Domenico Ribatti

University of Catania, Catania, Sicily, Italy

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Publications (650)2371.88 Total impact

  • Enrico Crivellato, Luciana Travan, Domenico Ribatti
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    ABSTRACT: Mast cells (MCs) are tissue-based immune cells that participate to both innate and adaptive immunities as well as to tissue-remodelling processes. Their evolutionary history appears as a fascinating process, whose outline we can only partly reconstruct according to current remnant evidence. MCs have been identified in all vertebrate classes, and a cell population with the overall characteristics of higher vertebrate MCs is identifiable even in the most evolutionarily advanced fish species. In invertebrates, cells related to vertebrate MCs have been recognized in ascidians, a class of urochordates which appeared approximately 500 million years ago. These comprise the granular hemocyte with intermediate characteristics of basophils and MCs and the "test cell" (see below). Both types of cells contain histamine and heparin, and provide defensive functions. The test cell releases tryptase after stimulation with compound 48/80. A leukocyte ancestor operating in the context of a primitive local innate immunity probably represents the MC phylogenetic progenitor. This cell was likely involved in phagocytic and killing activity against pathogens and operated as a general inducer of inflammation. This early type of defensive cell possibly expressed concomitant tissue-reparative functions. With the advent of recombinase activating gene (RAG)-mediated adaptive immunity in the Cambrian era, some 550 million years ago, and the emergence of early vertebrates, MC progenitors differentiated towards a more complex cellular entity. Early MCs probably appeared in the last common ancestor we shared with hagfish, lamprey, and sharks about 450-500 million years ago.
    Methods in molecular biology (Clifton, N.J.) 01/2015; 1220:11-27. · 1.29 Impact Factor
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    ABSTRACT: Bcl-6 translocation is a genetic alteration that is commonly detected in Primary Central Nervous System Lymphoma. The role of this protein in cerebral tumors is unclear. In this study we investigated Bcl-6 translocation and its transcriptional and translational levels in formalin-fixed, paraffin-embedded cerebral tissue sections from Glioblastoma (GBM), low-grade glioma (Astrocytoma grade II and III), and meningioma patients, and correlated them with apoptotic processes and p53 and caspase-3 expression. The results showed a frequency of 36.6% of Bcl-6 translocation in GBM patients and a decreased expression in low-grade glioma patients, correlated with the severity of the disease. Bcl-6 translocation induced an overexpression of both Bcl-6 protein and messenger in GBM, inhibiting apoptotic processes and caspases 3 expression. On the contrary, in low-grade gliomas and meningiomas Bcl-6 expression was reduced, resulting in an increase of apoptotic processes. Finally, p53 expression levels in brain tumors were comparable to Bcl-6 levels. Overall, these data demonstrate, for the first time, that the Bcl-6 gene translocates in GBM patients and that its translocation and expression are correlated with apoptosis inhibition, indicating a key role for this gene in the control of cellular proliferation. This study offers further insights into Glioblastoma biology, and supports Bcl-6 as a new diagnostic marker to evaluate the disease severity.
    Cancer Letters. 10/2014; 353(1):41.
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    ABSTRACT: Interleukin (IL)-31 A binds to an heterodimer composed of IL-31 receptor A (IL-31RA) and Oncostatin M Receptor (OSMR). The IL-31/IL-31 R complex is involved in pathogenesis of various skin diseases, including cutaneous T cell lymphoma. No information is available on the relations between the IL-31/IL-31 R complex and B cell lymphoma. Here we have addressed this issue in follicular lymphoma (FL), a prototypic germinal center(GC)-derived B cell malignancy. IL-31 enhanced primary FL cell proliferation through IL-31 R-driven STAT1/3, ERK1/2, Akt phosphorylation. In contrast, GC B cells did not signal to IL-31 in spite of IL-31 R expression. GC B cells expressed predominantly the inhibitory short IL-31RA isoform, whereas FL cells expressed predominantly the long signaling isoform. Moreover, GC B cells lacked expression of other IL-31RA isoforms potentially involved in the signaling pathway. IL-31 protein expression was significantly higher in surface membrane than in cytosol of both FL and GC B cells. IL-31 was detected in plasma membrane microvescicles from both cell types, but not released in soluble form in culture supernatants. IL-31 and IL-31RA expression was higher in lymph nodes from FL patients with grade IIIa compared to grade I/II, suggesting a paracrine and/or autocrine role of IL-31/IL-31RA complex in tumor progression through microvescicle shedding.Leukemia accepted article preview online, 06 October 2014. doi:10.1038/leu.2014.291.
