Ferdinando Chiaradonna

Ferdinando Chiaradonna
Università degli Studi di Milano-Bicocca | UNIMIB · Department of Biotechnology and Biosciences

PhD

About

114
Publications
29,558
Reads
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3,138
Citations
Additional affiliations
October 2019 - present
Università degli Studi di Milano-Bicocca
Position
  • Professor (Associate)
October 2002 - September 2019
Università degli Studi di Milano-Bicocca
Position
  • Professor (Assistant)
September 1997 - September 2002
IEO - Istituto Europeo di Oncologia
Position
  • PhD-Fellowship

Publications

Publications (114)
Article
Macrophages undergo extensive metabolic reprogramming during classical pro-inflammatory polarization (M1-like). The accumulation of itaconate has been recognized as both a consequence and mediator of the inflammatory response. In this study we first examined the specific functions of itaconate inside fractionated mitochondria. We show that M1 macro...
Article
To assess the evidence on SARS-CoV2 infection and Covid-19 in relation to deficiency and supplementation of vitamin D, we conducted a systematic review up to April 2021. We summarised data from 38 eligible studies, which presented risk estimates for at least one endpoint, including two RCT and 27 cohort-studies: 205565 patients with information on...
Article
Full-text available
DJ-1, also called Parkinson’s protein 7 (PARK7), is ubiquitously expressed and plays multiple actions in different physiological and, especially, pathophysiological processes, as evidenced by its identification in neurodegenerative diseases and its high expression in different types of cancer. To date, the exact activity of DJ-1 in carcinogenesis h...
Article
Ovarian cancer is the deadliest gynecologic cancer, and novel therapeutic options are crucial to improve overall survival. Here we provide evidence that impairment of oxidative phosphorylation (OXPHOS) can help control ovarian cancer progression, and this benefit correlates with expression of the two mitochondrial master regulators PGC1α and PGC1β....
Article
Full-text available
Recent evidence has shown a number of extra-skeletal functions of Vitamin D (VD), primarily involving the immune system. One of these functions is mediated by the modulation of gut microbiota, whose alterations are linked to many diseases. Our purpose is to contribute to the understanding of existing evidence on the association between VD and gastr...
Article
Full-text available
Several studies have investigated the beneficial effects of vitamin D on survival of cancer patients. Overall evidence has been accumulating with contrasting results. This paper aims at narratively reviewing the existing articles examining the link between vitamin D supplementation and cancer mortality. We performed two distinct searches to identif...
Article
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Cancer cells exhibit common hallmarks consisting of specific competencies acquired during the tumorigenesis process, including stimulation of cancer cell proliferation, insensitivity to growth signal inhibition, apoptosis evasion, enhancement of replicative potential, induction of angiogenesis, and tissue invasion and metastasis [...]
Article
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The first-line chemotherapies for patients with unresectable pancreatic cancer (PC) are 5-fluorouracil (5-FU) and gemcitabine therapy. However, due to chemoresistance the prognosis of patients with PC has not been significantly improved. Mitochondria are essential organelles in eukaryotes that evolved from aerobic bacteria. In recent years, many st...
Article
Full-text available
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death and the search for a resolutive therapy is still a challenge. Since KRAS is commonly mutated in PDAC and is one of the main drivers of PDAC progression, its inhibition should be a key strategy for treatment, especially considering the recent development of specific K...
Article
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Preprint
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Preprint
Full-text available
the PDF can be download freely on pubmed. https://pubmed.ncbi.nlm.nih.gov/33634751/
Cover Page
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In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Article
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Article
Full-text available
Different evidence has indicated metabolic rewiring as a necessity for pancreatic cancer (PC) growth, invasion, and chemotherapy resistance. A relevant role has been assigned to glucose metabolism. In particular, an enhanced flux through the Hexosamine Biosynthetic Pathway (HBP) has been tightly linked to PC development. Here, we show that enhancem...
