Lorenzo Pignataro

Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T cell responses

Dendritic cells (DC) have the unique capacities to induce primary T-cell responses. In mice, CD8α(+)DC are specialized to cross-prime CD8(+) T cells and produce interleukin-12 (IL-12) that promotes cytotoxicity. Human BDCA-3(+)DC share several relevant characteristics with CD8α(+)DC, but the capacities of human DC subsets to induce CD8(+) T-cell responses are incompletely understood. Here we compared CD1c(+) myeloid DC (mDC)1, BDCA-3(+)mDC2, and plasmacytoid DC (pDC) in peripheral blood and lymphoid tissues for phenotype, cytokine production, and their capacities to prime cytotoxic T cells. mDC1 were surprisingly the only human DC that secreted high amounts of IL-12p70, but they required combinational Toll-like receptor (TLR) stimulation. mDC2 and pDC produced interferon-λ and interferon-α, respectively. Importantly, mDC1 and mDC2 required different combinations of TLR ligands to cross-present protein antigens to CD8(+) T cells. pDC were inefficient and also expressed lower levels of major histocompatibility complex and co-stimulatory molecules. Nevertheless, all DC induced CD8(+) memory T-cell expansions upon licensing by CD4(+) T cells, and primed naive CD8(+) T cells following appropriate TLR stimulation. However, because mDC1 produced IL-12, they induced the highest levels of cytotoxic molecules. In conclusion, CD1c(+)mDC1 are the relevant source of IL-12 for naive T cells and are fully equipped to cross-prime cytotoxic T-cell responses.

Genetic and acquired prothrombotic risk factors and sudden hearing loss.

Objectives: Idiopathic sudden sensorineural hearing loss (ISSNHL) is a frequently encountered condition, and various pathogenetic mechanisms have been hypothesized, such as viral infections, autoimmune processes, and ischemic events; however, whatever the cause, impaired cochlear perfusion appears to be the most important event. A number of inherited prothrombotic risk factors and their related genetic alterations have recently been correlated with vascular disorders.

Clinical relevance of cyclin D1 protein overexpression in laryngeal squamous cell carcinoma.

PURPOSE To investigate the prognostic relevance of cyclin D1 gene overexpression in laryngeal squamous cell carcinomas (LSCCs). PATIENTS AND METHODS The overexpression of cyclin D1 was analyzed in 149 LSCC patients with a median follow-up duration of 60 months using the DCS6 monoclonal antibody; only cases that overexpressed cyclin D1 in more than 5% of neoplastic cells were considered positive. RESULTS Forty-eight cases (32.2%) were immunoreactive to the DCS6 antibody. Cyclin D1 overexpression was significantly associated with tobacco smoking and alcohol consumption, tumor extension, advanced clinical stage, and the presence of lymph node metastases. Univariate analysis showed that a shorter disease-free and overall survival were significantly associated with supraglottic site, tumor extension, advanced clinical stage, and cyclin D1 overexpression. At multivariate analysis, tumor extension and cyclin D1 overexpression were significantly associated with tumor recurrence, whereas tumor extension, supraglottic site and, at a borderline level of statistical significance, cyclin D1 overexpression, were associated with reduced overall survival. CONCLUSION The overexpression of cyclin D1 in LSCC is associated with unfavorable clinicopathologic features and represents an independent significant predictor of laryngeal carcinoma prognosis, particularly for disease-free survival. This indicates that cyclin D1 evaluation may be a further useful element for selecting subgroups of patients who should be treated with more aggressive therapies.

Clinical relevance of expression of the CIP/KIP cell-cycle inhibitors p21 and p27 in laryngeal cancer.

PURPOSE To investigate the prognostic relevance of p21 and p27 protein expression in laryngeal squamous cell carcinoma (LSCC). PATIENTS AND METHODS We have analyzed by immunohistochemistry p21 and p27 expression in a series of 132 patients who underwent surgical resection of their LSCC and who had previously been investigated for p53 gene mutations and cyclin D1 expression. The tumors were considered low expressors when they had </= 10% of p21 and </= 50% of p27 immunoreactive neoplastic cells. RESULTS In 41 cases (31.1%), p21 was expressed in </= 10% of neoplastic cells; in 91 cases (68.9%), it was expressed in more than 10% of neoplastic cells. In 11 cases (8.3%), p27 was expressed in less than 5% of neoplastic cells; in 39 cases (29.6%), it was expressed in 5% to 50% of neoplastic cells; and in 82 cases (62.1%), it was expressed in more than 50% of the neoplastic cells. Low levels of p21 expression were associated with poor histologic differentiation and lymph node metastases. Low levels of p27 expression were associated with tumor extension and advanced clinical stage. Expression of p21 and p27 was not correlated with p53 gene status, and low p27 expression was more frequently detected in the cyclin D1-positive cases, with a borderline level of statistical significance. At univariate analysis, anatomic site, tumor extension, clinical stage, high cyclin D1 expression, and low p27 expression were significantly associated with reduced disease-free and overall survival rates. At multivariate analysis, high cyclin D1 expression and low p27 expression were the only significant covariates. The patients with a cyclin D1(+)/p27(-) phenotype had the poorest disease-free and overall survival rates. CONCLUSION Our study provides evidence that the immunohistochemical evaluation of p27 expression is a significant independent predictor of prognosis in laryngeal carcinoma.

