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Nicola Pimpinelli

Publications and source records attributed to Nicola Pimpinelli.

At least 19 recordsLinked to original sources
PubMed2006

Stem cell factor affects tumour progression markers in metastatic melanoma cells.

Stem cell factor (SCF), next to various relevant biological effects exerted on many cell types, is able to keep melanocyte homeostasis through its receptor c-kit. Only a minority of metastatic melanoma cells (MMC) express c-kit receptor, but c-kit positive MMC move more slowly towards tumour progression and have a more natural tendency to undergo apoptosis. In our study c-kit positive MMC from human melanoma metastases and a c-kit positive human melanoma cell line-SK-MEL-28-showed a clear-cut reduction of cytokines normally up-regulated along melanoma progression after SCF stimulation. SCF was also able to maintain all MMC and SK-MEL-28 cells in a well differentiated status with an increase in organellogenesis and in particular of melanosomes in various degree of differentiation, but it did not induce apoptosis as observed in other in vitro models. The increase of melanosomes matched an increase of tyrosinase production. SCF did not modify the expression of NOS while it enhanced the expression of HLA-DR molecules on MMC membranes. Taken altogether these data stress the biological activity of SCF as a cytokine which is able to maintain MMC in a well differentiated status, and suggest a more in depth evaluation of possible effects of SCF on melanoma cells.

Biomarkers, Tumor↗
PubMed2006

Role of conventional treatments on circulating and monocyte-derived dendritic cells in colorectal cancer.

We investigated the effects of metastasis, surgery and chemotherapy on both circulating dendritic cells (DCs) and monocyte-derived-DCs (MoDCs) in colorectal cancer (CRC) patients. Metastatic or nonmetastatic CRC patients had significantly reduced DC subsets compared to healthy subjects (p < 0.001). These cells were significantly higher in metastatic than in nonmetastatic patients. MoDCs were significantly lower in metastatic than healthy and nonmetastatic subjects (p < 0.001). Surgically treated patients had nearly one-half circulating DC subsets compared to healthy subjects (p < 0.001) while no difference was found between unoperated and healthy subjects. MoDCs obtained from tumor-bearing were significantly higher than in operated subjects. In both cases, MoDCs were significantly lower than in healthy subjects (p < 0.001). Circulating DCs and MoDCs were significantly lower in CRC patients, with or without chemotherapy, compared to healthy subjects (p < 0.001). Compared to untreated, chemotherapy-treated patients had 30% fewer DC subsets and lower MoDCs. Characterization of circulating DC subsets and MoDCs may elucidate CRC patients' immune system status.

Aged↗
PubMed2006

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome.

Several reviews and guidelines on the management of mycosis fungoides and Sézary syndrome (MF/SS) have been published; however, treatment strategies for patients with MF/SS vary from institution to institution and no European consensus has yet been established. There are few phase III trials to support treatment decisions for MF/SS and treatment is often determined by institutional experience. In order to summarise the available evidence and review 'best practices' from each national group, the European Organisation for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Task Force met in September 2004 to establish European guidelines for the treatment of MF/SS. This article reviews the treatment regimens selected for inclusion in the guidelines and summarises the clinical data for treatments appropriate for each stage of MF/SS. Guideline recommendations are presented according to the quality of supporting data, as defined by the Oxford Centre for Evidence-Based Medicine. Skin-directed therapies are the most appropriate option for early-stage MF/SS and most patients can look forward to a normal life expectancy. Patients with advanced disease should be encouraged to participate in clinical trials and maintenance of quality of life should be paramount.

Antineoplastic Agents↗
PubMed2006

Prognostic factors in primary cutaneous B-cell lymphoma: the Italian Study Group for Cutaneous Lymphomas.

