Nicola Pimpinelli

University of Florence, Florens, Tuscany, Italy

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Publications (190)607.44 Total impact

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    ABSTRACT: Bexarotene is a synthetic retinoid effective in early and advanced stages of mycosis fungoides (MF)/Sezary Syndrome (SS) both in monotherapy and combination schemes. We aimed to assess disease response to low dose bexarotene and PUVA in maintenance in refractory and/or resistant patients with early and advanced stage MF/SS. We followed prospectively 21 patients (stages IB-IV): 15 with early stage MF and 6 with advanced disease. "Mini" and standard protocols were respectively applied to patients who failed PUVA or several systemic regimens. The dose of bexarotene and the administration of PUVA were titrated individually and tailored during induction and maintenance according to previous therapy, disease stage and toxicity. We evaluated overall response (OR) at the end of maintenance, safety and event-free survival (EFS). After induction phase, OR was 85.6%, higher in early MF (93.4%) than in advanced disease (66.6%). At the end of maintenance, OR was 76.2%, including 33.3% of CR. Median EFS for the whole group was 31 months. Bexarotene was well tolerated due to side effects prophylaxis and progressive drug increase in the induction phase of the protocol. Side effects were mainly of low and moderate grades. We observed a favorable rate of therapeutic effects and few, generally mild, side effects with low doses of bexarotene combined with PUVA.
    No preview · Article · Dec 2015
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    ABSTRACT: Purpose: Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Patients and methods: Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Results: Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). Conclusion: To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value, which, used together in a prognostic index, may be useful to stratify advanced-stage patients.
    Full-text · Article · Oct 2015 · Journal of Clinical Oncology
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    ABSTRACT: The objective of this study was to provide further insights into the prognostic role of female sex in skin melanoma. The prognostic effect of sex in a population-based case series of 3900 skin melanomas in central Italy has been evaluated considering the possible confounding role of many demographic and clinical variables (age, period of diagnosis, Breslow's thickness, Clark level, ulceration, lymph node status, metastasis, histological type, skin site, and pathological T and N). Multiple imputations, according to chained equations, have been used for imputing incomplete values. A Cox proportional hazards model on the risk of death caused by melanoma was fitted. Univariate and multivariate effects of sex and of other variables were computed. The 5-year cause-specific survival was 87% (95% confidence interval: 86-89%) for women and 80% (78-82%) for men. Women had higher rates at any time since diagnosis. After adjustment for other confounders, women had a 34% reduced risk compared with men of dying from skin melanoma (hazard ratio=0.66, 95% confidence interval: 0.56-0.79). The present study confirmed a strong protective effect of female sex on skin melanoma mortality. The protective factor is still unknown.
    No preview · Article · Aug 2015 · European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP)
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    ABSTRACT: The capacity of cancer cells to undergo epithelial-to-mesenchymal transition (EMT) is now considered a hallmark of tumor progression, and it is known that interactions between cancer cells and mesenchymal stem cells (MSCs) of tumor microenvironment may promote this program. Herein, we demonstrate that MSC-conditioned medium (MSC-CM) is a potent inducer of EMT in melanoma cells. The EMT profile acquired by MSC-CM-exposed melanoma cells is characterized by an enhanced level of mesenchymal markers, including TGFβ/TGFβ-receptors system upregulation, by increased invasiveness and uPAR expression, and in vivo tumor growth. Silencing TGFβ in MSC is found to abrogate ability of MSC to promote EMT characteristics in melanoma cells, together with uPAR expression, and this finding is strengthened using an antagonist peptide of TGFβRIII, the so-called P17. Finally, we demonstrate that the uPAR antisense oligonucleotide (uPAR aODN) may inhibit EMT of melanoma cells either stimulated by exogenous TGFβ or MSC-CM. Thus, uPAR upregulation in melanoma cells exposed to MSC-medium drives TGFβ-mediated EMT. On the whole, TGFβ/uPAR dangerous liaison in cancer cell/MSC interactions may disclose a new strategy to abrogate melanoma progression. Mesenchymal stem cell (MSC)-conditioned medium induces EMT-like profile in melanoma. MSC-derived TGFβ promotes uPAR and TGFβ/TGFβ-receptor upregulation in melanoma. TGFβ gene silencing in MSCs downregulates uPAR expression and EMT in melanoma. uPAR downregulation prevents MSC-induced EMT-like profile in melanoma cells. Inhibition of the dangerous TGFβ/uPAR relationship might abrogate melanoma progression.
    Full-text · Article · Feb 2015 · Journal of Molecular Medicine
