[Show abstract][Hide abstract] ABSTRACT: Cutaneous melanoma incidence is increasing. Most new cases are thin (≤ 1 mm) with favorable prognoses, but survival is nonetheless variable. Our aim was to investigate new prognostic factors and construct a nomogram for predicting survival in individual patients.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 07/2014;
[Show abstract][Hide abstract] ABSTRACT: The aim of followup programs for patients diagnosed with melanoma is early detection of local, regional and distant metastasis, as well as early recognition of eventual subsequent primary tumors. Currently, no universally accepted recommendations exist for monitoring patients with cutaneous melanoma. The present recommendations have been developed on the basis of the experience of a group of clinicians affiliated to referral centers dealing with melanoma diagnosis and management in Italy. Clinical evaluation is mandatory at any stage and is intended to be lifelong, with time frequencies of followup visits depending on the specific stage of disease. Sonography of regional lymph nodes has been demonstrated to have the highest accuracy and highest diagnostic validity to detect early regional relapse, and can be considered once per year starting from stage I melanoma. Total body CT scan should be considered in the follow up of patients with higher risk of developing distant metastasis. In stage II and III it should be performed once per year, alternated with abdomen and lymph node ultrasonography. Our aim is to provide a simplified schedule for the routine follow up of melanoma patients. These recommendations are intended as an initial guideline that must be tailored on the individual patient needs.
Giornale italiano di dermatologia e venereologia: organo ufficiale, Societa italiana di dermatologia e sifilografia 06/2014; · 0.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The CD63 tetraspanin is highly expressed in the early stages of melanoma and decreases in advanced lesions, suggesting it as a possible suppressor of tumor progression. We employed loss- and gain-of-gene function approaches to investigate CD63 role in melanoma progression and acquisition of the epithelial-to-mesenchymal transition (EMT) program. We used two human melanoma cell lines derived from primary tumors and one primary human melanoma cell line isolated from a cutaneous metastasis, differing by levels of CD63 expression. CD63 silenced melanoma cells showed enhanced motility and invasiveness with down-regulation of E-cadherin and up-regulation of N-cadherin and Snail. In parallel experiments, transient and stable ectopic expression of CD63 resulted in a robust reduction of cell motility, invasiveness and protease activities, which was proportional to the increase of CD63 protein level. Transfected cells overexpressing the highest level of CD63 when transplanted into immunodeficient mice showed a reduced incidence and rate of tumor growth. Moreover, these cells showed a reduction of N-cadherin, Vimentin, Zeb1 and a-SMA, and a significant resistance to undergo an EMT program both in basal condition and following stimulation with TGFβ. Thus, our results establish a previously unreported mechanistic link between the tetraspanin CD63 and EMT abrogation in melanoma.Journal of Investigative Dermatology accepted article preview online, 18 June 2014; doi:10.1038/jid.2014.258.
The Journal of investigative dermatology. 06/2014;
[Show abstract][Hide abstract] ABSTRACT: The receptor for the urokinase-type plasminogen activator (uPAR) accounts for many features of cancer progression, and is therefore considered a target for anti-tumoral therapy. Only full length uPAR mediates tumor progression. Matrix-metallo-proteinase-12 (MMP12)-dependent uPAR cleavage results into the loss of invasion properties and angiogenesis. MMP12 can be employed in the field of “targeted therapies” as a biological drug to be delivered directly in patient’s tumor mass. Endothelial Progenitor Cells (EPCs) are selectively recruited within the tumor and could be used as cellular vehicles for delivering anti-cancer molecules. The aim of our study is to inhibit cancer progression by engeneering ECFCs, a subset of EPC, with a lentivirus encoding the anti-tumor uPAR-degrading enzyme MMP12. Ex vivo manipulated ECFCs lost the capacity to perform capillary morphogenesis and acquired the anti-tumor and anti-angiogenetic activity. In vivo MMP12-engineered ECFCs cleaved uPAR within the tumor mass and strongly inhibited tumor growth, tumor angiogenesis and development of lung metastasis.
