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Sica A.,Istituto Clinico Humanitas | Sica A.,University of Piemonte Orientale
Experimental Oncology | Year: 2010

The construction of an inflammatory microenvironment provides the fuel for cancer development and progression. Hence, solid tumors promote infiltration of leukocyte populations, among which tumor-associated macrophages (TAM) represent a paradigm for cancer promoting inflammation. TAM orchestrate various aspects of cancer, including diversion and skewing of adaptive responses, cell growth, angiogenesis, matrix deposition and remodeling, the construction of a metastatic niche and actual metastasis, response to hormones and chemotherapeutic agents. Several evidence indicate that TAM show a remarkable degree of plasticity and functional heterogeneity, suggesting that during tumor progression macrophages undergo a phenotypic 'switch', eventually exhibiting the alternatively activated, 'M2', phenotype, associated with immunosuppression, promotion of tumor angiogenesis and metastasis. While recent studies have attempted to address the role of microenvironment signals on the TAM « reprogramming», the interplay between innate and adaptive immunity is emerging as a crucial step of this event. Here I discuss the evidence for the functional reprogramming of TAM during the course of tumor progression and the molecular mechanisms that regulate such event. Finally, I discuss the implications of this phenomenon for anti-cancer therapies aimed at prompting TAM to mount an effective antitumor response. Copyright © Experimental Oncology, 2010.

Livraghi T.,Istituto Clinico Humanitas
Surgical Oncology Clinics of North America | Year: 2011

Radiofrequency ablation (RFA), usually performed under percutaneous ultrasound guidance, is considered the gold standard among minimally invasive therapies. On the strength of some recent randomized trials, its indications include operable patients with small hepatocellular carcinoma and inoperable patients with more advanced disease also in combination with other therapies. RFA has lower complication rates and costs less than surgery. © 2011.

Ponticelli C.,Istituto Clinico Humanitas
Nephrology Dialysis Transplantation | Year: 2012

IgA nephritis (IgAN) is an autoimmune disease characterized by deposits of IgA in the glomerular mesangium. Clinically, the disease may be punctuated by episodes of macroscopic haematuria often associated with pharingotonsillitis or may be oligosyntomatic with microscopic haematuria and mild proteinuria. The natural course of IgAn may be indolent and benign; however, some 3050 of patients may progress to end-stage renal disease when follow-up is extended to <20 years. In patients with IgAN, circulating IgA1 molecules have an aberrant structure of O-glycans in the hinge region, which is characterized by abbreviated glycans composed of N-acetylgalactosamine, with or without sialic acid. These aberrant IgA1 trigger the production of autoantibodies, with formation of immune complexes that deposit in the mesangium causing inflammation and production of extracellular matrix. A number of experimental and clinical data outlined a possible pathogenetic role of tonsillitis. As a consequence, tonsillectomy has been frequently performed in Japan. Observational studies, made in patients with normal renal function and mild proteinuria, reported that tonsillectomy could reduce the episodes of macrohaematuria as well as the entity of microhaematuria and proteinuria. However, the available studies had short-term follow-up and could not asses the role of tonsillectomy in protecting from renal function deterioration. In a longitudinal retrospective study, Isseki et al. compared the outcome of tonsillectomized patients with IgAn with that of IgAn patients who did not receive tonsillectomy. Tonsillectomized patients had a higher number of remissions and a better slope of glomerular filtration rate in comparison with controls. These data are interesting and suggest that tonsillectomy may prevent renal dysfunction in patients with IgAn and normal renal function. However, the retrospective nature of the study and the presence of some confounding factors require further investigations to confirm these promising data. © 2012 The Author.

Livraghi T.,Istituto Clinico Humanitas
Journal of Hepato-Biliary-Pancreatic Sciences | Year: 2010

In the EASL and AASLD guidelines, hepatic resection (HR) is considered the first option for patients in stage 0 (very early HCC). This statement was not based on randomized controlled trials (RCTs) versus other therapies, but on the oncological assumption that HR is the better procedure for obtaining complete tumor ablation including a safety margin. Subsequently, three RCTs compared percutaneous radiofrequency ablation (RFA) versus HR in patients with early HCC. All failed to demonstrate better survival in favor of HR, even though the larger size of the early stage needs a larger area of necrosis. A recent study focused on stage 0 demonstrated a sustained local complete response after RFA comparable with that of HR. All these trials established that RFA is less invasive and associated with lower complication rates and lower costs. These data suggest that RFA can be considered the first option for operable patients with very early HCC. Other options (HR, PEI, selective TAE/TACE) can be used as salvage therapy for the few cases in which RFA is unsuccessful or unfeasible. © Japanese Society of Hepato-Biliary-Pancreatic Surgery and Springer 2009.

Anders H.-J.,Ludwig Maximilians University of Munich | Romagnani P.,University of Florence | Mantovani A.,Istituto Clinico Humanitas | Mantovani A.,University of Milan
Trends in Molecular Medicine | Year: 2014

Homeostatic chemokines control stem and progenitor cell migration and activation during vasculogenesis and organ development. They orchestrate hematopoietic stem cell (HSC) homing to their bone marrow niches and direct immature lymphocytes to a series of maturation sites within lymphoid organs. Along these lines, homeostatic chemokines regulate the niches of peripheral committed progenitor cell populations for tissue renewal. These biological functions support neovascularization and wound healing, including the recruitment of endothelial and other progenitor cells from the bone marrow. Here, we summarize the roles of homeostatic chemokines, their signaling receptors, and atypical decoy receptors during homeostasis and tissue regeneration in order to better understand their pathogenic roles in disease, for example, in diabetes complications, cancer, autoimmunity, epithelial hyperplasia, or hypertrophic scarring and fibrosis. © 2013 Elsevier Ltd.

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