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Marech I.,Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology | Leporini C.,University of Catanzaro | Ammendola M.,University of Catanzaro | Porcelli M.,Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology | And 4 more authors.
Cancer Letters | Year: 2015

Angiogenesis is sustained by classical and non-classical proangiogenic factors (PFs) acting in tumor microenvironment and these factors are also potential targets of antiangiogenic therapies. All PFs induce the overexpression of several signaling pathways that lead to migration and proliferation of endothelial cells contributing to tumor angiogenesis and survival of cancer cells. In this review, we have analyzed each PF with its specific receptor/s and we have summarized the available antiangiogenic drugs (e.g. monoclonal antibodies) targeting these PFs, some of these agents have already been approved, others are currently in development for the treatment of several human malignancies. © 2015 Elsevier Ireland Ltd. Source


Ammendola M.,University of Catanzaro | Ammendola M.,Surgery Unit | Patruno R.,Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology | Sacco R.,University of Catanzaro | And 11 more authors.
Expert Opinion on Therapeutic Targets | Year: 2016

Objective. The density of mast cells positive to tryptase (MCDPT) and tumor-associated macrophages (TAMs) were evaluated in a series of 87 patients with stage B and C colorectal cancer who had undergone radical surgery. Methods. MCDPT, TAMs, microvascular density (MVD), endothelial area (EA) and CD8+ tumor infiltrating lymphocytes (CD8+ TILs) were evaluated in tumor tissue samples by immunohistochemistry and image analysis. Each of the above parameters was correlated with the others and with the main clinico-pathological features. Results. A significant correlation between MCDPT, TAMs, MVD and EA was found by Pearson t-test analysis. With special references to the clinico-pathological features a minimal correlation using univariate analysis was found but it was not retained at multivariate analysis. Conclusions. Our data suggest that MCDPT and TAMs are linked in the tumor microenvironment and play a role in CRC angiogenesis in a synergistic manner. The assessment of the combination MCDPT and TAMs could be evaluated as a target of novel anti-angiogenic therapies in colorectal cancer patients. © 2016 Informa UK Limited, trading as Taylor & Francis Group Source


Marech I.,Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology | Ammendola M.,University of Catanzaro | Sacco R.,University of Catanzaro | Sammarco G.,University of Catanzaro | And 11 more authors.
Journal of Cellular and Molecular Medicine | Year: 2016

Tumour-associated macrophages (TAMs) represent pivotal components of tumour microenvironment promoting angiogenesis, tumour progression and invasion. In colorectal cancer (CRC), there are no conclusive data about the role of TAMs in angiogenesis-mediated tumour progression. In this study, we aimed to evaluate a correlation between TAMs, TAM immunostained area (TAMIA) microvascular density (MVD), endothelial area (EA) and cancer cells positive to VEGF-A (CCP-VEGF-A) in primary tumour tissue of locally advanced CRC patients undergone to radical surgery. A series of 76 patients with CRC were selected and evaluated by immunohistochemistry and image analysis. An anti-CD68 antibody was employed to assess TAMs and TAMIA expression, an anti-CD34 antibody was utilized to detect MVD and EA expression, whereas an anti-VEGF-A antibody was used to detect CCP-VEGF-A; then, tumour sections were evaluated by image analysis methods. The mean ± S.D. of TAMs, MVD and CCP-VEGF-A was 65.58 ± 21.14, 28.53 ± 7.75 and 63% ± 37%, respectively; the mean ± S.D. of TAMIA and EA was 438.37 ± 124.14μ2 and 186.73 ± 67.22μ2, respectively. A significant correlation was found between TAMs, TAMIA, MVD and EA each other (r ranging from 0.69 to 0.84; P ranging from 0.000 to 0.004). The high level of expression of TAMs and TAMIA in tumour tissue and the significant correlation with both MVD and EA illustrate that TAMs could represent a marker that plays an important role in promoting angiogenesis-mediated CRC. In this context, novel agents killing TAMs might be evaluated in clinical trials as a new anti-angiogenic approach. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. Source


Ammendola M.,University of Catanzaro | Ammendola M.,Surgery Unit | Sacco R.,University of Catanzaro | Marech I.,Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology | And 8 more authors.
Oncology Letters | Year: 2015

Previous experimental and clinical data have indicated that tumour cell proliferation is associated with angiogenesis; in addition, an increased microvascular density (MVD) of tumours has been associated with poor prognosis in solid and haematological malignancies. However, limited data exists regarding the association between tumour cell proliferation and angiogenesis in primary tumour tissue from pancreatic ductal adenocarcinoma (PDAC) patients; therefore, the present study aimed to investigate this association. A series of 31 PDAC patients with stage Tumour (T)2-3 Node (N)0-1 Metastasis (M)0 were recruited into the present study and subsequently underwent surgery. PDAC tissue and adjacent normal tissue (ANT), resected during surgery, were evaluated using immunohistochemistry and image analysis methods to determine MVD, endothelial area (EA) and Ki-67 expression, which is an indicator of cell proliferation rate. The results demonstrated a correlation between the above parameters with each other as well as the main clinico-pathological features of PDAC. Significant differences were identified in MVD, EA and Ki-67 proliferation index between PDAC and ANT. It was demonstrated that MVD, EA and Ki-67 proliferation index were significantly correlated with each other in tumour tissue (r=0.69-0.81; P=0.001-0.003). However, no other significant correlations were identified. These data therefore suggested that angiogenesis and cell proliferation rate were significantly increased in PDAC compared with ANT, which provides a biological basis for the potential use of novel combinations of angiogenesis inhibitors and anti-proliferative chemotherapeutic drugs in the treatment of PDAC. © 2015, Spandidos Publications. All rights reserved. Source

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