    Leukemia. 10/2014;
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    ABSTRACT: Diffuse Large B-cell lymphoma (DLBCL) is the most common form of Non-Hodgkin lymphoma characterized by clinical and biological heterogeneity attributable both to the tumor cells and the complex tumor-microenvironment surrounding them. Tumor-associated macrophages (TAMs) and mast cells are two major components of the tumor inflammatory infiltrate with a definite role in enhancing tumor angiogenesis. In this study, we have investigated CD68 and tryptase expression and their relationship with microvascular density (MVD) in chemo-resistant and chemosensitive patients affected by DLBCL. CD68 and tryptase expression as well as MVD were increased in chemo-resistant patients when compared with chemosensitive patients. Tryptase expression showed a positive correlation with MVD, supporting a role for mast cell in DLBCL tumor angiogenesis, while CD68 correlation with MVD was not significant, indicating a different role for TAMs than angiogenesis in DLBCL.
    Leukemia Research. 09/2014;
  • Domenico Ribatti
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    ABSTRACT: This article outlines the fundamental contribution of Max D. Cooper to the analysis of the role of the thymus and of the bursa of Fabricius in the development of immunologic competence both before and after birth, placing a new scientific paradigm in the definition of the ontogeny of the lymphoid tissues.
    Immunology letters. 09/2014;
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    ABSTRACT: Purpose: To investigate the angiogenic role of the HGF/cMET pathway and its inhibition in bone marrow (BM) endothelial cells (ECs) from patients with multiple myeloma (MM) vs those with monoclonal gammopathy of undetermined significance (MGUS) or benign anemia (controls). Experimental Design: The HGF/cMET pathway was evaluated in ECs from MM patients (MMECs) at diagnosis, at relapse after bortezomib- or lenalidomide-based therapies or on refractory phase to these drugs, in ECs from patients with MGUS (MGECs), and in those from controls. The effects of a selective cMET tyrosine kinase inhibitor (SU11274) on the MMECs angiogenic activities were studied in vitro and in vivo. Results: MMECs express more HGF, cMET, and activated cMET (phospho (p)-cMET) at both RNA and protein level vs MGECs and control ECs. MMECs are able to maintain the HGF/cMET pathway activation in absence of external stimulation, while treatment with anti-HGF and anti-cMET neutralizing antibodies (Abs) is able to inhibit the cMET activation. The cMET pathway regulates several MMECs activities including chemotaxis, motility, adhesion, spreading, and whole angiogenesis. Its inhibition by SU11274 impairs these activities in a statistically significant fashion when combined with bortezomib or lenalidomide, both in vitro and in vivo. Conclusions: An autocrine HGF/cMET loop sustains MM angiogenesis, and represents an appealing new target to potentiate the antiangiogenic management of MM patients.
