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Biomedical subjects

Sergio Chimenti

Publications and source records attributed to Sergio Chimenti.

At least 19 recordsLinked to original sources
PubMed2006

CD56-positive haematological neoplasms of the skin: a multicentre study of the Cutaneous Lymphoma Project Group of the European Organisation for Research and Treatment of Cancer.

BACKGROUND: Cutaneous lymphomas expressing CD56, a neural cell adhesion molecule, are characterised in most cases by a highly aggressive clinical course and a poor prognosis. However, prognostic subsets within the CD56+ group have been difficult to identify due to the lack of uniform clinicopathological and immunophenotypical criteria. METHODS: A multicentre study was conducted by the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer to define prognostic parameters and establish diagnostic and therapeutic guidelines for CD56+ haematological neoplasms presenting primarily in the skin. RESULTS: Four different subtypes of lymphoproliferations with CD56 expression were identified: (1) haematodermic neoplasm; (2) skin infiltration as the first manifestation of CD56+ acute myeloid leukaemia; (3) nasal-type extranodal natural killer/T-cell lymphoma; and (4) "classical" cases of cutaneous T-cell lymphoma (CTCL) with co-expression of the CD56 molecule. Patients in the first three groups had a poor outcome (93% died) with a median survival rate of 11 months (95% CI 2-72 months), whereas all patients with CD56+ CTCL were alive at the last follow-up. CONCLUSION: Results show that CD56+ cutaneous lymphoproliferative disorders, with the exception of CD56+ CTCL have a very poor prognosis. It is therefore clinically important to separate CD56+ CTCL from the remaining CD56+ haematological disorders.

Adolescent↗
PubMed2006

Cross-talks in the p53 family: deltaNp63 is an anti-apoptotic target for deltaNp73alpha and p53 gain-of-function mutants.

The p53 family of transcription factors plays a pivotal role in the control of the cellular response to DNA damaging agents. In addition to pro-apoptotic molecules such as p53, TAp73 and TAp63, this gene family also encodes for the anti-apoptotic molecules deltaNp73, deltaNp63, deltaNp53, and p53 mutants are often found in tumor cells, that have the role to limit and to modulate the pro-apoptotic side of the family. The ratio between the different members of the family is critical to make the life or death decision following DNA damage and is tightly regulated by post-translational and transcriptional mechanisms. In this study we have uncovered a novel positive feedback that involves the transcriptional activation of the anti-apoptotic molecule deltaNp63 by the anti-apoptotic molecules deltaNp73 and mutant p53, and that is put into motion upon treatment with a subset of DNA damaging agents such as Doxorubicin and 5-FU. DeltaNp73 and mutant p53 associate with the deltaNp63 promoter inducing its transcription and this is enhanced by doxorubicin treatment. Furthermore we have observed that deltaNp73- and mutp53-mediated activation of the deltaNp63 promoter requires the functionality of the proximal CCAAT boxes of this promoter, being hampered by mutation of CCAAT boxes or by dominant negative NFYA expression. This mechanism may serve as an additional control of the response of a normal cell to DNA damage or as an anti-apoptotic barrier of cancer cells subjected to DNA damage.

Animals↗
PubMed2006

Co-localization of susceptibility loci for psoriasis (PSORS4) and atopic dermatitis (ATOD2) on human chromosome 1q21.