PURPOSE: Primary cutaneous B-cell lymphomas (PCBCLs) are a distinct group of primary cutaneous lymphomas with few and conflicting data on their prognostic factors. PATIENTS AND METHODS: The study group included 467 patients with PCBCL who were referred, treated, and observed in 11 Italian centers (the Italian Study Group for Cutaneous Lymphomas) during a 24-year period (1980 to 2003). All of the patients were reclassified according to the WHO-European Organisation for Research and Treatment of Cancer (EORTC) classification. RESULTS: Follicle center lymphoma (FCL) accounted for 56.7% of occurrences, followed by marginal-zone B-cell lymphoma (MZL; 31.4%); diffuse large B-cell lymphoma (DLBCL), leg type, was reported in 10.9% of patients. Radiotherapy was the first-line treatment in 52.5% of patients and chemotherapy was the first-line treatment in 24.8% of patients. The complete response rate was 91.9% and the relapse rate was 46.7%. The 5- and 10-year overall survival (OS) rates were 94% and 85%, respectively. Compared with FCL/MZL, DLBCL, leg type, was characterized by statistically significant lower complete response rates, higher incidence of multiple cutaneous relapses and extracutaneous spreading, shorter time to progression, and shorter OS rates. The only variable with independent prognostic significance on the OS was the clinicopathologic diagnosis according to the WHO-EORTC classification (DLBCL, leg-type, showed a significantly worse prognosis v FCL and MZL; P < .001), whereas the only variable with independent prognostic significance on disease-free survival was the presence of a single cutaneous lesion (P = .001). CONCLUSION: Our study identifies a possible PCBCL subclassification and the extent of cutaneous involvement as the two most relevant prognostic factors in PCBCL. These data can be considered reasonably as the clinical background for an appropriate management strategy.

Aged↗
PubMed2006

Topical photodynamic therapy for primary cutaneous B-cell lymphoma: a pilot study.

Photodynamic therapy (PDT) is a treatment based on the accumulation of a photosensitizer in the target cells and their selective destruction by irradiation with visible light. In the past 10 years, several patients with cutaneous T cell lymphoma have been successfully treated. The use of PDT in cutaneous B cell lymphoma has not been reported to date. We report the successful PDT treatment of 3 patients with early primary cutaneous B cell lymphoma.

Adult↗
PubMed2006

New aspects in the biology of cutaneous B-cell lymphomas.

Immunologic and molecular genetic studies greatly contributed to a better understanding and interpretation of the distinct clinico-pathologic features of primary cutaneous B-cell lymphomas (CBCL), which are the basis for the consensus WHO-EORTC classification. There is increasingly accumulating evidence that these well defined clinico-pathologic entities of CBCL have specific immunologic and molecular features, which further support their nosologic categorization as well as either interesting similarities with other extranodal B-cell lymphomas or definite peculiarities as compared to nodal B-cell lymphomas of similar histotype (specifically, follicle center lymphoma and diffuse large B-cell lymphoma).

Humans↗
PubMed2005

Gemcitabine as frontline treatment for cutaneous T-cell lymphoma: phase II study of 32 patients.

BACKGROUND: Based on the activity of gemcitabine in heavily pretreated patients with cutaneous T-cell lymphoma (CTCL), the objective of the current study was to determine the role of gemcitabine in the treatment of patients with advanced, untreated CTCL. METHODS: Between June 2002 and February 2004, 32 untreated patients with mycosis fungoides (MF) (n = 26 patients); peripheral T-cell lymphoma, unspecified (PTCLU) with exclusive skin involvement (n = 5 patients); and Sezary syndrome (SS) (n = 1 patient) were enrolled in a 7-institution, Phase II trial and treated with gemcitabine. This drug was given on Days 1, 8, and 15 of a 28-day schedule at a dose of 1200 mg/m2 intravenously over 30 minutes for a total of 6 cycles. RESULTS: Of the 32 patients studied, 7 (22%) achieved a complete response (CR) and 17 (53%) achieved a partial response (PR), whereas the remaining 8 patients showed no benefit from the treatment. Five of the CRs were confirmed histologically. The CR and PR rates were found to be the same for patients with MF and PTCLU, respectively. The median duration of CR was 10 months (range, 4-22 mos). Treatment appeared to be well tolerated; hematologic toxicity was mild and no nausea/emesis or organ toxicity was noted. CONCLUSIONS: The results of the current Phase II study demonstrate the activity of gemcitabine as a single agent in untreated CTCL patients. Further studies using gemcitabine in combination, either contemporary or sequentially, with other drugs in patients with advanced stage, untreated CTCL are needed.

Adult↗
PubMed2005

WHO-EORTC classification for cutaneous lymphomas.

