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  • 1
    In: Journal of Investigative Dermatology, Elsevier BV, Vol. 128, No. 2 ( 2008-02), p. 489-492
    Type of Medium: Online Resource
    ISSN: 0022-202X
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2008
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  • 2
    In: British Journal of Haematology, Wiley, Vol. 78, No. 4 ( 1991-08), p. 494-499
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
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    Language: English
    Publisher: Wiley
    Publication Date: 1991
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  • 3
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 5587-5587
    Abstract: We created a relational database of patients with cutaneous T-cell lymphoma (CTCL) to collect in a standardised fashion, anagraphic variables, clinical history, clinical, histological, haematological, and immunological information on CTCL patients hospitalised at IDI-IRCCS, Rome, Italy. At present, there are data on 424 patients, hospitalised from 1983 to July 2005. Active follow-up is performed yearly to ensure a standardised ascertainment of survival time. For deceased patients, the actual date of death (for all causes) is recorded, while surviving patients are censored at the date of last contact. The database includes 29 patients with Sezary syndrome (SS). Follow-up times ranged from 0 to 105 months. At first hospitalisation the median values of cells/mL were: white blood cells (WBC) 8750, neutrophils 4250, eosinophils 140, basophils 120, lymphocytes 2760, monocytes 500, CD3+ 2780, CD4+ 2431, CD8+ 192, CD19+ 96. Seventeen patients were deceased. We included in the Kaplan-Meier survival analysis only patients who were diagnosed before July 2004 (n=26). Median survival time from diagnosis was 52 months. No significant differences were observed in mortality for WBC (cutoff 9000 cells/uL), neutrophils (cutoff 4500 cells/uL), basophils (cutoff 200 cells/uL), lymphocytes (cutoff 3000 cells/uL), monocytes (cutoff 500 cells/uL), CD3+ (cutoff 2000 cells/uL), CD4+ (cutoff 2000 cells/uL), CD8+ (cutoff 200 cells/uL), CD19+ (cutoff 70 cells/uL). A lower survival was observed for patients with eosinophils & lt;200 cells/uL (p=.08). Survival in patients with SS does not seem to be influenced by haemathologic parameters. However, patients with long-term survival ( & gt;90 months) are observed, and their characteristics should be further investigated. Survival analysis of 26 patients with Sézary syndrome, Rome, Italy, 1991–2004. Survival analysis of 26 patients with Sézary syndrome, Rome, Italy, 1991–2004.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
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  • 4
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 4489-4489
    Abstract: Sezary Syndrome (SS) is a rare form of Cutaneous T-Cell Lymphoma (CTCL) characterised by a distinct metastatic pattern mainly involving skin and blood. Chemokine and chemokine receptors have been implicated in the spreading process of many cancers including various forms of non-Hodgkin T-cell lymphomas (NHL). In this study we report that chemokine receptor CXCR4 is over-expressed by both circulating and skin-homing neoplastic T-lymphocytes of SS patients and is functionally active as demonstrated by the migration of freshly isolated Sezary (SzS) cells along the chemical gradient of its natural ligand SDF-1. To shed light on the regulation of CXCR4/SDF1 interaction, we also investigated the enzymatic activity of CD26/dipeptidylpeptidase IV (DPPIV) since SDF-1 is efficiently inactivated by CD26, in physiological condition.. This is of particular relevance because one of the hallmark of the circulating SzS cells is the loss of CD26 from the cell surface. We first demonstrated that the CD26 negative phenotype is similarly maintained also in the skin-homing neoplastic T lymphocytes; we then observed that the addition of exogenus soluble CD26 reduces the migratory response of SS cells to SDF-1 whereas the inhibition of the CD26 peptidase activity in Hut78, a CD26-positive CTCL cell line, enhances the SDF-1-induced migration of these cells. We finally showed that SS individuals exhibit a reduced activity of the soluble CD26 as revealed by the measurements performed on the patients derived plasma. Our findings suggest that the SDF-1-CXCR4 axis could play an important role in skin homing of SS through the regulatory activity of CD26.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
