Medical and Experimental Oncology Unit

Sammichele di Bari, Italy

Medical and Experimental Oncology Unit

Sammichele di Bari, Italy

Time filter

Source Type

Porcelli L.,National Cancer Research Center Giovanni Paolo | Quatrale A.E.,National Cancer Research Center Giovanni Paolo | Mantuano P.,National Cancer Research Center Giovanni Paolo | Leo M.G.,Health-U | And 6 more authors.
Molecular Oncology | Year: 2013

Cancer cells may use PARP enzymes and Homologous Recombination to repair single and double strand breaks caused by genotoxic insults. In this study, the PARP-1 inhibitor Rucaparib was utilized to increase the sensitivity to chemoradiotherapy treatment in BRCA-2-deficient and -proficient pancreatic cancer cells. We used the pancreatic cancer cell lines, Capan-1 with mutated BRCA-2 and Panc-1, AsPC-1 and MiaPaCa-2 with BRCA-1/2 wild type. Cells were treated with Rucaparib and/or radiotherapy (4-10 Gy) plus Gemcitabine then the capability to proliferate was evaluated by colony formation, cell counting and MTT assays. Flow cytometry, immunocytochemistry and western blotting were utilized to assess cell response to Rucaparib plus irradiation. The antitumour effectiveness of combining the PARP-1 inhibitor before, together and after radiotherapy evidenced the first as the optimal schedule in blocking cell growth. Pre-exposure to Rucaparib increased the cytotoxicity of Gemcitabine plus radiotherapy by heavily inducing the accumulation of cells in G2/M phase, impairing mitosis and finally inducing apoptosis and authophagy. The upregulation of p-Akt and downregulation of p53 were evidenced in MiaPaCa-2 which displayed replication stress features. For the first time, the rationale of using a PARP inhibitor as chemoradiosensitizer in pancreatic cancer models has been hypothesized and demonstrated. © 2012 Federation of European Biochemical Societies.


Bellizzi A.,National Cancer Center Giovanni Paolo | Sebastian S.,National Cancer Center Giovanni Paolo | Ceglia P.,National Cancer Center Giovanni Paolo | Centonze M.,National Cancer Center Giovanni Paolo | And 13 more authors.
Journal of Cellular Physiology | Year: 2013

Although relatively good therapeutic results are achieved in non-advanced cancer, the prognosis of the advanced colon cancer still remains poor, dependent on local or distant recurrence of the disease. One of the factors responsible for recurrence is supposed to be cancer stem cells (CSCs) or tumor-initiating cells, which are a population of cancer cells with ability to perpetuate themselves through self-renewal and to generate differentiated cells, thought to be responsible for tumor recurrence. This study globally approach the possible role of tissue-derived stem cells in the initiation of colon cancer and its metastatic process in the liver. Fresh surgical specimens from colon cancer, non-tumor tissue and liver metastasis were obtained directly from the operating room, examined, and immediately processed. CSCs were selected under serum-free conditions and characterized by CD44 and CD133 expression levels. CD133+/CD44+ cell populations were then investigated in paraffin-embedded tissues and circulating tumor cells isolated from peripheral blood of the same group of colon cancer patients. Our data demonstrate that metastatic properties of cell populations from blood and liver metastasis, differently from primitive tumors, seem to be strictly related to the phenotype CD133 positive and CD44 positive. © 2012 Wiley Periodicals, Inc.


Silvestris N.,Medical and Experimental Oncology Unit | Marech I.,Interventional Radiology Unit | Brunetti A.E.,Medical and Experimental Oncology Unit | Azzariti A.,National Cancer Research Center Giovanni Paolo | And 6 more authors.
Cancer Biomarkers | Year: 2014

Most cancers are traditionally treated with either chemotherapeutic agents, radiotherapy, or both. Identification of specific molecular characteristics of tumors and the advent of molecular-targeted drugs not only enhance the efficacy but also decrease the toxicity of treatment. These new therapies may target pathways critical to tumor development or specific driver mutations in cancer cells. This understanding of the molecular pathways of cancer cells has led to the ability to predict cancer development, behaviour and prognosis, as well as response or resistance to current therapeutic agents. As a result, pathologic analyses play a vital role in the detection of cancer biomarkers, which are important not only in the diagnosis of cancers but also in the selection of appropriate therapeutic agents and in the development of new targeted therapies. © 2014 - IOS Press and the authors.