Primary cutaneous lymphomas are currently classified by the European Organization for Research and Treatment of Cancer (EORTC) classification or the World Health Organization (WHO) classification, but both systems have shortcomings. In particular, differences in the classification of cutaneous T-cell lymphomas other than mycosis fungoides, Sezary syndrome, and the group of primary cutaneous CD30+ lymphoproliferative disorders and the classification and terminology of different types of cutaneous B-cell lymphomas have resulted in considerable debate and confusion. During recent consensus meetings representatives of both systems reached agreement on a new classification, which is now called the WHO-EORTC classification. In this paper we describe the characteristic features of the different primary cutaneous lymphomas and other hematologic neoplasms frequently presenting in the skin, and discuss differences with the previous classification schemes. In addition, the relative frequency and survival data of 1905 patients with primary cutaneous lymphomas derived from Dutch and Austrian registries for primary cutaneous lymphomas are presented to illustrate the clinical significance of this new classification.

Humans↗
PubMed2005

Skin cancer and immunosuppression.

All immunosuppressive treatments, either pharmacological or physical, have the potential to impair the skin immune system network of cells and cytokines, thus leading to an increased incidence of skin cancer. Since skin cancer in transplant recipients may show uncommon clinical features and have an unusually aggressive course, transplant patients should be strictly followed up by experienced dermatologists in order to diagnose and treat properly any skin cancer in an early phase. Importantly, due to the fact that sun exposure increases immunosuppression in the skin, patients should be clearly informed about the additional risk of sun exposure and the preventive measures to be taken.

Humans↗
PubMed2005

Defining early mycosis fungoides.

This editorial review summarizes the results of 5 meetings sponsored by the International Society for Cutaneous Lymphoma at which the clinicopathologic and ancillary features of early mycosis fungoides were critically examined. Based on this analysis, an algorithm was developed for the diagnosis of early mycosis fungoides involving a holistic integration of clinical, histopathologic, immunopathologic, and molecular biological characteristics. A novel aspect of this algorithm is that it relies on multiple types of criteria rather than just one, for example, histopathology. Before its finalization, the proposed diagnostic algorithm will require validation and possibly further refinement at multiple centers during the next several years. It is anticipated that a more standardized approach to the diagnosis of early mycosis fungoides will have a beneficial impact on the epidemiology, prognostication, treatment, and analysis of clinical trials pertaining to this most common type of cutaneous lymphoma.

Algorithms↗
PubMed2005

WHO/EORTC classification of cutaneous lymphomas 2005: histological and molecular aspects.

UNLABELLED: The new WHO/EORTC classification for cutaneous lymphomas comprises mature T-cell and natural killer (NK)-cell neoplasms, mature B-cell neoplasms, and immature hematopoietic malignancies. It reflects the unique features of lymphoproliferative diseases of the skin, and at the same time it is as compatible as possible with the concepts underlying the WHO classification for nodal lymphomas and the EORTC classification of cutaneous lymphomas. This article reviews the histological, phenotypical, and molecular genetic features of the various nosological entities included in this new classification. These findings always have to be interpreted in the context of the clinical features and biologic behavior. AIM: To review the histological, phenotypical and molecular genetic features of the various nosological entities of the new WHO/EORTC classification for cutaneous lymphomas. METHODS: Extensive review of the literature cited in Medline and own data of the authors. RESULTS: The WHO/EORTC classification of cutaneous lymphomas comprises mature T-cell and NK-cell neoplasms, mature B-cell neoplasms and immature hematopoietic malignancies. It reflects the unique features of primary cutaneous lymphoproliferative diseases. CONCLUSION: This classification is as much as possible compatible with the concept of the WHO classification for nodal lymphomas and the EORTC classification of cutaneous lymphomas. The histological, phenotypical and molecular genetic features always have to be interpreted in the context of the clinical features and biologic behavior.

Europe↗
PubMed2004

Monochromatic excimer light (308 nm) in patch-stage IA mycosis fungoides.

