Search Results
You are looking at 1 - 7 of 7 items for
- Author: Giovanni Vitale x
- Refine by Access: All content x
Laboratory of Geriatric and Oncologic Neuroendocrinology Research, Istituto Auxologico Italiano IRCCS, Milan, Italy
Search for other papers by Giovanni Vitale in
Google Scholar
PubMed
Search for other papers by Alessandra Dicitore in
Google Scholar
PubMed
Search for other papers by Concetta Sciammarella in
Google Scholar
PubMed
Search for other papers by Sergio Di Molfetta in
Google Scholar
PubMed
Search for other papers by Manila Rubino in
Google Scholar
PubMed
Search for other papers by Antongiulio Faggiano in
Google Scholar
PubMed
Search for other papers by Annamaria Colao in
Google Scholar
PubMed
Somatostatin analogs have an important role in the medical therapy of neuroendocrine tumors (NETs). Octreotide and lanreotide, both somatostatin analogs binding with high affinity for the somatostatin receptor (SSTR)2, can control symptoms in functional NETs. In addition, these compounds, because of their antiproliferative effects, can stabilize growth of well-differentiated NETs. Pasireotide is a novel multireceptor-targeted somatostatin analog with high affinity for SSTR1, 2, 3, and 5. This review provides an overview of the state of the art of pasireotide in the treatment of NETs, with the aim of addressing clinical relevance and future perspectives for this molecule in the management of NETs.
Department of Clinical Sciences and Community Health (DISCCO), Laboratory of Endocrine and Metabolic Research, Department of Biosciences, Endocrinology Unit, University of Milan, Milan, Italy
Search for other papers by Giovanni Vitale in
Google Scholar
PubMed
Search for other papers by Germano Gaudenzi in
Google Scholar
PubMed
Search for other papers by Alessandra Dicitore in
Google Scholar
PubMed
Search for other papers by Franco Cotelli in
Google Scholar
PubMed
Search for other papers by Diego Ferone in
Google Scholar
PubMed
Department of Clinical Sciences and Community Health (DISCCO), Laboratory of Endocrine and Metabolic Research, Department of Biosciences, Endocrinology Unit, University of Milan, Milan, Italy
Search for other papers by Luca Persani in
Google Scholar
PubMed
Tumor models have a relevant role in furthering our understanding of the biology of malignant disease and in preclinical cancer research. Only few models are available for neuroendocrine tumors (NETs), probably due to the rarity and heterogeneity of this group of neoplasms. This review provides insights into the current state-of-the-art of zebrafish as a model in cancer research, focusing on potential applications in NETs. Zebrafish has a complex circulatory system similar to that of mammals. A novel angiogenesis assay based on the injection of human NET cell lines (TT and DMS79 cells) into the subperidermal space of the zebrafish embryos has been developed. Proangiogenic factors locally released by the tumor graft affect the normal developmental pattern of the subintestinal vessels by stimulating the migration and growth of sprouting vessels toward the implant. In addition, a description of the striking homology between zebrafish and humans of molecular targets involved in tumor angiogenesis (somatostatin receptors, dopamine receptors, mammalian target of rapamycin), and currently used as targeted therapy of NETs, is reported.
Search for other papers by Germano Gaudenzi in
Google Scholar
PubMed
Search for other papers by Silvia Carra in
Google Scholar
PubMed
Search for other papers by Alessandra Dicitore in
Google Scholar
PubMed
Search for other papers by Maria Celeste Cantone in
Google Scholar
PubMed
Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy
Search for other papers by Luca Persani in
Google Scholar
PubMed
Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy
Search for other papers by Giovanni Vitale in
Google Scholar
PubMed
Neuroendocrine tumors (NETs) are a class of rare and heterogeneous neoplasms that originate from the neuroendocrine system. In several cases, these neoplasms can release bioactive hormones leading to characteristic clinical syndromes and hormonal dysregulations with detrimental impact on the quality of life and survival of these patients. Only few animal models are currently available to investigate pathogenesis, progression and functional syndromes in NETs and to identify new therapeutic strategies. The tropical teleost zebrafish (Danio rerio) is a popular vertebrate model system that offers unique advantages for the study of several biological processes, ranging from embryonic development to human diseases such as cancer. In this review, we summarize recent advances on zebrafish models for NET preclinical research that take advantage of modern genetic and transplantable technologies. In the future, these tools may have a role in the treatment decision-making and tertiary prevention of NETs.
