Cutaneous lesions in patients with mastocytosis are highly heterogeneous and encompass localized and disseminated forms. Although a classification and criteria for cutaneous mastocytosis (CM) have ...been proposed, there remains a need to better define subforms of cutaneous manifestations in patients with mastocytosis. To address this unmet need, an international task force involving experts from different organizations (including the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology) met several times between 2010 and 2014 to discuss the classification and criteria for diagnosis of cutaneous manifestations in patients with mastocytosis. This article provides the major outcomes of these meetings and a proposal for a revised definition and criteria. In particular, we recommend that the typical maculopapular cutaneous lesions (urticaria pigmentosa) should be subdivided into 2 variants, namely a monomorphic variant with small maculopapular lesions, which is typically seen in adult patients, and a polymorphic variant with larger lesions of variable size and shape, which is typically seen in pediatric patients. Clinical observations suggest that the monomorphic variant, if it develops in children, often persists into adulthood, whereas the polymorphic variant may resolve around puberty. This delineation might have important prognostic implications, and its implementation in diagnostic algorithms and future mastocytosis classifications is recommended. Refinements are also suggested for the diagnostic criteria of CM, removal of telangiectasia macularis eruptiva perstans from the current classification of CM, and removal of the adjunct solitary from the term solitary mastocytoma.
Background Angiogenesis and lymphangiogenesis are critical for several allergic, inflammatory, and neoplastic disorders. Mast cells infiltrate the sites of inflammation and tumors. Objective We ...sought to characterize the expression and functions of vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) in human mast cells. Methods VEGF expression was evaluated by means of RT-PCR and Western blotting in primary human lung mast cells and in the mast cell lines LAD-2 and HMC-1. Angiogenic activity of mast cell supernatants was determined by using the chick embryo chorioallantoic membrane assay. VEGFR expression was assessed by means of RT-PCR and flow cytometry. Modified Boyden chambers were used for chemotaxis assay. Results Human mast cells express VEGF-A, VEGF-B, VEGF-C, and VEGF-D at both the mRNA and protein level. Prostaglandin E2 (PGE2 ) enhanced the expression of VEGFA , VEGFB , and VEGFC , whereas an adenosine analog (5′-N-ethylcarboxamido adenosine NECA) increased VEGFA , VEGFC , and VEGFD expression. In addition, PGE2 and NECA enhanced VEGF-A release, and supernatants of PGE2 - and NECA-activated human lung mast cells induced angiogenic responses in the chorioallantoic membrane assay that were inhibited by an anti-VEGF-A antibody. Mast cells expressed mRNA for VEGFR1 and VEGFR2 . These receptors were present on the mast cell surface. VEGF-A165 , VEGF-B167 , VEGF-C, VEGF-D, and placental growth factor 1 induced mast cell chemotaxis. These chemotactic effects were mediated by the activation of both VEGFR-1 and VEGFR-2. Conclusion Our data indicate that human mast cells are both a source and a target of angiogenic and lymphangiogenic factors and therefore might play a role in inflammatory and neoplastic angiogenesis through the expression of several forms of VEGFs and their receptors.
Background Secreted phospholipases A2 (sPLA2 s) are released in plasma and other biologic fluids of patients with inflammatory, autoimmune, and allergic diseases. Objective We sought to evaluate ...sPLA2 activity in the bronchoalveolar lavage fluid (BALF) of asthmatic patients and to examine the expression and release of sPLA2 s from primary human lung mast cells (HLMCs). Methods sPLA2 activity was measured in BALF and supernatants of either unstimulated or anti-IgE–activated HLMCs as hydrolysis of oleic acid from radiolabeled Escherichia coli membranes. Expression of sPLA2 s was examined by using RT-PCR. The release of cysteinyl leukotriene (LT) C4 was measured by means of enzyme immunoassay. Results Phospholipase A2 (PLA2 ) activity was higher in the BALF of asthmatic patients than in the control group. BALF PLA2 activity was blocked by the sPLA2 inhibitors dithiothreitol and Me-Indoxam but not by the cytosolic PLA2 inhibitor AZ-1. HLMCs spontaneously released a PLA2 activity that was increased on stimulation with anti-IgE. This PLA2 activity was blocked by dithiothreitol and Me-Indoxam but not by AZ-1. HLMCs constitutively express mRNA for group IB, IIA, IID, IIE, IIF, III, V, X, XIIA, and XIIB sPLA2 s. Anti-IgE did not modify the expression of sPLA2 s. The cell-impermeable inhibitor Me-Indoxam significantly reduced (up to 40%) the production of LTC4 from anti-IgE–stimulated HLMCs. Conclusions sPLA2 activity is increased in the airways of asthmatic patients. HLMCs express multiple sPLA2 s and release 1 or more of them when activated by anti-IgE. The sPLA2 s released by mast cells contribute to LTC4 production by acting in an autocrine fashion. Mast cells can be a source of sPLA2 s in the airways of asthmatic patients.
