ; Cell Cycle Proteins/metabolism ; Cell Nucleus/metabolism ; Chromosome Segregation ; Mitosis/genetics ; Models, Theoretical ; Protein Binding ; Schizosaccharomyces/cytology ; Schizosaccharomyces pombe Proteins/metabolism ; Signal Transduction ; Spindle Apparatus/metabolism
Chemical Substances	Cdc20 Proteins ; Cdc20 protein, S pombe ; Cell Cycle Proteins ; Schizosaccharomyces pombe Proteins ; Anaphase-Promoting Complex-Cyclosome (EC 2.3.2.27)
Language	English
Publishing date	2018-09-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1006449
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