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Curigliano G.,Istituto Europeo di Oncologia
Breast | Year: 2011

Summary: Evading immune destruction should be considered an emerging hallmark of cancer. Highly immunogenic cancer cells can be eliminated in immunocompetent hosts as a result of the "immunoediting" process. Weakly immunogenic variants can grow and generate solid tumors. Regulatory T cells (Tregs) were found to be involved in the maintenance of the immune tolerance both preventing autoimmune disease and curtailing antitumour immune response. Modulation of immune response in cancer patients is the result of a balanced activity of Tregs and T effector cells. In cancer patients increased number of Tregs was found in blood and tumour tissue: it was demonstrated that Tregs suppress T-cell response and natural killer (NK) cells proliferation and function, thus interfering both with acquired and innate immunity. Upregulation of Tregs in tumor bed can be associated with worse prognosis. Drugs blocking function of Tregs increase activity of T effectors and, as side effect, induce an autoimmune disease. Issues of biology and prognosis of breast cancer in the presence of a deregulation of the immune system needs to be studied. The identification of immunological and genetic features affecting immune response in patients with minimal tumor burden are the optimal background for development of clinical studies in the adjuvant setting. © 2011 Elsevier Ltd. Source


Colombo N.,Istituto Europeo di Oncologia
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society | Year: 2011

The results of the OVA-301 study show that trabectedin in combination with pegylated liposomal doxorubicin (PLD) results in improved progression-free survival and response rate in patients with advanced ovarian cancer. The trial has also demonstrated a trend toward improvement in overall survival. A subgroup analysis indicates that in the subset of patients with platinum-free interval (PFI) of 6 to 12 months, the combined treatment resulted in a 6-month improvement in overall survival. Furthermore, in the patients who have received third-line treatment with a platinum agent, it was found that the survival was better in those who had received trabectedin and PLD. These results suggest that prolonging the PFI by a nonplatinum-effective regimen improves the outcome with subsequent, third-line platinum treatment. This strategy may also have positive effects in treatment tolerability, as it allows extra time to recover from platinum-induced toxicities. This hypothesis is currently been tested in the INOVATYON (INternational OVArian Cancer Patients Trial With YONdelis) phase III study. Source


Bogani G.,University of Insubria | Cliby W.A.,Gynecologic Surgery Unit | Aletti G.D.,Istituto Europeo di Oncologia
Gynecologic Oncology | Year: 2015

Objective. To reviewthe current evidence on the effects of intra-abdominalmorcellation on survival outcomes of patients affected by unexpected uterine leiomyosarcoma (ULMS) and to estimate the risk of recurrence in those patients. Methods. PubMed (MEDLINE), Scopus, Embase, Web of Science databases as well as ClinicalTrails.gov, were searched for data evaluating the effects of intra-abdominal morcellation on survival outcomes of patients with undiagnosed ULMS. Studies were evaluated per the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) and the American College of Obstetricians and Gynecologists (ACOG) guidelines. Results. Sixty manuscripts were screened, 11 (18%) were selected and four (7%) were included. Overall, 202 patients were included: 75 (37%) patients had morcellation of ULMS, while 127 (63%) patients had not. A meta-analysis of these studies showed that morcellation increased the overall (62% vs. 39%; OR: 3.16 (95% CI: 1.38, 7.26)) and intra-abdominal (39% vs. 9%; OR: 4.11 (95% CI: 1.92, 8.81)) recurrence rates as well as death rate (48% vs. 29%; OR: 2.42 (95% CI: 1.19, 4.92)). No between-group difference in cumulative extra-abdominal recurrence (OR: 0.34 (95% CI: 0.07, 1.59)) rate was observed. Conclusions. Our data support a significant correlation between uterinemorcellation and an increased risk of intra-abdominal recurrence in patients affected by unexpected ULMS. However, the limited data on this issue and the absence of high level of evidence suggest the need of further studies designed to estimate the risk to benefit ratio of morcellation in patients with uterine fibroids and undiagnosed ULMS. © 2014 Elsevier Inc. All rights reserved. Source


Di Fiore P.P.,Istituto Europeo di Oncologia | Di Fiore P.P.,University of Milan | von Zastrow M.,University of California at San Francisco
Cold Spring Harbor Perspectives in Biology | Year: 2014

The endocytic network comprises a vast and intricate system of membrane-delimited cell entry and cargo sorting routes running between biochemically and functionally distinct intracellular compartments. The endocytic network caters to the organization and redistribution of diverse subcellular components, and mediates appropriate shuttling and processing of materials acquired from neighboring cells or the extracellular milieu. Such trafficking logistics, despite their importance, represent only one facet of endocytic function. The endocytic network also plays a key role in organizing, mediating, and regulating cellular signal transduction events. Conversely, cellular signaling processes tightly control the endocytic pathway at different steps. The present article provides a perspective on the intimate relationships that exist between particular endocytic and cellular signaling processes in mammalian cells, within the context of understanding the impact of this nexus on integrated physiology. © 2014 Cold Spring Harbor Laboratory Press; all rights reserved. Source


Criscitiello C.,Istituto Europeo di Oncologia | Curigliano G.,Istituto Europeo di Oncologia
Current Opinion in Oncology | Year: 2013

PURPOSE OF REVIEW: We review recent advances leading to a new understanding of immunology of breast cancer with its potential clinical applications. RECENT FINDINGS: With the exception of antibody-based HER2 targeting, immunotherapy in breast cancer has largely been an unsatisfying experience. To improve the efficacy of breast cancer immunotherapeutics, a better understanding of the relation between innate and adaptive immune responses, of the immune escape mechanisms, the discovery of mechanisms underlying immunological tolerance, and the acknowledgment of the importance of both cell-mediated and humoral adaptive immunity for the control of tumor growth are needed. SUMMARY: Cancer takes advantage of the ability to hide from the immune system by exploiting a series of immune escape mechanisms. Among these mechanisms are the hijackings of immune cell-intrinsic checkpoints that are induced on T-cell activation. Blockade of these checkpoints - cytotoxic T-lymphocyte-associated antigen 4 or the programmed death 1 receptor - recently provided the first evidence of activity of an immune-modulation approach in the treatment of solid tumors. The future frontier in the immunotherapeutics of breast cancer requires identification of predictive factors. The immune system remembers what it targets, so once the system is correctly activated, it may mediate a long-lasting tumor response. © 2013 Wolters Kluwer Health Lippincott Williams & Wilkins. Source

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