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  • 5
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 150-150
    Abstract: Sezary syndrome (SS) represents a very aggressive form of Cutaneous T Cell Lymphomas with a median overall survival of 5.1 years (range, 0.4-18.6 years). As it appears evident there are in this disease either short survivors than long survivors. Previous studies of prognostic indicators in SS showed that circulating Sézary cell count, high CD4/CD8 ratio, advanced age, high lactate dehydrogenase serum level and a high white blood cell count were associated with an unfavorable outcome. Up to now, few data have been provided concerning possible associations between immunological and genetic markers, who might provide also clues on tumor progression in this disease. In the last 10 years we have observed more than 50 Sezary Syndromes in our Institute and phenotyped them with new immunologic markers. We have also performed genetic analysis with Single Nucleotide polymorphysms (SNPs) for evaluation of genomic imbalances, mRNA expression and lately microRNA(miRNA) expression profiling. In this study we have analyzed the expression profile of 470 miRNAs using Agilent platform array in 22 SS patients. We investigated the relationship between the expression level of miRNAs and the clinical outcome of SS patients by Kaplan-Meier method and risk assessment by multivariate analysis. We also functionally investigated the role of miR-21, mapping in one of the region more frequently amplified in SS and some of its targets. We identified 45 miRNAs differentially expressed between SS and healthy controls. Using predictive analysis, a list of 19 miRNAs, including miR-21 and miR-18a, miR-342, miR-31 and let-7 members were also found. Moreover, we defined a signature of 14 miRNAs able to discriminate patients with unfavorable and favorable outcome. We show that miR-21 knockdown increases apoptosis and modulates TGF beta receptor 2 expression in vitro. The antipoptotic effect appears to be regulated through PTEN. Conversely, we were not able to observe a direct miR-21 regulation on PDCD4 gene mapping to chromosome 10q24, a frequently imbalanced region in SS. In conclusion we have identified a new prognostic miRNAs signature in SS and characterized the role of miR-21, one of the most involved in cancer, recognized as a disease and prognostic classifier in this disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 150. doi:10.1158/1538-7445.AM2011-150
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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  • 6
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 4814-4814
    Abstract: Abstract 4814 Sezary Syndrome (SS) is characterized by specific chromosomal abnormalities, however is not completely clarified yet which are the genetics hits associated to the initial phase or associated to disease progression. In this study, employing both high density Comparative Genomic Hybridization array (aCGH) and Single Nucleotide Polymorphism (SNP) array technologies, we elucidated the most frequent and significant chromosomal gain and loss regions, and new potentially relevant aberration for the disease progression onset. A total of 30 samples derived from 18 SS patients were analyzed on the Gene Chip Human Mapping 10K Array (Affymetrix). Genotype call and signal information performed by dChip SNP Software (http://www.dchip.org) provided us normalization and simultaneous measurement of Loss of Heterozygosity (LOH) and DNA Copy Number (CN) changes. We have further refined our analysis with a systematic method, Genomic Identification of Significant Targets in Cancer (GISTIC), able to identify regions that were significantly amplified o deleted, assigning a G-score that considers the amplitude of the aberration as well as the frequency of its occurrence across samples (http://genepattern.broadinstitute.org). Our data, generating by the integration of this two methods (see Table 1), revealed 19 significant focal event, including 10 amplification (10p, 17q, 8q, 6p, 4p, 1q, 18q, 21q, 3q, 1p) and 9 deletions (14q, 17p, 10p, 9p, 8p, 13q, 12p, 6q, 2p). In addition, new