Manlio Vinciguerra
I hold Principal Investigator positions at the Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy, and at the University College London (UCL) - Institute of Liver and Digestive Health, Division of Medicine, Royal Free Hospital, London, United Kingdom.
I have 14 years of research training and experience conducted in 5 different European countries (Italy, Holland, Switzerland, Germany, UK).
I am an eclectic and curious scientist with a wide range of interests, ranging from cell biology, growth factor signaling, epigenetics to aging and pre-clinical medicine in various organ systems. I have authored about 65 publications with Impact Factor, between research papers, reviews, editorials and book chapters.
My activity is strongly driven by the belief that cross-disciplinary science and collaborative work, bringing together minds to work on a common goal, are key aspects to progress in human knowledge.
I believe that sky is the limit.
Address: University College London (UCL) - Institute for Liver & Digestive Health
UCL Medical School – Royal Free Campus
U3rd Floor
Rowland Hill Street
London NW3 2PF
United Kingdom
I have 14 years of research training and experience conducted in 5 different European countries (Italy, Holland, Switzerland, Germany, UK).
I am an eclectic and curious scientist with a wide range of interests, ranging from cell biology, growth factor signaling, epigenetics to aging and pre-clinical medicine in various organ systems. I have authored about 65 publications with Impact Factor, between research papers, reviews, editorials and book chapters.
My activity is strongly driven by the belief that cross-disciplinary science and collaborative work, bringing together minds to work on a common goal, are key aspects to progress in human knowledge.
I believe that sky is the limit.
Address: University College London (UCL) - Institute for Liver & Digestive Health
UCL Medical School – Royal Free Campus
U3rd Floor
Rowland Hill Street
London NW3 2PF
United Kingdom
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Papers by Manlio Vinciguerra
BACKGROUND:
The parasympathetic nervous system (PNS), via neurotransmitter Acetylcholine (ACh), modulates fibrogenesis in animal models. However, the role of ACh in human hepatic fibrogenesis is unclear.
AIMS:
We aimed to determine the fibrogenic responses of human hepatic stellate cells (hHSC) to ACh and the relevance of the PNS in hepatic fibrosis in patients with non-alcoholic steatohepatitis (NASH).
METHODS:
Primary hHSC were analysed for synthesis of endogenous ACh and acetylcholinesterase (AChE), and gene expression of choline acetyltransferase (ChAT) and muscarinic acetylcholine receptors (mAChR). Cell proliferation and fibrogenic markers were analysed in hHSC exposed to ACh, Atropine (Atrop), Mecamylamine (Mec), methoctramine and 4-Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP). MAChR expression was analysed in human NASH scored for fibrosis.
RESULTS:
We observed that hHSC synthesise ACh and AChE, and express ChAT and M1-M5 mAChR. We also show that M2 was increased during NASH progression, while both M2 and M3 were found upregulated in activated hHSC. Furthermore, endogenous ACh is required for hHSC basal growth. Exogenous ACh resulted in hHSC hyperproliferation via mAChR and PI-3 K and MEK signalling pathways, as well as increased fibrogenic markers.
CONCLUSION:
We show that ACh regulates hHSC activation via M2 and M3 mAChR involving the PI-3 K and MEK pathways in vitro. Finally, we provide evidence that the PNS may be involved in human NASH fibrosis. This article is protected by copyright. All rights reserved.
OBJECTIVE:
The Death-Associated Protein Kinase 1 (DAPK1) gene has been frequently investigated in cervical cancer (CC). The aim of the present study was to carry out a systematic review and a meta-analysis in order to evaluate DAPK1 promoter methylation as an epigenetic marker for CC risk.
METHODS:
A systematic literature search was carried out. The Cochrane software package Review Manager 5.2 was used. The fixed-effects or random-effects models, according to heterogeneity across studies, were used to calculate odds ratios (ORs) and 95% Confidence Intervals (CIs). Furthermore, subgroup analyses were conducted by histological type, assays used to evaluate DAPK1 promoter methylation, and control sample source.
RESULTS:
A total of 20 papers, published between 2001 and 2014, on 1929 samples, were included in the meta-analysis. DAPK1 promoter methylation was associated with an increased CC risk based on the random effects model (OR: 21.20; 95%CI = 11.14-40.35). Omitting the most heterogeneous study, the between study heterogeneity decreased and the association increased (OR: 24.13; 95% CI = 15.83-36.78). The association was also confirmed in all the subgroups analyses.
CONCLUSIONS:
A significant strong association between DAPK1 promoter methylation and CC was shown and confirmed independently by histological tumor type, method used to evaluate methylation and source of control samples. Methylation markers may have value in early detection of CC precursor lesions, provide added reassurances of safety for women who are candidates for less frequent screens, and predict outcomes of women infected with human papilloma virus.
Pancreatic cancer (PC) is ranked as the fourth leading cause of cancer-related deaths worldwide. Despite recent advances in treatment options, a modest impact on the outcome of the disease is observed so far. Short-term fasting cycles have been shown to potentiate the efficacy of chemotherapy against glioma. The aim of this study was to assess the effect of fasting cycles on the efficacy of gemcitabine, a standard treatment for PC patients, in vitro and in an in vivo pancreatic cancer mouse xenograft model.
MATERIALS AND METHODS:
BxPC-3, MiaPaca-2 and Panc-1 cells were cultured in standard and fasting mimicking culturing condition to evaluate the effects of gemcitabine. Pancreatic cancer xenograft mice were subjected to 24h starvation prior to gemcitabine injection to assess the tumor volume and weight as compared to mice fed ad libitum.
RESULTS:
Fasted pancreatic cancer cells showed increased levels of equilibrative nucleoside transporter (hENT1), the transporter of gemcitabine across the cell membrane, and decreased ribonucleotide reductase M1 (RRM1) levels as compared to those cultured in standard medium. Gemcitabine was more effective in inducing cell death on fasted cells as compared to controls. Consistently, xenograft pancreatic cancer mice subjected to fasting cycles prior to gemcitabine injection displayed a decrease of more than 40% in tumor growth.
CONCLUSION:
Fasting cycles enhance gemcitabine effect in vitro and in the in vivo PC xenograft mouse model. These results suggest that restrictive dietary interventions could enhance the efficacy of existing cancer treatments in pancreatic cancer patients.