The possibility to exploit tumor homing and activity of autologous MMP12-engineered ECFCs represents a novel way to combat melanoma by a “personalized therapy”, without rejection risk.
The i.v. injection of radiolabelled MMP12-ECFCs can thus provide a new theranostic approach to control melanoma progression and metastasis.
[Show abstract][Hide abstract] ABSTRACT: In order to promote widespread adoption of appropriate clinical practice, the Italian Society of Hematology (SIE), and the affiliate societies SIES (Italian Society of Experimental Hematology) and GITMO (Italian Group for Bone Marrow Transplantation) established to produce guidelines in the most relevant hematological areas. Here we report the recommendations for management of T/NK-cell lymphomas, excluding mature T-cell leukemias.
By using the GRADE (Grades of Recommendations, Assessment, Development, and Evaluation) system we produced evidence-based recommendations for the key clinical questions that needed to be addressed by a critical appraisal of evidence. The consensus methodology was applied to evidence-orphan issues.
Six courses of CHOP or CHOEP chemotherapy were recommended for first-line therapy of patients with nodal, intestinal or hepatosplenic T-cell lymphomas (evidence: low; recommendation: do, weak). Except for ALK+ anaplastic large cell lymphoma and elderly unfit patients, consolidation with high-dose chemotherapy was recommended (evidence: low; recommendation: do, weak). 50 Gy radiotherapy was the recommended first-line therapy for localized extranodal T/NK-cell lymphoma nasal type (evidence: low; recommendation: do, strong), while L-asparaginase containing chemotherapy regimens were recommended for patients with systemic disease (evidence: very low; recommendation: do, strong).
In adult T/NK-cell lymphomas, GRADE methodology was applicable to a limited number of key therapeutic issues. For the remaining key issues, due to lack of appraisable evidence, recommendations was based on consensus methodology.
[Show abstract][Hide abstract] ABSTRACT: We report dermatologists' opinions and clinical practice patterns about clinical factors driving decision making in the management of actinic keratosis (AK) in Italy.
We carried out a cross-sectional survey among 33 Italian dermatologists. Physicians were asked to report their management choices in consecutive patients with AK seen at their practice within 2 weeks since study initiation. We collected patients' clinical and socio-demographic characteristics with a standardized data collection form and assessed physicians' opinions on AK management with a self-reported questionnaire.
Six hundred fifty-seven patients with new, single AK lesions without evidence of photo-damaged skin in the surrounding areas, were predominantly treated with lesion-directed therapies (primarily cryotherapy). In contrast, physicians preferentially prescribed field-directed therapies to patients with multiple lesions and evidence of photo-damaged skin in AK surrounding areas. However we observed a wide variation in treatment choices and physicians' opinions on AK management. Dermatologists underlined the importance of fostering patients' adherence and minimize therapy side effects.
Overall, our results show that current guidelines regarding management of AK are only partially integrated in dermatology practice. The active dissemination of up-to-date national guidelines might help harmonize clinical decision making in this complex and fast growing therapeutic area.