Article
Full-text available
Motivation: The elucidation of dysfunctional cellular processes that can induce the onset of a disease is a challenging issue from both experimental and computational perspectives. Here we introduce a novel computational method based on the coupling between fuzzy logic modeling and a global optimization algorithm, whose aims are to (1) predict the...
Article
Full-text available
Metabolism and mitochondrial biology have gained a prominent role as determinants of stem cell fate and function. In the context of regenerative medicine, innovative parameters predictive of therapeutic efficacy could be drawn from the association of metabolic or mitochondrial parameters to different degrees of stemness and differentiation potentia...
Chapter
An understanding of the mechanism of apoptosis has received a substantial amount of interest over the past decades. It is evident from many works that mitochondria play a pivotal role in keeping cell homeostasis in both physiological and pathological conditions. The ability of mitochondria to reprogram cell metabolism is a key function to cell life...
Article
Full-text available
Alterations in glucose and glutamine utilizing pathways and in fatty acid metabolism are currently considered the most significant and prevalent metabolic changes observed in almost all types of tumors. Glucose, glutamine and fatty acids are the substrates for the hexosamine biosynthetic pathway (HBP). This metabolic pathway generates the “sensing...
Conference Paper
Full-text available
Introduction Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumour progression. Recent studies reported an association between the tumorigenic potential, metastasis and chemoresistance of several type of breast cancer cells...
Article
Full-text available
A library of GlcNAc-6 or 1P analogues was designed and each compound was computationally evaluated through docking studies for its binding affinity to AGM1/PGM3. The compounds with the highest binding affinity ranked through a docking score, were synthesized and screened for their ability to inhibit the production of UDP-GlcNAc. A glycofused oxazol...
Article
Full-text available
Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumor progression. However, the low specificity and toxicity of the existing HBP inhibitors prevented their use for cancer treatment. Here we report the preclinical evaluation...
Article
Full-text available
To date, it is well-established that mitochondrial dysfunction does not only play a vital role in cancer but also in other pathological conditions such as neurodegenerative diseases and inflammation. An important tool for the analysis of cellular metabolism is the application of stable isotope labeled substrates, which allow for the tracing of atom...
Article
Full-text available
Forskolin (FSK) induces activation of protein kinase A (PKA). This activation protects specifically some cancer cells from death induced by glucose starvation. Cell effects upon FSK treatment prompted us to investigate in detail the physiological role of PKA in the activation of pro-survival mechanisms in glucose starvation. In this regard we perfo...
Article
Full-text available
Cancer cells often rely on glycolysis to obtain energy and support anabolic growth. Several studies showed that glycolytic cells are susceptible to cell death when subjected to low glucose availability or to lack of glucose. However, some cancer cells, including glycolytic ones, can efficiently acquire higher tolerance to glucose depletion, leading...
Article
Full-text available
Cancer cells often rely on glycolysis to obtain energy and support anabolic growth. Several studies showed that glycolytic cells are susceptible to cell death when subjected to low glucose availability or to lack of glucose. However, some cancer cells, including glycolytic ones, can efficiently acquire higher tolerance to glucose depletion, leading...
Data
The genes regulated by FSK in Transformed cells show a low degree of connection. In the figure the network of predicted associations for all DEGs-encoded proteins in TF/T comparison is shown. The STRING analysis of the protein-protein interactions was performed to DEGs with fold change ≥2 in the comparison. (PDF)
Data
The treatment with FSK induces a relevant change in the expression of genes related to the glutamine metabolism. Transcriptional data from microarray analysis regarding glutamine metabolism-related genes in Transformed cells at 72h of culture in LG, daily treated with DMSO or FSK. Data express the ratio in TF/T comparison. (PDF)
Data
FSK-treated MDA-MB-231 cells show a different expression of glutamine metabolism-related genes as compared to untreated cells. The expression of genes related to the glutamine metabolism was performed in MDA-MB-231 cells daily treated with DMSO or FSK after 48h and 72h of cultivation in LG. mRNA expression of glutamine metabolism-related genes was...
