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PubMed | Angers University Hospital Center, Chaim Sheba Medical Center, Seoul National University, Center Henri Becquerel and 16 more.
Type: | Journal: Blood | Year: 2017

Anti-PD-1 monoclonal antibodies are being increasingly tested in patients with advanced lymphoma. Following treatment, many of those patients are likely to be candidates for allogeneic hematopoietic stem cell transplant (HSCT). However, the safety and efficacy of HSCT may be affected by prior PD-1 blockade. We conducted an international retrospective analysis of 39 patients with lymphoma who received prior treatment with a PD-1 inhibitor, at a median time of 62 days (7-260) before HSCT. After a median follow-up of 12 months, the one-year cumulative incidences of grade 2-4 and grade 3-4 acute graft-versus-host disease (GVHD) were 44% and 23% respectively, while the one-year incidence of chronic GVHD was 41%. There were 4 treatment-related deaths, (1 from hepatic sinusoidal obstruction syndrome, 3 from early acute GVHD). In addition, 7 patients developed a non-infectious febrile syndrome shortly after transplant requiring prolonged courses of steroids. One-year overall and progression-free survival rates were 89% (95% CI, 74-96) and 76% (95% CI, 56-87), respectively. One-year cumulative incidences of relapse and non-relapse mortality were 14% (95% CI, 4-29) and 11% (95% CI, 3-23), respectively. Circulating lymphocyte subsets were analyzed in 17 patients. Compared with controls, patients previously treated with PD-1 blockade had significantly decreased PD-1+ T cells, and decreased ratios of T regulatory cells to conventional CD4 and CD8 T cells. In conclusion, HSCT after PD-1 blockade appears feasible with a low rate of relapse. However, there may be an increased risk of early immune toxicity, which could reflect long-lasting immune alterations triggered by prior PD-1 blockade.


PubMed | Papa Giovanni XXIII Hospital, University of Verona, General Hospital, San Vincenzo Hospital and 21 more.
Type: Journal Article | Journal: Future oncology (London, England) | Year: 2016

To assess clinical outcomes in octogenarians treated with docetaxel (DOC) for metastatic castration-resistant prostate cancer.The multicenter retrospective study was based on a review of the pre- and post-DOC clinical history, DOC treatment and outcomes.We reviewed the records of 123 patients (median age: 82 years) who received DOC every 3 weeks or weekly, without significant grade 3-4 toxicities. Median progression-free survival was 7 months; median overall survival from the start of DOC was 20 months, but post-progression treatments significantly prolonged overall survival.The findings of this study suggest that toxicity is acceptable, survival is independent of patients age and survival can be significantly prolonged by the use of new agents.


Garlanda C.,Humanitas Clinical Research Center | Jaillon S.,Humanitas Clinical Research Center | Doni A.,Humanitas Clinical Research Center | Bottazzi B.,Humanitas Clinical Research Center | And 2 more authors.
Current Opinion in Immunology | Year: 2016

Innate immunity consists of a cellular and a humoral arm. PTX3 is a fluid patter recognition molecule (PRM) with antibody-like properties. Gene targeted mice and genetic associations in humans suggest that PTX3 plays a non-redundant role in resistance against selected pathogens ( e.g. Aspergillus fumigatus, Pseudomonas aeruginosa, uropathogenic Escherichia coli) and in the regulation of inflammation. PTX3 acts as an extrinsic oncosuppressor by taming complement elicited tumor-promoting inflammation. Recent results indicate that, by interacting with provisional matrix components, PTX3 contributes to the orchestration of tissue repair. An acidic pH sets PTX3 in a tissue repair mode, while retaining anti-microbial recognition. Based on these data and scattered information on humoral PRM and matrix components, we surmise that matrix and microbial recognition are related functions in evolution. © 2015 Elsevier Ltd.