Giornale Italiano di Dermatologia e Venereologia 04/2014; 149(2):185-92. · 0.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
In primary cutaneous B-cell lymphomas (PCBCL), radiotherapy – or surgery in a minority of cases – is the first-line treatment in follicle center lymphoma (PCFCL) and marginal zone B-cell lymphoma (PCMZL). Conversely, patients with multifocal skin involvement or relapsed/refractory disease deserve a systemic chemotherapy. In diffuse large B-cell lymphoma, leg type (PCLBCL-LT), due its poorer outcome, CHOP-like regimens are the most commonly used frontline, although hard to propose in elderly patients. In this regard, the association of rituximab (R) and pegylated liposomal doxorubicin (PLD) can be considered a promising, alternative approach.AimsBased on the favourable results reported with R and PLD in several recent trials, we decided to test efficacy and safety of this combination.Methods
Twelve patients with PCBCL were treated with R plus PLD, 7 had relapsed disease. Treatment plan consisted of 2 monthly cycles of R 375mg/m2 and PLD 20mg/m2 day 1;15, followed (in responders) by 2 cycles given only at day 1. All patients received prophylactic pyridoxine to prevent Palmar-Plantar Erythrodysesthesia (PPE).ResultsTen out of 12 patients had a response (8 complete; 2 partial), remarkably 2/3 with primary cutaneous diffuse large B-cell lymphoma, leg type. Two patients did not respond (1 progressive disease, PD, and 1 stable disease). Three patients died after a median follow-up of 56 months, 2 patients due to PD and 1 due to a second neoplasm. Two out of 10 responders relapsed after 31 and 32 months, respectively. Haematological toxicity was negligible (1 case of grade 2 neutropenia), as well as extra-haematological toxicity (2 cases of grade 2 PPE).Conclusions
These preliminary data suggest that R-PLD is effective and well tolerated in all subsets of PCBCL and may be offered front-line in indolent cases unsuitable for radiotherapy or surgery as well as in more aggressive cases with contraindications to CHOP-like regimens.This article is protected by copyright. All rights reserved.
European Journal Of Haematology 03/2014; · 2.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Two different optical fiber probes for combined Raman and fluorescence spectroscopic measurements were designed, developed and used for tissue diagnostics. Two visible laser diodes were used for fluorescence spectroscopy, whereas a laser diode emitting in the NIR was used for Raman spectroscopy. The two probes were based on fiber bundles with a central multimode optical fiber, used for delivering light to the tissue, and 24 surrounding optical fibers for signal collection. Both fluorescence and Raman spectra were acquired using the same detection unit, based on a cooled CCD camera, connected to a spectrograph. The two probes were successfully employed for diagnosing melanocytic lesions in a good agreement with common routine histology. The obtained results demonstrated that the multimodal approach is crucial for improving diagnostic capabilities. Further investigations were performed on colon and brain tissue samples in order to have a benchmark for diagnosing a broader range of tissue lesions and malignancies. The system presented here can improve diagnostic capabilities on a broad range of tissues and has the potential of being used for endoscopic inspections in the near future.
[Show abstract][Hide abstract] ABSTRACT: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease of controversial origin recently recognized as a neoplasm deriving from plasmacytoid dendritic cells (pDCs). Nevertheless, it remains an orphan tumor with obscure biology and dismal prognosis. To better understand the pathobiology of BPDCN and discover new targets for effective therapies, the gene expression profile (GEP) of 25 BPDCN samples was analyzed and compared with that of pDCs, their postulated normal counterpart. Validation was performed by immunohistochemistry (IHC), while functional experiments were carried out ex vivo. For the first time at the molecular level, we definitely recognized the cellular derivation of BPDCN, which proved to originate from the myeloid lineage and in particular from resting pDCs. Furthermore, thanks to an integrated bio-informatic approach we discovered aberrant activation of the NF-kB pathway and suggested it as a novel therapeutic target. We tested the efficacy of anti-NF-kB-treatment on the BPDCN cell line CAL-1, and successfully demonstrated by GEP and IHC the molecular shut-off of the NF-kB pathway. In conclusion, we identified a molecular signature representative of the transcriptional abnormalities of BPDCN and developed a cellular model proposing a novel therapeutic approach in the setting of this otherwise incurable disease.Leukemia accepted article preview online, 7 February 2014; doi:10.1038/leu.2014.64.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 02/2014; · 10.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The degree to which interferon (IFN) alpha-2b offers real clinical benefits in the adjuvant therapy of melanoma at high risk of recurrence is a subject of debate. This, together with questions over optimal treatment scheme and concerns over toxicity, has limited its clinical use. On the basis of a review of the literature, an Italian Expert Panel has made practical recommendations for a consistent approach in the use of IFN. Although it is clear that more research into predictive factors to identify patients most likely to benefit from adjuvant IFN therapy is required, IFN remains the only currently available adjuvant option for melanoma. Based on meta-analyses of clinical trials, there is clear evidence that treatment with IFN is beneficial with regard to overall and recurrence-free survival (RFS). As such, IFN should be offered to patients who are at high risk of recurrence. Specific recommendations with regard to disease stage are provided.