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    ABSTRACT: The capacity of cancer cells to undergo epithelial-to-mesenchymal transition (EMT) is now considered a hallmark of tumor progression, and it is known that interactions between cancer cells and mesenchymal stem cells (MSCs) of tumor microenvironment may promote this program. Herein, we demonstrate that MSC-conditioned medium (MSC-CM) is a potent inducer of EMT in melanoma cells. The EMT profile acquired by MSC-CM-exposed melanoma cells is characterized by an enhanced level of mesenchymal markers, including TGFβ/TGFβ-receptors system upregulation, by increased invasiveness and uPAR expression, and in vivo tumor growth. Silencing TGFβ in MSC is found to abrogate ability of MSC to promote EMT characteristics in melanoma cells, together with uPAR expression, and this finding is strengthened using an antagonist peptide of TGFβRIII, the so-called P17. Finally, we demonstrate that the uPAR antisense oligonucleotide (uPAR aODN) may inhibit EMT of melanoma cells either stimulated by exogenous TGFβ or MSC-CM. Thus, uPAR upregulation in melanoma cells exposed to MSC-medium drives TGFβ-mediated EMT. On the whole, TGFβ/uPAR dangerous liaison in cancer cell/MSC interactions may disclose a new strategy to abrogate melanoma progression.
    Full-text · Article · Feb 2015 · Journal of molecular medicine
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    ABSTRACT: Background: No studies are available in the literature on the distribution of different melanoma features and risk factors in the Italian geographical areas. Objective: To identify the differences in clinical-pathological features of melanoma, the distribution of risk factors and sun exposure in various Italian macro-areas. Methods: Multicentric-observational study involving 1,472 melanoma cases (713 north, 345 centre, 414 south) from 26 referral centres belonging to the Italian Multidisciplinary Group for Melanoma. Results: Melanoma patients in northern regions are younger, with thinner melanoma, multiple primaries, lower-intermediate phototype and higher counts of naevi with respect to southern patients; detection of a primary was mostly connected with a physician examination, while relatives were more involved in the south. Northern patients reported a more frequent use of sunbeds and occurrence of sunburns before melanoma despite sunscreen use and a lower sun exposure during the central hours of the day. Conclusions: The understanding of differences in risk factors distribution could represent the basis for tailored prevention programmes. © 2015 S. Karger AG, Basel.
    Full-text · Article · Jan 2015 · Dermatology
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    ABSTRACT: The body image (BI) is very important to take into account, especially in cancer patients. It's important an adequate psychological support is recalled as it has been widely demonstrated that problems connected to the body image interfere negatively with the quality of life of patients, especially in the oncology field. Such support has the aim of containing those aspects that can compromise our patients' equilibrium. We administered the Body Image Scales, with a specifically created semi--structured questionnaire which includes items that investigate the level of awareness and the degree of acceptance of the disease of the patient7, was administered to patients giving their written informed consent to participate to the study. The results show that our population sample got an average score of 17.25 showing precisely problems related to body image.
    No preview · Article · Jan 2015 · Giornale italiano di dermatologia e venereologia: organo ufficiale, Societa italiana di dermatologia e sifilografia
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    ABSTRACT: Psoriasis is traditionally defined as an inflammatory chronic--relapsing disease of the skin. It is also -- as widely demonstrated -- a disease associated with multiple comorbidities: arthropathy, inflammatory bowel disease, metabolic, cardiovascular, ocular and psychological disorders. The disease also has a significant impact on patients' quality of life, whose work ability decreases considerably with clear consequences for the social costs. Therefore, if we consider that in Tuscany, more than 100,000 people out of 3,672,202 suffer from psoriasis, it is of paramount importance focusing the attention on a rational model of clinical and therapeutic management of the disease. All the leading experts in Tuscany have come together with the aim of ● defining regional universally accepted guidelines for the diagnosis, treatment, follow--up and management of psoriasis ● providing practical guidance / protocol on diagnosis, treatment, follow up and management of special cases of moderate--to--severe plaque psoriasis METHODS: ● working groups ● discussion on the main topics and approval by plenary vote RESULTS: The diagnosis includes a proper general health condition overview, a careful evaluation of skin and joints, the assessment and management of other comorbidities and the definition of disease severity. With regards to the therapy the best time to start a systemic treatment, the therapeutic goal, the most appropriate drug and blood tests to be performed in case of moderate severe--psoriasis have been taken into account. During the follow--up, proper monitoring of systemic therapy and its management in the long term have also been considered. Eventually, the experts have addressed the problem of how to manage the disease in special conditions such as during surgery, pregnancy, in children and in case of infections (HBV, HCV, HIV ) (TAB.1) CONCLUSIONS: The main aim of the CONSENSUS was to find out the criteria for the diagnosis, treatment and follow up of psoriasis, shared by all the Dermatology Therapeutic Units of Tuscany. The need to create an easier way for the patient to access to specialized dermatological outpatient services and to reduce the waiting list and the costs related to the management of such a disease has been highlighted. The most important fact that came out during the CONSENSUS was the shared opinion of all the participants on the central role of the patient and the need of a multidisciplinary management of the disease, among the various specialists and the regional centers, in order to build on the gained experiences.