    Clinical cancer research : an official journal of the American Association for Cancer Research. 09/2014;
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    ABSTRACT: Rearrangements involving the Anaplastic Lymphoma Kinase (ALK) gene are defining events in several tumors, including Anaplastic Large Cell Lymphoma (ALCL) and Non-Small Cell Lung Carcinoma (NSCLC). In such cancers, the oncogenic activity of ALK stimulates signaling pathways that induce cell transformation and promote tumor growth. In search for common pathways activated by oncogenic ALK across different tumors types, we found that hypoxia pathways were significantly enriched in ALK-rearranged ALCL and NSCLC, as compared to other types of T cell lymphoma or EGFR and K-RAS mutated NSCLC, respectively. Consistently, in both ALCL and NSCLC we found that under hypoxic conditions ALK directly regulated the abundance of Hypoxia-Inducible Factors (HIFs), which are key players of the hypoxia response in normal tissues and cancers. In ALCL, the upregulation of HIF-1α and HIF-2α in hypoxic conditions required ALK activity and its downstream signaling proteins Stat3 and C/EBPβ. In vivo, ALK regulated VEGFA production and tumor angiogenesis in ALCL and NSCLC, and the treatment with the anti-VEGFA antibody bevacizumab strongly impaired ALCL growth in mouse xenografts. Finally, HIF-2α, but not HIF-1α, was required for ALCL growth in vivo whereas the growth and metastasis potential of ALK-rearranged NSCLC required both HIF-1α and HIF-2α. In conclusion, we uncovered an ALK specific regulation of the hypoxia response across different ALK positive tumor types, and propose HIFs as a powerful specific therapeutic target in ALK-rearranged ALCL and NSCLC.
    Cancer research. 09/2014;
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    ABSTRACT: Tumour pathogenesis in multiple myeloma (MM) correlates with a high vascular index. Therefore, targeting angiogenesis is an important therapeutic tool to reduce MM progression. This study aimed to investigate the role of invariant natural killer T (iNKT) cells in angiogenesis and the mechanisms behind the stimulation by α-Galactosylceramide (α-GalCer). We have previously found that α-GalCer could increase the survival of 5T33MM mice and here we demonstrate that α-GalCer reduces the microvessel density. We performed both in vivo and in vitro angiogenic assays to confirm this observation. We found that conditioned medium of α-GalCer stimulated iNKT cells reduced neovascularization in the chick chorioallantoic membrane and in matrigel plug assays. Moreover, we observed a reduction in proliferation, migration and network formation and an induction of apoptosis upon exposure of murine endothelial cell lines to this conditioned medium. We furthermore observed that the JAK-STAT signaling pathway was highly activated in endothelial cells in response to stimulated iNKT cells, indicating the possible role of IFN-γ in the anti-angiogenic process. In conclusion, these results highlight the possibility of recruiting iNKT cells to target MM and angiogenesis. This gives a rationale for combining immunotherapy with conventional anti-tumour treatments in view of increasing their therapeutic potential.
    British Journal of Haematology 08/2014; · 4.94 Impact Factor
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    ABSTRACT: Tryptase is a serine protease released from mast cells that plays a role in tumor angiogenesis. In this study we aimed to evaluate serum tryptase levels in 105 female early breast cancer patients before (STLBS) and after(STLAS) radical surgical resection, mast cell density positive to tryptase (MCDPT) and microvascular density (MVD).
    BMC Cancer 07/2014; 14(1):534. · 3.33 Impact Factor
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    ABSTRACT: Angiogenesis, the formation of new vessels, is found in Multiple Sclerosis (MS) demyelinating lesions following Vascular Endothelial Growth Factor (VEGF) release and the production of several other angiogenic molecules. The increased energy demand of inflammatory cuffs and damaged neural cells explains the strong angiogenic response in plaques and surrounding white matter. An angiogenic response has also been documented in an experimental model of MS, experimental allergic encephalomyelitis (EAE), where blood¿brain barrier disruption and vascular remodelling appeared in a pre-symptomatic disease phase. In both MS and EAE, VEGF acts as a pro-inflammatory factor in the early phase but its reduced responsivity in the late phase can disrupt neuroregenerative attempts, since VEGF naturally enhances neuron resistance to injury and regulates neural progenitor proliferation, migration, differentiation and oligodendrocyte precursor cell (OPC) survival and migration to demyelinated lesions. Angiogenesis, neurogenesis and oligodendroglia maturation are closely intertwined in the neurovascular niches of the subventricular zone, one of the preferential locations of inflammatory lesions in MS, and in all the other temporary vascular niches where the mutual fostering of angiogenesis and OPC maturation occurs. Angiogenesis, induced either by CNS inflammation or by hypoxic stimuli related to neurovascular uncoupling, appears to be ineffective in chronic MS due to a counterbalancing effect of vasoconstrictive mechanisms determined by the reduced axonal activity, astrocyte dysfunction, microglia secretion of free radical species and mitochondrial abnormalities. Thus, angiogenesis, that supplies several trophic factors, should be promoted in therapeutic neuroregeneration efforts to combat the progressive, degenerative phase of MS.