Psoriasis (PS) is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation and altered differentiation. Atopic dermatitis (ATOD) is a chronic inflammatory, pruritic and eczematous disease frequently associated with respiratory atopy. These diseases are associated with distinct immunologic abnormalities and represent typical examples of complex diseases triggered by both genetic and environmental factors, as demonstrated by independent twin studies. Genome wide linkage studies have mapped susceptibility loci on several chromosomes (PSORS1-9; ATOD1-5). Four of them overlap on chromosomes 1q21, 3q21, 17q25 and 20p although ATOD is quite distinct from PS and these two diseases rarely occur together in the same patient. An association fine-mapping study has been performed to refine PSORS4 and ATOD2 susceptibility loci on chromosome 1q21 analyzing two independently collected cohorts of 128 PS and 120 ATOD trios. Genotype and haplotype analysis of PSORS4 and ATOD2 led us to detect significant p value for haplotypes defined by MIDDLE and ENDAL16 markers in both PS (p = 0.0000036) and ATOD (p = 0.0276), suggesting a strict co-localization within an interval of 42 kb. This genomic interval contains a single gene, LOR, encoding for loricrin. Polymorphic markers mapping in regulatory and coding regions did not show evidence of association in neither of the two diseases. However, expression profiles of LOR in skin biopsies have shown reduced levels in PS and increased levels in ATOD, suggesting the existence of a specific misregulation in LOR mRNA production.

Chromosome Mapping↗
PubMed2006

Prevention of dermatologic side effects of bimatoprost 0.03% topical therapy.

PURPOSE: To investigate the efficacy of reducing the drop-skin contact to prevent dermatologic side effects of bimatoprost 0.03% topical therapy. DESIGN: Prospective, randomized, single-blinded, internally controlled study. METHODS: Enrolled subjects started bimatoprost 0.03% therapy once at night in both eyes and were instructed to wipe selectively only one eye (eye 1) with an adsorbent pad during and after drops administration for four months. The fellow eye acted as the internal control. Eyelash growth, regional skin hypertrichosis, and pigmentation on the periocular skin were assessed at baseline and during the four months of follow-up. RESULTS: A lower incidence of eyelash growth and skin pigmentation in the inferonasal pericanthal region were observed in eye 1. The incidence of pigmentation in the inferotemporal skin region and skin hypertrichosis were similar in the two eyes. CONCLUSION: The reduction of the drop-skin contact affects the regional incidence and the extent of dermatologic skin changes that are related to bimatoprost 0.03% topical therapy.

Adult↗
PubMed2006

Identical TCR beta-chain rearrangements in streptococcal angina and skin lesions of patients with psoriasis vulgaris.

Tonsillar infection with Streptococcus pyogenes may induce several nonsuppurative autoimmune sequelae. The precise pathogenetic mechanisms behind this clinically well-established association are still unresolved. Using TCR analysis, we sought to identify a link between streptococcal tonsillitis and the T cell-mediated autoimmune response in psoriasis. Three patients with streptococcal-induced psoriasis underwent tonsillectomy. Using size spectratyping and sequencing of TCR beta-chain variable region gene (TCRBV) rearrangements, we compared the TCR usage of psoriatic skin lesions, blood, tonsils, and tonsillar T cells fractionated according to the expression of the skin address in "cutaneous lymphocyte-associated Ag" (CLA). TCRBV-size spectratype analysis of the blood lymphocytes, tonsils, and the CLA-negative tonsillar T cells revealed largely unselected T cell populations. Instead, TCRBV gene families of the psoriatic lesions and skin-homing CLA-positive tonsillar T cells displayed highly restricted spectratypes. Sequencing of TCRBV cDNA identified various clonal TCRBV rearrangements within the psoriatic lesions that indicated Ag-driven T cell expansion. Several of these clonotypes were also detected within the tonsils and, in one of the patients, within the small subset of CLA-positive tonsillar T cells, suggesting that T cells from the same T cell clones were simultaneously present within skin and tonsillar tissue. Because after tonsillectomy psoriasis cleared in all three patients our observations indicate that T cells may connect psoriatic inflammation to streptococcal angina. They suggest that the chronic streptococcal immune stimulus within the tonsils could act as a source for pathogenic T cells in poststreptococcal disorders, and they may help to explain why eliminating this source with tonsillectomy may improve streptococcal-induced sequelae.

Adult↗
PubMed2006

PSORS2 markers are not associated with psoriatic arthritis in the Italian population.