significant aberrant regions were identified, such as losses of 9p21.3, locus of an important tumor-suppressor gene CDKN2A (p16INK4a/p14ARF) and CDKN2B (p15INK4b). Recently, several study have reported the great influence of alteration in p16INK4a/p14ARF for prognosis of Diffuse large B-cell lymphoma (DLBL), primary cutaneous DLBCL leg-type, Blastic plasmacytoid dendritic cell neoplasm (BPDCN). Across our set of samples, 9p21.3 deletion occur in 8/30 samples from 6 patient, prevalently in heterozygosity state (Log2 ratio from −0.3484 to –0.7691). Two cases presented homozygous deletion (Log2 ratio from −1.2157 to –1.5342), and in four patients losses appeared only in a following phase of observation, suggesting a tumor progression event. Table 1 Significant regions of chromosomal gain Genes in Region Significant regions of chromosomal loss Genes in Region Cytoband Q value GISTIC peak Cytoband Q value GISTIC peak 10p12.33 8.07E-13 17765313-19264851 8 14q11.2 1.85E-40 21395737-22130391 1 17q11.1 3.54E-09 20147238-62034035 563 17p13.1 2.15E-10 1-15053486 234 8q22.3 2.93E-07 70887466-146274826 314 10p11.22 1.98E-07 30280444-32664641 8 6p25.3 0.0020062 1-1263549 6 9p21.3 0.00074825 21283632-22089567 11 4p15.32 0.0071803 17395812-20340589 4 8p23.3 0.00076308 1-32177352 179 1q23.3 0.039674 158849705-159641626 8 13q21.31 0.0028295 63681448-65120691 0 18q22.3 0.1913 1-76117153 251 12p13.1 0.025412 9304151-17414118 85 21q22.3 0.1913 1-46944323 223 6q24.1 0.029124 139319577-141635965 4 3q29 0.2191 169050880-199505740 163 2p23.3 0.043403 24636437-43910832 126 1p36.31 0.11633 1-20338260 239 Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 7
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-01), p. 2292-2292
    Abstract: Sézary Syndrome (SS) is a rare and aggressive form of Cutaneous T-Cell Lymphoma (CTCL) characterised by a distinct metastatic pattern mainly involving blood and skin. Our expression analyses performed by microarrays demonstrated that many chemokines resulted up-regulated in this type of lymphoma. Since these chemoattractant molecules play a critical role in cellular recruitment and homing to tissues and in the metastatic process of several tumors, we focused our attention on one of them named CXCL13, a lymphoid chemokine involved in B-cell compartmental homing within secondary lymphoid organs. Peripheral Blood Mononuclear cells (PBMCs) were isolated from blood obtained from SS patients and controls by Ficoll-Hypaque density gradient centrifugation (Sigma Aldrich). SS cells and healthy resting CD4+ lymphocytes were purified by positive selection using an anti-human-CD4 conjugated dynabeads (Oxoid). Total RNA was extracted using the Trizol reagent (Life Technologies). Quantitative-Real Time RT-PCR analysis was performed on CD4+ sorted from 14 SS patients and 3 controls. CXCL13 primers were designed by means of the Primer Express software package (Applied Biosystems). The qRT-PCR were performed with a SYBR Green I dye chemistry and AmpliTaq Gold DNA Polymerase on an ABI PRISM 7000 machine (Applied Biosystems). Immunohistochemistry analyses for CXCL13 were performed on formalin-fixed, paraffin-embedded skin biopsies from 15 SS, 15 MF, 6 MF-B cell rich patients using streptoavidin-biotin peroxidase labeling method (DAKO). Sections were counterstained with hematoxylin. Plasma CXCL13 levels were determined using a CXCL13 ELISA kit (BD Pharmingen). Results can be summarized as follow: qRT-PCR analysis revealed that 6 out 13 of SS patients showed an high mRNA levels of CXCL13; Immunohistochemistry analysis showed that CXCL13 is abundantly expressed by neoplastic skin-infiltrating lymphocytes of 9 out 15 SS skin biopsies. Conversely, CXCL13 is weakly expressed on scattered neoplastic skin-infiltrating lymphocytes of 1 out 15 MF and 1 out 6 MF-B cell rich biopsies. Plasma CXCL13 concentrations in SS patients (n = 10) were 1362 ± 134 pg/mL. Conversely, those in MF patients (n = 10) and healthy donors (n = 5) were 70 ± 43 and 13 ± 10 pg/mL, respectively. Compared with healthy controls, plasma CXCL13 levels were significantly higher in patients with SS (p 〈 0.001) and with MF (p=0.04). In this study we report that both circulating and skin-infiltrating neoplastic lymphocytes of SS patients abundantly express CXCL13. Furthermore, this chemokine is also detectable at high level on plasma of SS patients. Conversely, CXCL13 is not observable in healthy controls as well as in Mycosis Fungoides, a variant of low grade of CTCL. These findings indicate that CXCL13 could play a role in pathobiology of Sézary Syndrome and that the expression of this chemokine could be used as diagnostic marker for this kind of tumor