    Acta neuropathologica communications. 07/2014; 2(1):84.
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    ABSTRACT: The aim of the present study was to identify and characterize in tissue samples of clear cell-renal cell carcinoma (ccRCC) a population of CD133+/CD24+ cancer cells (RCC-derived cells-RDCs) and to study the differences with their non-neoplastic counterpart, tubular Adult Renal Progenitor Cells (ARPCs).
    The Journal of urology. 06/2014;
  • Domenico Ribatti
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    ABSTRACT: Among the in vivo models, the chick embryo chorioallantoic membrane (CAM) has been used to implant several tumor types as well as malignant cell lines to study their growth rate, angiogenic potential and metastatic capability. This review article is focused on the major compelling literature data on the use of the CAM to investigate tumor growth and the metastatic process.
    Experimental cell research. 06/2014;
  • Domenico Ribatti, Michele Moschetta, Angelo Vacca
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    ABSTRACT: In patients with multiple myeloma (MM), the bone marrow (BM) contains hematopoietic stem cells (HSCs) and non-hematopoietic cells. HSCs are able to give rise to all types of mature blood cells, while the non hematopoietic component includes mesenchymal stem cells (MSCs), fibroblasts, osteoblasts, osteoclasts, chondroclasts, endothelial cells, endothelial progenitor cells (EPCs), B and T lymphocytes, NK cells, erythrocytes, megakaryocytes, platelets, macrophages and mast cells. All of these cells form specialized "niches" in the BM microenvironment which are close to the vasculature ("vascular niche") or to the endosteum ("osteoblast niche"). The "vascular niche" is rich in blood vessels where endothelial cells and mural cells (pericytes and smooth muscle cells) create a microenvironment that affects the behavior of several stem and progenitor cells. The vessel wall serves as an independent niche for the recruitment of endothelial progenitor cells, MSCs and HSCs. The activation by angiogenic factors and inflammatory cytokines switch the "vascular niche" to promote MM tumor growth and spread. This review will focus on the mechanisms involved in the generation of signals released by endothelial cells in the "vascular niche" that promote tumor growth and spread in MM. © 2014 Elsevier Ltd. All rights reserved.
    Thrombosis Research 05/2014; 133 Suppl 2:S102-6. · 3.13 Impact Factor
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    ABSTRACT: Calbindin-D28k (CB) is a calcium-binding protein largely distributed in the cerebellum of various species of vertebrates. As regards the human cerebellar cortex, precise data on the distribution of CB have not yet been reported. Aim of the present work was to analyze the distribution of CB in postmortem samples of human cerebellar cortex using light microscopy immunohistochemical techniques. Immunoreactivity to CB was detected within neuronal bodies and processes distributed in all cortex layers. In the molecular layer, the immunoreactivity was observed in subpopulations of stellate and basket neurons. In the Purkinje neuron layer, the immunoreactivity was observed in practically all the Purkinje neurons. In the granular layer, the immunoreactivity was observed in subpopulations of granules, of Golgi neurons, and also of other types of large neurons (candelabrum, Lugaro neurons, etc.). Immunoreactivity to CB was also observed in axon terminals distributed throughout the cortex according to layer-specific patterns of distribution. The qualitative and quantitative patterns of distribution of CB showed no difference among the different lobes of the cerebellar cortex. This study reports that CB is expressed by different neuron types, both inhibitory (GABAergic) and excitatory (glutamatergic), involved in both intrinsic and extrinsic circuits of the human cerebellar cortex. The study provides further insights on the functional role of CB and on the neuronal types of the cerebellar cortex in which it is expressed. Anat Rec, 2014. © 2014 Wiley Periodicals, Inc.