Jaillon S.,Humanitas Clinical Research Center | Bonavita E.,Humanitas Clinical Research Center | Gentile S.,Humanitas Clinical Research Center | Rubino M.,Humanitas Clinical Research Center | And 4 more authors.
International Archives of Allergy and Immunology | Year: 2014

The innate immune system is composed of a cellular arm and a humoral arm. Components of the humoral arm include members of the complement cascade and soluble pattern recognition molecules (PRMs). These PRMs recognize pathogen-associated molecular patterns and are functional ancestors of antibodies, playing a role in complement activation, opsonization and agglutination. Pentraxins consist of a set of multimeric soluble proteins and represent the prototypic components of humoral innate immunity. The prototypic long pentraxin PTX3 is highly conserved in evolution and produced by somatic and innate immune cells after proinflammatory stimuli. PTX3 interacts with a set of self, nonself and modified self ligands and exerts essential roles in innate immunity, inflammation control and matrix deposition. In addition, translational studies suggest that PTX3 may be a useful biomarker of human pathologies complementary to C-reactive protein. In this study, we will review the general functions of pentraxins in innate immunity and inflammation, focusing our attention on the prototypic long pentraxin PTX3. © 2014 S. Karger AG, Basel.


Ivanova T.,University of Manchester | Jalil A.,University of Manchester | Antoniou Y.,University of Manchester | Bishop P.N.,University of Manchester | And 3 more authors.
Eye (Basingstoke) | Year: 2016

Floaters are a common ocular condition which form as a consequence of aging changes in the vitreous. Although in most patients the symptoms are minimal, they can cause significant impairment in vision-related quality of life in a small population of patients. Recently there has been an increase in awareness of the visual disability caused by floaters, and the evidence-base for treatment of this condition using small-gauge vitrectomy has increased. In this review, we define the term 'floaters' as symptomatic vitreous opacities (SVO). We suggest a classification dependent on the presence or absence of posterior vitreous detachment and discuss their pathogenesis and natural history. We review their impact on patients' quality of life related to visual function. We review the psychological factors that may have a role in some patients who appear to be affected by SVO to the extent that they pursue all options including surgery with all its attendant risks. We summarise the available evidence-base of treatment options available for SVO with special emphasis on the safety and efficacy of vitrectomy for this condition. © 2016 Macmillan Publishers Limited.


Barry J.,Hunter Medical Research Institute | Loh Z.,University of Queensland | Collison A.,Hunter Medical Research Institute | Mazzone S.,University of Queensland | And 10 more authors.
American Journal of Respiratory Cell and Molecular Biology | Year: 2013

Allergic asthma is a chronic inflammatory disease predominately associated with the activation of CD4+ T helper Type 2 (Th2) cells. Innate pattern recognition receptors are widely acknowledged to shape the adaptive immune response. For example, the activation of airway epithelial Toll-like receptor-4 (TLR4) is necessary for the generation of house dust mite(HDM)-specific Th2 responses and the development of asthma in mice. Here we sought to determine whether the absence of Toll-interleukin-1 receptor (TIR)-8, a negative regulator of TLR4 signaling that is highly expressed in airway epithelial cells, would exacerbate HDM-induced asthma in a murine model. We found that Th2 but not Th1 or Th17 cytokine expression was significantly reduced in the lung and draining lymph nodes in HDM-sensitized/challenged TIR8 gene-deleted mice. Mucus-producing goblet cells, HDM-specific IgG1, and airway hyperreactivity were also significantly reduced in HDM-exposed, TIR8-deficient mice. Consistent with the attenuated Th2 response, eotaxin-2/CCL24 expression and airway and peribronchial eosinophils were significantly reduced in the absence of TIR8. In contrast, IL-17A- responsive chemokines and neutrophil numbers were unaffected. Similar findings were obtained for cockroach allergen. HDM sensitization alone up-regulated the expression of IL-1F5, a putative TIR8 ligand and inducer of IL-4. Of note, innate IL-4, IL-5, IL-13, and IL-33 cytokine expression was reduced during HDM sensitization in the absence of TIR8, as was the recruitment of conventional dendritic cells and basophils to the draining lymph nodes. Our findings suggest that TIR8 enhances the development of HDM-induced innate and adaptive Th2, but not Th1 or Th17 type immunity. Copyright © 2013 by the American Thoracic Society.