Recently, numerous studies have been reported concerning the treatment of early-stage mycosis fungoides (MF) with narrowband (311-nm) UVB, claiming a beneficial response. We have used for the first time a 308-nm monochromatic excimer light, a new kind of xenon-chloride lamp, in the treatment of patch stage IA MF. We treated 7 patch lesions in 4 patients with unequivocal clinicopathologic diagnosis of MF. All lesions achieved clinical and histologic complete remission. The number of weekly sessions varied from 4 to 11 (mean 6.5; median 5.5). The total UVB 308-nm irradiation dose ranged from 5 to 9.3 J/cm(2) (mean 7.1 J/cm(2); median 7 J/cm(2)). All lesions remained in stable complete remission after a follow-up of 3 to 28 months. No remarkable side effects were reported. Our preliminary results suggest that monochromatic excimer light phototherapy is a possibly very useful treatment modality in patch stage IA MF.

Adult↗
PubMed2004

Metastatic melanoma secreted IL-10 down-regulates CD1 molecules on dendritic cells in metastatic tumor lesions.

CD1 molecules are expressed by antigen-presenting cells such as dendritic cells and mediate primary immune responses to lipids and glycolipids which have been shown to be expressed by various tumors. Glycolipids are expressed by melanoma cells but, despite their immunogenicity, no efficient spontaneous immune responses are elicited. As IL-10 has previously been shown to down-regulate CD1a on dendritic cells and is known to be expressed by various melanoma cell lines, we investigated if melanoma-derived IL-10 could down-regulate CD1 molecule expression on dendritic cells as a possible way to circumvent immune recognition. We found that CD1a, CD1b, CD1c, and CD1d were significantly down-regulated on dendritic cells in metastatic (n = 10) but not in primary melanoma lesions (n = 10). We further detected significantly higher IL-10 protein levels in metastatic than in primary melanomas. Moreover, supernatants from metastatic melanomas were significantly more effective in down-regulating CD1 molecules on dendritic cells than supernatants from primary melanoma cultures. This effect was blocked using a neutralizing IL-10 antibody in a dose dependent manner. Our findings suggest that metastatic but not primary melanomas can down-regulate CD1 molecules on infiltrating dendritic cells by secreting IL-10 which may represent a novel way to escape the immune response directed against the tumor.

Antigens, CD1↗
PubMed2004

Atypical CD30+ cutaneous lymphoid proliferation in a patient with tuberculosis infection.

We describe the case of a 65-year-old woman affected by a diffuse lymphadenopathy consistent with tuberculous infection who developed a papular eruption on the head and neck region. Histopathologic examination of one papule showed an atypical CD30+ lymphoid infiltrate, which initially was cause of concern for the pathologists but was eventually regarded as reactive in nature. The case reported herein enlarges the spectrum of inflammatory infiltrates in which atypical CD30+ cells may be found. Since the reactive atypical CD30+ cells are morphologically similar to those cells observed in CD30+ lymphoproliferative disorders, including lymphomatoid papulosis, complete clinical history and laboratory findings are necessary to make the final and correct diagnosis. Although the pathogenetic relevance of the presence of CD30+ cells within the cutaneous infiltrate of patients with systemic tuberculosis remains to be determined, our findings support the hypothesis that the cytokine profile associated with tuberculosis may not be strictly TH1-like, and that a TH1-like to TH2-like switch may also occur.

Aged↗
PubMed2004

Primary cutaneous B-cell lymphomas. Current concepts. I.

BACKGROUND: Primary cutaneous B-cell lymphoma (pCBCL) has only recently been recognized as a distinct clinicopathologic entity. This entity represents a wide spectrum of lymphoproliferative disorders that must be separated from non-Hodgkin's B-cell lymphomas secondarily involving the skin and cutaneous B-cell pseudolymphomas. They are defined as B-cell lymphomas originating in the skin, with no evidence of extracutaneous disease at presentation, as assessed by adequate staging procedures. INFORMATION SOURCES: With the advent of improved immunophenotyping and immunogenotyping, increasing numbers of pCBCL cases are being diagnosed. However, there is still confusion regarding the classification, treatment, and prognosis of these patients. The aim of this paper is to provide the clinician with a concise summary of the diagnosis, course, and treatment of pCBCL. Currently, the European Organization for Research and Treatment of Cancer classification is the most adequate classification scheme, identifying the subtypes of pCBCL by clinical behavior and histopathologic findings, and allowing a better management of the patients. STATE OF THE ART: Based on this classification, the most common subtypes of pCBCL are follicular center cell lymphoma and marginal zone B-cell lymphoma, indolent lymphomas with an excellent prognosis (>95% 5-year survival rate in our series). Although local cutaneous recurrences are observed in about 25% of patients, dissemination to internal organs is rare. A less common, specific subtype - the so-called large B-cell lymphoma of the leg(s) - generally has a poorer prognosis, with a 5-year survival rate of approximately 60%. PERSPECTIVES: As a rule, pCBCL is highly responsive to radiation therapy, which should be considered the treatment of choice. Polychemotherapy should be restricted to patients with involvement of several noncontiguous anatomic sites, those refractory or plurirelapsed after radiotherapy, or those with extracutaneous spread.