    The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology 04/2014; · 1.34 Impact Factor
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    ABSTRACT: Angiogenesis is a common finding in chronic inflammatory diseases; however, its role in Sjögren's syndrome (SS) remains to be elucidated. Previous SS studies have demonstrated an increase in VEGF-A/VEGFR-2 system expression in minor salivary gland (MSG) biopsies from patients with SS, but differences in the new blood vessel formation between the different grades of disease severity have not been reported. Therefore, experiments were performed to demonstrate angiogenesis during different phases of primary SS (pSS) and to define the relationship between the microvessel density (MVD), macrophage infiltration and histiocyte distribution in SS MSG inflammatory lesions. In this series of experiments, immunohistochemistry was used to examine angiogenesis in serial sections of pSS MSG. Patients with pSS were classified accordingly with the grade of inflammatory lesions as I = low-grade (low focus score of 1 or 2), II = intermediate-grade (focus score of 3–6) and III = extensive inflammation in the MSG (high focus score of 12). Histological examination demonstrated that the MVD increased with the severity of the inflammatory lesions, and in addition, we found an increased infiltration of inflammatory and pro-angiogenic cells.These findings reveal that angiogenesis is intimately involved in the progression of pSS, may be central to the propagation of the chronic immune response observed in pSS and could represent a novel potential biomarker of pSS disease activity.
    International Journal of Experimental Pathology 04/2014; 95(2):131-7. · 2.04 Impact Factor
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    Domenico Ribatti
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    ABSTRACT: Angiogenesis is regulated, under both physiological and pathological conditions, by numerous "non-classic" pro-angiogenic factors, including fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF), and "non-classic" pro-angiogenic factors, including granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), and erythropoietin (EPO). In the context of the most important discoveries in this field, this review article summarizes the important role played by the Italian scientists in the course of the last twenty years.
    Vascular cell. 04/2014; 6(1):8.
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    ABSTRACT: Primary Sjögren's syndrome (pSS) is a chronic autoimmune exocrine disease associated with variable lymphocytic infiltration of the affected organs (primarily salivary and lachrymal glands). To investigate the potential implication of nerve growth factor-β (NGF-β) and its high affinity receptor tyrosine kinase receptor A (TrkA) in the regulation of pSS inflammatory responses, we studied their expression in the human salivary gland epithelial cells (SGEC) cultures from pSS minor salivary glands (MSG) biopsies and their relationship with histopathological disease parameters. Here, we demonstrated an increased expression of the NGF-β/TrkA system in pSS SGEC, correlated with the MSG inflammation grade. The results demonstrate that the pro-inflammatory cytokines TNF-α and IL-6 enhance NGF-β production; on the contrary, NGF-β production was reduced in the presence of both Raf-1 kinase and MEK inhibitors. Furthermore, TNF-α/IL-6 treatment increased ERK1/2 phosphorylation. Inhibition of the EGF/EGFR system also decreased NGF-β release by pSS SGEC, indicating that the chronic inflammatory condition characteristic of pSS enhances NGF-β production via EGFR/Raf-1/MEK/ERK pathway activation. NGF-β and TrkA expression is elevated in salivary gland epithelial cells of primary Sjögren's syndrome (pSS). Overexpression of NGF-β/TrkA system in pSS occurs via EGFR/Raf-1/MEK/ERK pathway. In pSS, NGF-β overexpression was prevented by EGFR/Raf-1/MEK/ERK pathway inhibition.