Jaillon S.,Humanitas Clinical Research Center | Moalli F.,Humanitas Clinical Research Center | Ragnarsdottir B.,Lund University | Bonavita E.,Humanitas Clinical Research Center | And 16 more authors.
Immunity | Year: 2014

Immunity in the urinary tract has distinct and poorly understood pathophysiological characteristics and urinary tract infections (UTIs) are important causes of morbidity and mortality. We investigated the role of the soluble pattern recognition molecule pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity, in UTIs. PTX3-deficient mice showed defective control of UTIs and exacerbated inflammation. Expression of PTX3 was induced in uroepithelial cells by uropathogenic Escherichia coli (UPEC) in a Toll-like receptor 4 (TLR4)- and MyD88-dependent manner. PTX3 enhanced UPEC phagocytosis and phagosome maturation by neutrophils. PTX3 was detected in urine of UTI patients and amounts correlated with disease severity. In cohorts of UTI-prone patients, PTX3 gene polymorphisms correlated with susceptibility to acute pyelonephritis and cystitis. These results suggest that PTX3 is an essential component of innate resistance against UTIs. Thus, the cellular and humoral arms of innate immunity exert complementary functions in mediating resistance against UTIs. © 2014 Elsevier Inc.


PubMed | French Institute of Health and Medical Research, Lund University, University of Milan, University of Zagreb and Humanitas Clinical Research Center
Type: Journal Article | Journal: Immunity | Year: 2014

Immunity in the urinary tract has distinct and poorly understood pathophysiological characteristics and urinary tract infections (UTIs) are important causes of morbidity and mortality. We investigated the role of the soluble pattern recognition molecule pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity, in UTIs. PTX3-deficient mice showed defective control of UTIs and exacerbated inflammation. Expression of PTX3 was induced in uroepithelial cells by uropathogenic Escherichia coli (UPEC) in a Toll-like receptor 4 (TLR4)- and MyD88-dependent manner. PTX3 enhanced UPEC phagocytosis and phagosome maturation by neutrophils. PTX3 was detected in urine of UTI patients and amounts correlated with disease severity. In cohorts of UTI-prone patients, PTX3 gene polymorphisms correlated with susceptibility to acute pyelonephritis and cystitis. These results suggest that PTX3 is an essential component of innate resistance against UTIs. Thus, the cellular and humoral arms of innate immunity exert complementary functions in mediating resistance against UTIs.


Fuoco C.,University of Rome Tor Vergata | Sangalli E.,IRCCS MultiMedica | Vono R.,IRCCS MultiMedica | Testa S.,IRCCS MultiMedica | And 14 more authors.
Frontiers in Physiology | Year: 2014

Skeletal muscle tissue engineering is a promising approach for the treatment of muscular disorders. However, the complex organization of muscle, combined with the difficulty in finding an appropriate source of regenerative cells and in providing an adequate blood supply to the engineered tissue, makes this a hard task to face. In the present work, we describe an innovative approach to rejuvenate adult skeletal muscle-derived pericytes (MP) based on the use of a PEG-based hydrogel scaffold. MP were isolated from young (piglet) and adult (boar) pigs to assess whether aging affects tissue regeneration efficiency. In vitro, MP from boars had similar morphology and colony forming capacity to piglet MP, but an impaired ability to form myotubes and capillary-like structures. However, the use of a PEG-based hydrogel to support adult MP significantly improved their myogenic differentiation and angiogenic potentials in vitro and in vivo. Thus, PEG-based hydrogel scaffolds may provide a progenitor cell "niche" that promotes skeletal muscle regeneration and blood vessel growth, and together with pericytes may be developed for use in regenerative applications. © 2014 Fuoco, Sangalli, Vono, Testa, Sacchetti, Latronico, Bernardini, Madeddu, Cesareni, Seliktar, Rizzi, Bearzi, Cannata, Spinetti and Gargioli.

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