Journal of chemotherapy (Florence, Italy) 12/2013; · 0.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Animal-type melanoma (ATM) is a rare tumor, characterized histologically by a predominantly dermal proliferation of heavily pigmented epithelioid and spindle dendritic melanocytes. Five patients with ATM, who had undergone sentinel node biopsy, were studied: three male and two female, between 4 and 62 years of age (mean, 28.0). Lesion size ranged from 4 to 18 mm and thickness from 0.7 to 5.1 mm. Nodal deposits were found in three patients. Of the patients with positive sentinel nodes, the first showed a minimal nodal involvement in one node, the second multiple deposits in one node, and the third multiple deposits in one sentinel node and a single deposit in another; this last patient also had additional tumor deposits in a nonsentinel regional node. Fluorescence in-situ hybridization tumor analysis proved negative in all cases. All patients are alive and free of disease at 36-95-month follow-up (mean, 53 months). Results showed ATM as a neoplasm characterized by a somewhat high rate of lymph node involvement but relatively low rate of visceral metastases and mortality, appearing as a low-grade malignant tumor.
[Show abstract][Hide abstract] ABSTRACT: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma; it evolves slowly in its classical presentation, while can have an aggressive course in a subset of patients.
To investigate the impact of epigenetic mechanisms on early stage MF progression.
We analyzed DNA methylation at twelve different loci and long interspersed nucleotide elements-1 (LINE-1), as a surrogate marker of global methylation, on tissue samples from 41 stage I MF patients followed up for at least 12 years or until disease progression. The methylation profiles were also analyzed in two T-cell lymphoma cell lines and correlated with gene expression.
The selected loci were methylated in a tumour-specific manner; concomitant hypermethylation of at least 4 loci was more frequent in cases progressing within 1-3 and 3-6 years than in late-progressive or non-progressive cases. LINE-1 methylation was significantly lower in rapidly progressive MF at 3 years (61%, p< 0.001) than in those at 12 years (66.5%). PPARG, SOCS1 and NEUROG1 methylation showed remarkable differences among the prognostic groups, but only PPARG was a significant predictor of disease progression within 6 years after adjustment for patients' age or gender. Strikingly, a methylation profile similar to progressive cases was found in highly proliferative Sézary-derived HUT78 cells but not in MF-derived HUT102 cells. Exposure to a DNA demethylating agent restored sensitivity to apoptosis and cell cycle arrest.
Epigenetic silencing of specific biomarkers can predict the risk of disease progression in early stage MF, providing insights into its pathogenesis, prognosis and therapy. This article is protected by copyright. All rights reserved.
British Journal of Dermatology 11/2013; · 3.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of lymphoid neoplasms. The incidence of CTCLs has risen over the last three decades. The most common CTCLs are mycosis fungoides and Sèzary syndrome. Therapies for CTCLs are various and range from skin-directed therapy to chemotherapy. Retinoids have been used in CTCL treatment since the 1980s with good results. Bexarotene is the first retinoid approved by the US FDA for CTCL therapy. Since then, numerous experiences of both its efficacy and mechanism of action have been reported. The aim of this paper is to review bexarotene action on CTCLs, as well as to highlight its immunological targets.
[Show abstract][Hide abstract] ABSTRACT: Dermoscopy is the conventional technique used for the clinical inspection of human skin lesions. However, the identification of diagnostically relevant morphologies can become a complex task. We report on the development of a polarization multispectral dermoscope for the in vivo imaging of skin lesions. Linearly polarized illumination at three distinct spectral regions (470, 530 and 625 nm), is performed by high luminance LEDs. Processing of the acquired images, by means of spectral and polarization filtering, produces new contrast images, each one specific for melanin absorption, hemoglobin absorption, and single scattering. Analysis of such images could facilitate the identification of pathological morphologies.