Data
PKA and autophagy activation in suspended MDA-MB-231 cells. A MDA-MB-231 cells treated with FSK were collected and stained with fluorescent substrate of the active caspase-3 and then newly attached to the coverslip using cytospin. Then they were fixed and labeled with the antibody for PKA substrates. The images were visualized by using fluorescent...
Data
Genes and proteins identified in our study and used for the Gene set enrichment analysis. Transcriptional and proteomic data have been mapped in the 202 KEGG pathways (metabolic and signaling). (XLS)
Data
Graphical representation of the experimental workflow -/+FSK. A, D For the analyses upon treatment with FSK Normal and Transformed cells (A) as well as MDA-MB-231 (D) were cultured in LG medium (1mM as initial concentration) 16h after seeding. Then, starting from 24h the cells were daily treated with DMSO (vehicle) or 10μM FSK. When required, at 72...
Data
The genes regulated by FSK in Normal cells show a high degree of connection. In the figure the network of predicted associations for all DEGs-encoded proteins in NF/N comparison is shown. The STRING analysis of the protein-protein interactions was performed to DEGs with fold change ≥2 in the comparison. (PDF)
Data
Network of predicted associations for all the differentially expressed proteins identified by 2-DIGE. The STRING analysis of the protein-protein interactions was performed using proteins with spot variation ≥10% in NF/N (A) and TF/T (B) comparisons. (PDF)
Data
The inhibition of PKA prevents the resistance to glucose deprivation and anoikis. A Graphical representation of the experimental workflow for analyses in anoikis-resistant floating cells. MDA-MB-231 cells were cultured in LG. At 72h, when a significant part of the cell population was detached from the plate, the suspended cells were collected and t...
Data
PKA pathway is endogenously activated in Transformed cells cultured in glucose deprivation, mediating their resistance to anoikis. A At indicated time points of culture in LG, floating cells were stained with trypan blue and counted to verify whether floating cells were resistant to anoikis. Percentage of floating and dead cells was reported over t...
Data
Glucose depletion induces low anoikis-resistance in MIA PaCa-2 when cultivated on standard support. A MIA PaCa-2 cells were cultured in LG (1mM glucose as initial concentration). The amount of glucose in the medium was measured using an enzymatic kit. B-C MIA PaCa-2 cells cultured in HG and LG were counted at different time points with Trypan blue,...
Data
Highly differentially expressed genes in the two comparisons NF/N and TF/T. The two spreadshits represent the genes with logFC > = 1 in the two comparisons NF/N and TF/T and shown in the heatmap of Fig 1B (XLS)
Data
List of primers used for qPCR amplification of target genes. Table A: Normal and Transformed cells. Table B: MDA- MB-231 cells (PDF)
Data
Analysis of transcriptomic and proteomic data using PIANO method. The heatmap shows the result obtained by applying the PIANO tool to gene (A) and protein (B) datasets separately. In particular, the top 10-ranked pathways associated to each comparison, NF/N and TF/T, are shown. The different color of the heatmap represents the rank position of the...
Data
The FSK treatment attenuates UPR in both Normal and Transformed cells. The analysis shown here was performed in cells cultured for 72h in LG and daily treated with DMSO or 10μM FSK. A-B mRNA expression of UPR-related genes was analyzed by qPCR for Transformed (A) and Normal (B) cells. mRNA expression levels in FSK-treated cells are reported as chan...
Data
The induction of the PKA pathway mediates the autophagy activation in Transformed cells in glucose deprivation. A PKA activation was evaluated by Western blot analysis of p-(Ser/Thr) PKA substrates and pCREB S133 in Transformed cells daily treated with FSK and/or 2μM H89. B The cellular morphology of the cells -/+ FSK and -/+H89 was observed at 96h...
Data
FSK-protective role is not mediated by Epac. A Schematic representation of FSK-mediated activation of PKA and Epac proteins upon intracellular cAMP enhancement. To analyze the effect of Epac inhibition, the cells were daily treated with FSK and/or 1μM Epac inhibitor (ESI-09). B Cells -/+FSK and -/+ESI-09 were counted with trypan blue at 72h of cult...