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy characterized by the association of arthritis and psoriasis (Ps). The precise etiology of PsA is unknown, but epidemiological studies supported the existence of a genetic component for the disease. Here we report an association study on a large PsA Italian cohort for DNA variants recently reported as associated alleles at PSORS2 (17q25) in Ps cohorts from the US. We focused on discovering a possible involvement of PSORS2 associated SNPs in pathogenesis of PsA. We selected two SNPs (rs7420, rs734232) within the proximal peak and two SNPs (rs869190 and rs1561946) within distal peak of PSORS2. Our results ruled out PSORS2 alleles as susceptibility factors in arthritis psoriatic patients of Italian origin and suggested that previous linkage signal reported for chromosome 17q25 should be independent on the presence of PsA.

Alleles↗
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

Imiquimod 5% cream in the treatment of Bowen's disease and invasive squamous cell carcinoma.

BACKGROUND: Imiquimod has been successfully used for treatment of various epithelial cutaneous neoplasms. OBJECTIVE: Our aim was to evaluate the efficacy and tolerability of imiquimod 5% cream for treatment of Bowen's disease and invasive squamous cell carcinoma (SCC) in patients who were unsuitable candidates for surgery. METHOD: Five Bowen's disease lesions and 7 invasive SCC lesions on 10 patients were treated with imiquimod once daily 5 times a week for a maximum of 16 weeks. RESULTS: After 8 to 12 weeks of treatment, 4 of 5 Bowen's disease lesions (80%) and 5 of 7 invasive SCCs (71.4%) showed complete clinicopathologic regression. The remaining 3 lesions showed partial regression after 16 weeks of treatment. No recurrence has been detected after a follow-up period of 24 to 38 months (mean, 31 months). LIMITATIONS: The study is an open-label clinical trial on a small number of selected patients, with lack of excision with serial step sections. CONCLUSION: Topical application of imiquimod 5% cream might represent an alternative topical treatment to surgery in selected cases of Bowen's disease and invasive SCC.

Adjuvants, Immunologic↗
PubMed2006

Contribution of melanocortin-1 receptor gene variants to sporadic cutaneous melanoma risk in a population in central Italy: a case-control study.

The melanocortin-1 receptor (MC1R) gene is a key determinant of the physiological variation in human skin pigmentation. It is highly polymorphic, and specific MC1R allelic variants have been shown to be low-penetrance melanoma susceptibility alleles. We investigated the contribution of the MC1R genotype to the risk of sporadic cutaneous melanoma in a population in central Italy. One hundred patients with sporadic cutaneous melanoma of any stage and 100 unrelated control individuals were consecutively recruited between 1 September 2000 and 31 December 2001. Information on ethnic background and residential history, phenotypic risk factors for melanoma and ultraviolet exposure habits was collected through a standardized questionnaire and total skin examination. Sequence analysis of the entire coding region of the MC1R gene was performed. A total of 26 MC1R variants, including a novel 123_124insT allele, was identified in our population, with the most frequent allele being V60L. Carriers of high-penetrance 'R' MC1R alleles, that define MC1R variants strongly associated with the red hair colour phenotype, showed a statistically significant increase in melanoma risk [odds ratio (OR), 2.55; 95% confidence interval (CI), 1.19-5.55]. No significant association with melanoma risk was observed for carriers of 'r' variants (OR, 0.90; 95% CI, 0.45-1.82). Amongst individual MC1R variants, the R151C allele was significantly associated with melanoma, with an OR of 2.94 (95% CI, 1.04-8.31). After stratification for clinical and ultraviolet exposure risk factors, the melanoma risk associated with high-penetrance 'R' variants appeared to increase significantly, mainly in the presence of clinically atypical naevi, more than 50 melanocytic naevi, high recreational sun exposure and occupational sun exposure. These results support the contribution of high-penetrance MC1R variant alleles to genetic predisposition to sporadic cutaneous melanoma in a population in central Italy.

Adolescent↗
PubMed2006

Hypoepiluminescence microscopy of pigmented skin lesions: new approach to improve recognition of dermoscopic structures.

