Adelina Spallanzani

Immunohistochemical evidence of cytokine networks during progression of human melanocytic lesions

Melanoma cells in culture express a variety of growth factors and cytokines and some of their autocrine and paracrine roles have been investigated. However, less information is available on the potential dynamic changes in expression of these molecules on cells during melanoma development and progression in situ. Using immunohistochemistry, we tested 40 nevi and primary and metastatic melanoma lesions for the expression of 10 growth factors and cytokines and the respective receptors representing 10 cell surface molecules. Nevi and thin (< 1 mm) primary melanomas showed little expression of ligands except weak reactivity of tumor necrosis factor‐α (TNF‐α), transforming growth factor‐β (TGF‐β), interleukin‐8 (IL‐8) and reactivity of TGF‐βR and c‐kit. Marked up‐regulation of growth factors, cytokines and receptor expression was observed in thick (> 1 mm) primary melanomas, which were stained with polyclonal or monoclonal antibodies (MAbs) for IL‐1α, IL‐1β, IL‐6, IL‐8, TNF‐α, TGF‐β, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and stem cell factor (SCF), but not IL‐2. Metastases showed similar expression patterns except that SCF was absent. Co‐expression of ligand and receptor was observed for TGF‐β, GM‐CSF and IL‐6, suggesting an autocrine role for these ligands. TNF‐α appears to be a marker of benign lesions; IL‐6 and IL‐8 expression is associated with biologically early malignancy; TGF‐β, GM‐CSF and IL‐1α are highly expressed in biologically late lesions; and TNF‐β is an apparent marker of metastatic dissemination. Our results indicate that melanoma cells utilize cascades of growth factors and cytokines for their progression. Int. J. Cancer (Pred. Oncol.) 84:160–168, 1999.

Fibrosis in regressing melanoma versus nonfibrosis in halo nevus upon melanocyte disappearance: Could it be related to a different cytokine microenvironment?

Background:  It is not clear why melanocyte disappearance occurs without fibrotic evolution in halo nevus and with fibrotic evolution in regressing melanoma.

Oral carcinoma in a young man: a case of dyskeratosis congenita

We report a 28‐year‐old male with a voluminous growth of the tongue, present for 6 months. The histological examination revealed a squamous cell carcinoma. The patient was also affected by oral leukoplakia, nail dystrophy, reticulated poikiloderma of the neck and hyperkeratosis of palms and soles. On the basis of clinical features and histological findings, as well as findings from the family, the diagnosis of dyskeratosis congenita (DKC) was made.

Sequential effects of photodynamic treatment of basal cell carcinoma

Background:  Photodynamic therapy (PDT) of superficial basal cell carcinoma (SBCC) acts as a biological response modifier or killing target cells, but sequential biological effects have not been reported in depth in humans.

Mast cells do not play a role in vitiligo

ejd.2011.1459 Auteur(s) : Samantha Berti1 s.berti@meyer.it, Laura Amato1, Meena Arunachalam1, Adelina Spallanzani1, Francesca Prignano1, Romina Nassini2, Daniela Massi3, Roberta Colucci1, Silvia Moretti1 1 Departments of Dermatological Sciences 2 Preclinical and Clinical Pharmacology 3 Pathological Anatomy, University of Florence, Piazza Indipendenza 11, 50129 Florence, Italy Stem cell factor (SCF), produced by keratinocytes and endotheliocytes, acts as a ligand for the c-KIT receptor which is expressed [...]

Skin angiogenesis : Biologic bases for pathological processes

Angiogenesis is a complex biologic process characterized by the development of new blood vessels from existing vasculature. It is essential in reproduction, development, and wound repair.1 Under these conditions, angiogenesis is highly regulated (ie, turned on for short periods and then completely inhibited). In contrast, persistent unregulated angiogenesis can drive many diseases, such as growth of primary tumors and metastases, chronic arthropathies, and diabetic retinopathy. Common to all forms of angiogenesis is a general pattern of response by the capillary endothelial cell. Capillary blood vessels consist of endothelial cells and pericytes: these two cell types carry all genetic information to form tubes, branches, and whole capillary networks. Specific stimulatory molecules can initiate the process and specific inhibitory molecules can stop it. These molecules with opposing functions appear to be continuously acting in concert to maintain a quiescent microvasculature in which endothelial cell turnover is slow. Endothelial cells, however, can undergo rapid proliferation (few days’ turnover) during active angiogenesis (eg, in wound healing). The proteins involved in angiogenesis have been discovered in the past decades and their properties are well known, but their interactions with each other are not yet completely clarified. In addition, other entities such as nonvascular cells can modulate angiogenic response. This point may be crucial within a specific microenvironment, such as the skin, where resident cells—in particular, mast cells, macrophages, and fibroblasts—may exert modulation of the process. New blood vessel occurrence in the skin may be observed in several physiological and pathological circumstances, such as wound healing, psoriasis, hemangiomas, and benign and malignant cutaneous neoplasia. Morphological and Functional Bases of Angiogenesis: Vasculature in the Embryo

Collagen vascular diseases: unapproved treatments or indications.

Because a large variety of diseases are included under the term collagen vascular diseases, therapy is a complex issue. In general terms, accurate patient evaluation requires the integration of clinical, pathologic, and serologic data. Diagnostic characterization of the disease will direct its prognosis and therapy. In most cases symptomatically oriented anti-inflammatory immunosuppressive agents are used, and corticosteroids are the primary choice. But when adequate disease control is not obtained, or just to taper the dosage of corticosteroids, other less common drugs may be associated or may become the treatment of choice. Unapproved drugs can be considered in selected cases that do not improve with conventional therapy and appear as severe, recurrent, or life-threatening. The efficacy of these drugs is often controversial and/or anecdotal. Appropriate management of collagen vascular diseases might include supplementary medications that act on the single altered mechanism involved in the pathogenesis of the disease, thus leading to the sudden relief of some or all the symptoms. Some of the drugs less frequently used or unapproved are experimental and expensive for routine management. Undoubtedly future multicentric and multidisciplinary studies corroborated by meta-analysis evaluation will provide useful information to improve the treatment of this wide spectrum of clinical disorders.

Arachidonate transforming and immunomodulating agents: unapproved uses or indications

Arachidonic acid is the major component of membrane phospholipids. Stimulation of cell membrane activates the enzyme phospholipase A, eventually releasing fatty acids (ie, arachidonic acid) to form inflammatory and vasoactive metabolites named eicosanoids, such as prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs). Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes by platelets (thrombocytes), and leukotrienes by leukocytes, hence the derivation of their names.1 The eicosanoids produce several biological effects on inflammatory responses, in particular those of the skin, eyes and, joints; on the intensity and duration of pain and fever; in pregnancy and, in particular, in induction of labor; in inhibiting gastric acid secretion, regulating blood pressure through vasodilation or constriction, and inhibiting or activating platelet aggregation and thrombosis. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent and can cause evident physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis, through receptor-mediated G-proteinlinked signaling pathways leading to an increase in cAMP levels.1 Two main pathways are involved in the biosynthesis of eicosanoids (ie, the prostaglandins and thromboxanes are synthesized by the “cyclic” pathway and the leukotrienes by the “linear” pathway).