Adult↗
PubMed2003

Cytotoxic/natural killer cell cutaneous lymphomas. Report of EORTC Cutaneous Lymphoma Task Force Workshop.

BACKGROUND: Cutaneous lymphomas expressing a cytotoxic or natural killer (NK) cell phenotype represent a group of lymphoproliferative disorders for which there is currently much confusion and little consensus regarding the best nomenclature and classification. METHODS: This study analyzes 48 cases of primary cutaneous lymphoma expressing cytotoxic proteins and/or the NK cell marker, CD56. These cases were collected for a workshop of the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Task Force, to better clarify the clinical, morphologic, and phenotypic features of these uncommon tumors. RESULTS: Several categories with different clinical and pathologic features were delineated: 1) aggressive, CD8+, epidermotropic, cytotoxic T-cell lymphoma; 2) mycosis fungoides, cytotoxic immunophenotype variant; 3) subcutaneous panniculitis-like T-cell lymphoma; 4) NK/T-cell lymphoma, nasal type; 5) CD4+, NK cell lymphoma; 6) blastoid NK cell lymphoma; (7) intravascular NK-like lymphoma; and 8) cytotoxic, peripheral T-cell lymphoma. CONCLUSIONS: Our data show that primary cutaneous cytotoxic/NK cell lymphomas include distinct groups of diseases, clinically, histologically, and biologically. Because the finding of a cytotoxic phenotype often has prognostic significance, the routine use of cytotoxic markers in the diagnosis and classification of cutaneous lymphomas should be expanded.

CD4-Positive T-Lymphocytes↗
PubMed2003

Expression and prognostic significance of matrix metalloproteinases and their tissue inhibitors in primary neuroendocrine carcinoma of the skin.

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been implicated in the development and progression of many tumors, but data for primary neuroendocrine carcinoma (PNC) of the skin are lacking. The aim of the study was to assess the expression of MMPs and TIMPs in PNC and to evaluate their prognostic significance. Expression of MMP-1, MMP-2, MMP-3, MMP-9, MMP-11, MMP-13, and MMP-14 and TIMP-1, TIMP-2, and TIMP-3 was evaluated by immunohistochemistry on 23 samples of PNC of the skin. The results were matched with clinical features and patient survival. In the 23 specimens of PNC, high (>20% of positive neoplastic cells) MMP-1 expression was found in 13 (56.5%) cases. MMP-2 was evidenced in 12 (52.1%) cases, 8 (34.7%) of which showed high expression in neoplastic cells. MMP-3 was detected in 11 cases (47.8%), with high expression in 9 (39.1%) of them. High MMP-9 expression was observed in 3 (13%) cases, whereas high MMP-14 expression was detected in 11 (47.8%) specimens. Expression of TIMP-1 by neoplastic cells was found in 8 (34.7%) cases, with high expression in 3 cases, whereas high TIMP-3 expression was detected in 21 (91.3%) cases. No immunoreactivity for MMP-11, MMP-13, or TIMP-2 was found. Statistical analysis failed to identify a significant correlation between MMP/TIMP expression and clinical parameters. By univariate analysis, stage >I (P = 0.01), high expression of MMP-1 (P = 0.04) and MMP-3 (P = 0.01) resulted significant negative prognostic factors, whereas by multivariate analysis, stage was the only factor that affected survival (P = 0.02). Our results suggest that MMP-1 and MMP-3 may influence the invasive and metastatic potential of PNCs. It is conceivable that future attempts to specifically block MMP-1 and MMP-3 activity may provide a novel means to inhibit invasiveness and distant spread in selected patients with PNC.

Aged↗