    Journal of Molecular Medicine 02/2014; · 4.77 Impact Factor
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    ABSTRACT: The lysosomal hydrolase galactocerebrosidase (GALC) catalyzes the removal of galactose from galactosylceramide and from other sphingolipids. GALC deficiency is responsible for globoid cell leukodystrophy (GLD), or Krabbe's disease, an early lethal inherited neurodegenerative disorder characterized by the accumulation of the neurotoxic metabolite psychosine in the central nervous system (CNS). The poor outcome of current clinical treatments calls for novel model systems to investigate the biological impact of GALC down-regulation and for the search of novel therapeutic strategies in GLD. Zebrafish (Danio rerio) represents an attractive vertebrate model for human diseases. Here, lysosomal GALC activity was demonstrated in the brain of zebrafish adults and embryos. Accordingly, we identified two GALC co-orthologs (named galca and galcb) dynamically co-expressed in CNS during zebrafish development. Both genes encode for lysosomal enzymes endowed with GALC activity. Single down-regulation of galca or galcb by specific antisense morpholino oligonucleotides results in a partial decrease of GALC activity in zebrafish embryos that was abrogated in double galca/galcb morphants. However, no psychosine accumulation was observed in galca/galcb double morphants. Nevertheless, double galca/galcb knockdown caused reduction and partial disorganization of the expression of the early neuronal marker neuroD and an increase of apoptotic events during CNS development. These observations provide new insights into the pathogenesis of GLD, indicating that GALC loss-of-function may have pathological consequences in developing CNS independent of psychosine accumulation. Also, they underscore the potentiality of the zebrafish system in studying the pathogenesis of lysosomal neurodegenerative diseases, including GLD.
    Biochimica et Biophysica Acta 01/2014; · 4.66 Impact Factor
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    ABSTRACT: TRAIL, a cytokine of the Tumor Necrosis Factor (TNF) superfamily, is a potent cell-apoptosis inducer, although its effects vary as a function of concentration. In fact, low concentrations of TRAIL are associated with non-apoptotic effects, such as cell proliferation. Here, the effects of TRAIL at different concentrations have been evaluated on mitogenesis and migration on human umbilical vein endothelial cells (HUVEC) in vitro, as well as in the chick embryo chorioallantoic membrane (CAM) angiogenesis model in vivo. TRAIL at low concentrations promoted either mitogenesis or migration of HUVEC cells, evaluated with the wound healing method. Cleavage of caspase-8 was evaluated along with the expression of the caspase-8-like molecule c-FLIPL . Low concentrations of TRAIL failed to induce caspase-8 processing whereas high concentrations induced apoptosis of HUVEC and activation of caspase-8. Moreover, TRAIL induced a significant angiogenic response in the CAM assay in vivo, comparable to that of vascular endothelial growth factor. These data suggest that non-apoptotic effects of TRAIL include mitogenesis and increased mobility of endothelial cells, as well as eventually angiogenesis. In addition, results demonstrate that c-FLIPL level is also modulated by different TRAIL concentration suggesting its involvement in the divergent effects of TRAIL. In conclusion, this study envisions a pro-angiogenic role of TRAIL, suggesting that the TRAIL may represent a target for pharmacological manipulation. This article is protected by copyright. All rights reserved.
    FEBS Journal 01/2014; · 4.25 Impact Factor
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    ABSTRACT: Hepatocellular carcinoma (HCC) is the fifth most common cause of cancer in the world. According to Barcelona Clinic Liver Cancer modified criteria, patients with early stage disease are candidate to radiofrequency ablation (RFA), while patients with intermediate stage HCC are usually treated by transarterial chemoembolization (TACE). TACE and RFA induce a transient devascularisation effect followed by strong neo-angiogenic stimulus. In fact, after these procedures, it has been demonstrated an up-regulation of pro-angiogenic and growth factors such as vascular endothelial growth factor-A, which might contribute to accelerated progression in patients with incomplete response. Several studies have demonstrated that MAP-kinase and AKT pathways, in addition to neo-angiogenesis, have an important role in the development of HCC. In advanced HCC, anti-angiogenic therapy and tyrosine kinases inhibitors showed potential clinical benefit. Actually, a number of clinical studies are ongoing testing these agents in combination with TACE or RFA. In this paper, we have reviewed the most recent preclinical and clinical results of such trials.