To provide an overview of primary and secondary mechanisms associated with anti-IgE therapy and their relation to other potential indications in diseases affecting the respiratory tract.
Literature ...from PubMed searches for publications providing insight into secondary mechanisms resulting from anti-IgE therapy and publications reporting on the use of omalizumab to treat conditions that affect the respiratory tract, other than severe atopic asthma.
Clinical trials or case reports were identified for asthma in patients without atopy, allergic rhinitis, nasal polyposis, and allergic bronchopulmonary aspergillosis.
There is substantial evidence from controlled trials supporting a benefit for allergic rhinitis. Case reports and series on more than 50 patients with allergic bronchopulmonary aspergillosis have been published, including patients with or without cystic fibrosis; most have reported benefits in terms of decreased steroid use, exacerbation rates, and, in patients with cystic fibrosis, improvement in lung function. Several small controlled studies on nasal polyposis have shown equivocal results. One small controlled trial in patients with nonatopic asthma showed a significant improvement for lung function but not in exacerbation rate or asthma scores.
Recent insight into the immunopathology of respiratory diseases should be used to identify patient populations likely to respond to anti-IgE therapy. Controlled clinical trials are needed to confirm efficacy and determine the clinical significance of the effects of omalizumab in these populations.
Background Histamine modulates several functions in human monocytes, macrophages, and dendritic cells. However, responses elicited by histamine differ depending on cell type, suggesting variable ...expression of histamine receptors in the monocyte/macrophage lineage. Objective We sought to examine whether the expression of H1 receptors was regulated by cell differentiation of human monocytes into macrophages or dendritic cells. Methods Expression of H1 receptor was evaluated by RT-PCR and western blot in monocytes, monocyte-derived macrophages (MDMs), monocyte-derived dendritic cells (DCs) and human lung macrophages (HLMs). Results Expression of H1 receptor mRNA and protein was higher in HLMs and DCs than in monocytes. H1 expression was approximately 15-fold and 4-fold higher in MDMs and HLMs, respectively, as compared with that seen in monocytes. H1 receptor protein was undetectable in monocytes, whereas it was conspicuous in MDMs. Simultaneous analysis of H2 and H1 mRNA expression indicated that the H2 /H1 ratio decreased from 202.7 ± 14.8 in monocytes to 2.2 ± 0.4 in MDM and 39.5 ± 5.0 in DCs. Incubation of monocytes with histamine neither affected intracellular Ca2+ concentrations nor influenced IL-8 production. In contrast, histamine rapidly induced a Ca2+ signal and stimulated IL-8 production in MDMs. Both effects were inhibited by H1 blockade with levocetirizine, but not by H2 blockade with ranitidine. Conclusions Differentiation of monocytes into macrophages or dendritic cells is associated with profound changes of histamine receptor expression. Upregulation of H1 receptors confers on macrophages the capacity of being activated by histamine. Clinical implications Regulation of H1 and H2 receptor expression in the monocyte/macrophage lineage can be relevant to the pathogenesis of allergic inflammation.
Purpose
The aim of this study was to describe the safety and efficacy profiles of TACE using DC Beads LUMI.
Materials and methods
We retrospectively analyzed 90 patients with HCC who underwent TACE ...with DC Bead LUMI™ between November 2018 and November 2020 at Fondazione IRCCS Cà Granda Policlinico Hospital in Milan, Italy. Patient- and tumour-related factors were registered, including the number of treated lesions, dose of DC Beads LUMI™, dose of Epirubicin, DC Beads LUMI™ target tumour coverage (LC) according to the percentage of target nodule involvement (LC1-0%–25%, LC2-25%–50%, LC3-50%–75%, LC4 75%–100%). Treatment efficacy was obtained through reviewing the follow-up imaging for evidence of response in target lesion(s), according to modified response criteria in solid tumours (mRECIST) criteria with the following outcomes: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Safety assessment was based on the quantitative and qualitative recording of the adverse events, classified according to CIRSE classification.
Results
Seventy-two patients were enrolled, and 95 procedures were carried out. We observed a target tumour response rate at 1 month with CR in 68%, PR in 10.3% 11.8%, SD in 13%, PD in 7.2%, and an overall tumour(s) (whole liver) response at 1 month with CR in 58.9%, PR in 12.6%, SD in 10.5% and PD in 18%. We found a significant association (p < 0.01) between tumour response CR or CR + PR and the number of the target lesion(s). CIRSE classification grade I and grade II complications were recorded, respectively, in 11 (11.6%) and 6 (6.3%) procedures. No grade III-IV-V complications occurred.
Conclusion
TACE using DC Beads LUMI is a safe and effective treatment option for patients with HCC.
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