Molecular and immunohistochemical analysis of the bcl-1/cyclin D1 gene in laryngeal squamous cell carcinomas: Correlation of protein expression with lymph node metastases and advanced clinical stage

The molecular pathogenesis of laryngeal squamous cell carcinomas (LSCCs) is still only partially understood, although genetic alterations affecting various protooncogenes or tumor suppressor genes have often been detected.

Myringoplasty in children: anatomical and functional results

To assess the results of myringoplasty in children and determine the factors influencing post-operative results a retrospective study of the anatomical and functional results of 41 myringoplasties in children was performed, considering only the cases of uncomplicated perforation that did not require ossiculoplasty or mastoidectomy. The overall success rate was 80.5 per cent after a mean follow-up of 39 months. The mean post-operative air conduction threshold significantly improved in the successful cases with a mean audiological improvement of 11 dB (p<0.05). No post-operative sensorineural hearing loss was observed. There was a significant statistical association between the presence of a dry ear at the time of surgery and good surgical results (p<0.01). Surgical outcome was not affected by the patients age, the site and size of the perforation, previous adenoidectomy, surgical technique (overlay vs underlay), or the status of the contralateral ear. Our findings suggest that myringoplasty is a valid procedure in the paediatric population that gives good anatomical and functional results. The status of the middle ear (i.e. the presence of a dry ear), significantly improves surgical outcome; and so careful inflammatory changes in the middle-ear mucosa should be evaluated and medical treatment considered before surgery.

Cyclin D1 expression is predictive of occult metastases in head and neck cancer patients with clinically negative cervical lymph nodes

The aim of this study was to investigate the value of p53 and cyclin D1 gene expression in predicting the risk of occult lymph node metastases in patients with head and neck squamous cell carcinoma (HNSCC).

Clinical relevance of p53 and bcl‐2 protein over‐expression in laryngeal squamous‐cell carcinoma

We investigated immunohistochemically the clinical relevance of the over‐expression of the apoptosis‐regulating proteins p53 and bcl‐2 in a homogeneous series of 149 laryngeal squamous‐cell carcinomas. p53 was over‐expressed in 75 cases and bcl‐2 in 39 cases. p53 and bcl‐2 co‐expression was found in 21 cases. p53 and bcl‐2 immunoreactivity was significantly associated with poor histological differentiation and lymph‐node metastases. Moreover, a significant statistical correlation was found between bcl‐2 expression, supraglottic tumor site and advanced disease stage. p53/bcl‐2 co‐expression was significantly associated with poor differentiation, tumor extension, the presence of lymph‐node metastases and advanced clinical stage. Univariate analysis showed that a lower probability of survival was significantly associated with supraglottic site, tumor extension, advanced clinical stage and p53/bcl‐2 co‐expression, but not with p53 or bcl‐2 considered separately. In multivariate analysis, only tumor extension and supraglottic site retained their prognostic value. Our data suggest that clinical staging remains the most reliable predictive indicator of survival in patients with laryngeal carcinoma. Int. J. Cancer (Pred. Oncol.) 79:263–268, 1998.© 1998 Wiley‐Liss, Inc.

Tonsillectomy in Children with Periodic Fever with Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome

OBJECTIVE To seek evidence supporting a role for tonsillectomy or adenotonsillectomy in the management of affected children with periodic fever with aphthous stomatitis, pharnygitis, and adenitis (PFAPA) syndrome. STUDY DESIGN A comprehensive literature search was conducted to identify all published English-language observational and randomized studies evaluating the efficacy of tonsillectomy or adenotonsillectomy on PFAPA syndrome. A combination of keywords was used to identify relevant articles. RESULTS A total of 15 studies including 149 treated children were found, including 13 observational noncomparative studies and 2 randomized controlled trials. The pooled rate of complete resolution emerging from the combined analysis of all treated children was 83% (95% CI, 77%-89%). A meta-analysis of the two randomized controlled trials showed homogeneity of the results (P=.37, Breslow-Day test) and a common odds ratio for complete resolution of 13 (95% CI, 4-43; P<.001). CONCLUSIONS Surgery appears to be a possible option for management of PFAPA syndrome. Available evidence is limited, however, and the precise role of surgery remains to be clarified. We suggest considering this option when symptoms markedly interfere with the childs quality of life and medical treatment has failed.

Different therapeutic strategies for burning mouth syndrome: preliminary data.

BACKGROUND To compare different therapeutic supportive approaches in patients with burning mouth syndrome. A prospective study was carried out for this purpose. MATERIALS AND METHODS The study involved 56 patients with burning mouth syndrome. They were randomly assigned to treatment with capsaicin, alpha-lipoic acid or lysozyme-lactoperoxidase (test drugs) or boric acid (control group). Symptoms were scored after 60 days treatment and 60 days after drug discontinuation. RESULTS At the end of the treatment period, there was a significant reduction in the symptom scores of all of the patients who received the test drugs (P<0.01), and at the end of the follow-up period in the test groups as a whole (P<0.01); the reduction was not significant when considering each test group separately after the treatment period. All of the treatments were more effective than boric acid and there was no significant difference in the symptom scores of the control group at either of the study time-points. CONCLUSIONS Our results demonstrate the similar effectiveness of capsaicin and alpha-lipoic acid in controlling the symptoms of burning mouth syndrome. Lysozyme-lactoperoxidase may be effective in the supportive care of BMS patients with xerostomia. The transitory effect observed after discontinuing drug administration justifies the use of prolonged therapy in chronically affected patients.