Search for other papers by Annemiek Walenkamp in
Google Scholar
PubMed
Search for other papers by Guillermo Crespo in
Google Scholar
PubMed
Search for other papers by Felipe Fierro Maya in
Google Scholar
PubMed
Search for other papers by Reidar Fossmark in
Google Scholar
PubMed
Search for other papers by Peter Igaz in
Google Scholar
PubMed
Search for other papers by Anja Rinke in
Google Scholar
PubMed
Search for other papers by Gianluca Tamagno in
Google Scholar
PubMed
Department of Medical Oncology, Department of Medical Oncology, Department of Endocrine Oncology, Department of Cancer Research and Molecular Medicine, 2nd Department of Medicine, Department of Gastroenterology, Department of General Internal Medicine, Department of Clinical Sciences and Community Health (DISCCO), Laboratory of Endocrine and Metabolic Research, Department of Endocrine Oncology, UCL Cancer Institute, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
Search for other papers by Giovanni Vitale in
Google Scholar
PubMed
Search for other papers by Kjell Öberg in
Google Scholar
PubMed
Search for other papers by Tim Meyer in
Google Scholar
PubMed
In the past few years, there have been advances in the treatment of neuroendocrine tumours (NETs) and improvements in our understanding of NET biology. However, the benefits to patients have been relatively modest and much remains yet to be done. The ‘Hallmarks of Cancer’, as defined by Hanahan and Weinberg, provide a conceptual framework for understanding the aberrations that underlie tumourigenesis and to help identify potential targets for therapy. In this study, our objective is to review the major molecular characteristics of NETs, based on the recently modified ‘Hallmarks of Cancer’, and highlight areas that require further research.
Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, Milan, Italy
Search for other papers by Giovanni Vitale in
Google Scholar
PubMed
Search for other papers by Germano Gaudenzi in
Google Scholar
PubMed
Search for other papers by Luisa Circelli in
Google Scholar
PubMed
Search for other papers by Marco F Manzoni in
Google Scholar
PubMed
Search for other papers by Andrea Bassi in
Google Scholar
PubMed
Search for other papers by Niccolò Fioritti in
Google Scholar
PubMed
Search for other papers by Antongiulio Faggiano in
Google Scholar
PubMed
Search for other papers by Annamaria Colao in
Google Scholar
PubMed
Search for other papers by on behalf of NIKE Group in
Google Scholar
PubMed
Medullary thyroid carcinoma is a neuroendocrine tumour originating from parafollicular C cells accounting for 5–10% of thyroid cancers. Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid carcinoma. These drugs increase progression-free survival; however, they are often poorly tolerated and most treatment responses are transient. Animal models are indispensable tools for investigating the pathogenesis, mechanisms for tumour invasion and metastasis and new therapeutic approaches for cancer. Unfortunately, only few models are available for medullary thyroid carcinoma. This review provides an overview of the state of the art of animal models in medullary thyroid carcinoma and highlights future developments in this field, with the aim of addressing salient features and clinical relevance.
Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, Brescia, Italy
Search for other papers by Chiara Alessandra Cella in
Google Scholar
PubMed
Metal Targeted Therapy & Immunology lab, Childrens’ cancer institute, Sydney, NSW, Australia
Search for other papers by Riccardo Cazzoli in
Google Scholar
PubMed
Search for other papers by Nicola Fazio in
Google Scholar
PubMed
Search for other papers by Giuseppina De Petro in
Google Scholar
PubMed
Search for other papers by Germano Gaudenzi in
Google Scholar
PubMed
Search for other papers by Silvia Carra in
Google Scholar
PubMed
Search for other papers by Mauro Romanenghi in
Google Scholar
PubMed
Search for other papers by Francesca Spada in
Google Scholar
PubMed
Search for other papers by Ilaria Grossi in
Google Scholar
PubMed
Search for other papers by Isabella Pallavicini in
Google Scholar
PubMed
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
Search for other papers by Saverio Minucci in
Google Scholar
PubMed
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
Search for other papers by Giovanni Vitale in
Google Scholar
PubMed
Neuroendocrine tumors (NETs) are highly vascularized malignancies in which angiogenesis may entail cell proliferation and survival. Among the emerging compounds with antivascular properties, cabozantinib (CAB) appeared promising. We analyzed the antitumor activity of CAB against NETs utilizing in vitro and in vivo models. For cell cultures, we used BON-1, NCI-H727 and NCI-H720 cell lines. Cell viability was assessed by manual count coupled with quantification of cell death, performed through fluorescence-activated cell sorting analysis as propidium iodide exclusion assay. In addition, we investigated the modulation of the antiapoptotic myeloid cell leukemia 1 protein under CAB exposure, as a putative adaptive pro-survival mechanism, and compared the responses with sunitinib. The activity of CAB was also tested in mouse and zebrafish xenograft tumor models. Cabozantinib showed a dose-dependent and time-dependent effect on cell viability and proliferation in human NET cultures, besides a halting of cell cycle progression for endoduplication, never reported for other tyrosine kinase inhibitors. In a transplantable zebrafish model, CAB drastically inhibited NET-induced angiogenesis and migration of implanted cells through the embryo body. CAB showed encouraging activity in NETs, both in vitro and in vivo models. On this basis, we envisage future research to further investigate along these promising lines.
Search for other papers by Peter M van Koetsveld in
Google Scholar
PubMed
Division of Endocrinology, Department of Pathology, Dipartimento di Scienze Mediche, IRCCS Istituto Auxologico Italiano, Department of Pathology, Department of Internal Medicine, Erasmus Medical Center, Erasmus MC, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands
Division of Endocrinology, Department of Pathology, Dipartimento di Scienze Mediche, IRCCS Istituto Auxologico Italiano, Department of Pathology, Department of Internal Medicine, Erasmus Medical Center, Erasmus MC, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands
Search for other papers by Giovanni Vitale in
Google Scholar
PubMed
Search for other papers by Richard A Feelders in
Google Scholar
PubMed
Search for other papers by Marlijn Waaijers in
Google Scholar
PubMed
Search for other papers by Diana M Sprij-Mooij in
Google Scholar
PubMed
Search for other papers by Ronald R de Krijger in
Google Scholar
PubMed
Search for other papers by Ernst-Jan M Speel in
Google Scholar
PubMed
Search for other papers by Johannes Hofland in
Google Scholar
PubMed
Search for other papers by Steven W J Lamberts in
Google Scholar
PubMed
Search for other papers by Wouter W de Herder in
Google Scholar
PubMed
Search for other papers by Leo J Hofland in
Google Scholar
PubMed
Adrenocortical carcinoma (ACC) is an aggressive tumor with very poor prognosis. Novel medical treatment opportunities are required. We investigated the effects of interferon-β (IFN-β), alone or in combination with mitotane, on cell growth and cortisol secretion in primary cultures of 13 human ACCs, three adrenal hyperplasias, three adrenal adenomas, and in two ACC cell lines. Moreover, the interrelationship between the effects of IGF2 and IFN-β was evaluated. Mitotane inhibited cell total DNA content/well (representing cell number) in 7/11 (IC50: 38±9.2 μM) and cortisol secretion in 5/5 ACC cultures (IC50: 4.5±0.1 μM). IFN-β reduced cell number in 10/11 (IC50: 83±18 IU/ml) and cortisol secretion in 5/5 ACC cultures (IC50: 7.3±1.5 IU/ml). The effect of IFN-β on cell number included the induction of apoptosis. IFN-β strongly inhibited mRNA expression of STAR, CYP11A1, CYP17A1, and CYP11B1. Mitotane and IFN-β induced an additive inhibitory effect on cell number and cortisol secretion. IGF2 (10 nM) inhibited apoptosis and increased cell number and cortisol secretion. These effects were counteracted by IFN-β treatment. Finally, IFN-β inhibited IGF2 secretion and mRNA expression. In conclusion, IFN-β is a potent inhibitor of ACC cell growth in human primary ACC cultures, partially mediated by an inhibition of the effects of IGF2, as well as its production. The increased sensitivity of ACC cells to mitotane induced by treatment with IFN-β may open the opportunity for combined treatment regimens with lower mitotane doses. The inhibition of the expression of steroidogenic enzymes by IFN-β is a novel mechanism that may explain its inhibitory effect on cortisol production.