Data
PKA activation protects MIA PaCa-2 pancreatic cancer cells by glucose deprivation-induced cell death. A-H For the analyses of -/+FSK MIA PaCa-2 cells were cultured in LG and daily treated with DMSO or FSK. A Microscopy images of cell morphology. B PKA activity after FSK treatment was evaluated by Western blot analysis of p-(Ser/Thr) PKA substrates...
Data
Proteins identified by mass spectrometry in the two comparisons NF/N and TF/T. The two spreadsheets show the mass spectrometry data, the UniProtKB accession number and percentage of the volume spot variation. (XLS)
Data
Total gene expression analysis. The table show the 17669 transcripts used for PIANO analysis and represented as hetamap in Fig 1C. N: Normal cells; N+F: Normal cells + FSK; T: Transformed cells; T+F: Transformed cells + FSK. (XLS)
Data
The inhibition of PKA counteracts the protective effects of FSK in MDA-MB-231. MDA-MB-231 cells were analyzed upon daily treatment with FSK and 2μM H89. A PKA activation by Western blot analysis of p-(Ser/Thr) PKA substrates and pCREB S133. B Microscopy images of the cells were collected at 72h of culture. C Western blot analysis of Grp78 and CHOP...
Data
The table reports the rankings obtained by each KEGG pathway (rows) in the two comparisons (N+F vs N and T+F vs T) in the transcript, in the proteomic, and in the integrated/aggregated dataset for the three directionality classes (down- and up-regulation, and non-directional regulation). Pathways in the first 10 positions for the transcript and int...
Data
Pathways used for Venn diagram. (XLS)
Data
NMR identified metabolite in N, N+F, T and T+F cells. Metabolite identified by NMR analysis for three independent biological replicates and mean and standard deviation thereof. (XLS)
Conference Paper
Cancer cells are characterized by metabolic alterations in particular intracellular pathways that should be exploitable in diagnosis and therapy of cancer. A key role in the development and in the maintenance of the proliferative aptitude of cancer cells is known to be associated to a disregulation of Nand O-glycosylation patterns of proteins that...
Article
Full-text available
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-...
Article
Full-text available
Environmental contributions to cancer development are widely accepted, but only a fraction of all pertinent exposures have probably been identified. Traditional toxicological approaches to the problem have largely focused on the effects of individual agents at singular endpoints. As such, they have incompletely addressed both the pro-carcinogenic c...
Article
Full-text available
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-...
Article
Full-text available
Vorinostat (SAHA) is a histone deacetylase inhibitor approved in the clinics for the treatment of T cell lymphoma and with the potential to be effective also in breast cancer. We investigated the responsiveness to SAHA in human breast primary tumors and cancer cell lines. We observed a differential response to drug treatment in both human breast pr...
Article
Full-text available
Significance: Histone deacetylases (HDACs) activity and cell metabolism are considered important targets for cancer therapy, as both are deregulated and associated with the onset and maintenance of tumors. Recent advances: Besides the classical function of HDACs as HDAC enzymes controlling the transcription, it is becoming increasingly evident t...
Article
Full-text available
Cancer stem cells (CSC) have a central role in driving tumor growth. Since metabolism is becoming an important diagnostic and therapeutic target, characterization of CSC line energetic properties is an emerging need. Embryonic and adult stem cells, compared to differentiated cells, exhibit a reduced mitochondrial activity and a stronger dependence...
Article
Full-text available
Cancer cells, which use more glucose than normal cells and accumulate extracellular lactate even under normoxic conditions (Warburg effect), have been reported to undergo cell death under glucose deprivation, whereas normal cells remain viable. As it may be relevant to exploit the molecular mechanisms underlying this biological response to achieve...
Article
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Brought to you by the editorial team of Cell Death and Differentiation, Cell Death and Disease is a peer-reviewed author-pays online journal in the field of translational cell death. It seeks to promote diverse and integrated areas of Experimental and Internal Medicine with its specialties, including Cancer, Immunity and Neuroscience.