Guarini A.,Haematology Unit | Minoia C.,Haematology Unit | Giannoccaro M.,Haematology Unit | Rana A.,Haematology Unit | And 6 more authors.
Current Medicinal Chemistry | Year: 2012

Despite impressive treatment advances, few options for refractory or relapsed Hodgkin Lymphoma (HL) are available and there is a need for new compounds development. A number of promising agents with multiple mechanisms of action are under investigation. Microenvironment and neoangiogenesis are acquiring a rising relevance in the pathophysiology and progression of HL. Everolimus (RAD001) is an oral antineoplastic agent derived from rapamycin, a macrocyclic lactone antibiotic, targeting the mammalian target of rapamycin (mTOR). Although the importance of mTOR signaling in the deregulated cell growth of human neoplastic cells has been recognized, this pathway is also emerging as a key regulator of the tumor response to hypoxia, as well as endothelial and stromal cells function, thereby regulating neoangiogenesis. Furthermore, mTOR plays an important role in anticancer drug resistance. The actions of everolimus within the mTOR pathway in HL result in decreased protein synthesis and cell cycle arrest, as well as in decreased angiogenesis. Everolimus has shown preliminary evidence of efficacy as a single-agent in heavily pretreated relapsed/refractory HL, with an overall fair safety profile. The purpose of this review is to discuss the employment of everolimus as an antiproliferative and antiangiogenic agent in HL and to report the critical role of the mTOR pathway and angiogenesis in this malignancy. © 2012 Bentham Science Publishers.


Giuliani F.,Medical and Experimental Oncology Unit | Colucci G.,Medical and Experimental Oncology Unit
Expert Opinion on Therapeutic Targets | Year: 2012

Introduction: In the last decade, the introduction of imatinib mesilate into the clinical practice has resulted in a dramatic improvement in the treatment of gastrointestinal stromal tumor (GIST). Nowadays, the median overall survival in patients with advanced disease has increased to 5 years, while recent Phase III trials demonstrated that imatinib mesilate can be successfully employed as adjuvant therapy in patients at significant risk of recurrence. Despite these good results, the emergence of secondary resistance represents the main cause of treatment failure. In recent years, many efforts have been made in search of drugs to overcome imatinib mesilate resistance; some of these have been employed as second-line treatment or salvage therapy. Areas covered: Summarized and investigated in this paper are the results obtained by imatinib mesilate in advanced and adjuvant setting, the role of sunitinib malate as second-line therapy in imatinib mesilate-resistant patients and the clinical results concerning new drugs, mainly tyrosine-kinase inhibitors. Expert opinion: Current research on novel therapeutic agents, as third-line treatments in GIST, is ongoing. However, despite the promising results obtained with the new molecules, imatinib mesilate remains the cornerstone in the medical treatment of GIST and to date no other drugs can replace it. © Informa UK, Ltd.


PubMed | Medical and Experimental Oncology Unit
Type: | Journal: Expert opinion on therapeutic targets | Year: 2012

In the last decade, the introduction of imatinib mesilate into the clinical practice has resulted in a dramatic improvement in the treatment of gastrointestinal stromal tumor (GIST). Nowadays, the median overall survival in patients with advanced disease has increased to 5 years, while recent Phase III trials demonstrated that imatinib mesilate can be successfully employed as adjuvant therapy in patients at significant risk of recurrence. Despite these good results, the emergence of secondary resistance represents the main cause of treatment failure. In recent years, many efforts have been made in search of drugs to overcome imatinib mesilate resistance; some of these have been employed as second-line treatment or salvage therapy.Summarized and investigated in this paper are the results obtained by imatinib mesilate in advanced and adjuvant setting, the role of sunitinib malate as second-line therapy in imatinib mesilate-resistant patients and the clinical results concerning new drugs, mainly tyrosine-kinase inhibitors.Current research on novel therapeutic agents, as third-line treatments in GIST, is ongoing. However, despite the promising results obtained with the new molecules, imatinib mesilate remains the cornerstone in the medical treatment of GIST and to date no other drugs can replace it.

Loading Medical and Experimental Oncology Unit collaborators
Loading Medical and Experimental Oncology Unit collaborators