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    In: The Lancet, Elsevier BV, Vol. 338, No. 8772 ( 1991-10), p. 958-
    Type of Medium: Online Resource
    ISSN: 0140-6736
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 1991
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    detail.hit.zdb_id: 3306-6
    detail.hit.zdb_id: 1476593-7
    SSG: 5,21
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  • 9
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 5540-5540
    Abstract: Cutaneous lymphoma is a visible cutaneous malignancy, which especially in the more severe forms may have a profound effect on patients lives. The aim of this study was to evaluate quality of life (QoL), psychological distress, and alexithymia in patients with cutaneous lymphoma referring to a dermatological hospital, and to correlate these results with clinical parameters. QoL was evaluated with the Skindex-29, that measures QoL in skin conditions on three scale (symptoms, emotions, and functioning), and the EORTC QLQ-C30, that assesses the QoL of cancer patients. Presence of minor non-psychotic psychiatric disorders was assessed using the GHQ-12, defining as case patients scoring 4 or more; alexithymia was evaluated using the TAS-20 questionnaire. In our ongoing study, we analysed data from the first 66 patients. Of them, 67% were men, the mean age was 58 years (range: 26–85y), and there were 15 patients (23%) with cutaneous B-cell lymphoma (CTBL), and 51 with T-cell lymphoma (CTCL), 6 of them with Sézary Syndrome. In our population, 31.3% of patients were GHQ-cases, 18.6% had alexithymia, and another 22% possible alexithymia. Dermatology-specific QoL was particularly impaired in the symptoms and the emotions scales. QoL was always significantly more impaired in patients with CTCL than in those with CBCL. Also, the prevalence of GHQ-cases was higher (35% in CTCL vs 13% in CBCL), as well as the prevalence of people with alexithymia (48% vs 20%). Skindex-29 and TAS-20 scores significantly correlated with the T stage of lymphoma (i.e., the higher the stage, the lower the QoL and the higher the prevalence of alexithymia). The evaluation of quality of life and psychological problems in patients with cutaneous lymphomas may help clinicians to better manage the disease and its burden on patients life. Also, the relation between quality of life impairment and clinical variables may give important information on the course of the disease as well as the possible effect of treatment.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: Blood, American Society of Hematology, Vol. 107, No. 3 ( 2006-02-01), p. 1108-1115
    Abstract: Sézary syndrome (SS) is a rare form of cutaneous T-cell lymphoma (CTCL) characterized by a distinct metastatic pattern mainly involving blood and skin. Chemokines and their receptors play a critical role in cellular recruitment and homing to tissues and in the metastatic process of several tumors including non-Hodgkin T-cell lymphomas (NHLs). Here we report that SS cells express a functionally active CXCR4 and that its ligand SDF-1 is abundantly produced in the skin, which represents the main destination of SS cell spreading. SDF-1 is normally inactivated by proteolytic cleavage by the CD26/dipeptidylpeptidase IV (DPPIV). The lack of CD26 from the cell surface is a hallmark of circulating SS cells. We also show that the CD26- phenotype is maintained also in skin-infiltrating neoplastic T lymphocytes and that SS-affected individuals exhibit a reduced activity of plasma soluble CD26. Finally, we observe that the addition of soluble CD26 reduces the migratory response of SS cells to SDF-1 whereas the inhibition of the CD26 peptidase activity in Hut78, a CD26+ CTCL cell line, enhances the SDF-1-induced migration of these cells. Our findings suggest that the SDF-1-CXCR4 axis could play an important role in skin homing of SS through the regulatory activity of CD26.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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