    No preview · Article · Jan 2015 · Giornale italiano di dermatologia e venereologia: organo ufficiale, Societa italiana di dermatologia e sifilografia
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    ABSTRACT: Detection of pre-malignant lesions in skin could help in reducing the 5 year patient mortality rates and greatly advancing the quality of life. Current gold standard for the detection of skin pathologies is a tissue biopsy and followed by a series of steps before it is examined under a light microscope by a pathologist. The disadvantage with this method is its invasiveness. Light based biomedical point spectroscopic techniques offers an adjunct technique to invasive tissue pathology. In this context, we have implemented a simple multiplexed ratiometric approach (F470/F560 and F510/F580) based on fluorescence at two excitation wavelengths 378 nm and 445 nm respectively. The emission profile at these excitation wavelengths showed a shift towards the longer wavelengths for melanoma when compared with normal and nevus. At both excitation wavelengths, we observed an increased intensity ratios for normal, followed by nevus and melanoma. This intensity ratios provide a good diagnostic capability in differentiating normal, nevus and melanocytic skin lesions. This method could be applied in vivo because of the simplicity involved in discriminating normal and pathological skin tissues.
    No preview · Article · Jan 2015
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    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 diagnostic purposes on various tissues in a good agreement with common routine histology. This study included skin, brain and bladder tissues and in particular the classification of: malignant melanoma against melanocytic lesions and healthy skin; urothelial carcinoma against healthy bladder mucosa; brain tumor against dysplastic brain tissue. The diagnostic capabilities were determined using a cross-validation method with a leave-one-out approach, finding very high sensitivity and specificity for all the examined tissues. The obtained results demonstrated that the multimodal approach is crucial for improving diagnostic capabilities. 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.
    No preview · Article · Jan 2015
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    ABSTRACT: Unilesional mycosis fungoides (UMF) was firstly described in 1981 as solitary lesion with clinical and histological features of MF. Although over 100 cases have been reported in the literature, there is a lack of clear-cut criteria characterising UMF. Only 10 cases featured by follicolotropism of the neoplastic T-cells have been reported: the so-called unilesional folliculotropic MF (UFMF). This paper questions whether or not UFMF should be considered as a true rarity in MF clinico-pathological spectrum. We retrieved 28 folliculotropic MF cases in the database of the Dermatological Divisions of Bologna (12 patients) and Florence University (16 patients). Four of them were UFMF patients (2 males and 2 females, mean age 45 years; median age: 39 years). All patients achieved after therapy disease complete remission. Notably, only one patient was treated with radiotherapy, that seems the most recommended strategy in UMF. For the remaining patients, we choose different managements in order to achieve both clinical efficacy and the best aesthetical outcome. No definitive conclusions can be drawn whether or not UFMF has the same indolent clinical course of UMF. Recently, Kempf et al. reported 2 UFMF patients with progression to tumour stage and large-cell transformation, respectively. UFMF in our database is 14.3% of the 28 FMF cases. Our data suggest that UFMF can be regarded as a true rarity in MF clinico-pathological spectrum.
    No preview · Article · Dec 2014 · Giornale italiano di dermatologia e venereologia: organo ufficiale, Societa italiana di dermatologia e sifilografia
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    ABSTRACT: We developed two different probes for combined Raman-fluorescence spectroscopy on human tissues. The device was successfully used for diagnosing melanocytic lesions in a good agreement with histology and further tested on bladder and brain tissues.
    No preview · Article · Nov 2014
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    Full-text · Dataset · Oct 2014
  • A Bassi · P Campolmi · M Dindelli · N Bruscino · R Conti · G Cannarozzo · N Pimpinelli
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    ABSTRACT: Background: Rhinophyma is a benign, disfiguring disorder, commonly reffered to as the end stage of severe rosacea and characterized by a progressive thickening and hypertrophy of the nasal skin and soft tissues.. Objectives: To evaluate the efficacy of CO2 laser compared to other laser techniques and surgical methods in the treatment of rhinophyma. Methods: 24 rhinophyma patients were treated with CO2 laser in our institution from 2003 to 2013. A 10,600--nm CO2 pulsed laser was used in all patients, with a 6--month, post--treatment follow up. Results: Six months after the last laser session, all patients showed global improvement of their clinical conditions: 19 (79.1%) high improvement (>75%), 4 (16.7%) moderate improvement (50--75%), and 1 (4.2%) low improvement (<25%).. Conclusions: Our study demonstrates that carbon dioxide laser warrants a careful nasal surface ablation, allowing the remodeling of the hypertrophic areas, with an excellent cosmetic result, a very short healing time, and virtually no side effects.