    World Journal of Gastroenterology 01/2014; 20(2):486-497. · 2.55 Impact Factor

Publication Stats

13k Citations
2,371.88 Total Impact Points

Institutions

  • 2014
    • University of Catania
      Catania, Sicily, Italy
    • Brazilian National Cancer Institute
      Rio de Janeiro, Rio de Janeiro, Brazil
  • 1985–2014
    • Università degli Studi di Bari Aldo Moro
      • Dipartimento di Scienze Biomediche ed Oncologia Umana (DIMO)
      Bari, Apulia, Italy
  • 2013
    • University of Rome Tor Vergata
      • Department of Industrial Engineering
      Roma, Latium, Italy
  • 2009–2013
    • Ospedale Oncologico "Giovanni Paolo II" di Bari
      Bari, Apulia, Italy
    • Centro Cardiologico Monzino
      Milano, Lombardy, Italy
    • Hebrew University of Jerusalem
      • School of Pharmacy
      Jerusalem, Jerusalem District, Israel
  • 2005–2013
    • Università degli studi di Foggia
      • Department of Medical and Surgical Sciences
      Foggia, Apulia, Italy
    • Ospedali Vito Fazzi
      Lecce, Apulia, Italy
  • 2003–2013
    • Policlinico di Bari
      • Department of Surgery
      Bari, Apulia, Italy
  • 2007–2012
    • IRCCS Istituto G. Gaslini
      • Department of Experimental and Laboratory Medicine
      Genova, Liguria, Italy
    • Vascular and Interventional Radiology
      Chicago, Illinois, United States
  • 2001–2012
    • University of Leuven
      • Department of Biomedical Kinesiology
      Louvain, Flanders, Belgium
  • 2008–2011
    • University-Hospital of Padova
      Padua, Veneto, Italy
    • Victor Babes University of Medicine and Pharmacy of Timisoara
      Freidorf, Timiş, Romania
    • Mario Negri Institute for Pharmacological Research
      • Department of Oncology
      Milano, Lombardy, Italy
  • 2007–2011
    • University of Padova
      • • Department of Biomedical Sciences - DSB
      • • Department of Biology
      Padova, Veneto, Italy
  • 2003–2011
    • University of Udine
      • • Department of Experimental and Clinical Medical Sciences
      • • Department of Medical and Biological Sciences
      Udine, Friuli Venezia Giulia, Italy
  • 2010
    • Università degli studi di Parma
      • Department of Clinical and Experimental Medicine
      Parma, Emilia-Romagna, Italy
    • National Research Council
      Roma, Latium, Italy
  • 2009–2010
    • Università degli studi di Cagliari
      • Department of Environmental and Life Science
      Cagliari, Sardinia, Italy
    • Universitatea de Medicina si Farmacie Craiova
      • Faculty of Dentistry
      Croiova, Dolj, Romania
  • 2003–2010
    • CRO Centro di Riferimento Oncologico di Aviano
      • Division of Experimental and Clinical Pharmacology
      Aviano, Friuli Venezia Giulia, Italy
  • 2002–2010
    • Istituto Dermopatico dell'Immacolata
      Roma, Latium, Italy
  • 2002–2009
    • Azienda Ospedaliera Pugliese Ciaccio
      • Department of Oncology and Hematology
      Catanzaro, Calabria, Italy
  • 1996–2009
    • Università degli Studi di Brescia
      • Department of Clinical and Experimental Sciences
      Brescia, Lombardy, Italy
  • 2004–2008
    • The Human Anatomy and Physiology Society
      Italy, Texas, United States
  • 2006
    • Università degli Studi di Siena
      Siena, Tuscany, Italy
    • Istituto Superiore di Sanità
      • Department of Haematology, Oncology and Molecular Medicine
      Roma, Latium, Italy
  • 2002–2004
    • Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni
      Milano, Lombardy, Italy
  • 2000
    • Istituto Ortopedico Rizzoli
      • Laboratory of Experimental Oncology
      Bolonia, Emilia-Romagna, Italy