BACKGROUND: Hypoepiluminescence microscopy (HELM) is a new dermoscopic approach for analysis of pigmented skin lesions (PSLs) after surgical excision. OBJECTIVES: The objective was to verify whether this method could provide additional morphologic information for diagnostic or didactic purposes compared to conventional epiluminescence microscopy (ELM). PATIENTS AND METHODS: Thirty-one PSLs from 30 patients were consecutively evaluated by ELM and, after excision, by HELM. For HELM examination, the lesion was positioned on a glass slide and illuminated from above with a halogen lamp and from underneath with an LED source. All lesions were subsequently examined histopathologically. RESULTS: In 11 of 31 (35.5%) lesions, a typical pigment network, as assessed by ELM, appeared bidimensional with HELM. In 9 lesions (9/31; 29%) ELM showed a gray-blue area, while HELM allowed us to distinguish 5 lesions (5/9, 55.5%) with gray area predominant showing a lichenoid lymphocytic infiltration and few melanophages from the other 4 lesions (4/9, 44,5%) with heavy dermal accumulation of pigmented melanocytes or melanophages where a blue area was clearly visible at HELM. In 9 other cases (29%), ELM analysis revealed a central homogeneous dark brown/black pigmentation that in 7 cases was seen under HELM examination to consist of globules. CONCLUSIONS: HELM is particularly useful in evaluating heavily PSLs or structures located in the reticular dermis.

Adolescent↗
PubMed2006

An Italian study on psoriasis and depression.

BACKGROUND: Psoriasis is often associated with the risk of physical disability, social discomfort and psychological disorders. OBJECTIVES: The aim of this study was to investigate the prevalence of depressive symptomatology among Italian patients with psoriasis vulgaris, in order to better evaluate the disease severity in this patient population. METHODS: Five thousand Italian patients with psoriasis were mailed the Center for Epidemiological Studies-Depression Scale (CES-D) questionnaire, a 20-item instrument developed to perform epidemiological studies of depressive symptomatology in the general population. Questionnaires with responses to 16 or more items were considered evaluable. RESULTS: We received evaluable questionnaires from 2,391 patients, including 1,528 men (63.9%) and 863 women (36.1%). Depressive symptomatology was observed in 1,482/2,391 patients (62% overall; females, 63%; males, 61%). Men < 40 years of age were significantly more likely to report depressive symptoms than were men > or =40 years of age (67 vs. 58%, respectively; p = 0.002). Depressive symptomatology was more prevalent in psoriatic patients with only primary or secondary education than in psoriatic patients with higher education (51 vs. 32%, respectively; p < 0.02). CONCLUSION: Our results are consistent with previous studies showing that psoriasis is associated with profound psychological morbidity, in particular with depression in a large number of patients. It is important to consider this association in the overall management of psoriasis.

Adult↗
PubMed2006

Short contact therapy with tazarotene in psoriasis vulgaris.

BACKGROUND: We present the results of a multicentre, not controlled, clinical study on the tolerability and efficacy of tazarotene gel, used as short contact therapy (SCT), in psoriasis vulgaris. OBJECTIVE: To evaluate whether irritant contact dermatitis caused by tazarotene was less frequent and/or less severe with SCT than with traditional therapy, and whether SCT with tazarotene was as effective as traditional therapy. METHODS: Forty-three patients with plaque psoriasis were treated by SCT with 0.1% tazarotene gel (once daily application for 20 min, followed by washing with water). Treatment duration was 45 days. RESULTS: Irritant contact dermatitis caused by tazarotene used as SCT was much less frequent and severe than traditional treatment with the same drug. SCT with tazarotene was effective in the treatment of plaque psoriasis. CONCLUSION: Tazarotene, used as SCT, was better tolerated than the same drug used as traditional treatment. Furthermore, SCT appeared to be as effective as traditional therapy with the same drug.

Administration, Topical↗