    No preview · Article · Sep 2014 · Giornale italiano di dermatologia e venereologia: organo ufficiale, Societa italiana di dermatologia e sifilografia
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    Full-text · Article · Sep 2014 · Journal of the European Academy of Dermatology and Venereology
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    ABSTRACT: The most frequent site for melanoma is the back in men and the lower limbs in women, where intermittent sun exposure has been reported to be an environmental agent, although studies on age-specific incidence have suggested that melanoma in chronically sun-exposed areas, such as the face, increases with age. To identify the preferential development of melanoma in chronically or intermittently sun-exposed areas and the relationship between body site distribution and parameters such as sex, age, distribution of melanocytic naevi, atypical naevi and actinic keratoses, a prospective epidemiological multicentre study was carried out on all the consecutive melanoma cases diagnosed in a 2-year period from 27 Italian GIPMe centres (GIPMe: the Italian Multidisciplinary Group on Melanoma). Both the relative density of melanoma (RDM), defined as the ratio between observed and expected melanoma for a specific body site, and the average nevi density were identified. The most common melanoma site was the back, a factor that was not affected by either age or sex, even if men had higher density values. Statistically significant higher RDM values were observed in women aged more than 50 years for leg lesions and in the anterior thighs for young women (<50 years), whereas the lowest values were observed in the posterior thighs in women of any age. Facial RDM was statistically significantly higher than expected in both male and female patients more than 50 years of age. Melanoma was associated with a significantly higher atypical naevi density only for the back, chest and thighs. Indeed, facial melanoma was related to the presence of more than four actinic keratoses and not naevi density. To the best of our knowledge, the RDM method was applied for the first time together with naevus density calculation to obtain these data, which strongly substantiate the 'divergent pathway' hypothesis for the development of melanoma, but not find a direct correlation between melanoma and nevi for each anatomical site.
    No preview · Article · Aug 2014 · Melanoma Research
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    ABSTRACT: Purpose: 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. Patients and methods: Data from 2,243 patients with thin melanoma were retrieved from prospectively maintained databases at six centers. Kaplan-Meier survival and crude cumulative incidences of recurrence were estimated, and competing risks were taken into account. Multivariable Cox regression was used to investigate survival predictors. Results: Median follow-up was 124 months (interquartile range, 106 to 157 months); 12-year overall survival was 85.3% (95% CI, 83.4% to 87.2%). Median times to local, regional, and distant recurrence were 79, 78, and 107 months, respectively. Relapse was significantly related to age, Breslow thickness, mitotic rate (MR), ulceration, lymphovascular invasion (LVI), and regression; incidence was lower and subgroup differences were less marked for distant metastasis than for regional relapse. The worst prognosis categories were age older than 60 years, Breslow thickness more than 0.75 mm, MR ≥ 1, presence of ulceration, presence of LVI, and regression ≥ 50%. Breslow thickness more than 0.75 mm, MR ≥ 1, presence of ulceration, and LVI (all P = .001) were significantly associated with sentinel node positivity. Age, MR, ulceration, LVI, regression, and sentinel node status were independent predictors of survival and were used to construct a nomogram to predict 12-year overall survival. The nomogram was well calibrated and had good discriminative ability (adjusted Harrell C statistic, 0.88). Conclusion: Our findings suggest including LVI and regression as new prognostic factors in the melanoma staging system. The nomogram appears useful for risk stratification in clinical management and for recruiting patients to clinical trials.
    Full-text · Article · Jul 2014 · Journal of Clinical Oncology
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    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.
    Full-text · Article · Jun 2014 · Journal of Investigative Dermatology
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    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.
    Full-text · Article · Jun 2014 · Giornale italiano di dermatologia e venereologia: organo ufficiale, Societa italiana di dermatologia e sifilografia
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    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.
    Full-text · Article · May 2014 · Oncotarget

Publication Stats

6k Citations
607.44 Total Impact Points

Institutions

  • 1987-2015
    • University of Florence
      • • Dipartimento di Chirurgia e Medicina Traslazionale (DCMT)
      • • Dipartimento di Scienze Biomediche, Sperimentali e Cliniche
      Florens, Tuscany, Italy
  • 2014
    • University of Bologna
      • Department of Experimental, Diagnostic and Specialty Medicine DIMES
      Bolonia, Emilia-Romagna, Italy